In Vitro Gastrointestinal Digestion of Various Sweet Potato Leaves: Polyphenol Profiles, Bioaccessibility and Bioavailability Elucidation.

The chemical composition discrepancies of five sweet potato leaves (SPLs) and their phenolic profile variations during in vitro digestion were investigated. The results indicated that Ecaishu No. 10 (EC10) provided better retention capacity for phenolic compounds after drying. Furthermore, polyphenols were progressively released from the matrix as the digestion process proceeded. The highest bioaccessibility of polyphenols was found in EC10 intestinal chyme at 48.47%. For its phenolic profile, 3-, 4-, and 5-monosubstituted caffeoyl quinic acids were 9.75%, 57.39%, and 79.37%, respectively, while 3,4-, 3,5-, and 4,5-disubstituted caffeoyl quinic acids were 6.55, 0.27 and 13.18%, respectively. In contrast, the 3,4-, 3,5-, 4,5-disubstituted caffeoylquinic acid in the intestinal fluid after dialysis bag treatment was 62.12%, 79.12%, and 62.98%, respectively, which resulted in relatively enhanced bioactivities (DPPH, 10.51 µmol Trolox/g; FRAP, 8.89 µmol Trolox/g; ORAC, 7.32 µmol Trolox/g; IC50 for α-amylase, 19.36 mg/g; IC50 for α-glucosidase, 25.21 mg/g). In summary, desirable phenolic acid release characteristics and bioactivity of EC10 were observed in this study, indicating that it has potential as a functional food ingredient, which is conducive to the exploitation of the sweet potato processing industry from a long-term perspective.

Characteristics of the phyllosphere microbial community and its relationship with major aroma precursors during the tobacco maturation process.

Numerous bacteria, fungi and other microorganisms in the tobacco phyllosphere interstellar area participate in the physiological metabolism of plants by interacting with the host. However, there is currently little research on the characteristics of tobacco phyllosphere microbial communities, and the correlation between tobacco phyllosphere microbial communities and phyllosphere factor indicators is still unknown. Therefore, high-throughput sequencing technology based on the 16S rRNA/ITS1 gene was used to explore the diversity and composition characteristics of tobacco phyllosphere bacterial and fungal communities from different maturation processes, and to identify marker genera that distinguish phyllosphere microbial communities. In this study, the correlations between tobacco phyllosphere bacterial and fungal communities and the precursors of major aroma compounds were explored. The results showed that as the tobacco plants matured, the density of glandular trichomes on the tobacco leaves gradually decreased. The surface physicochemical properties of tobacco leaves also undergo significant changes. In addition, the overall bacterial alpha diversity in the tobacco phyllosphere area increased with maturation, while the overall fungal alpha diversity decreased. The beta diversity of bacteria and fungi in the tobacco phyllosphere area also showed significant differences. Specifically, with later top pruning time, the relative abundances of Acidisoma, Ralstonia, Bradyrhizobium, Alternaria and Talaromyces gradually increased, while the relative abundances of Pseudomonas, Filobassidium, and Tausonia gradually decreased. In the bacterial community, Acidisoma, Ralstonia, Bradyrhizobium, and Alternaria were significantly positively correlated with tobacco aroma precursors, with significant negative correlations with tobacco phyllosphere trichome morphology, while Pseudomonas showed the opposite pattern; In the fungal community, Filobasidium and Tausonia were significantly negatively correlated with tobacco aroma precursors, and significantly positively correlated with tobacco phyllosphere trichome morphology, while Alternaria showed the opposite pattern. In conclusion, the microbiota (bacteria and fungi) and aroma precursors of the tobacco phyllosphere change significantly as tobacco matures. The presence of Acidisoma, Ralstonia, Bradyrhizobium and Alternaria in the phyllosphere microbiota of tobacco may be related to the aroma precursors of tobacco.

Identification of potential biomarkers of gout through weighted gene correlation network analysis.

