Cutaneous adaptive immunity and uraemia: a narrative review.

Chronic kidney disease affects 1 in 10 people globally, with a prevalence twenty times that of cancer. A subset of individuals will progress to end-stage renal disease (ESRD) where renal replacement therapy is required to maintain health. Cutaneous disease, including xerosis and pruritus, are endemic amongst patients with ESRD. In the uraemia-associated immune deficiency of ESRD, impaired circulating immune responses contribute to increased infection risk and poorer vaccination response. Clinical manifestations of dysregulated adaptive immunity within the skin have been well-described and have been posited to play a role in cutaneous features of ESRD. However, our understanding of the mechanisms by which adaptive immunity within the skin is affected by uraemia is relatively limited. We provide an overview of how the cutaneous adaptive immune system is impacted both directly and indirectly by uraemia, highlighting that much work has been extrapolated from the circulating immune system and often has not been directly evaluated in the skin compartment. We identify knowledge gaps which may be addressed by future research. Ultimately, greater understanding of these pathways may facilitate novel therapeutic approaches to ameliorate widespread cutaneous symptomatology in ESRD.

Unraveling cadmium-driven liver inflammation with a focus on arachidonic acid metabolites and TLR4/ IκBα /NF-κB pathway.

Epidemiological studies have demonstrated exposure to cadmium ion (Cd2+) is significantly associated with the incidence and aggravation of nonalcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH). Cd2+ exposure could alter lipid metabolism, and changed lipid metabolites are significantly associated with NASH. Arachidonic acid (ArA) is an omega-6 polyunsaturated fatty acid. Promotion of ArA synthesis and profile changes by Cd2+ exposure potentially to cause NAFLD. ArA metabolism pathway has been identified to enrich in Cd2+ exposure-facilitated NASH. ArA could be generation an impressive metabolic profile through mainly three pathways, including Cyclooxygenases (COX), Lipoxygenases (LOX) and Cytochrome P450 (CYP450) pathway. However, the functions of these metabolites and underlying mechanism in hepatic inflammation are still not clear. In present study, by integrative transcriptomics and metabolomics analysis, we identified that the fatty acid metabolic process and the pro-inflammatory NF-κB signaling pathway were enriched in Cd2+-regulated differentially expressed genes (DEGs) and Cd2+-altered differential metabolites, such as, fatty acid biosynthesis, degradation, and ArA metabolism. The metabolites levels of LOX pathway products 5-HETE and leukotriene C4 (LTC4), and COX catalytic product prostaglandin D2 (PGD2) were significantly elevated in Cd2+ exposed mouse livers. 5-HETE, LTC4, and PGD2 were significantly positive correlated with NF-κB signaling. In addition, the synthase of 20-Hydroxyeicosatetraenoic acid (20-HETE), CYP450 gene 4 family (CYP4A32), was also involved in NF-κB signaling network. Results from both in vitro and in vivo proved that Cd2+ exposure increased ArA metabolite to PGD2 and 20-HETE, and upregulated the mRNA level of their catalytic enzyme PGDS and CYP4A32. Cd2+-induced ArA metabolite to PGD2 and 20-HETE promoted activation of TLR4/IκBα/NF-κB signaling and pro-inflammatory of hepatocytes. Our study explores novel molecular mechanism of Cd2+ exposure-aggravated liver diseases and provides potential novel targets for in hepatic inflammatory treatments and prevention.

Variability in Lipid Profiles During Young Adulthood and the Risk of Coronary Artery Calcium Incidence in Midlife: Insights From the CARDIA Study.

