Clinical outcomes of radiofrequency catheter ablation guided by intracardiac echocardiography for Chinese atrial fibrillation patients: a single-center, retrospective study.

Background: Intracardiac echocardiography (ICE) is a novel technology with certain advantages in treatment of atrial fibrillation (AF), yet there is limited research on the use of ICE in radiofrequency ablation for AF treatment in China. The aim of this study was to investigate the total fluoroscopy time and dose, safety, and effectiveness of ICE guided vs. traditional fluoroscopy (non-ICE) guided radiofrequency ablation for AF in China. Methods: We conducted a single-center retrospective analysis of patients who underwent ICE or traditional fluoroscopy-guided radiofrequency ablation for AF. The primary endpoint of this study was total fluoroscopy time, and the secondary endpoints included total fluoroscopy dose, acute surgery failure, transseptal puncture time, ablation time, total procedure time, and 6-month surgery success (no AF recurrence or atrial flutter). As an exploratory analysis, outcomes of interest by different types of AF were examined. Results: A total of 97 patients were included in the analysis. Forty-eight were in the ICE group and 49 were in the non-ICE group with comparable demographic and clinical characteristics at the baseline. None of patients experienced acute surgery failure with no major procedure-related complications occurred. The fluoroscopic time and dose were significantly lower in the ICE group compared to the non-ICE group (0.00 vs. 9.67±4.88 min, P<0.001; 0.00 vs. 77.10±44.28 mGy/cm2, P<0.001, respectively). There were no statistically significant differences in transseptal puncture time, ablation time and total procedure time between the two groups. There were two AF recurrences observed during the 6-month follow-up in each group (P>0.99). Conclusions: ICE significantly reduced the fluoroscopic time and dose for radiofrequency catheter ablation in AF patients. There were no significant differences in safety or effectiveness outcomes between the ICE and non-ICE groups.

Mitochondria-localizing triphenylphosphine-8-hydroxyquinoline Ru complexes induce ferroptosis and their antitumor evaluation.

Ruthenium complexes are one of the most promising anticancer drugs and ferroptosis is a novel form of regulated cell death, the study on the effect of Ru complexes on ferroptosis is helpful to find more effective antitumor drugs. Here, the synthesis and characterization of two Ru complexes containing 8-hydroxylquinoline and triphenylphosphine as ligands, [Ru(L1) (PPh3)2Cl2] (Ru-1), [Ru(L2) (PPh3)2Cl2] (Ru-2), were reported. Complexes Ru-1 âˆ¼ Ru-2 showed good anticancer activity in Hep-G2 cells. Researches indicated that complexes Ru-1 âˆ¼ Ru-2 could be enriched and appear as red fluorescence in the mitochondria, arouse dysfunction of mitochondria, induce the accumulation of reactive oxygen species (ROS) and lipid peroxidation (LPO), while the morphology of nuclei and cell apoptosis had no significant change. Further experiments proved that GPX4 and Ferritin were down-regulated, which eventually triggered ferroptosis in Hep-G2 cells. Remarkably, Ru-1 showed high inhibitory activity against xenograft tumor growth in vivo (TGIR = 49%). This study shows that the complex Ru-1 could act as a novel drug candidate by triggering cell ferroptosis.

Bioaccessibility and human health risks of arsenic from geological origin in lateritic red soil on construction land.

