Lignin: A multi-faceted role/function in 3D printing inks.

3D printing technology demonstrates significant potential for the rapid fabrication of tailored geometric structures. Nevertheless, the prevalent use of fossil-derived compositions in printable inks within the realm of 3D printing results in considerable environmental pollution and ecological consequences. Lignin, the second most abundant biomass source on earth, possesses attributes such as cost-effectiveness, renewability, biodegradability, and non-toxicity. Enriched with active functional groups including hydroxyl, carbonyl, carboxyl, and methyl, coupled with its rigid aromatic ring structure and inherent anti-oxidative and thermoplastic properties, lignin emerges as a promising candidate for formulating printable inks. This comprehensive review presents the utilization of lignin, either in conjunction with functional materials or through the modification of lignin derivatives, as the primary constituent (≥50 wt%) for formulating printable inks across photo-curing-based (SLA/DLP) and extrusion-based (DIW/FDM) printing technologies. Furthermore, lignin as an additive with multi-faceted roles/functions in 3D printing inks is explored. The effects of lignin on the properties of printing inks and printed objects are evaluated. Finally, this review outlines future perspectives, emphasizing key obstacles and potential opportunities for facilitating the high-value utilization of lignin in the realm of 3D printing.

Case report: Cutaneous anthrax diagnosed using mNGS of a formalin-fixed paraffin-embedded tissue sample.

The metagenomic next-generation sequencing (mNGS) method is preferred for genotyping useful for the identification of organisms, illumination of metabolic pathways, and determination of microbiota. It can accurately obtain all the nucleic acid information in the test sample. Anthrax is one of the most important zoonotic diseases, infecting mainly herbivores and occasionally humans. The disease has four typical clinical forms, cutaneous, gastrointestinal, inhalation, and injection, all of which may result in sepsis or meningitis, with cutaneous being the most common form. Here, we report a case of cutaneous anthrax diagnosed by mNGS in a butcher. Histopathology of a skin biopsy revealed PAS-positive bacilli. Formalin-fixed paraffin-embedded (FFPE) tissue sample was confirmed the diagnosis of anthrax by mNGS. He was cured with intravenous penicillin. To our knowledge, this is the first case of cutaneous anthrax diagnosed by mNGS using FFPE tissue. mNGS is useful for identifying pathogens that are difficult to diagnose with conventional methods, and FFPE samples are simple to manage. Compared with traditional bacterial culture, which is difficult to cultivate and takes a long time, mNGS can quickly and accurately help us diagnose anthrax, so that anthrax can be controlled in a timely manner and prevent the outbreak of epidemic events.

Carfilzomib activates ER stress and JNK/p38 MAPK signaling to promote apoptosis in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly cancers in the world, which is frequently diagnosed at a late stage. HCC patients have a poor prognosis due to the lack of an efficacious therapeutic strategy. Approved drug repurposing is a way for accelerating drug discovery and can significantly reduce the cost of drug development. Carfilzomib (CFZ) is a second-generation proteasome inhibitor, which is highly efficacious against multiple myeloma and has been reported to possess potential antitumor activities against multiple cancers. However, the underlying mechanism of CFZ on HCC is still unclear. Here, we show that CFZ inhibits the proliferation of HCC cells through cell cycle arrest at the G2/M phase and suppresses the migration and invasion of HCC cells by inhibiting epithelial-mesenchymal transition. We also find that CFZ promotes reactive oxygen species production to induce endoplasmic reticulum (ER) stress and activate JNK/p38 MAPK signaling in HCC cells, thus inducing cell death in HCC cells. Moreover, CFZ significantly inhibits HCC cell growth in a xenograft mouse model. Collectively, our study elucidates that CFZ impairs mitochondrial function and activates ER stress and JNK/p38 MAPK signaling, thus inhibiting HCC cell and tumor growth. This indicates that CFZ has the potential as a therapeutic drug for HCC.

