Cardiovascular Risk Associated With Social Determinants of Health at Individual and Area Levels.

Importance: The benefit of adding social determinants of health (SDOH) when estimating atherosclerotic cardiovascular disease (ASCVD) risk is unclear. Objective: To examine the association of SDOH at both individual and area levels with ASCVD risks, and to assess if adding individual- and area-level SDOH to the pooled cohort equations (PCEs) or the Predicting Risk of CVD Events (PREVENT) equations improves the accuracy of risk estimates. Design, Setting, and Participants: This cohort study included participants data from 4 large US cohort studies. Eligible participants were aged 40 to 79 years without a history of ASCVD. Baseline data were collected from 1995 to 2007; median (IQR) follow-up was 13.0 (9.3-15.0) years. Data were analyzed from September 2023 to February 2024. Exposures: Individual- and area-level education, income, and employment status. Main outcomes and measures: ASCVD was defined as the composite outcome of nonfatal myocardial infarction, death from coronary heart disease, and fatal or nonfatal stroke. Results: A total of 26 316 participants were included (mean [SD] age, 61.0 [9.1] years; 15 494 women [58.9%]; 11 365 Black [43.2%], 703 Chinese American [2.7%], 1278 Hispanic [4.9%], and 12 970 White [49.3%]); 11 764 individuals (44.7%) had at least 1 adverse individual-level SDOH and 10 908 (41.5%) had at least 1 adverse area-level SDOH. A total of 2673 ASCVD events occurred during follow-up. SDOH were associated with increased risk of ASCVD at both the individual and area levels, including for low education (individual: hazard ratio [HR], 1.39 [95% CI, 1.25-1.55]; area: HR, 1.31 [95% CI, 1.20-1.42]), low income (individual: 1.35 [95% CI, 1.25-1.47]; area: HR, 1.28 [95% CI, 1.17-1.40]), and unemployment (individual: HR, 1.61 [95% CI, 1.24-2.10]; area: HR, 1.25 [95% CI, 1.14-1.37]). Adding area-level SDOH alone to the PCEs did not change model discrimination but modestly improved calibration. Furthermore, adding both individual- and area-level SDOH to the PCEs led to a modest improvement in both discrimination and calibration in non-Hispanic Black individuals (change in C index, 0.0051 [95% CI, 0.0011 to 0.0126]; change in scaled integrated Brier score [IBS], 0.396% [95% CI, 0.221% to 0.802%]), and improvement in calibration in White individuals (change in scaled IBS, 0.274% [95% CI, 0.095% to 0.665%]). Adding individual-level SDOH to the PREVENT plus area-level social deprivation index (SDI) equations did not improve discrimination but modestly improved calibration in White participants (change in scaled IBS, 0.182% [95% CI, 0.040% to 0.496%]), Black participants (0.187% [95% CI, 0.039% to 0.501%]), and women (0.289% [95% CI, 0.115% to 0.574%]). Conclusions and Relevance: In this cohort study, both individual- and area-level SDOH were associated with ASCVD risk; adding both individual- and area-level SDOH to the PCEs modestly improved discrimination and calibration for estimating ASCVD risk for Black individuals, and adding individual-level SDOH to PREVENT plus SDI also modestly improved calibration. These findings suggest that both individual- and area-level SDOH may be considered in future development of ASCVD risk assessment tools, particularly among Black individuals.

The prognostic model and immune landscape based on cancer-associated fibroblast features for patients with locally advanced rectal cancer.

Background: This study aimed to construct a nomogram based on CAF features to predict the cancer-specific survival (CSS) rates of locally advanced rectal cancer (LARC) patients. Methods: The EPIC algorithm was employed to calculate the proportion of CAFs. based on the differentially expressed genes between the high and low CAF proportion subgroups, prognostic genes were identified via LASSO and Cox regression analyses. They were then used to construct a prognostic risk signature. Moreover, the GSE39582 and GGSE38832 datasets were used for external validation. Lastly, the level of immune infiltration was evaluated using ssGSEA, ESTIMATE, CIBERSORTx, and TIMER. Results: A higher level of CAF infiltration was associated with a worse prognosis. Additionally, the number of metastasized lymph nodes and distant metastases, as well as the level of immune infiltration were higher in the high CAF proportion subgroup. Five prognostic genes (SMOC2, TUBAL3, C2CD4A, MAP1B, BMP8A) were identified and subsequently incorporated into the prognostic risk signature to predict the 1-, 3-, and 5-year CSS rates in the training and validation sets. Differences in survival rates were also determined in the external validation cohort. Furthermore, independent prognostic factors, including TNM stage and risk score, were combined to established a nomogram. Notably, our results revealed that the proportions of macrophages and neutrophils and the levels of cytokines secreted by M2 macrophages were higher in the high-risk subgroup. Finally, the prognostic genes were significantly associated with the level of immune cell infiltration. Conclusion: Herein, a nomogram based on CAF features was developed to predict the CSS rate of LARC patients. The risk model was capable of reflecting differences in the level of immune cell infiltration.