BACKGROUND: Intraindividual variability in lipid profiles is recognized as a potential predictor of cardiovascular events. However, the influence of early adulthood lipid profile variability along with mean lipid levels on future coronary artery calcium (CAC) incidence remains unclear. METHODS: A total of 2395 participants (41.6% men; mean±SD age, 40.2±3.6 years) with initial CAC =0 from the CARDIA study (Coronary Artery Risk Development in Young Adults) were included. Serial lipid measurements were obtained to calculate mean levels and variability of total cholesterol, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides. CAC incidence was defined as CAC >0 at follow-up. RESULTS: During a mean follow-up of 9.0 years, 534 individuals (22.3%) exhibited CAC incidence. Higher mean levels of total cholesterol, LDL-C, and non-HDL-C were associated with a greater risk of future CAC incidence. Similarly, 1-SD increment of lipid variability, as assessed by variability independent of the mean, was associated with an increased risk of CAC incidence (LDL-C: hazard ratio, 1.139 [95% CI, 1.048-1.238]; P=0.002; non-HDL-C: hazard ratio, 1.102 [95% CI, 1.014-1.198]; P=0.022; and triglycerides: hazard ratio, 1.480 [95% CI, 1.384-1.582]; P<0.001). Combination analyses demonstrated that participants with both high lipid levels and high variability in lipid profiles (LDL-C and non-HDL-C) faced the greatest risk of CAC incidence. Specifically, elevated variability of LDL-C was associated with an additional risk of CAC incidence even in low mean levels of LDL-C (hazard ratio, 1.396 [95% CI, 1.106-1.763]; P=0.005). These findings remained robust across a series of sensitivity and subgroup analyses. CONCLUSIONS: Elevated variability in LDL-C and non-HDL-C during young adulthood was associated with an increased risk of CAC incidence in midlife, especially among those with high mean levels of atherogenic lipoproteins. These findings highlight the importance of maintaining consistently low levels of atherogenic lipids throughout early adulthood to reduce subclinical atherosclerosis in midlife. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005130.

Borate bioactive glass enhances 3D bioprinting precision and biocompatibility on a sodium alginate platform via Ca2+ controlled self-solidification.

Sodium alginate (SA) has gained widespread acclaim as a carrier medium for three-dimensional (3D) bioprinting of cells and a diverse array of bioactive substances, attributed to its remarkable biocompatibility and affordability. The conventional approach for fabricating alginate-based tissue engineering constructs entails a post-treatment phase employing a calcium ion solution. However, this method proves ineffectual in addressing the predicament of low precision during the 3D printing procedure and is unable to prevent issues such as non-uniform alginate gelation and substantial distortions. In this study, we introduced borate bioactive glass (BBG) into the SA matrix, capitalizing on the calcium ions released from the degradation of BBG to incite the cross-linking reaction within SA, resulting in the formation of BBG-SA hydrogels. Building upon this fundamental concept, it unveiled that BBG-SA hydrogels greatly enhance the precision of SA in extrusion-based 3D printing and significantly reduce volumetric contraction shrinkage post-printing, while also displaying certain adhesive properties and electrical conductivity. Furthermore, in vitro cellular experiments have unequivocally established the excellent biocompatibility of BBG-SA hydrogel and its capacity to actively stimulate osteogenic differentiation. Consequently, BBG-SA hydrogel emerges as a promising platform for 3D bioprinting, laying the foundation for the development of flexible, biocompatible electronic devices.

Observational and genetic association of non-alcoholic fatty liver disease and calcific aortic valve disease.