Background: Although hyperuricemia is not always associated with acute gouty arthritis, uric acid is a significant risk factor for gout. Therefore, we investigated the specific mechanism of uric acid activity. Methods: Using the gout-associated transcriptome dataset GSE160170, we conducted differential expression analysis to identify differentially expressed genes (DEGs). Moreover, we discovered highly linked gene modules using weighted gene coexpression network analysis (WGCNA) and evaluated their intersection. Subsequently, we screened for relevant biomarkers using the cytoHubba and Mcode algorithms in the STRING database, investigated their connection to immune cells and constructed a competitive endogenous RNA (ceRNA) network to identify upstream miRNAs and lncRNAs. We also collected PBMCs from acute gouty arthritis patients and healthy individuals and constructed a THP-1 cell gout inflammatory model, RT-qPCR and western blotting (WB) were used to detect the expression of C-X-C motif ligand 8 (CXCL8), C-X-C motif ligand 2 (CXCL2), and C-X-C motif ligand 1 (CXCL1). Finally, we predicted relevant drug targets through hub genes, hoping to find better treatments. Results: According to differential expression analysis, there were 76 upregulated and 28 downregulated mRNAs in GSE160170. Additionally, WGCNA showed that the turquoise module was most strongly correlated with primary gout; 86 hub genes were eventually obtained upon intersection. IL1ß, IL6, CXCL8, CXCL1, and CXCL2 are the principal hub genes of the protein-protein interaction (PPI) network. Using RT-qPCR and WB, we found that there were significant differences in the expression levels of CXCL8, CXCL1, and CXCL2 between the gouty group and the healthy group, and we also predicted 10 chemicals related to these proteins. Conclusion: In this study, we screened and validated essential genes using a variety of bioinformatics tools to generate novel ideas for the diagnosis and treatment of gout.

Impact of rice variety, cooking equipment and pretreatment method on the quality of lightly milled rice.

Lightly milled rice is a healthier choice compared to refined white rice. In this study, the effects of variety, cooking equipment and pretreatment method on the quality of six varieties of lightly milled rice from China after cooking was investigated through physics, chemistry and instrumental analysis method. Nanjing-No.5055 has the best eating quality, Xiadao-No.1 has higher appearance score, and Fengliangyouxiang-No.1 has the lowest glycemic index. Compared with microwave oven and electric cooker, steamer has a more significant positive impact on component retention, eating quality and sensory quality, but the former has lower cooking time and higher glycemic index. Soaking can effectively improve the water absorption rate, thus reducing hardness. Cleaning affects component retention but is beneficial for sensory quality. The most obvious variation in organizational structure can be observed in the steamer and soaking processes. These findings could serve as a valuable reference for the processing of lightly milled rice.

Risk stratification by systemic manifestations secondary to hemodynamic disorders of patients with severe tricuspid regurgitation.

BACKGROUND: Tricuspid regurgitation (TR) is a prevalent disease that triggers systemic pathological changes including cardiac, respiratory, hepatic and digestive, hematopoietic, renal and skin issues. The burden of extra-cardiac manifestations has not been well described in TR patients and the clinical impact is unknown. METHODS: Patients with severe or more-than-severe TR during hospitalization, who did not have any previous cardiac procedures, hemodynamically significant congenital heart disease or concomitant severe aortic or mitral valve disease, were retrospectively analyzed. Pre-specified criteria and diagnosis of baseline characteristics were used to evaluate the presence of extra-cardiac manifestations secondary to TR after excluding comorbidities that may also lead to corresponding abnormalities. Extra-cardiac involvements encompass respiratory, hepatic and, digestive, renal, hematopoietic and dermatic system. Staging criteria are defined as no extra-cardiac system involvement in Stage 1, one in Stage 2, at least two extra-cardiac involvements in Stage 3 and any end-stage organ failure in Stage 4. A telephone follow-up was conducted to record the composite endpoint namely all-cause death or cardiac rehospitalization after the index hospitalization. RESULTS: A total of 258 patients were identified with a median age of 73 (interquartile range [IQR]: 62-83) years and 52.3% were female. Severe TR and more-than-severe TR patients accounted for 92.6% and 7.4% of the cohort. There were 20.5%, 27.5%, 37.6% and 14.3% of patients from Stage 1 to 4 respectively. The follow-up time was at a median of 251 (IQR: 183-324) days. TR Patients in Stage 3&4 were at an increased risk with borderline statistical significance to experience the composite endpoint compared to patients in Stage 1&2 (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.0 to 3.7, P = 0.049). CONCLUSIONS: Approximately half of patients with at least severe TR presented with two or more extra-cardiac systemic manifestations, which may incur a 1.9-fold higher risk of all-cause death or cardiac rehospitalization than TR patients with one or less extra-cardiac involvement.