Association Between Young Adult Characteristics and Blood Pressure Trajectories.

BACKGROUND: Blood pressure (BP) trajectories from young adulthood through middle age are associated with cardiovascular risk. We examined the associations of hypertension risk factors with BP trajectories among a large diverse sample. METHODS AND RESULTS: We analyzed data from young adults, aged 18 to 39 years, with untreated BP <140/90 mm Hg at baseline from Kaiser Permanente Southern California (N=355 324). We used latent growth curve models to identify 10-year BP trajectories and to assess the associations between characteristics in young adulthood and BP trajectories. We identified the following 5 distinct systolic BP trajectories, which appeared to be determined mainly by the baseline BP with progressively higher BP at each year: group 1 (lowest BP trajectory, 7.9%), group 2 (26.5%), group 3 (33.0%), group 4 (25.4%), and group 5 (highest BP trajectory, 7.3%). Older age (adjusted odds ratio for 30-39 versus 18-29 years, 1.23 [95% CI, 1.18-1.28]), male sex (13.38 [95% CI, 12.80-13.99]), obesity (body mass index ≥30 versus 18.5-24.9 kg/m2, 14.81 [95% CI, 14.03-15.64]), overweight (body mass index 25-29.9 versus 18.5-24.9 kg/m2, 3.16 [95% CI, 3.00-3.33]), current smoking (1.58 [95% CI, 1.48-1.67]), prediabetes (1.21 [95% CI, 1.13-1.29]), diabetes (1.60 [95% CI, 1.41-1.81]) and high low-density lipoprotein cholesterol (≥160 versus <100 mg/dL, 1.52 [95% CI, 1.37-1.68]) were associated with the highest BP trajectory (group 5) compared with the reference group (group 2). CONCLUSIONS: Traditional hypertension risk factors including smoking, diabetes, and elevated lipids were associated with BP trajectories in young adults, with obesity having the strongest association with the highest BP trajectory group.

Macrophage-Capturing Self-Assembly Photosensitizer Nanoparticles Induces Immune Microenvironment Re-Programming and Golgi-Responsive Immunogenic Cell Death in Head and Neck Carcinoma.

Head and neck carcinoma treatment is shifted toward the combination of therapy causing immune checkpoint blockade (ICB) and immunogenic cell death. In this study, a CSFRi-chimeric TAMCSFR+-targeting extracellular vesicle (EV@CSFRi) platform is developed and designed an intracellular protoporphyrin conjugated with RVRR peptide sequence for furin-cleavage to perform Golgi-targeting and generating ROS (GT-RG). The graphical abstract illustrates the self-assembly of GT-RG nanoparticles into nanofiber through the hydrophily of RVRR and hydrophobicity of RG, and the red line indicates the site of furin cleavage. As is shown in the Graphical abstract, the Golgi-targeting Protoporphyrin-RVRR platform is composed with CSFRi-chimeric extracellular vesicles and forms the tumor-responsive TAM-reprogramming bilayers (GT-RGEV@CSFRi). The GT-RGEV@CSFRi acted as a multifunctional theranostic platform, which can induce immunogenic cell death and further help modulate TAM, thus suppressing the HNC xenograft model by combination therapy with anti-PD-1.

Ca2+ oscillation in vascular smooth muscle cells control myogenic spontaneous vasomotion and counteract post-ischemic no-reflow.