Background: Non-alcoholic fatty liver disease (NAFLD) has emerged as a predominant driver of chronic liver disease globally and is associated with increased cardiovascular disease morbidity and mortality. However, the association between NAFLD and calcific aortic valve disease remains unclear. We aimed to prospectively investigate the association between NAFLD and incident aortic valve calcification (AVC), as well as its genetic relationship with incident calcific aortic valve stenosis (CAVS). Methods: A post hoc analysis was conducted on 4226 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) database. We employed the adjusted Cox models to assess the observational association between NAFLD and incident AVC. Additionally, we conducted two-sample Mendelian randomization (MR) analyses to investigate the genetic association between genetically predicted NAFLD and calcific aortic valve stenosis (CAVS), a severe form of CAVD. We repeated the MR analyses by excluding NAFLD susceptibility genes linked to impaired very low-density lipoprotein (VLDL) secretion. Results: After adjustment for potential risk factors, participants with NAFLD had a hazard ratio of 1.58 (95% CI: 1.03-2.43) for incident AVC compared to those without NAFLD. After excluding genes associated with impaired VLDL secretion, the MR analyses consistently showed the significant associations between genetically predicted NAFLD and CAVS for 3 traits: chronic elevation of alanine aminotransferase (odds ratio = 1.13 [95% CI: 1.01-1.25]), imaging-based NAFLD (odds ratio = 2.81 [95% CI: 1.66-4.76]), and biopsy-confirmed NAFLD (odds ratio = 1.12 [95% CI: 1.01-1.24]). However, the association became non-significant when considering all NAFLD susceptibility genes. Conclusions: NAFLD was independently associated with an elevated risk of incident AVC. Genetically predicted NAFLD was also associated with CAVS after excluding genetic variants related to impaired VLDL secretion.

Cadmium promoted LPS-induced inflammation through TLR4/IκBα/NFκ-B signaling by increasing ROS-mediated incomplete autophagy.

Cadmium (Cd) exposure is considered as non-infectious stressor to human and animal health. Recent studies suggest that the immunotoxicity of low dose Cd is not directly apparent, but disrupts the immune responses when infected with some bacteria or virus. But how Cd alters the adaptive immunity organ and cells remains unclear. In this study, we applied lipopolysaccharide (LPS, infectious stressor) to induced inflammation in spleen tissues and T cells, and investigated the effects after Cd exposure and the underlying mechanism. Cd exposure promoted LPS-induced the expressions of the inflammatory factors, induced abnormal initiation of autophagy, but blocked autophagic flux. The effects Cd exposure under LPS activation were reversed by the autophagy promoter Rapamycin. Under LPS activation conditions, Cd also induced oxidative stress by increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and reducing total antioxidant capacity (T-AOC) activity. The increased superoxide dismutase (SOD) activity after Cd exposure might be a negative feedback or passive adaptive regulation of oxidative stress. Cd-increased autophagic flux inhibition and TNF-α expression were reversed by ROS scavenger α-tocopherol (TCP). Furthermore, under LPS activation condition, Cd promoted activation of toll-like receptor 4 (TLR4)/IκBα/NFκ-B signaling pathway and increased TLR4 protein stability, which were abolished by the pretreatment of Rapamycin. The present study confirmed that, by increasing ROS-mediated inhibiting autophagic degradation of TLR4, Cd promoted LPS-induced inflammation in spleen T cells. This study identified the mechanism of autophagy in Cd-aggravated immunotoxicity under infectious stress, which could arouse public attention to synergistic toxicity of Cd and bacterial or virus infection.

Prevotella copri promotes vascular calcification via lipopolysaccharide through activation of NF-κB signaling pathway.

Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri (P. copri) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri-derived LPS (Pc-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc-LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.

Critical role of the gut microbiota in immune responses and cancer immunotherapy.

The gut microbiota plays a critical role in the progression of human diseases, especially cancer. In recent decades, there has been accumulating evidence of the connections between the gut microbiota and cancer immunotherapy. Therefore, understanding the functional role of the gut microbiota in regulating immune responses to cancer immunotherapy is crucial for developing precision medicine. In this review, we extract insights from state-of-the-art research to decipher the complicated crosstalk among the gut microbiota, the systemic immune system, and immunotherapy in the context of cancer. Additionally, as the gut microbiota can account for immune-related adverse events, we discuss potential interventions to minimize these adverse effects and discuss the clinical application of five microbiota-targeted strategies that precisely increase the efficacy of cancer immunotherapy. Finally, as the gut microbiota holds promising potential as a target for precision cancer immunotherapeutics, we summarize current challenges and provide a general outlook on future directions in this field.

A new preparation method of covalent annular nanodiscs based on MTGase.