Disulfiram ameliorates STING/MITA-dependent inflammation and autoimmunity by targeting RNF115.

STING (also known as MITA) is an adaptor protein that mediates cytoplasmic DNA-triggered signaling, and aberrant activation of STING/MITA by cytosolic self-DNA or gain-of-function mutations causes severe inflammation. Here, we show that STING-mediated inflammation and autoimmunity are promoted by RNF115 and alleviated by the RNF115 inhibitor disulfiram (DSF). Knockout of RNF115 or treatment with DSF significantly inhibit systemic inflammation and autoimmune lethality and restore immune cell development in Trex1-/- mice and STINGN153S/WT bone marrow chimeric mice. In addition, knockdown or pharmacological inhibition of RNF115 substantially downregulate the expression of IFN-α, IFN-γ and proinflammatory cytokines in PBMCs from patients with systemic lupus erythematosus (SLE) who exhibit high concentrations of dsDNA in peripheral blood. Mechanistically, knockout or inhibition of RNF115 impair the oligomerization and Golgi localization of STING in various types of cells transfected with cGAMP and in organs and cells from Trex1-/- mice. Interestingly, knockout of RNF115 inhibits the activation and Golgi localization of STINGN153S as well as the expression of proinflammatory cytokines in myeloid cells but not in endothelial cells or fibroblasts. Taken together, these findings highlight the RNF115-mediated cell type-specific regulation of STING and STINGN153S and provide potential targeted intervention strategies for STING-related autoimmune diseases.

Solvent- and pH-Stable Eu(III)-Based Metal-Organic Framework with Phosphate-Ratio Fluorescence Sensing and Significant Proton Conduction.

Lanthanide-based metal-organic frameworks show good potential for applications due to their unique structures and functional properties. A highly thermally and acid-base stable Eu-MOF was synthesized by a solvothermal method with the molecular formula {[(CH3)2NH2]2[Eu2(NDDP)2(H2O)2]·H2O}n (Eu-MOF, H4NDDP = 5,5'-(naphthalene-2,6-diyl)diisophthalic acid). Eu-MOF takes a three-dimensional (4,4,8)-connected topology. The water molecules involved in the coordination, free water molecules, and [(CH3)2NH2]+ cations in the pore can be used as proton carriers. The proton conductivity attains 1.25 × 10-4 S cm-1 at room temperature and 2.42 × 10-3 S cm-1 at 70 °C and 98% relative humidity. Combined with the dual-emission properties from the ligands and Eu(III) ions enables Eu-MOF to be used as a ratiometric fluorescent sensor for phosphate efficiently and rapidly, with a limit of detection of 0.12 µM in the Tris-HCl buffer solution. These results provide a new approach for the construction of MOFs with high proton conductivity and a ratiometric fluorescence response.

Optimal treatment of asymptomatic patients with severe aortic stenosis: protocol of a prospective, multicentre, registry study.

INTRODUCTION: Decisions regarding the optimal timing of intervention for asymptomatic aortic stenosis (AS) are controversial. The study aims to identify potential risk factors for asymptomatic patients with severe AS that are associated with worse prognosis and to evaluate the benefits of early interventions for asymptomatic patients presenting with one or more additional risk factors. METHODS AND ANALYSIS: This is a non-interventional, prospective, open-label, multicentre registry study across China. A total of 1000 patients will be enrolled and categorised as symptomatic or asymptomatic. The primary endpoint is the occurrence of all-cause mortality, stroke, acute myocardial infarction and heart failure-related hospitalisation at 1-year follow-up. In asymptomatic severe AS patients presenting with one or more risk factors, the occurrence rate of the primary endpoint between those who undergo transcatheter aortic valve replacement (TAVR) and those who do not will be compared. We will also compare the occurrence rate of the primary endpoint for asymptomatic severe AS patients with additional risk factors who undergo TAVR with those presenting with symptoms. This study is believed to provide additional evidence to help clinicians identify and refer severe AS patients who are asymptomatic but present with additional risk factors for early intervention of TAVR. ETHICS AND DISSEMINATION: The study protocol has been approved by the local ethics committee of each participating site: West China Hospital, Sichuan University; Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Second Hospital of Hebei Medical University; Tianjin Chest Hospital; and First Affiliated Hospital of Nanchang University. All participants will provide written informed consent. Study results will be published through academic conferences and peer-reviewed journals. TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trial Registry (https:// www.chictr.org.cn), with the registration number ChiCTR2200064853.

