Design, synthesis, and evaluation of formylpiperazine analogs of Ferrostatin-1 as novel improved ferroptosis inhibitors.

In this study, a series of new formylpiperazine-derived ferroptosis inhibitors were designed and synthesized based on the structure of a known ferroptosis inhibitor, ferrostatin-1 (Fer-1). The anti-ferroptosis activity of these synthetic compounds in human umbilical vein endothelial cells (HUVECs) induced by Erastin was evaluated. It was found that some of the new compounds, especially compound 26, showed potent anti-ferroptosis activity, as evidenced by its ability to restore cell viability, reduce iron accumulation, scavenge reactive oxygen species, maintain mitochondrial membrane potential, increase GSH levels, decrease LPO and MDA content, and upregulate GPX4 expression. Moreover, compound 26 exhibited superior microsomal stability than Fer-1. The present results suggest that compound 26 is a promising lead compound for the development of new ferroptosis inhibitors for the treatment of vascular diseases.

Design, synthesis, and evaluation of novel ferrostatin derivatives for the prevention of HG-induced VEC ferroptosis.

Ferroptosis is a nonapoptotic, iron-catalyzed form of regulated cell death. It has been shown that high glucose (HG) could induce ferroptosis in vascular endothelial cells (VECs), consequently contributing to the development of various diseases. This study synthesized and evaluated a series of novel ferrostatin-1 (Fer-1) derivatives fused with a benzohydrazide moiety to prevent HG-induced VEC ferroptosis. Several promising compounds showed similar or improved inhibitory effects compared to positive control Fer-1. The most effective candidate 12 exhibited better protection against erastin-induced ferroptosis and high glucose-induced ferroptosis in VECs. Mechanistic studies revealed that compound 12 prevented mitochondrial damage, reduced intracellular ROS accumulation, upregulated the expression of GPX4, and decreased the amounts of ferrous ion, LPO and MDA in VECs. However, compound 12 still exhibited undesirable microsomal stability like Fer-1, suggesting the need for further optimization. Overall, the present findings highlight ferroptosis inhibitor 12 as a potential lead compound for treating ferroptosis-associated vascular diseases.

Uptake of SGLT2i and Outcomes in Patients with Diabetes and Heart Failure: A Population-Based Cohort and a Specialized Clinic Cohort.

BACKGROUND: Sodium/glucose cotransporter 2 inhibitors (SGLT2i) are effective in adults with diabetes mellitus (DM) and heart failure (HF) based on randomized clinical trials. We compared SGLT2i uptake and outcomes in two cohorts: a population-based cohort of all adults with DM and HF in Alberta, Canada and a specialized heart failure clinic (HFC) cohort. METHODS: The population-based cohort was derived from linked provincial healthcare datasets. The specialized clinic cohort was created by chart review of consecutive patients prospectively enrolled in the HFC between February 2018 and August 2022. We examined the association between SGLT2i use (modeled as a time-varying covariate) and all-cause mortality or deaths/cardiovascular hospitalizations. RESULTS: Of the 4,885 individuals from the population-based cohort, 64.2% met the eligibility criteria of the trials proving the effectiveness of SGLT2i. Utilization of SGLT2i increased from 1.2% in 2017 to 26.4% by January 2022. In comparison, of the 530 patients followed in the HFC, SGLT2i use increased from 9.8% in 2019 to 49.1 % by March 2022. SGLT2i use in the population-based cohort was associated with fewer all-cause mortality (aHR 0.51, 95% CI 0.41-0.63) and deaths/cardiovascular hospitalizations (aHR 0.65, 95% CI 0.54-0.77). However, SGLT2i usage rates were far lower in HF patients without DM (3.5% by March 2022 in the HFC cohort). CONCLUSIONS: Despite robust randomized trial evidence of clinical benefit, the uptake of SGLT2i in patients with HF and DM remains low, even in the specialized HFC. Clinical care strategies are needed to enhance the use of SGLT2i and improve implementation.

Evaluation of the mechanism of Gong Ying San activity on dairy cows mastitis by network pharmacology and metabolomics analysis.