Ischemic stroke produces the highest adult disability. Despite successful recanalization, no-reflow, or the futile restoration of the cerebral perfusion after ischemia, is a major cause of brain lesion expansion. However, the vascular mechanism underlying this hypoperfusion is largely unknown, and no approach is available to actively promote optimal reperfusion to treat no-reflow. Here, by combining two-photon laser scanning microscopy (2PLSM) and a mouse middle cerebral arteriolar occlusion (MCAO) model, we find myogenic vasomotion deficits correlated with post-ischemic cerebral circulation interruptions and no-reflow. Transient occlusion-induced transient loss of mitochondrial membrane potential (ΔΨm) permanently impairs mitochondria-endoplasmic reticulum (ER) contacts and abolish Ca2+ oscillation in smooth muscle cells (SMCs), the driving force of myogenic spontaneous vasomotion. Furthermore, tethering mitochondria and ER by specific overexpression of ME-Linker in SMCs restores cytosolic Ca2+ homeostasis, remotivates myogenic spontaneous vasomotion, achieves optimal reperfusion, and ameliorates neurological injury. Collectively, the maintaining of arteriolar myogenic vasomotion and mitochondria-ER contacts in SMCs, are of critical importance in preventing post-ischemic no-reflow.

The role of microbial metabolites in endocrine tumorigenesis: From the mechanistic insights to potential therapeutic biomarkers.

Microbial metabolites have been indicated to communicate with the host's endocrine system, regulating hormone production, immune-endocrine communications, and interactions along the gut-brain axis, eventually affecting the occurrence of endocrine cancer. Furthermore, microbiota metabolites such as short-chain fatty acids (SCFAs) have been found to affect the tumor microenvironment and boost immunity against tumors. SCFAs, including butyrate and acetate, have been demonstrated to exert anti-proliferative and anti-protective activity on pancreatic cancer cells. The employing of microbial metabolic products in conjunction with radiation and chemotherapy has shown promising outcomes in terms of reducing treatment side effects and boosting effectiveness. Certain metabolites, such as valerate and butyrate, have been made known to improve the efficiency of CAR T-cell treatment, whilst others, such as indole-derived tryptophan metabolites, have been shown to inhibit tumor immunity. This review explores the intricate interplay between microbial metabolites and endocrine tumorigenesis, spanning mechanistic insights to the discovery of potential therapeutic biomarkers.

Genetic testing for familial hypercholesterolemia.

PURPOSE OF REVIEW: Despite familial hypercholesterolemia (FH) being the most common genetic cause of cardiovascular disease (CVD), genetic testing is rarely utilized in the US. This review summarizes what is known about the clinical utility of genetic testing and its role in the diagnosis and screening of FH. RECENT FINDINGS: The presence of an FH-causative variant is associated with a substantially higher risk of CVD, even when low-density lipoprotein cholesterol (LDL-C) levels are only modestly elevated. Genetic testing can facilitate the identification of FH cases who may be missed by clinical diagnostic criteria, improve risk stratification beyond LDL-C and family history, guide treatment decisions, and improve treatment initiation and adherence. Genetic testing can be incorporated into FH screening and diagnosis algorithms, including cascade, targeted, and universal screening. Integrating genetic testing into cascade screening can enhance the effectiveness of the process. Several models of universal FH screening with coordinated genetic and lipid testing are feasible and effective. SUMMARY: More systematic integration of genetic testing into FH diagnosis and screening can significantly reduce the burden of this condition through early detection and treatment. Further pragmatic implementation studies are needed to determine how to more effectively and affordably integrate genetic testing into clinical lipid screening programs.

Multifunctional emitter based on inverse design for infrared stealth, thermal imaging and radiative cooling.

In contrast to conventional emitters fashioned from traditional materials, tunable thermal emitters exhibit a distinct propensity to fulfill the demands of diverse scenarios, thereby engendering an array of prospects within the realms of communications, military applications, and control systems. In this paper, a tunable thermal emitter without continuous external excitation is introduced using Ge2Sb2Te5 (GST) and high-temperature-resistant material Mo. It is automatically optimized by inverse design with genetic algorithm (GA) to switch between different functions according to the object temperature to adapt to diverse scenarios. In "off" mode, the emitter orchestrates a blend of infrared (IR) stealth and thermal management. This is evidenced by average absorptivity values of 0.08 for mid-wave infrared (MIR, 3-5 µm), 0.19 for long-wave infrared (LIR, 8-14 µm), and 0.68 for the non-atmospheric window (NAW, 5-8 µm). Conversely, when confronted with high-temperature entities, the emitter seamlessly transitions to "on" mode, instigating a process of radiative cooling. This transformation is reflected in the augmented emissivity of the dual-band atmospheric window including MIR and LIR, attaining peak values of 0.96 and 0.97. This transition yields a cooling potential, quantified at 64 W/m2 at the ambient temperature of 25°C. In addition, our design employs a layered structure, which avoids complex patterned resonators and facilitates large-area fabrication. The emitter in this paper evinces robust insensitivity to polarization variations and the angle of incidence. We believe that this work will contribute to the development in the fields of dynamic tunability for IR stealth, dynamic radiative cooling systems, and thermal imaging.