Phenolic Profile and Bioactivity Changes of Lotus Seedpod and Litchi Pericarp Procyanidins: Effect of Probiotic Bacteria Biotransformation.

Theoretically, lactic acid bacteria (LABs) could degrade polyphenols into small molecular compounds. In this study, the biotransformation of lotus seedpod and litchi pericarp procyanidins by Lactobacillus plantarum 90 (Lp90), Streptococcus thermophilus 81 (ST81), Lactobacillus rhamnosus HN001 (HN001), and Pediococcus pentosus 06 (PP06) were analysed. The growth curve results indicated that procyanidins did not significantly inhibit the proliferation of LABs. Ultra-high-performance liquid chromatography high-resolution mass spectrometry (UPLC-HRMS) revealed that procyanidin B2 and procyanidin B3 in lotus seedpod decreased by 62.85% and 25.45%, respectively, with ST81 metabolised, while kaempferol and syringetin 3-O-glucoside content increased. Although bioconversion did not increase the inhibitory function of procyanidins against glycosylation end-products in vitro, the 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) free radical scavenging capacity and ferric reducing antioxidant power of litchi pericarp procyanidins increased by 157.34% and 6.8%, respectively, after ST81 biotransformation. These findings may inspire further studies of biological metabolism of other polyphenols and their effects on biological activity.

Outcomes Following Transcatheter Aortic Valve Replacement for Aortic Stenosis in Patients With Type 0 Bicuspid, Type 1 Bicuspid, and Tricuspid Aortic Valves.

BACKGROUND: Data concerning the outcomes of transcatheter aortic valve replacement in type 0 bicuspid aortic stenosis (AS) are scarce. The study aims to compare the outcomes of transcatheter aortic valve replacement for AS in patients with type 0 bicuspid, type 1 bicuspid, and tricuspid aortic valve anatomy. METHODS: We enrolled consecutive patients undergoing transcatheter aortic valve replacement for severe AS between 2012 and 2022 in this single-center retrospective cohort study. The primary outcome was mortality, while secondary outcomes included in-hospital complications such as stroke and pacemaker implantation and transcatheter heart valve hemodynamic performance. RESULTS: The number of patients with AS with type 0 bicuspid, type 1 bicuspid, and tricuspid aortic valve anatomy was 328, 302, and 642, respectively. Self-expanding transcatheter heart valves were used in the majority of patients (n=1160; 91.4%). In the matched population, differences in mortality (30 days: 4.2% versus 1.7% versus 1.7%, Poverall=0.522; 1 year: 10% versus 2.3% versus 6.2%, Poverall=0.099) and all stroke (30 days: 1.0% versus 0.9% versus 0.0%, Poverall=0.765; 1 year: 1.4% versus 1.6% versus 1.3%, Poverall=NS) were nonsignificant, and the incidence of overall in-hospital complications was comparable among groups. Ascending aortic diameter was the single predictor of 1-year mortality in type 0 bicuspid patients (hazard ratio, 1.59 [95% CI, 1.03-2.44]; P=0.035). The proportion of patients with a mean residual gradient ≥20 mm Hg was the highest in those with type 0 bicuspid anatomy, although the need for permanent pacemaker implantation was the lowest in this group. CONCLUSIONS: Major clinical outcomes of transcatheter aortic valve replacement for AS in patients with type 0 bicuspid, type 1 bicuspid, and tricuspid aortic valve anatomy are equivalent at short- and mid-term follow-up. These observations merit further exploration in prospective international registries and randomized controlled trials.