OBJECTIVES: The goal of this investigation was to identify the main compounds and the pharmacological mechanism of the traditional Chinese medicine formulation, Gong Ying San (GYS), by infrared spectral absorption characteristics, metabolomics, network pharmacology, and molecular-docking analysis for mastitis. The antibacterial and antioxidant activities were determined in vitro. METHODS: The chemical constituents of GYS were detected by ultra-high-performance liquid chromatography Q-extractive mass spectrometry (UHPLC-QE-MS). Related compounds were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP, http://tcmspw.com/tcmsp.php) and the Encyclopedia of Traditional Chinese Medicine (ETCM, http://www.tcmip.cn/ETCM/index.php/Home/) databases; genes associated with mastitis were identified in DisGENT. A protein-protein interaction (PPI) network was generated using STRING. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment screening was conducted using the R module. Molecular-docking analyses were performed with the AutoDockTools V1.5.6. RESULTS: Fifty-four possible compounds in GYS with forty likely targets were found. The compound-target-network analysis showed that five of the ingredients, quercetin, luteolin, kaempferol, beta-sitosterol, and stigmasterol, had degree values >41.6, and the genes TNF, IL-6, IL-1ß, ICAM1, CXCL8, CRP, IFNG, TP53, IL-2, and TGFB1 were core targets in the network. Enrichment analysis revealed that pathways associated with cancer, lipids, atherosclerosis, and PI3K-Akt signaling pathways may be critical in the pharmacology network. Molecular-docking data supported the hypothesis that quercetin and luteolin interacted well with TNF-α and IL-6. CONCLUSIONS: An integrative investigation based on a bioinformatics-network topology provided new insights into the synergistic, multicomponent mechanisms of GYS's anti-inflammatory, antibacterial, and antioxidant activities. It revealed novel possibilities for developing new combination medications for reducing mastitis and its complications.

Finite-time synchronization of delayed semi-Markov reaction-diffusion systems: An asynchronous boundary control scheme.

This paper tries to study the problem of finite-time synchronization for delayed semi-Markov reaction-diffusion systems. Based on the spatial and parametric characteristics of the considered systems, a new asynchronous boundary control scheme is proposed to ensure the finite-time synchronization of the drive and response systems. In the asynchronous boundary control scheme, only an actuator should be placed at the spatial boundary, which is more easier to implement and economical than the other non-boundary control strategies. Besides, the system parameters and controller follow two asynchronous semi-Markov chains for jumping, which is more practical than obeying one semi-Markov chain. Moreover, for the considered systems, we proposes a new lemma of finite-time stability, and by employing the inequality methods and variable substitution, we derive the criterion of finite-time synchronization and a correlative corollary. Finally, a numerical example and an application example on secure communication are carried out to support the developed approach.

Protocol to identify biomarkers in patients with post-COVID condition using multi-omics and machine learning analysis of human plasma.

Here, we present a workflow for analyzing multi-omics data of plasma samples in patients with post-COVID condition (PCC). Applicable to various diseases, we outline steps for data preprocessing and integrating diverse assay datasets. Then, we detail statistical analysis to unveil plasma profile changes and identify biomarker-clinical variable associations. The last two steps discuss machine learning techniques for unsupervised clustering of patients based on their inherent molecular similarities and feature selection to identify predictive biomarkers. For complete details on the use and execution of this protocol, please refer to Wang et al.1.

Synthesis and biological evaluation of 1-phenyl-tetrahydro-ß-carboline-based first dual PRMT5/EGFR inhibitors as potential anticancer agents.

Protein arginine methyltransferase 5 (PRMT5) and epidermal growth factor receptor (EGFR) are both involved in the regulation of various cancer-related processes, and their dysregulation or overexpression has been observed in many types of tumors. In this study, we designed and synthesized a series of 1-phenyl-tetrahydro-ß-carboline (THßC) derivatives as the first class of dual PRMT5/EGFR inhibitors. Among the synthesized compounds, 10p showed the most potent dual PRMT5/EGFR inhibitory activity, with IC50 values of 15.47 ± 1.31 and 19.31 ± 2.14 µM, respectively. Compound 10p also exhibited promising antiproliferative activity against A549, MCF7, HeLa, and MDA-MB-231 cell lines, with IC50 values below 10 µM. Molecular docking studies suggested that 10p could bind to PRMT5 and EGFR through hydrophobic, π-π, and cation-π interactions. Furthermore, 10p displayed favorable pharmacokinetic properties and oral bioavailability (F = 30.6%) in rats, and administrated orally 10p could significantly inhibit the growth of MCF7 orthotopic xenograft tumors. These results indicate that compound 10p is a promising hit compound for the development of novel and effective dual PRMT5/EGFR inhibitors as potential anticancer agents.