Familial Hypercholesterolemia Variant and Cardiovascular Risk in Individuals With Elevated Cholesterol.

Importance: Familial hypercholesterolemia (FH) is a genetic disorder that often results in severely high low-density lipoprotein cholesterol (LDL-C) and high risk of premature coronary heart disease (CHD). However, the impact of FH variants on CHD risk among individuals with moderately elevated LDL-C is not well quantified. Objective: To assess CHD risk associated with FH variants among individuals with moderately (130-189 mg/dL) and severely (≥190 mg/dL) elevated LDL-C and to quantify excess CHD deaths attributable to FH variants in US adults. Design, Setting, and Participants: A total of 21 426 individuals without preexisting CHD from 6 US cohort studies (Atherosclerosis Risk in Communities study, Coronary Artery Risk Development in Young Adults study, Cardiovascular Health Study, Framingham Heart Study Offspring cohort, Jackson Heart Study, and Multi-Ethnic Study of Atherosclerosis) were included, 63 of whom had an FH variant. Data were collected from 1971 to 2018, and the median (IQR) follow-up was 18 (13-28) years. Data were analyzed from March to May 2023. Exposures: LDL-C, cumulative past LDL-C, FH variant status. Main Outcomes and Measures: Cox proportional hazards models estimated associations between FH variants and incident CHD. The Cardiovascular Disease Policy Model projected excess CHD deaths associated with FH variants in US adults. Results: Of the 21 426 individuals without preexisting CHD (mean [SD] age 52.1 [15.5] years; 12 041 [56.2%] female), an FH variant was found in 22 individuals with moderately elevated LDL-C (0.3%) and in 33 individuals with severely elevated LDL-C (2.5%). The adjusted hazard ratios for incident CHD comparing those with and without FH variants were 2.9 (95% CI, 1.4-6.0) and 2.6 (95% CI, 1.4-4.9) among individuals with moderately and severely elevated LDL-C, respectively. The association between FH variants and CHD was slightly attenuated when further adjusting for baseline LDL-C level, whereas the association was no longer statistically significant after adjusting for cumulative past LDL-C exposure. Among US adults 20 years and older with no history of CHD and LDL-C 130 mg/dL or higher, more than 417 000 carry an FH variant and were projected to experience more than 12 000 excess CHD deaths in those with moderately elevated LDL-C and 15 000 in those with severely elevated LDL-C compared with individuals without an FH variant. Conclusions and Relevance: In this pooled cohort study, the presence of FH variants was associated with a 2-fold higher CHD risk, even when LDL-C was only moderately elevated. The increased CHD risk appeared to be largely explained by the higher cumulative LDL-C exposure in individuals with an FH variant compared to those without. Further research is needed to assess the value of adding genetic testing to traditional phenotypic FH screening.

Effectiveness of Hypertension Management Strategies in SPRINT-Eligible US Adults: A Simulation Study.

BACKGROUND: Despite reducing cardiovascular disease (CVD) events and death in SPRINT (Systolic Blood Pressure Intervention Trial), intensive systolic blood pressure goals have not been adopted in the United States. This study aimed to simulate the potential long-term impact of 4 hypertension management strategies in SPRINT-eligible US adults. METHODS AND RESULTS: The validated Blood Pressure Control-Cardiovascular Disease Policy Model, a discrete event simulation of hypertension care processes (ie, visit frequency, blood pressure [BP] measurement accuracy, medication intensification, and medication adherence) and CVD outcomes, was populated with 25 000 SPRINT-eligible US adults. Four hypertension management strategies were simulated: (1) usual care targeting BP <140/90 mm Hg (Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care), (2) intensive care per the SPRINT protocol targeting BP <120/90 mm Hg (SPRINT intensive), (3) usual care targeting guideline-recommended BP <130/80 mm Hg (American College of Cardiology/American Heart Association usual care), and (4) team-based care added to usual care and targeting BP <130/80 mm Hg. Relative to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care, among the 18.1 million SPRINT-eligible US adults, an estimated 138 100 total CVD events could be prevented per year with SPRINT intensive, 33 900 with American College of Cardiology/American Heart Association usual care, and 89 100 with team-based care. Compared with the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care, SPRINT intensive care was projected to increase treatment-related serious adverse events by 77 600 per year, American College of Cardiology/American Heart Association usual care by 33 300, and team-based care by 27 200. CONCLUSIONS: As BP control has declined in recent years, health systems must prioritize hypertension management and invest in effective strategies. Adding team-based care to usual care may be a pragmatic way to manage risk in this high-CVD-risk population.