Effects of degree of milling on nutritional quality, functional characteristics and volatile compounds of brown rice tea.

This study investigated the effects of rice preparation using different degrees of milling (DOM) from 0% to 13% on the nutritional composition, functional properties, major volatile compounds and safety of brown rice tea (BRT). We found that 2% DOM reduced 52.33% of acrylamide and 31.88% of fluorescent AGEs. When DOM was increased from 0% to 13%, the total phenolic content (TPC) of brown rice tea decreased by 48.12%, and the total flavonoid content (TFC) and condensed tannin content (CTC) also decreased significantly, with the smallest decrease at 2% DOM. In addition, the inhibitory activities of α-amylase, α-glucosidase and pancreatic lipase as well as the antioxidant activity also decreased gradually. Analysis by electronic nose and gas chromatography-mass spectrometry (GC-MS) showed that alkanes, furans, aldehydes, pyrazines and alcohols were the major volatiles in BRT, with 2% DOM having the greatest retention of aroma compounds. An orthogonal partial least squares discriminant analysis (OPLS-DA) and VIP score (VIP > 1 and p < 0.05) analysis were used to screen 25 flavor substances that contributed to the differences in BRT aroma of different DOMs. These results suggest that 2% milled BRT can improve safety and palatability while maximizing the retention of flavor compounds and nutrients. The findings of this study contribute to an enhanced understanding of the dynamics of changes and preservation of aroma compounds and nutrients present during the processing of BRT.

Insights into nutrition, flavor and edible quality changes of golden pomfret (Trachinotus ovatus) fillets prepared by different cooking methods.

Introduction: In recent years, Asia has seen an increase in demand for golden pomfret (Trachinotus ovatus). Especially in instant (ready-to-eat) and prepared (ready-to-cock) food processing industry. Thermal processing is a vital part of food processing. However, no comprehensive analysis has been reported on its flavor, nutrition and edible quality changes during the key thermal processing. Methods: Accordingly, in this study, we evaluated the effects of different cooking methods (steaming, frying, microwaving and baking) on the color, texture, cooking loss, nutrition composition, volatile flavor substances and other indicators of golden pomfret filets. Results and Discussion: The results showed that the steamed samples (SS) had the lowest cooking loss and fat content, the highest moisture content, complete appearance and the lowest levels of hardness and chewiness. Fried samples (FS) had a notable difference in fatty acid composition. The content of unsaturated fatty acids (UFAs) increased significantly, while the relative content of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) decreased from 7.88 to 1.42%, lower than other groups. The essential amino acid index (EAAI) of microwaved samples (MS) was 94.89, which was higher than other groups. Baked samples (BS) had the highest relative content of umami amino acids (UAAs) and sweet amino acids (SAAs), which was 8.08 mg/100 mg and 5.19 mg/100 mg, respectively. Hexanal and nonanal were detected in control samples (CK), SS, FS, MS and BS. While pyrazine compounds were detected only in FS and BS. Steaming and microwaving treatment of golden pomfret resulted in better nutritional preservation, which was more conducive to human health. Frying and baking treatment of golden pomfret had better taste and flavor and higher sensory scores. The nutrition, flavor and edible quality of golden pomfret under different cooking methods were related and interactive. Cooking loss and fat content can be used as simple evaluation indicators to compare the overall quality of different cooking methods. This study provides a reference for the thermal processing technology and industrial production of golden pomfret.

Concomitant aortic regurgitation predicts better left ventricular reverse remodeling after transcatheter aortic valve replacement.

BACKGROUND: We aim to determine predictors of inadequate left ventricular mass index (LVMi) regression at mid-term after transcatheter aortic valve replacement (TAVR), including the potential role of epicardial adipose tissue (EAT). METHODS: We retrospectively reviewed patients with both echocardiographic assessments and multi-slice computed tomography (MSCT) obtained one year after TAVR. The change of LVMi, the volume and the average CT attenuation of EAT from baseline to one-year follow-up was calculated. Patients were divided into two groups by the percentage change of LVMi at a cut-off of 15%. RESULTS: A total of 152 patients were included with a median age of 74 years (interquartile range [IQR] 69-78 years) and 56.6% being male. LVMi decreased (P < 0.0001) while EAT volume increased and the average CT attenuation decreased (both P < 0.0001) at one year. Baseline atrial fibrillation (P = 0.042), mitral regurgitation ≥ mild (P = 0.006), aortic regurgitation (AR) > mild (P = 0.001) and the change in the average CT attenuation of EAT (P = 0.026) were different between the decrease of LVMi ≥ 15% and < 15%. AR > mild at baseline was the only statistically significant predictor of a decrease of LVMi < 15% at one year (OR 0.33, 95% CI: 0.13 to 0.84, P = 0.021) in multivariate regression. CONCLUSIONS: Concomitant more-than-mild AR might predict better left ventricular reverse remodeling regression after TAVR.