The preservation of the native conformation and functionality of membrane proteins has posed considerable challenges. While detergents and liposome reconstitution have been traditional approaches, nanodiscs (NDs) offer a promising solution by embedding membrane proteins in phospholipids encircled by an amphipathic helical protein MSP belt. Nevertheless, a drawback of commonly used NDs is their limited homogeneity and stability. In this study, we present a novel approach to construct covalent annular nanodiscs (cNDs) by leveraging microbial transglutaminase (MTGase) to catalyze isopeptide bond formation between the side chains of terminal amino acids, specifically Lysine (K) and Glutamine (Q). This methodology significantly enhances the homogeneity and stability of NDs. Characterization of cNDs and the assembly of membrane proteins within them validate the successful reconstitution of membrane proteins with improved homogeneity and stability. Our findings suggest that cNDs represent a more suitable tool for investigating interactions between membrane proteins and lipids, as well as for analyzing membrane protein structures.

A biomimetic camouflaged metal organic framework for enhanced siRNA delivery in the tumor environment.

Gene silencing through RNA interference (RNAi), particularly using small double-stranded RNA (siRNA), has been identified as a potent strategy for targeted cancer treatment. Yet, its application faces challenges such as nuclease degradation, inefficient cellular uptake, endosomal entrapment, off-target effects, and immune responses, which have hindered its effective delivery. In the past few years, these challenges have been addressed significantly by using camouflaged metal-organic framework (MOF) nanocarriers. These nanocarriers protect siRNA from degradation, enhance cellular uptake, and reduce unintended side effects by effectively targeting desired cells while evading immune detection. By combining the properties of biomimetic membranes and MOFs, these nanocarriers offer superior benefits such as extended circulation times, enhanced stability, and reduced immune responses. Moreover, through ligand-receptor interactions, biomimetic membrane-coated MOFs achieve homologous targeting, minimizing off-target adverse effects. The MOFs, acting as the core, efficiently encapsulate and protect siRNA molecules, while the biomimetic membrane-coated surface provides homologous targeting, further increasing the precision of siRNA delivery to cancer cells. In particular, the biomimetic membranes help to shield the MOFs from the immune system, avoiding unwanted immune responses and improving their biocompatibility. The combination of siRNA with innovative nanocarriers, such as camouflaged-MOFs, presents a significant advancement in cancer therapy. The ability to deliver siRNA with precision and effectiveness using these camouflaged nanocarriers holds great promise for achieving more personalized and efficient cancer treatments in the future. This review article discusses the significant progress made in the development of siRNA therapeutics for cancer, focusing on their effective delivery through novel nanocarriers, with a particular emphasis on the role of metal-organic frameworks (MOFs) as camouflaged nanocarriers.

Fabrication of Uniform Anionic Polymeric Nanoplatelets as Building Blocks for Constructing Conductive Hydrogels with Enhancing Conductive and Mechanical Properties.

Conductive hydrogels play a crucial role in advancing technologies like implantable bioelectronics and wearable electronic devices, owing to their favorable conductivity and appropriate mechanical properties. Here, a novel bottom-up approach is reported for crafting conductive nanocomposite hydrogels to achieve enhancing conductive and mechanical properties. In this approach, new poly(ɛ-caprolactone)-based block copolymers with sulfonic groups are first synthesized and self-assembled into uniform polyanionic nanoplatelets. Subsequently, these negatively charged nanoplatelets, with sulfonic groups on the surface, are employed as nanoadditives for the polymerization of 3,4-ethylenedioxythiophene (EDOT), resulting in poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS)/nanoplatelet complex with 3.8 times enhanced electrical conductivity compared with their counterparts prepared using block copolymers (BCPs). Blending the (PEDOT:PSS)/nanoplatelet complex with calcium alginate, nanocomposite hydrogels are successfully prepared. In comparison with hydrogels with (PEDOT:PSS)/BCP complexes prepared by a top-down method, the nanocomposite hydrogels are found to show twice as strong mechanical strength and 1.6 times higher conductivity. This work provides valuable insights into the bottom-up construction of conductive hydrogels for bioelectronics using well-controlled polymeric nanoplatelets.