Current human health risk assessments of soil arsenic (As) contamination rarely consider bioaccessibility (IVBA), which may overestimate the health risks of soil As. The IVBA of As (As-IVBA) may differ among various soil types. This investigation of As-IVBA focused As from geological origin in a typical subtropical soil, lateritic red soil, and its risk control values. The study used the SBRC gastric phase in vitro digestion method and As speciation sequential extraction based upon phosphorus speciation extraction method. Two construction land sites (CH and HD sites) in the Pearl River Delta region were surveyed. The results revealed a high content of residual As (including scorodite, mansfieldite, orpiment, realgar, and aluminum arsenite) in the lateritic red soils at both sites (CH: 84.9%, HD: 91.7%). The content of adsorbed aluminum arsenate (CH: 3.24%, HD: 0.228%), adsorbed ferrum arsenate (CH: 8.55%, HD: 5.01%), and calcium arsenate (CH: 7.33%, HD: 3.01%) were found to be low. The bioaccessible As content was significantly positively correlated with the As content in adsorbed aluminum arsenate, adsorbed ferrum arsenate, and calcium arsenate. A small portion of these sequential extractable As speciation could be absorbed by the human body (CH: 14.9%, HD: 3.16%), posing a certain health risk. Adsorbed aluminum arsenate had the highest IVBA, followed by calcium arsenate, and adsorbed ferrum arsenate had the lowest IVBA. The aforementioned speciation characteristics of As from geological origin in lateritic red soil contributed to its lower IVBA compared to other soils. The oxidation state of As did not significantly affect As-IVBA. Based on As-IVBA, the carcinogenic and non-carcinogenic risks of soil As in the CH and HD sites decreased greatly in human health risk assessment. The results suggest that As-IVBA in lateritic red soil should be considered when assessing human health risks on construction land.

Cerebrotendinous xanthomatosis with tremor as the main manifestation: A case report.

INTRODUCTION: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid metabolism disorder. It is caused by a defect in the sterol-27-hydroxylase gene, leading to the deposition of cholesteryl and bile alcohol in large amounts, causing a variety of clinical manifestations; however, tremor as the main manifestation of CTX has not been reported. PATIENTS CONCERNS AND CLINICAL FINDINGS: Herein, we report a 27-year-old woman, who developed head and body tremors at the age of 12 years. Many hospitals misdiagnosed her condition as idiopathic tremor and Parkinson disease, with a poor curative effect. PRIMARY DIAGNOSIS AND INTERVENTION: We diagnosed her with CTX and treated with chenodeoxycholic acid and clonazepam. CONCLUSION: The patient's condition considerably improved. This case could help avoid misdiagnosis and mistreatment in clinical practice.

Concomitant treatment of ureteral calculi and ipsilateral pelvic sciatic nerve schwannoma with transperitoneal laparoscopic approach: A case report.

BACKGROUND: Schwannomas are rare peripheral neural myelin sheath tumors that originate from Schwann cells. Of the different types of schwannomas, pelvic sciatic nerve schwannoma is extremely rare. Definite preoperative diagnosis of pelvic schwannomas is difficult, and surgical resection is the gold standard for its definite diagnosis and treatment. CASE SUMMARY: We present a case of pelvic schwannoma arising from the sciatic nerve that was detected in a 40-year-old man who underwent computed tomography for intermittent right lower back pain caused exclusively by a right ureteral calculus. Subsequently, successful transperitoneal laparoscopic surgery was performed for the intact removal of the stone and en bloc resection of the schwannoma. The total operative time was 125 min, and the estimated blood loss was inconspicuous. The surgical procedure was uneventful. The patient was discharged on postoperative day 5 with the simultaneous removal of the urinary catheter. However, the patient presented with motor and sensory disorders of the right lower limb, caused by partial damage to the right sciatic nerve. No tumor recurrence was observed at the postoperative appointment. CONCLUSION: Histopathological examination of the specimen confirmed the diagnosis of a schwannoma. Thus, laparoscopic surgery is safe and feasible for concomitant extirpation of pelvic schwannomas and other pelvic and abdominal diseases that require surgical treatment.

A prospective and consecutive study assessing short-term clinical and radiographic outcomes of Chinese domestically manufactured 3D printing trabecular titanium acetabular cup for primary total hip arthroplasty: evaluation of 236 cases.