Stable Europium(III) Metal-Organic Framework Demonstrating High Proton Conductivity and Fluorescence Detection of Tetracyclines.

A europium(III) metal-organic framework (MOF), namely, {[[(CH3)2NH2]3Eu2(DTTP-2OH)2(HCOO)(H2O)]·4H2O}n (Eu-MOF, H4DTTP-2OH = 2',5'-dihydroxy-[1,1':4',1″-terphenyl]-3,3″,5,5″-tetracarboxylic acid) has been assembled through solvothermal method. The Eu-MOF is a three-dimensional (3D) (4,4,8)-connected topological framework with binuclear Eu(III) clusters as secondary building units, in which a richly ordered hydrogen bonding network formed among the free H2O molecules, dimethylamine cations, and phenolic hydroxyl groups provides a potential pathway for proton conduction. The proton conductivity reaches the category of superionic conductors (σ > 10-4 S cm-1) at room temperature with a maximum conductivity of 1.91 × 10-3 S cm-1 at 60 °C and 98% RH. Moreover, it also can be used as a fluorescence sensor in aqueous solution with detection limits of 0.14 µM for tetracycline, 0.13 µM for oxytetracycline and 0.11 µM for doxycycline. These results pave new methods for constructing MOFs with high proton conductivity and responsive fluorescence.

Rise and metabolic roles of Vibrio during the fermentation of crab paste.

Microbial community may systematically promote the development of fermentation process of foods. Traditional fermentation is a spontaneous natural process that determines a unique nutritional characteristic of crab paste of Portunus trituberculatus, However, rare information is available regarding the development pattern and metabolic role of bacterial community during the fermentation of crab paste. Here, using a 16S rRNA gene amplicon sequencing technology, we investigated dynamics of bacterial community and its relationship with metabolites during the fermentation of crab paste. The results showed that bacterial community changed dynamically with the fermentation of crab paste which highlighted by consistently decreased α-diversity and overwhelming dominance of Vibrio at the later days of fermentation. Vibrio had a positive correlation with trimethylamine, hypoxanthine, formate, and alanine while a negative correlation with inosine and adenosine diphosphate. In contrast, most of other bacterial indicators had a reverse correlation with these metabolites. Moreover, Vibrio presented an improved function potential in the formation of the significantly increased metabolites. These findings demonstrate that the inexorable rise of Vibrio not only drives the indicator OTUs turnover in the bacterial community but also has incriminated the quality of crab paste from fresh to perished.

A pH-responsive metal-organic framework for the co-delivery of HIF-2α siRNA and curcumin for enhanced therapy of osteoarthritis.

The occurrence of osteoarthritis (OA) is highly correlated with the reduction of joint lubrication performance, in which persistent excessive inflammation and irreversible destruction of cartilage dominate the mechanism. The inadequate response to monotherapy methods, suboptimal efficacy caused by undesirable bioavailability, short retention, and lack of stimulus-responsiveness, are few unresolved issues. Herein, we report a pH-responsive metal-organic framework (MOF), namely, MIL-101-NH2, for the co-delivery of anti-inflammatory drug curcumin (CCM) and small interfering RNA (siRNA) for hypoxia inducible factor (HIF-2α). CCM and siRNA were loaded via encapsulation and surface coordination ability of MIL-101-NH2. Our vitro tests showed that MIL-101-NH2 protected siRNA from nuclease degradation by lysosomal escape. The pH-responsive MIL-101-NH2 gradually collapsed in an acidic OA microenvironment to release the CCM payloads to down-regulate the level of pro-inflammatory cytokines, and to release the siRNA payloads to cleave the target HIF-2α mRNA for gene-silencing therapy, ultimately exhibiting the synergetic therapeutic efficacy by silencing HIF-2α genes accompanied by inhibiting the inflammation response and cartilage degeneration of OA. The hybrid material reported herein exhibited promising potential performance for OA therapy as supported by both in vitro and in vivo studies and may offer an efficacious therapeutic strategy for OA utilizing MOFs as host materials.