Sequential multi-omics analysis identifies clinical phenotypes and predictive biomarkers for long COVID.

The post-acute sequelae of COVID-19 (PASC), also known as long COVID, is often associated with debilitating symptoms and adverse multisystem consequences. We obtain plasma samples from 117 individuals during and 6 months following their acute phase of infection to comprehensively profile and assess changes in cytokines, proteome, and metabolome. Network analysis reveals sustained inflammatory response, platelet degranulation, and cellular activation during convalescence accompanied by dysregulation in arginine biosynthesis, methionine metabolism, taurine metabolism, and tricarboxylic acid (TCA) cycle processes. Furthermore, we develop a prognostic model composed of 20 molecules involved in regulating T cell exhaustion and energy metabolism that can reliably predict adverse clinical outcomes following discharge from acute infection with 83% accuracy and an area under the curve (AUC) of 0.96. Our study reveals pertinent biological processes during convalescence that differ from acute infection, and it supports the development of specific therapies and biomarkers for patients suffering from long COVID.

An Updated Overview of Synthetic α-glucosidase Inhibitors: Chemistry and Bioactivities.

Diabetes mellitus (DM) is a critical global health issue, affecting nearly half a billion people worldwide, with an increasing incidence rate and mortality. Type 2 diabetes is caused by the body's inability to effectively use insulin, and approximately 95% of patients have type 2 diabetes. α-glucosidase has emerged as an important therapeutic target for the treatment of type 2 diabetes. In the past years, three α-glucosidase inhibitors have been approved for clinical use, namely acarbose, voglibose, and miglitol. However, the undesirable effects associated with these carbohydrate mimic-based α-glucosidase inhibitors have limited their clinical applications. Consequently, researchers have shifted their focus towards the development of non-carbohydrate mimic α-glucosidase inhibitors that can safely and effectively manage postprandial hyperglycemia in type 2 diabetes. Herein, this article provides an overview of the synthetic α-glucosidase inhibitors, particularly those based on heterocycles, which have been reported from 2018 to 2022. This article aims to provide useful information for medicinal chemists in further developing clinically available anti-type 2 diabetes drugs.

Discovery of marine phidianidine-based Nrf2 activators and their potential against oxLDL- and HG-induced injury in HUVECs.

One effective strategy for treating atherosclerosis is to inhibit the injury of vascular endothelial cells (VECs) induced by oxidized low-density lipoprotein (oxLDL) and high glucose (HG). This study synthesized and evaluated a series of novel Nrf2 activators derived from the marine natural product phidianidine for their ability to protect human umbilical VECs against oxLDL- and HG-induced injury. The results of in vitro bioassays demonstrated that compound D-36 was the most promising Nrf2 activator, effectively inhibiting the apoptosis of HUVECs induced by oxLDL and HG. Furthermore, Nrf2 knockdown experiments confirmed that compound D-36 protected against oxLDL- and HG-induced apoptosis in HUVECs by activating the Nrf2 pathway. These findings provide important insights into a new chemotype of marine-derived Nrf2 activators that could potentially be optimized to develop effective anti-atherosclerosis agents.

Integrated analysis of circRNA, lncRNA, miRNA and mRNA to reveal the ceRNA regulatory network of postnatal skeletal muscle development in Ningxiang pig.

Introduction: The development of skeletal muscle is regulated by regulatory factors of genes and non-coding RNAs (ncRNAs). Methods: The objective of this study was to understand the transformation of muscle fiber type in the longissimus dorsi muscle of male Ningxiang pigs at four different growth stages (30, 90, 150, and 210 days after birth, n = 3) by histological analysis and whole transcriptome sequencing. Additionally, the study investigated the expression patterns of various RNAs involved in muscle fiber transformation and constructed a regulatory network for competing endogenous RNA (ceRNA) that includes circular RNA (circRNA)/long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA). Results: Histomorphology analysis showed that the diameter of muscle fiber reached its maximum at 150 days after birth. The slow muscle fiber transformation showed a pattern of initial decrease followed by an increase. 29,963 circRNAs, 2,683 lncRNAs, 986 miRNAs and 22,411 mRNAs with expression level ≥0 were identified by whole transcriptome sequencing. Furthermore, 642 differentially expressed circRNAs (DEc), 505 differentially expressed lncRNAs (DEl), 316 differentially expressed miRNAs (DEmi) and 6,090 differentially expressed mRNAs (DEm) were identified by differential expression analysis. Functions of differentially expressed mRNA were identified by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). GO enrichment analysis indicates that 40 known genes and 6 new genes are associated with skeletal muscle development. Additionally, KEGG analysis shows that these genes regulate skeletal muscle development via MAPK, FoxO, Hedgehog, PI3K-Akt, Notch, VEGF and other signaling pathways. Through protein-protein interaction (PPI) and transcription factor prediction (TFP), the action mode of skeletal muscle-related genes was explored. PPI analysis showed that there were stable interactions among 19 proteins, meanwhile, TFP analysis predicted 22 transcription factors such as HMG20B, MYF6, MYOD1 and MYOG, and 12 of the 19 interacting proteins were transcription factors. The regulatory network of ceRNA related to skeletal muscle development was constructed based on the correlation of various RNA expression levels and the targeted binding characteristics with miRNA. The regulatory network included 31 DEms, 59 miRNAs, 667 circRNAs and 224 lncRNAs. conclusion: Overall, the study revealed the role of ceRNA regulatory network in the transformation of skeletal muscle fiber types in Ningxiang pigs, which contributes to the understanding of ceRNA regulatory network in Ningxiang pigs during the skeletal muscle development period.