The Future of Checkpoint Inhibitors in Uveal Melanoma: A Narrative Review.

INTRODUCTION: Immune checkpoint inhibitors have made tremendous progress over the last decade in the treatment of cutaneous melanoma, but their application in uveal melanoma treatment is less successful, owing in part to the immunological privilege of the eye and the liver, the most frequent site of metastasis. Nevertheless, the therapeutic outcomes reported currently are less pessimistic. METHODS: In this review, we provide an overview of recent studies of immune checkpoint inhibitors in uveal melanoma and its metastasis and classify studies in this field into three groups: monotherapy of immune checkpoint inhibitors, dual-agent immune checkpoint inhibitors, and immune checkpoint inhibitors combined with other systemic or regional therapies. RESULTS: Briefly, monotherapy with immune checkpoint inhibitors performed poorly. Dual-agent immune checkpoint inhibitors had slightly better outcomes than traditional treatments, especially in specific patient populations. As for the combination therapy, the combination with other systemic therapies did not show superiority over dual-agent immune checkpoint inhibitors, but combination with hepatic regional therapies was quite promising. Moreover, research on emerging checkpoints is currently limited to the stage of mechanistic studies. CONCLUSION: We propose that immune checkpoint inhibitors remain alternative treatments for patients with uveal melanoma, but factors such as cost-effectiveness should also be taken into account. The combination therapy with immune checkpoint inhibitors deserves to be further explored.

Effects and mechanism of metal ions on the stability of glucosinolates in aqueous solution.

Glucosinolates (GLs) are important precursors of anticancer isothiocyanates in cruciferous plants. However, GLs in aqueous solution have been found to decompose under certain conditions, and the effect of metal ions remains unclear. In this study, high-purity glucoraphanin and glucoraphenin were used to explore the effects of metal ions with thermal treatment. The degree of GLs decomposition was affected by the type and concentration of metal ions, temperature, and duration of heating. Fe3+ (1 mM) was found to cause the decomposition of 78.1 % of glucoraphanin and 94.7 % of glucoraphenin in 12 h at 100 °C, while Cu2+ completely decomposed both GLs. The decomposition products were all the corresponding nitriles, and decomposition dynamic curves were first-order. In addition to accelerating hydrolysis, metal ions may promote the generation of nitriles as catalysts. The exploration of GLs decomposition could help to adopt more effective methods to avoid the formation of toxic compounds.

Dual Activity of Type III PI3K Kinase Vps34 is Critical for NK Cell Development and Senescence.

Vps34 is the unique member of the class III phosphoinositide 3-kinase family that performs both vesicular transport and autophagy. Its role in natural killer (NK) cells remains uncertain. In this study, a model without Vps34 (Vps34fl/fl/CD122Cre/+) is generated, deleting Vps34 during and after NK-cell commitment. These mice exhibit a nearly 90% decrease in NK cell count and impaired differentiation. A mechanistic study reveals that the absence of Vps34 disrupts the transport of IL-15 receptor subunit alpha CD122 to the cell membrane, resulting in reduced responsiveness of NK cells to IL-15. In mice lacking Vps34 at the terminal stage of NK-cell development (Vps34fl/fl/Ncr1Cre/+), NK cells gradually diminish during aging. This phenotype is associated with autophagy deficiency and the stress induced by reactive oxygen species (ROS). Therefore, terminally differentiated NK cells lacking Vps34 display an accelerated senescence phenotype, while the application of antioxidants effectively reverses the senescence caused by Vps34 deletion by neutralizing ROS. In summary, this study unveils the dual and unique activity of Vps34 in NK cells. Vps34-mediated vesicular transport is crucial for CD122 membrane trafficking during NK cell commitment, whereas Vps34-mediated autophagy can delay NK cell senescence.

TREX1 Inactivation Unleashes Cancer Cell STING-Interferon Signaling and Promotes Antitumor Immunity.