Polyoxometalate-Intercalated Tremella-Like CoNi-LDH Nanocomposites for Electrocatalytic Nitrite-Ammonia Conversion.

The electrocatalytic reduction of NO2- (NO2RR) holds promise as a sustainable pathway to both promoting the development of emerging NH3 economies and allowing the closing of the NOx loop. Highly efficient electrocatalysts that could facilitate this complex six-electron transfer process are urgently desired. Herein, tremella-like CoNi-LDH intercalated by cyclic polyoxometalate (POM) anion P8W48 (P8W48/CoNi-LDH) prepared by a simple two-step hydrothermal-exfoliation assembly method is proposed as an effective electrocatalyst for NO2- to NH3 conversion. The introduction of POM with excellent redox ability tremendously increased the electrocatalytic performance of CoNi-LDH in the NO2RR process, causing P8W48/CoNi-LDH to exhibit large NH3 yield of 0.369 mmol h-1 mgcat-1 and exceptionally high Faradic efficiency of 97.0% at -1.3 V vs the Ag/AgCl reference electrode in 0.1 M phosphate buffer saline (PBS, pH = 7) containing 0.1 M NO2-. Furthermore, P8W48/CoNi-LDH demonstrated excellent durability during cyclic electrolysis. This work provides a new reference for the application of POM-based nanocomposites in the electrochemical reduction of NO2- to obtain value-added NH3.

Glycyrrhiza polysaccharides may have an antitumor effect in γδT cells through gut microbiota and TLRs/NF-κB pathway in mice.

Tumor immunotherapy can be a suitable cancer treatment option in certain instances. Here we investigated the potential immunomodulatory effect of oral glycyrrhiza polysaccharides (GCP) on the antitumor function of γδT cells in intestinal epithelial cells in mice. We found that GCP can inhibit tumor growth and was involved in the regulation of systemic immunosuppression. GCP administration also promoted the differentiation of gut epithelia γδT cells into IFN-γ-producing subtype through regulation of local cytokines in gut mucosa. GCP administration increased local cytokine levels through gut microbiota and the gut mucosa Toll-like receptors / nuclear factor kappa-B pathway. Taken together, our results suggest that GCP might be a suitable candidate for tumor immunotherapy, although further clinical research, including clinical trials, are required to validate these results.

Comparison of Percutaneous Transforaminal Endoscopic Decompression and Full Endoscopic Lamina Fenestration Decompression in the Treatment of Degenerative Lumbar Spinal Stenosis with Unilateral Radicular Pain: A Retrospective Study.

BACKGROUND: Endoscopic decompression of the spinal canal is an emerging procedure for the treatment of degenerative lumbar spinal stenosis, but there are few reports of comparative studies of endoscopic techniques for transforaminal and non-transforaminal approaches. OBJECTIVE: To compare the clinical application of percutaneous transforaminal endoscopic decompression (PTED) and full endoscopic lamina fenestration decompression (Endo-LOVE) for treating degenerative lumbar spinal stenosis with unilateral radicular pain. METHODS: A total of 58 patients with degenerative lumbar spinal stenosis (DLSS) with unilateral radicular pain in the lower extremities who underwent endoscopic decompression treatment from June 2020 to December 2021 were retrospectively identified and divided into two groups (PTED vs Endo-LOVE). The two groups' perioperative data were analyzed according to surgical modalities. The Visual Analogue Score (VAS) for pain, Oswestry Disability Index (ODI), modified MacNab criteria, and dural sac cross-sectional area (DSCSA) were used to assess the post-operative outcomes of the two groups. RESULTS: All 58 patients completed the operation and received more than 12 months of follow-up. There was no significant difference in the operation time, number of intraoperative fluoroscopies, intraoperative bleeding, or postoperative hospitalization time between the two groups (p > 0.05); VAS scores and ODIs of the two groups at all postoperative time points were significantly lower than before the operation (p < 0.05), and there was no significant difference in the comparison of the clinical efficacy between the two groups (p > 0.05); the DSCSA of the two groups at the last postoperative follow-up was significantly larger than before the operation (p < 0.05), and there was no significant difference in the improvement of DSCSA between them (p > 0.05). CONCLUSIONS: Both procedures are safe and effective in the treatment of DLSS with unilateral lower extremity radicular pain, and we should be specific about the choice of spinal stenosis treatment.

zDHHC20-driven S-palmitoylation of CD80 is required for its costimulatory function.