Formation of oil-particle aggregates in the presence of marine algae.

After an oil spill, the formation of oil-particle aggregates (OPAs) is associated with the interaction between dispersed oil and marine particulate matter such as phytoplankton, bacteria and mineral particles. Until recently, the combined effect of minerals and marine algae in influencing oil dispersion and OPA formation has rarely been investigated in detail. In this paper, the impacts of a species of flagellate algae Heterosigma akashiwo on oil dispersion and aggregation with montmorillonite were investigated. This study has found that oil coalescence is inhibited due to the adhesion of algal cells on the droplet surface, causing fewer large droplets to be dispersed into the water column and small OPAs to form. Due to the role of biosurfactants in the algae and the inhibition of algae on the swelling of mineral particles, both the oil dispersion efficiency and oil sinking efficiency were improved, which reached 77.6% and 23.5%, respectively at an algal cell concentration (Ca) of 1.0 × 106 cells per mL and a mineral concentration of 300 mg L-1. The volumetric mean diameter of the OPAs decreased from 38.4 µm to 31.5 µm when Ca increased from 0 to 1.0 × 106 cells per mL. At higher turbulent energy, more oil tended to form larger OPAs. The findings may add knowledge about the fate and transport of spilled oil and provide fundamental data for oil spill migration modelling.

Synthesis and evaluation of folate-mediated targeting and poly (ß-amino ester)-mediated pH-responsive delivery system of riccardin D based on the O-carboxymethylated chitosan micelles.

This study aimed to combine the active targeting function of folate (FA) receptor-mediated endocytosis with the pH-responsive drug delivery of poly (ethylene glycol)-grafted-poly (-amino ester) copolymers (PEG-PAE) in cancer targeting therapy. Herein, O-carboxymethylated chitosan (OCMC) was grafted with hydrophobic deoxycholic acid (DOCA). Further, PEG-PAE and FA-conjugated DOCA modified OCMC were synthesized to develop the potential cancer-targeted carrier (PEG-PAE-DOMC-FA), for which the structure was investigated by 1H NMR and FTIR. Then riccardin D (RD) was successfully loaded for tumor-targeted drug delivery. The particle size, zeta potential, encapsulating efficiencies, and loading content profiles of PEG-PAE-DOMC-FA/RD showed a strong dependence on the environmental pH values. The cumulative release of PEG-PAE-DOMC-FA/RD at pH 5.0 (90.63 %) was higher than pH 7.4 (51.12 %), which also indicated the pH sensitivity. Moreover, a lower IC50 and higher coumarin-6 uptake were found because of the folate-receptor-mediated endocytosis. In pharmacokinetic study, PEG-PAE-DOMC-FA/RD significantly improved the mean retention time (MRT) and AUC(0-∞) from 7.89 h and 36.1 mg/L·h of control group to 10.03 h and 123.8 mg/L·h. In the xenograft mice model, stronger antitumor efficacy and lower toxicity were confirmed. In conclusion, the multi-functional micelles could be considered as a promising vehicle for delivering hydrophobic drugs to tumors.

Acid-tolerant Lactiplantibacillus plantarum ZDY2013 shows a colonization niche preference and interacts with enterotoxigenic Bacillus cereus in specific-pathogen-free mice.