A substantial fraction of cancers evade immune detection by silencing Stimulator of Interferon Genes (STING)-Interferon (IFN) signaling. Therapeutic reactivation of this program via STING agonists, epigenetic, or DNA-damaging therapies can restore antitumor immunity in multiple preclinical models. Here we show that adaptive induction of three prime exonuclease 1 (TREX1) restrains STING-dependent nucleic acid sensing in cancer cells via its catalytic function in degrading cytosolic DNA. Cancer cell TREX1 expression is coordinately induced with STING by autocrine IFN and downstream STAT1, preventing signal amplification. TREX1 inactivation in cancer cells thus unleashes STING-IFN signaling, recruiting T and natural killer (NK) cells, sensitizing to NK cell-derived IFNγ, and cooperating with programmed cell death protein 1 blockade in multiple mouse tumor models to enhance immunogenicity. Targeting TREX1 may represent a complementary strategy to induce cytosolic DNA and amplify cancer cell STING-IFN signaling as a means to sensitize tumors to immune checkpoint blockade (ICB) and/or cell therapies. SIGNIFICANCE: STING-IFN signaling in cancer cells promotes tumor cell immunogenicity. Inactivation of the DNA exonuclease TREX1, which is adaptively upregulated to limit pathway activation in cancer cells, recruits immune effector cells and primes NK cell-mediated killing. Targeting TREX1 has substantial therapeutic potential to amplify cancer cell immunogenicity and overcome ICB resistance. This article is featured in Selected Articles from This Issue, p. 695.

Chemoproteomic Profiling of Erastin-Interacting Proteins.

Ferroptosis is an iron-related cell death caused by irregular lipid peroxidation that has been implicated with a variety of disease. Erastin is a canonical ferroptosis inducer that is known to function by inhibiting system Xc- and cystine transport; however, the global interactome of erastin in cells remains unexplored. In this work, we employed a quantitative chemoproteomic approach to profile direct interacting proteins of erastin in living cells using a multifunctional photo-cross-linking probe. A number of novel erastin-interacting proteins were identified, including a serine hydrolase, ABHD6, whose overexpression showed a potentiating impact on ferroptosis. Further biochemical experiments revealed that erastin can allosterically activate ABHD6's activity to produce more arachidonic acids and elevate the level of lipid reactive oxygen species. Collectively, our work provided a global portrait of erastin-interacting proteins and discovered ABHD6 as a new ferroptosis regulator.

Glutathione supplementation improves fat graft survival by inhibiting ferroptosis via the SLC7A11/GPX4 axis.

BACKGROUND: Autologous fat grafting is hampered by unpredictable graft survival, which is potentially regulated by ferroptosis. Glutathione (GSH), a powerful antioxidant used in tissue preservation, has ferroptosis-regulating activity; however, its effects on fat grafts are unclear. This study investigated the effects and mechanisms of GSH in fat graft survival. METHODS: Human lipoaspirates were transplanted subcutaneously into the backs of normal saline-treated (control) or GSH-treated nude mice. Graft survival was evaluated by magnetic resonance imaging and histology. RNA sequencing was performed to identify differentially expressed genes and enriched pathways. GSH activity was evaluated in vitro using an oxygen and glucose deprivation (OGD) model of adipose-derived stem cells. RESULTS: Compared with control group, GSH induced better outcomes, including superior graft retention, appearance, and histological structures. RNA sequencing suggested enhanced negative regulation of ferroptosis in the GSH-treated grafts, which showed reduced lipid peroxides, better mitochondrial ultrastructure, and SLC7A11/GPX4 axis activation. In vitro, OGD-induced ferroptosis was ameliorated by GSH, which restored cell proliferation, reduced oxidative stress, and upregulated ferroptosis defense factors. CONCLUSIONS: Our study confirms that ferroptosis participates in regulating fat graft survival and that GSH exerts a protective effect by inhibiting ferroptosis. GSH-assisted lipotransfer is a promising therapeutic strategy for future clinical application.

Remnant cholesterol and the risk of aortic valve calcium progression: insights from the MESA study.