CD80 is a transmembrane glycoprotein belonging to the B7 family, which has emerged as a crucial molecule in T cell modulation via the CD28 or CTLA4 axes. CD80-involved regulation of immune balance is a finely tuned process and it is important to elucidate the underlying mechanism for regulating CD80 function. In this study we investigated the post-translational modification of CD80 and its biological relevance. By using a metabolic labeling strategy, we found that CD80 was S-palmitoylated on multiple cysteine residues (Cys261/262/266/271) in both the transmembrane and the cytoplasmic regions. We further identified zDHHC20 as a bona fide palmitoyl-transferase determining the S-palmitoylation level of CD80. We demonstrated that S-palmitoylation protected CD80 protein from ubiquitination degradation, regulating the protein stability, and ensured its accurate plasma membrane localization. The palmitoylation-deficient mutant (4CS) CD80 disrupted these functions, ultimately resulting in the loss of its costimulatory function upon T cell activation. Taken together, our results describe a new post-translational modification of CD80 by S-palmitoylation as a novel mechanism for the regulation of CD80 upon T cell activation.

Combined effects of Rhodiola rosea and caffeine supplementation on aerobic endurance and muscle explosiveness: a synergistic approach.

This study examined the synergistic effects of combining Rhodiola rosea (RHO) and caffeine (CAF) supplementation on muscle endurance and explosiveness in SD rats and human subjects, encompassing individuals without prior exercise training experience and seasoned aerobic athletes. Male SD rats and healthy human volunteers were randomly divided into four groups: CAF, RHO, CAF + RHO, and a control group (CTR). Nutritional supplements were administered throughout the training period, and pre-and post-measurement data were collected. In both the rat model and human subjects, the RHO+CAF group demonstrated significantly greater effects compared to the use of RHO or CAF supplements individually. Rats in the RHO+CAF group demonstrated extended running and swimming times and an increase in erythropoietin (EPO) mRNA expression in comparison to the CTR. Blood parameters, such as serum EPO levels, were enhanced in the CAF + RHO group, while blood urea nitrogen (BUN) and lactate (LA) levels significantly decreased in both the RHO and CAF + RHO groups. Hepatic and muscle glycogen contents were also higher in these groups. The gene expression analysis in rats demonstrated an elevation in the mRNA levels of glucose transporter-4 (GLUT-4), peroxisome proliferator-activated receptor γ coactivator-1 alpha (PGC-1α), Monocarboxylate transporter 1 (MCT-1), and Heme Oxygenase-1 (HO-1) in both the RHO and RHO+CAF groups. For individuals without prior aerobic training experience, the RHO+CAF group showed significant improvements compared to the CTR group in maximal oxygen consumption (VO2max), 5 km run, countermovement jump (CMJ), standing long jump, and 30 m sprint. For individuals with years of aerobic training experience, the RHO+CAF group exhibited enhanced performance in the 5 km run, CMJ, and standing long jump compared to the CTR group. In conclusion, the continuous 30 days supplementation of RHO, combined with a single dose of CAF, demonstrated superior effects on muscle endurance and explosiveness in both animal and human studies when compared to the use of RHO or CAF individually.