Probiotics have long been utilized as functional food and modulate gut microbial homeostasis, but their colonization niche is mostly unclear and transient, which restrains the development of microbiome-targeted strategies. Lactiplantibacillus (L.) plantarum ZDY2013 is an allochthonous species of the human gastrointestinal tract with acid-tolerant properties. It serves as an antagonistic agent against the food-borne pathogen Bacillus (B.) cereus and a potent regulator of the gut microbiota. However, there is a knowledge gap regarding the colonization dynamics of L. plantarum ZDY2013 in the host intestine and the colonization niche of its interaction with pathogens. Here, we designed a pair of specific primers targeting L. plantarum ZDY2013 based on its whole genome sequence. We evaluated their accuracy and sensitivity with other host-derived strains and confirmed their availability with artificially spiked fecal samples from different mouse models. Additionally, the content of L. plantarum ZDY2013 was quantified by qPCR in fecal samples from BALB/c mice, followed by the analysis of its colonization niche preference. Moreover, the interactions between L. plantarum ZDY2013 and enterotoxigenic B. cereus HN001 were also elucidated. The results revealed that the newly designed primers could identify L. plantarum ZDY2013 with high specificity and were resistant to the influence of the complex fecal matrix and gut microbes from different hosts. Interestingly, the content of mixed L. plantarum ZDY2013 and B. cereus HN001 when orally administered remained higher when compared with the single strain group in BALB/c mice upon discontinuation of intragastric administration. In addition, L. plantarum ZDY2013 was mainly enriched in the large intestine during the ingestion period and maintained the highest content in the stomach after discontinuing supplementation on day 7. Moreover, L. plantarum ZDY2013 colonization neither damaged the intestine nor ameliorated the damage triggered by B. cereus in BALB/c mice. Overall, our study constructed two efficient specific primers targeting L. plantarum ZDY2013 and provided the potential to explore the underlying mechanism of competition between L. plantarum ZDY2013 and pathogens in host species.

Circular Intronic RNA circTTN Inhibits Host Gene Transcription and Myogenesis by Recruiting PURB Proteins to form Heterotypic Complexes.

Muscle cell growth plays an important role in skeletal muscle development. Circular RNAs (circRNAs) have been proven to be involved in the regulation of skeletal muscle growth and development. In this study, we explored the effect of circTTN on myoblast growth and its possible molecular mechanism. Using C2C12 cells as a functional model, the authenticity of circTTN was confirmed by RNase R digestion and Sanger sequencing. Previous functional studies have showed that the overexpression of circTTN inhibits myoblast proliferation and differentiation. Mechanistically, circTTN recruits the PURB protein on the Titin (TTN) promoter to inhibit the expression of the TTN gene. Moreover, PURB inhibits myoblast proliferation and differentiation, which is consistent with circTTN function. In summary, our results indicate that circTTN inhibits the transcription and myogenesis of the host gene TTN by recruiting PURB proteins to form heterotypic complexes. This work may act as a reference for further research on the role of circRNA in skeletal muscle growth and development.

miR-100-5p Regulates Skeletal Muscle Myogenesis through the Trib2/mTOR/S6K Signaling Pathway.

MicroRNAs (miRNAs) are endogenous small non-coding RNAs that play crucial regulatory roles in many biological processes, including the growth and development of skeletal muscle. miRNA-100-5p is often associated with tumor cell proliferation and migration. This study aimed to uncover the regulatory mechanism of miRNA-100-5p in myogenesis. In our study, we found that the miRNA-100-5p expression level was significantly higher in muscle tissue than in other tissues in pigs. Functionally, this study shows that miR-100-5p overexpression significantly promotes the proliferation and inhibits the differentiation of C2C12 myoblasts, whereas miR-100-5p inhibition results in the opposite effects. Bioinformatic analysis predicted that Trib2 has potential binding sites for miR-100-5p at the 3'UTR region. A dual-luciferase assay, qRT-qPCR, and Western blot confirmed that Trib2 is a target gene of miR-100-5p. We further explored the function of Trib2 in myogenesis and found that Trib2 knockdown markedly facilitated proliferation but suppressed the differentiation of C2C12 myoblasts, which is contrary to the effects of miR-100-5p. In addition, co-transfection experiments demonstrated that Trib2 knockdown could attenuate the effects of miR-100-5p inhibition on C2C12 myoblasts differentiation. In terms of the molecular mechanism, miR-100-5p suppressed C2C12 myoblasts differentiation by inactivating the mTOR/S6K signaling pathway. Taken together, our study results indicate that miR-100-5p regulates skeletal muscle myogenesis through the Trib2/mTOR/S6K signaling pathway.