BACKGROUND: Remnant cholesterol (RC) is implicated in the risk of cardiovascular disease. However, comprehensive population-based studies elucidating its association with aortic valve calcium (AVC) progression are limited, rendering its precise role in AVC ambiguous. METHODS: From the Multi-Ethnic Study of Atherosclerosis database, we included 5597 individuals (61.8 ± 10.1 years and 47.5% men) without atherosclerotic cardiovascular disease at baseline for analysis. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), as estimated by the Martin/Hopkins equation. Using the adjusted Cox regression analyses, we examined the relationships between RC levels and AVC progression. Furthermore, we conducted discordance analyses to evaluate the relative AVC risk in RC versus LDL-C discordant/concordant groups. RESULTS: During a median follow-up of 2.4 ± 0.9 years, 568 (10.1%) participants exhibited AVC progression. After adjusting for traditional cardiovascular risk factors, the HRs (95% CIs) for AVC progression comparing the second, third, and fourth quartiles of RC levels with the first quartile were 1.195 (0.925-1.545), 1.322 (1.028-1.701) and 1.546 (1.188-2.012), respectively. Notably, the discordant high RC/low LDL-C group demonstrated a significantly elevated risk of AVC progression compared to the concordant low RC/LDL-C group based on their medians (HR, 1.528 [95% CI 1.201-1.943]). This pattern persisted when clinical LDL-C threshold was set at 100 and 130 mg/dL. The association was consistently observed across various sensitivity analyses. CONCLUSIONS: In atherosclerotic cardiovascular disease-free individuals, elevated RC is identified as a residual risk for AVC progression, independent of traditional cardiovascular risk factors. The causal relationship of RC to AVC and the potential for targeted RC reduction in primary prevention require deeper exploration.

Local modulation of Au/MoS2 Schottky barriers using a top ZnO nanowire gate for high-performance photodetection.

Schottky junctions are commonly used for fabricating heterojunction-based 2D transition metal dichalcogenide (TMD) photodetectors, characteristically offering a wide detection range, high sensitivity and fast response. However, these devices often suffer from reduced detectivity due to the high dark current, making it challenging to discover a simple and efficient universal way to improve the photoelectric performances. Here, we demonstrate a novel approach for integrating ZnO nanowire gates into a MoS2-Au Schottky junction to improve the photoelectric performances of photodetectors by locally controlling the Schottky barrier. This strategy remarkably reduces the dark current level of the device without affecting its photocurrent and the Schottky detectivity can be modified to a maximum detectivity of 1.4 × 1013 Jones with -20 V NG bias. This work provides potential possibilities for tuning the band structure of other materials and optimizing the performance of heterojunction photodetectors.

Hierarchical-Bioinspired MOFs Enhanced Electromagnetic Wave Absorption.

Proteins exhibit complex and diverse multi-dimensional structures, along with a wide range of functional groups capable of binding metal ions. By harnessing the unique characteristics of proteins, it is possible to enhance the synthesis of metal-organic frameworks (MOFs) and modify their morphology. Here, the utilization of biomineralized bovine serum albumin (BSA) protein as a template for synthesizing Mil-100 with superior microwave absorption (MA) properties is investigated. The multi-dimensional structure and abundant functional groups of biomineralized BSA protein make it an ideal candidate for guiding the synthesis of Mil-100 with intricate network structures. The BSA@Mil-100 synthesized using this method exhibits exceptional uniformity and monodispersity of nanocrystals. The findings suggest that the BSA protein template significantly influences the regulation of nanocrystal and microstructure formation of Mil-100, resulting in a highly uniform and monodisperse structure. Notably, the synthesized 2-BSA@Mil-100 demonstrates a high reflection loss value of -58 dB at 8.85 GHz, along with a maximum effective absorption bandwidth value of 6.79 GHz, spanning from 6.01 to 12.8 GHz. Overall, this study highlights the potential of utilizing BSA protein as a template for MOF synthesis, offering an effective strategy for the design and development of high-performance MA materials.