Transcatheter aortic valve implantation in patients with bicuspid valve morphology: a roadmap towards standardization.

Indications for transcatheter aortic valve implantation (TAVI) have expanded in many countries to include patients with aortic stenosis who are at low surgical risk, and a similar expansion to this cohort is anticipated elsewhere in the world, together with an increase in the proportion of patients with bicuspid aortic valve (BAV) morphology as the age of the patients being treated decreases. To date, patients with BAV have been excluded from major randomized trials of TAVI owing to anatomical considerations. As a consequence, BAV has been a relative contraindication to the use of TAVI in international guidelines. Although clinical experience and observational data are accumulating, BAV presents numerous anatomical challenges for successful TAVI, despite advances in device design. Furthermore, in those with BAV, substantial geographical variation exists in patient characteristics, clinical approach and procedural strategy. Therefore, in this Roadmap article, we summarize the existing evidence and provide consensus recommendations from an international group of experts on the application of TAVI in patients with BAV in advance of the anticipated growth in the use of this procedure in this challenging cohort of patients.

Ferroptosis and metabolic syndrome and complications: association, mechanism, and translational applications.

Metabolic syndrome is a medical condition characterized by several metabolic disorders in the body. Long-term metabolic disorders raise the risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Therefore, it is essential to actively explore the aetiology of metabolic syndrome (MetS) and its comorbidities to provide effective treatment options. Ferroptosis is a new form of cell death that is characterized by iron overload, lipid peroxide accumulation, and decreased glutathione peroxidase 4(GPX4) activity, and it involves the pathological processes of a variety of diseases. Lipid deposition caused by lipid diseases and iron overload is significant in metabolic syndrome, providing the theoretical conditions for developing ferroptosis. Recent studies have found that the major molecules of ferroptosis are linked to common metabolic syndrome consequences, such as T2DM and atherosclerosis. In this review, we first discussed the mechanics of ferroptosis, the regulatory function of inducers and inhibitors of ferroptosis, and the significance of iron loading in MetS. Next, we summarized the role of ferroptosis in the pathogenesis of MetS, such as obesity, type 2 diabetes, and atherosclerosis. Finally, we discussed relevant ferroptosis-targeted therapies and raised some crucial issues of concern to provide directions for future Mets-related treatments and research.

The E3 ubiquitin ligase ARIH1 promotes antiviral immunity and autoimmunity by inducing mono-ISGylation and oligomerization of cGAS.

The cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) plays a critical role in antiviral immunity and autoimmunity. The activity and stability of cGAS are fine-tuned by post-translational modifications. Here, we show that ariadne RBR E3 ubiquitin protein ligase 1 (ARIH1) catalyzes the mono-ISGylation and induces the oligomerization of cGAS, thereby promoting antiviral immunity and autoimmunity. Knockdown or knockout of ARIH1 significantly inhibits herpes simplex virus 1 (HSV-1)- or cytoplasmic DNA-induced expression of type I interferons (IFNs) and proinflammatory cytokines. Consistently, tamoxifen-treated ER-Cre;Arih1fl/fl mice and Lyz2-Cre; Arih1fl/fl mice are hypersensitive to HSV-1 infection compared with the controls. In addition, deletion of ARIH1 in myeloid cells alleviates the autoimmune phenotypes and completely rescues the autoimmune lethality caused by TREX1 deficiency. Mechanistically, HSV-1- or cytosolic DNA-induced oligomerization and activation of cGAS are potentiated by ISGylation at its K187 residue, which is catalyzed by ARIH1. Our findings thus reveal an important role of ARIH1 in innate antiviral and autoimmune responses and provide insight into the post-translational regulation of cGAS.