Oxygen-Vacancy-Rich Monolayer BiO2- X Nanosheets for Bacterial Sepsis Management via Dual Physically Antibacterial and Chemically Anti-inflammatory Functions.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Effective treatment of bacterial sepsis remains challenging due to the rapid progression of infection and the systemic inflammatory response. In this study, monolayer BiO2- X nanosheets (BiO2- X NSs) with oxygen-rich vacancies through sonication-assisted liquid-phase exfoliation are successfully synthesized. Herein, the BiO2- X NSs exhibit a novel nanozyme-enabled intervention strategy for the management of bacterial sepsis, based on its pH dependent dual antibacterial and anti-inflammatory functions. BiO2- X NSs exhibit effective antibacterial by utilizing oxidase (OXD)-like activity. Additionally, BiO2- X NSs can scavenge multiple reactive oxygen species (ROS) and mitigate systemic hyperinflammation by mimicking superoxide dismutase (SOD) and catalase (CAT). These dual capabilities of BiO2- X NSs allow them to address bacterial infection, proinflammatory cytokines secretion and ROS burst collaboratively, effectively reversing the progression of bacterial sepsis. In vivo experiments have demonstrated that BiO2- X NSs significantly reduce bacterial burden, attenuate systemic hyperinflammation, and rapidly rescued organ damage. Importantly, no obvious adverse effects are observed at the administered dose of BiO2- X NSs. This study presents a novel defect engineering strategy for the rational design of high-performance nanozymes and development of new nanomedicines for managing bacterial sepsis.

Circ_0001495 influences the development of endometriosis through the miRNA-34c-5p/E2F3 axis.

Endometriosis is a chronic gynecological condition characterized by the presence of endometrial glands and stroma outside the uterine cavity., accounting for 7% of all female malignant tumors and 20%- 30% of malignant tumors of the female reproductive system. Multiple studies have shown that circular RNA (circRNA) has the potential to become a targeted target and marker for EM. However, the roles of circ_0001495 in EM are still unclear. Our research aims to reveal the molecular mechanism of circ_0001495 in EM. In this study, RT-PCR or western blot were conducted to determine mRNA and protein expression. cell viability, proliferation, migration, invasion, and apoptosis were assessed by CCK-8, EdU, wound healing, transwell, and flow cytometry analyses, respectively. Additionally, the targeting relationship between miR-34c-5p and circ_0001495 or E2F3 was confirmed through dual-luciferase reporter gene assay. We found significant overexpression of circ_0001495 in EM tissues and cells. Knockdown of circ_0001495 inhibited the proliferation, migration and invasion of ectopic endometrial stromal cells (EESCs) and increased cell apoptosis. Moreover, we found that circ_0001495 regulated E2F3 levels by interacting with miR-34c-5p in EESC. Furthermore, in vitro, miR-34c-5p inhibition or E2F3 overexpression could attenuate the effect of circ_0001495 silencing on EM progression. In addition, the vivo experiment demonstrated that inhibition of circ_0001495 could repress the development of endometriosis by regulating the miR-34c-5p/E2F3 axis. In conclusion, our study suggested that circ_0001495 promoted EM progression in vitro and in vivo through the miR-34c-5p/E2F3 axis, which might be a potential therapeutic target for EM.

The power of many brains: Catalyzing neuropsychiatric discovery through open neuroimaging data and large-scale collaboration.

Recent advances in open neuroimaging data are enhancing our comprehension of neuropsychiatric disorders. By pooling images from various cohorts, statistical power has increased, enabling the detection of subtle abnormalities and robust associations, and fostering new research methods. Global collaborations in imaging have furthered our knowledge of the neurobiological foundations of brain disorders and aided in imaging-based prediction for more targeted treatment. Large-scale magnetic resonance imaging initiatives are driving innovation in analytics and supporting generalizable psychiatric studies. We also emphasize the significant role of big data in understanding neural mechanisms and in the early identification and precise treatment of neuropsychiatric disorders. However, challenges such as data harmonization across different sites, privacy protection, and effective data sharing must be addressed. With proper governance and open science practices, we conclude with a projection of how large-scale imaging resources and collaborations could revolutionize diagnosis, treatment selection, and outcome prediction, contributing to optimal brain health.