Synaptic-like transmission between neural axons and arteriolar smooth muscle cells drives cerebral neurovascular coupling.

Neurovascular coupling (NVC) is important for brain function and its dysfunction underlies many neuropathologies. Although cell-type specificity has been implicated in NVC, how active neural information is conveyed to the targeted arterioles in the brain remains poorly understood. Here, using two-photon focal optogenetics in the mouse cerebral cortex, we demonstrate that single glutamatergic axons dilate their innervating arterioles via synaptic-like transmission between neural-arteriolar smooth muscle cell junctions (NsMJs). The presynaptic parental-daughter bouton makes dual innervations on postsynaptic dendrites and on arteriolar smooth muscle cells (aSMCs), which express many types of neuromediator receptors, including a low level of glutamate NMDA receptor subunit 1 (Grin1). Disruption of NsMJ transmission by aSMC-specific knockout of GluN1 diminished optogenetic and whisker stimulation-caused functional hyperemia. Notably, the absence of GluN1 subunit in aSMCs reduced brain atrophy following cerebral ischemia by preventing Ca2+ overload in aSMCs during arteriolar constriction caused by the ischemia-induced spreading depolarization. Our findings reveal that NsMJ transmission drives NVC and open up a new avenue for studying stroke.

Highly Sensitive Gas Sensor for Detection of Air Decomposition Pollutant (CO, NOx): Popular Metal Oxide (ZnO, TiO2)-Doped MoS2 Surface.

When partial discharges occur in air-insulated equipment, the air decomposes to produce a variety of contamination products, resulting in a reduction in the insulation performance of the insulated equipment. By monitoring the concentration of typical decomposition products (CO, NO, and NO2) within the insulated equipment, potential insulation faults can be diagnosed. MoS2 has shown promising applications as a gas-sensitive semiconductor material, and doping metal oxides can improve the gas-sensitive properties of the material. Therefore, in this work, MoS2 has been doped using the popular metal oxides (ZnO, TiO2) of the day, and its gas-sensitive properties to the typical decomposition products of air have been analyzed and compared using density functional theory (DFT) calculations. The stability of the doped system was investigated using molecular dynamics methods. The related adsorption mechanism was analyzed by adsorption configuration, energy band structure, density of states (DOS) analysis, total electron density (TED) analysis, and differential charge density (DCD) analysis. Finally, the practical application of related sensing performance is evaluated. The results show that the doping of metal oxide nanoparticles greatly improves the conductivity, gas sensitivity, and adsorption selectivity of MoS2 monolayer to air decomposition products. The sensing response of ZnO-MoS2 for CO at room temperature (25 °C) reaches 161.86 with a good recovery time (0.046 s). TiO2-MoS2 sensing response to NO2 reaches 3.5 × 106 at 25 °C with a good recovery time (0.108 s). This study theoretically solves the industrial challenge of recycling sensing materials and provides theoretical value for the application of resistive chemical sensors in air-insulated equipment.

Transition-Metal-Free, Reductive Csp2-Csp3 Bond Constructions via Electrochemically Induced Alkyl Radicals.

Construction of the Csp2-Csp3 bond without the aid of transition metal catalysts has been achieved by coupling the electrogenerated alkyl radicals with electron deficient (hetero)arenes in an undivided cell. Simultaneous cathodic reduction of both unactivated alkyl halides and cyanobenzenes under high potential enables radical-radical cross-coupling to deliver alkylarenes in the absence of transition metals. Depending on the coupling partner, the electrogenerated alkyl radicals can also proceed the Minisci-type reaction with N-heteroarenes without redox agents.