Angiotensin-converting enzyme 2-at the heart of the COVID-19 pandemic.

ACE2 is the indispensable entry receptor for SARS-CoV and SARS-CoV-2. Because of the COVID-19 pandemic, it has become one of the most therapeutically targeted human molecules in biomedicine. ACE2 serves two fundamental physiological roles: as an enzyme, it alters peptide cascade balance; as a chaperone, it controls intestinal amino acid uptake. ACE2's tissue distribution, affected by co-morbidities and sex, explains the broad tropism of coronaviruses and the clinical manifestations of SARS and COVID-19. ACE2-based therapeutics provide a universal strategy to prevent and treat SARS-CoV-2 infections, applicable to all SARS-CoV-2 variants and other emerging zoonotic coronaviruses exploiting ACE2 as their cellular receptor.

Urinary angiotensin-converting enzyme 2 and metabolomics in COVID-19-mediated kidney injury.

Background: Angiotensin-converting enzyme 2 (ACE2), the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the kidneys. Beyond serving as a crucial endogenous regulator of the renin-angiotensin system, ACE2 also possess a unique function to facilitate amino acid absorption. Our observational study sought to explore the relationship between urine ACE2 (uACE2) and renal outcomes in coronavirus disease 2019 (COVID-19). Methods: In a cohort of 104 patients with COVID-19 without acute kidney injury (AKI), 43 patients with COVID-19-mediated AKI and 36 non-COVID-19 controls, we measured uACE2, urine tumour necrosis factor receptors I and II (uTNF-RI and uTNF-RII) and neutrophil gelatinase-associated lipocalin (uNGAL). We also assessed ACE2 staining in autopsy kidney samples and generated a propensity score-matched subgroup of patients to perform a targeted urine metabolomic study to describe the characteristic signature of COVID-19. Results: uACE2 is increased in patients with COVID-19 and further increased in those that developed AKI. After adjusting uACE2 levels for age, sex and previous comorbidities, increased uACE2 was independently associated with a >3-fold higher risk of developing AKI [odds ratio 3.05 (95% confidence interval 1.23‒7.58), P = .017]. Increased uACE2 corresponded to a tubular loss of ACE2 in kidney sections and strongly correlated with uTNF-RI and uTNF-RII. Urine quantitative metabolome analysis revealed an increased excretion of essential amino acids in patients with COVID-19, including leucine, isoleucine, tryptophan and phenylalanine. Additionally, a strong correlation was observed between urine amino acids and uACE2. Conclusions: Elevated uACE2 is related to AKI in patients with COVID-19. The loss of tubular ACE2 during SARS-CoV-2 infection demonstrates a potential link between aminoaciduria and proximal tubular injury.

Photocatalyst-free visible light driven synthesis of gem-dihaloenones from alkynes, tetrahalomethanes and water.

Photocatalytic reactions, in particular, processes without photosensitisers, have attracted increased attention due to their green aspect and high economic value and are considered valuable tools in organic synthesis. A new practical photocatalytic system was investigated in this study, and it can efficiently produce gem-dihaloenones by combining terminal alkynes with tetrahalomethanes (BrCCl3 and CBr4) and water without a photocatalyst, and the yield can reach up to 87%. The catalytic system is straightforward, the raw materials are inexpensive and easy to obtain, and the operation is simple.

Integrating Cardiac MRI Imaging and Multidisciplinary Clinical Care is Associated With Improved Outcomes in Patients With Fabry Disease.

Given the inherent complexities of Fabry disease (FD) and evolving landscape of cardiovascular clinical management, there is no established ideal clinical care model for these patients. We identified clinical factors predictive of increased risk of major adverse cardiac events (MACE) in patients with FD targeted to improve clinical outcomes. Ninety-five patients studied over a median follow-up time of 6.3 years, and 26 patients reached the composite endpoint with a high prevalence of heart failure and cerebrovascular events and no cardiac-related mortality. Patients with MACE had worse health-related quality of life scores. Hypertrophy and presence of myocardial fibrosis increase risk of MACE by 4-5 times, and dyslipidemia increases risk of MACE by 3 times. Early Fabry-specific treatment and close monitoring of comorbidities reduce cardiac complications and mortality. These findings highlight the importance of comprehensive multidisciplinary management to help improve outcomes in FD patients.