Genetic Basis and Evolutionary Forces of Sexually Dimorphic Color Variation in a Toad-Headed Agamid Lizard.

In the animal kingdom, sexually dimorphic color variation is a widespread phenomenon that significantly influences survival and reproductive success. However, the genetic underpinnings of this variation remain inadequately understood. Our investigation into sexually dimorphic color variation in the desert-dwelling Guinan population of the toad-headed agamid lizard (Phrynocephalus putjatai) utilized a multidisciplinary approach, encompassing phenotypic, ultrastructural, biochemical, genomic analyses, and behavioral experiments. Our findings unveil the association between distinct skin colorations and varying levels of carotenoid and pteridine pigments. The red coloration in males is determined by a genomic region on chromosome 14, housing four pigmentation genes: BCO2 and three 6-pyruvoyltetrahydropterin synthases. A Guinan population-specific nonsynonymous single nucleotide polymorphism in BCO2 is predicted to alter the electrostatic potential within the binding domain of the BCO2-ß-carotene complex, influencing their interaction. Additionally, the gene MAP7 on chromosome 2 emerges as a potential contributor to the blue coloration in subadults and adult females. Sex-specific expression patterns point to steroid hormone-associated genes (SULT2B1 and SRD5A2) as potential upstream regulators influencing sexually dimorphic coloration. Visual modeling and field experiments support the potential selective advantages of vibrant coloration in desert environments. This implies that natural selection, potentially coupled with assortative mating, might have played a role in fixing color alleles, contributing to prevalence in the local desert habitat. This study provides novel insights into the genetic basis of carotenoid and pteridine-based color variation, shedding light on the evolution of sexually dimorphic coloration in animals. Moreover, it advances our understanding of the driving forces behind such intricate coloration patterns.

Integrating network pharmacology, experimental validation and molecular docking to reveal the alleviation of Yinhuang granule on idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by the abnormal proliferation of fibroblast and excessive deposition of extracellular matrix (ECM), accompanied by inflammation and ultimately respiratory failure. Yinhuang granule (YHG), with clinical properties of clearing heat, detoxifying and anti-inflammation, is commonly used to heal upper respiratory diseases in China for decades. PURPOSE: To explore the improvement of YHG on bleomycin (BLM)-induced IPF in mice and its possible engaged mechanism. METHODS: The mortality rate was recorded, lung function was determined and hematoxylin-eosin (H&E) staining was carried out to explore the alleviation of YHG on BLM-caused IPF in mice. Hydroxyproline, collagen I and collagen III contents were detected, and Sirius red and Masson staining were conducted to evaluate YHG's alleviation on lung fibrosis. The underlying mechanism was predicted by network pharmacology, and confirmed by Real-time polymerase chain reaction (RT-PCR), Western-blot (WB) and enzyme linked immunosorbent assay (ELISA). The binding affinity between related key proteins and active compounds in YHG was calculated by using molecular docking, and further validated by cellular thermal shift assay (CESTA). RESULTS: YHG (400, 800 mg/kg) weakened lung damage and pulmonary fibrosis in mice induced by BLM. Network pharmacology and experimental validation displayed that inflammation and angiogenesis participated in the YHG-provided improvement on IPF, and key involved molecules included tumor necrosis factor-α (TNFα), vascular endothelial growth factor-A (VEGFA), interleukine-6 (IL-6), etc. The data of molecular docking presented that some main active compounds from YHG had a high binding affinity with TNFR1 or VEGFR2, and some of them were further validated by CESTA. CONCLUSION: YHG effectively improved the BLM-induced IPF in mice via reducing inflammation and angiogenesis.

Transcriptome analysis reveals key genes and pathways for prickle development in Zanthoxylumarmatum.