A transformer-based genomic prediction method fused with knowledge-guided module.

Genomic prediction (GP) uses single nucleotide polymorphisms (SNPs) to establish associations between markers and phenotypes. Selection of early individuals by genomic estimated breeding value shortens the generation interval and speeds up the breeding process. Recently, methods based on deep learning (DL) have gained great attention in the field of GP. In this study, we explore the application of Transformer-based structures to GP and develop a novel deep-learning model named GPformer. GPformer obtains a global view by gleaning beneficial information from all relevant SNPs regardless of the physical distance between SNPs. Comprehensive experimental results on five different crop datasets show that GPformer outperforms ridge regression-based linear unbiased prediction (RR-BLUP), support vector regression (SVR), light gradient boosting machine (LightGBM) and deep neural network genomic prediction (DNNGP) in terms of mean absolute error, Pearson's correlation coefficient and the proposed metric consistent index. Furthermore, we introduce a knowledge-guided module (KGM) to extract genome-wide association studies-based information, which is fused into GPformer as prior knowledge. KGM is very flexible and can be plugged into any DL network. Ablation studies of KGM on three datasets illustrate the efficiency of KGM adequately. Moreover, GPformer is robust and stable to hyperparameters and can generalize to each phenotype of every dataset, which is suitable for practical application scenarios.

Chloroquine Alleviates Atherosclerosis by Modulating Regulatory T Cells Through the ATM/AMPK/mTOR Signaling Pathway in ApoE -/- Mice.

BACKGROUND: Clinical observation suggests the atheroprotective effect of chloroquine and its derivatives, while its mechanism remains unclear. This study aimed to observe the protective effect of chloroquine against atherosclerosis and explore the underlying mechanism. METHODS: Ataxia telangiectasia mutated (ATM) wild-type or haploinsufficient apolipoprotein-E-knockout (ATM+/+ApoE-/- or ATM+/-ApoE-/-) mice were treated with different dosages of chloroquine. Anti-CD25 antibody was used to deplete natural Tregs in ATM+/+ApoE-/- mice. The atherosclerotic burden in different groups of mice was comprehensively evaluated by H&E staining and Masson staining. The effect of chloroquine on the regulatory T cells (Tregs) was assessed in vivo and in vitro by flow cytometry and immunohistochemical staining. The expression of related proteins was detected by real-time polymerase chain reaction and western blotting. RESULTS: In ATM+/+ApoE-/- mice, chloroquine alleviated atherosclerotic lesions, stabilized the plaque, and increased Treg counts in the atherosclerotic lesions and spleens. However, in ATM haploinsufficient mice (ATM+/-ApoE-/-), chloroquine no longer prevented atherosclerosis or impacted Treg counts. Abolishing Treg cells using an anti-CD25 antibody in vivo abrogated the atheroprotective effect of chloroquine. In vitro, chloroquine promoted the differentiation of Tregs from naïve T cells, which was accompanied by enhanced ATM/AMP-activated protein kinase (AMPK) activity and reduced downstream mammalian target of rapamycin (mTOR) activity. DISCUSSION: These findings suggest that chloroquine ameliorates atherosclerosis and stabilizes plaque by modulating Tregs differentiation through the regulation of the ATM/AMPK/mTOR pathway.

RHA2b-mediated MYB30 degradation facilitates MYB75-regulated, sucrose-induced anthocyanin biosynthesis in Arabidopsis seedlings.

Anthocyanins play diverse roles in plant physiology and stress adaptation. In Arabidopsis, the MYB-bHLH-WD40 (MBW) complex has a crucial role in the regulation of anthocyanin synthesis. Here, we report that the R2R3-MYB transcription factor MYB30 and the ubiquitin E3 ligase RHA2b participate in anthocyanin biosynthesis through regulation of the MBW complex. MYB30 was found to negatively regulate sucrose-induced anthocyanin biosynthesis in Arabidopsis seedlings. Expression of multiple genes involved in flavonoid or anthocyanin biosynthesis was affected in the myb30 mutant, and MYB30 directly repressed the expression of MYB75, which encodes a core component of the MBW complex, by binding to its promoter. Moreover, MYB30 physically interacted with MYB75 to inhibit its activity by repressing MBW complex assembly. In addition, sucrose treatment significantly promoted MYB30 degradation via the action of RHA2b. The ubiquitination and degradation of MYB30 were significantly attenuated in the rha2b mutant under high-sucrose treatment, and further analysis showed that MYB75 directly promoted RHA2b expression in response to high sucrose. Our work thus reveals an anthocyanin biosynthetic regulatory module, RHA2b-MYB30, that controls the function of the MBW complex via MYB75. The repression of MYB75 by MYB30 is released by MYB75-induced RHA2b expression, thus ensuring the self-activation of MYB75 when anthocyanin synthesis is needed.