Zanthoxylum armatum is an economically important tree species. However, well-developed prickles on its stems and leaves pose serious challenges in terms of management and harvesting. To investigate the molecular mechanism underlying prickle development, we sequenced different stages of prickle morphological development and transcriptomes of different tissues in the root tips (Gen), leaf buds (Ya), and fruits of Z. armatum. The results revealed that proteins related to cell division and genes related to the growth hormone signaling pathway were highly expressed in the prickle just protrusion (PC1). In addition, a high expression of lignin biosynthesis genes was observed during the developmental onset of lignification (PC2) and prickle lignification (PC3). These findings indicate that phenylpropanoid biosynthesis and plant hormone signal transduction are key pathways for the completion of lignification development in the prickle. During prickle development, ZaMYB2 and ZaWRKY3 were significantly upregulated in PC2 and PC3, suggesting their possible involvement in prickle development. Transcriptome and qRT-PCR analyses revealed differential gene expression of zaPAL3, za4CLL1, zaCOMT1, ZaWRKY3, and ZaCCD31 in the Gen, Ya, newly formed fruit (ZaF1), newly oil-spotted fruits (ZaF2), PC1, PC2, and PC3 of Zarmatum. zaCCD31 was highly expressed in leaf buds, whereas Za4CLL1 was highly expressed in root tips. During the lignification of prickles, the relative expression of genes including zaMYB2 increased gradually; however, the relative expression of zaCCD31 decreased during this process. Therefore, we inferred that these genes might be closely related to prickle development. Notably, zaMYB2 was expressed at higher levels in PC2 and PC3 than in PC1 and was not expressed in Gen, Ya, ZaF1, and ZaF2. Therefore, zaMYB2 is a key gene involved in prickle development of Z. armatum that exhibited tissue-specific expression. This study establishes a foundation for future analyses of the molecular mechanism underlying prickle development in Z. armatum.

Comprehensive assessment of the effects of concurrent strength and endurance training on lipid profile, glycemic control, and insulin resistance in type 2 diabetes: A meta-analysis.

BACKGROUND: To investigate the effect of concurrent strength combined with endurance training on the lipid and glucose profile of type 2 diabetes mellitus (T2DM) using Meta-analysis. METHODS: The literature was searched from PubMed, Web of Science, EBSCO, and China National Knowledge Infrastructure(CNKI) databases for relevant randomized controlled trials with dates from the date of establishment to June 2023, and the included studies were individually assessed according to the Cochrane Risk of Bias tool in the Cochrane Systematic Assessor's Handbook, and the data were analyzed using RevMan 5.4 analysis software to analyze and process the data. RESULTS: A total of 9 articles were included, including 589 subjects, including 308 in the experimental group and 281 in the control group. The results of Meta analysis showed that concurrent strength combined with endurance training improved TC (SMD = -1.12, 95% CI = [-1.81, -0.44], P < 0.01), TG (SMD = -0.46, 95% CI = [-0.85, -0.07], P < 0.05), LDL-C (SMD = -1.3, 95% CI = [-2.09, -0.50], P < 0.01), HDL-C (SMD = 0.61, 95% CI = [0.05, 1.17], P < 0.05), FBG (SMD = -0.65, 95% CI = [-1.27, -0.04], P < 0.05), HOMA-IR (SMD = -1.23, 95% CI = [-2.40, -0.06], P < 0.05). CONCLUSION: Concurrent strength combined with endurance training has a positive effect on the improvement of lipid and glucose profile in patients with type 2 diabetes.

High Sensitivity and Ultra-Broad-Range NH3 Sensor Arrays by Precise Control of Step Defects on The Surface of Cl2-Ndi Single Crystals.

Vapor sensors with both high sensitivity and broad detection range are technically challenging yet highly desirable for widespread chemical sensing applications in diverse environments. Generally, an increased surface-to-volume ratio can effectively enhance the sensitivity to low concentrations, but often with the trade-off of a constrained sensing range. Here, an approach is demonstrated for NH3 sensor arrays with an unprecedentedly broad sensing range by introducing controllable steps on the surface of an n-type single crystal. Step edges, serving as adsorption sites with electron-deficient properties, are well-defined, discrete, and electronically active. NH3 molecules selectively adsorb at the step edges and nearly eliminate known trap-like character, which is demonstrated by surface potential imaging. Consequently, the strategy can significantly boost the sensitivity of two-terminal NH3 resistance sensors on thin crystals with a few steps while simultaneously enhancing the tolerance on thick crystals with dense steps. Incorporation of these crystals into parallel sensor arrays results in ppb-to-% level detection range and a convenient linear relation between sheet conductance and semi-log NH3 concentration, allowing for the precise localization of vapor leakage. In general, the results suggest new opportunities for defect engineering of organic semiconductor crystal surfaces for purposeful vapor or chemical sensing.

Nanotherapeutics for Alleviating Anesthesia-Associated Complications.

Current management of anesthesia-associated complications falls short in terms of both efficacy and safety. Nanomaterials with versatile properties and unique nano-bio interactions hold substantial promise as therapeutics for addressing these complications. This review conducts a thorough examination of the existing nanotherapeutics and highlights the strategies for developing prospective nanomedicines to mitigate anesthetics-related toxicity. Initially, general, regional, and local anesthesia along with the commonly used anesthetics and related prevalent side effects are introduced. Furthermore, employing nanotechnology to prevent and alleviate the complications of anesthetics is systematically demonstrated from three aspects, that is, developing 1) safe nano-formulization for anesthetics; 2) nano-antidotes to sequester overdosed anesthetics and alter their pharmacokinetics; 3) nanomedicines with pharmacodynamic activities to treat anesthetics toxicity. Finally, the prospects and challenges facing the clinical translation of nanotherapeutics for anesthesia-related complications are discussed. This work provides a comprehensive roadmap for developing effective nanotherapeutics to prevent and mitigate anesthesia-associated toxicity, which can potentially revolutionize the management of anesthesia complications.

Sex Differences in Coronary Inflammation and Atherosclerosis Phenotypes in Response to Imaging Marker of Stress-Related Neural Activity.

BACKGROUND: Sex-specific differences in coronary phenotypes in response to stress have not been elucidated. This study investigated the sex-specific differences in the coronary computed tomography angiography-assessed coronary response to mental stress. METHODS: This retrospective study included patients with coronary artery disease and without cancer who underwent resting 18F-fluorodexoyglucose positron emission tomography/computed tomography and coronary computed tomography angiography within 3 months. 18F-flourodeoxyglucose resting amygdalar uptake, an imaging biomarker of stress-related neural activity, coronary inflammation (fat attenuation index), and high-risk plaque characteristics were assessed by coronary computed tomography angiography. Their correlation and prognostic values were assessed according to sex. RESULTS: A total of 364 participants (27.7% women and 72.3% men) were enrolled. Among those with heightened stress-related neural activity, women were more likely to have a higher fat attenuation index (43.0% versus 24.0%; P=0.004), while men had a higher frequency of high-risk plaques (53.7% versus 39.3%; P=0.036). High amygdalar 18F-flourodeoxyglucose uptake (B-coefficient [SE], 3.62 [0.21]; P<0.001) was selected as the strongest predictor of fat attenuation index in a fully adjusted linear regression model in women, and the first-order interaction term consisting of sex and stress-related neural activity was significant (P<0.001). Those with enhanced imaging biomarkers of stress-related neural activity showed increased risk of major adverse cardiovascular event both in women (24.5% versus 5.1%; adjusted hazard ratio, 3.62 [95% CI, 1.14-17.14]; P=0.039) and men (17.2% versus 6.9%; adjusted hazard ratio, 2.72 [95% CI, 1.10-6.69]; P=0.030). CONCLUSIONS: Imaging-assessed stress-related neural activity carried prognostic values irrespective of sex; however, a sex-specific mechanism linking psychological stress to coronary plaque phenotypes existed in the current hypothesis-generating study. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05545618.