BASHY Dyes Are Highly Efficient Lipid Droplet-Targeting Photosensitizers that Induce Ferroptosis through Lipid Peroxidation.

Ferroptosis is an iron-dependent lipid-peroxidation-driven mechanism of cell death and a promising therapeutic target to eradicate cancer cells. In this study, we discovered that boronic acid-derived salicylidenehydrazone (BASHY) dyes are highly efficient singlet-oxygen photosensitizers (PSs; ΦΔ up to 0.8) that induce ferroptosis triggered by photodynamic therapy. The best-performing BASHY dye displayed a high phototoxicity against the human glioblastoma multiform U87 cell line, with an IC50 value in the low nanomolar range (4.40 nM) and a remarkable phototoxicity index (PI > 22,700). Importantly, BASHY dyes were shown to accumulate in lipid droplets (LDs) and this intracellular partition was found to be essential for the enhanced phototoxicity and the induction of ferroptosis through lipid peroxidation. The safety and phototoxicity of this platform were validated using an in vivo zebrafish model (Danio rerio).

Tensor completion algorithm-aided structural color design.

In recent years, structural color has developed rapidly due to its distinct advantages, such as low loss, high spatial resolution and environmental friendliness. Various inverse design methods have been extensively investigated to efficiently design optical structures. However, the optimization method for the inverse design of structural color remains a formidable challenge. Traditional optimization approaches, such as genetic algorithms require time-consuming repetitions of structural simulations. Deep learning-assisted design necessitates prior simulations and large amounts of data, making it less efficient for systems with a small number of features. This study proposes a tensor completion algorithm capable of swiftly and accurately predicting missing datasets based on partially obtained datasets to assist in structural color design. Transforming the complex physical problem of structural color design into a spatial structure relationship problem linking geometric parameters and spectral data. The method utilizes tensor multilinear data analysis to effectively capture the complex relationships associated with geometric parameters and spectral data in higher-order data. Numerical and experimental results demonstrate that the algorithm exhibits high reliability in terms of speed and accuracy for diverse structures, datasets of varying sizes, and different materials, significantly enhancing design efficiency. The proposed algorithm offers a viable solution for inverse design problems involving complex physical systems, thereby introducing a novel approach to the design of photonic devices. Additionally, numerical experiments illustrate that the structural color of cruciform resonators with diamond can overcome the high loss issues observed in traditional dielectric materials within the blue wavelength region and enhance the corrosion resistance of the structure. We achieve a wide color gamut and a high-narrow reflection spectrum nearing 1 by this structure, and the theoretical analysis further verifies that diamond holds great promise in the realm of optics.

The role of iron and ferroptosis in the pathogenesis of acute pancreatitis.

Acute pancreatitis (AP) is an inflammatory disease of the pancreas. Iron is an essential element for life and is involved in many metabolic processes. Ferroptosis is a type of regulated cell death that is triggered by iron and oxidative stress. A well-established mouse AP model was adopted to study the role of iron and ferroptosis in the pathogenesis of pancreatitis. Mice were injected with cerulein to induce AP, and pancreatic tissue samples were analyzed to determine the pathology, cell death, iron deposition, expression of iron transporters, and lipid peroxidation. The role of iron was studied by giving mice extra iron or iron chelator. In vitro studies with acinar cells with ferroptosis activator and inhibitor were also performed to assess the inflammatory response. Iron was found accumulated in the pancreatic tissue of mice who suffered cerulein-induced pancreatitis. Cell death and lipid peroxidation increased in these tissues and could be further modulated by iron dextran or iron chelator. Mice given Hemin through gavage had reduced levels of GSH in pancreatic tissue and increased inflammatory response. Studies with acinar cells showed increased levels of lipid peroxidation and ferroptosis-specific mitochondrial damage when treated with ferroptosis inducer and inflammatory cytokines.