Purpose: We prospectively evaluate the short-term clinical and radiographic outcomes of the only Chinese domestically produced trabecular titanium acetabular cup(3D ACT™ cup) in primary total hip arthroplasty (THA), aiming to provide evidence-based support for its clinical application. Methods: A total of 236 patients, who underwent primary THA using 3D ACT™ cup in the Department of Joint Surgery at our hospital between January 2017 and June 2019, were included in this study. General patient data, imaging information, functional scores, and complications were collected to evaluate the early clinical efficacy. Results: All patients were followed up for 33-52 months, with an average of (42.2 ± 9.2) months. At the last follow-up, the preoperative HHS score increased significantly from 43.7 ± 6.8 to 85.6 ± 9.3 points (P < 0.01). Similarly, the preoperative WOMAC scores showed significant improvement from 59.2 ± 5.8 to 13.1 ± 3.5 points (P < 0.01). 92.3% of the patients expressed satisfaction or high satisfaction with the clinical outcome. Furthermore, 87.7% of the acetabular cups were positioned within the Lewinnek safe zone, achieving successful reconstruction of the acetabular rotation center. The cup survival rate at the last follow-up was 100%. Conclusions: The utilization of the only Chinese domestically manufactured 3D printing trabecular titanium acetabular cup in primary THA demonstrated favorable short-term clinical and radiographic outcomes. The acetabular cup exhibits excellent initial stability, high survival rate, and favorable osseointegration, leading to a significant enhancement in pain relief and functional improvement. In the future, larger sample sizes and multicenter prospective randomized controlled trials will be required to validate the long-term safety and effectiveness of this 3D ACT™ cup.

"Four-in-One" Nanozyme for Amplified Catalytic-Photothermal Therapy.

The cancer therapeutic efficacy of the peroxidase (POD)-mimicking nanozyme-based monotherapy is significantly hindered due to insufficient intratumoral hydrogen peroxide (H2O2) and glutathione (GSH) consumption effect on reactive oxygen species (ROS). In this study, we present the development of poly(o-phenylenediamine)@gold nanoparticles (AuNPs) (PoPD@Au) nanocomposites for multifunctional catalytic-photothermal therapy. These nanocomposites exhibit triple distinct nanozymatic activities, i.e., POD-like activity that catalyzes H2O2 to ROS, glucose oxidase (GOx)-like activity that supplements endogenous H2O2, and GSH depleting activity that decreases the ROS consumption efficiency. This open source and reduce expenditure strategy for ROS generation allows for the amplification of tumor oxidative stress, thereby enhancing anti-tumor efficiency. Additionally, the PoPD@Au nanocomposites demonstrate outstanding photothermal conversion efficiency, contributing to the synergistic effect between PoPD and AuNPs. Moreover, we reveal the improved photothermal performance of PoPD@Au triggered by the tumor microenvironment pH, which provides additional benefits for targeted catalytic-photothermal therapy. This "four-in-one" design of PoPD@Au enables efficient anti-tumor effects both in vitro and in vivo, making it a universal strategy for engineering catalytic-photothermal therapeutic nanoagents.

CH-VAD left ventricular assist implantation combined with the Bentall procedure and coronary artery bypass grafting.

Left ventricular assist device (LVAD) implantation is an effective alternative treatment to heart transplantation, especially for end-stage heart failure patients who are ineligible for or unable to await a heart transplant. This report describes a complex and innovative surgery where LVAD implantation was performed alongside multiple concomitant cardiac and aortic procedures. A 62-year-old male patient with complicated comorbidities developed acute myocardial infarction and subsequent refractory advanced heart failure. Given his critically ill condition and intractable anatomical malformations, the CH-VAD left ventricular assist system implantation was performed concomitantly with the Bentall procedure, coronary artery bypass grafting, tricuspid valvuloplasty, and foramen ovale closure. The patient was successfully discharged. This case details the medical decision-making process and surgical strategy and demonstrates the feasibility of LVAD implantation combined with multiple additional cardiac and aortic procedures in expert cardiac centres. Success relies on experienced cardiac surgeons and a multidisciplinary LVAD Heart Team, ensuring excellence in surgical techniques, preoperative evaluation, post-operative care, and rehabilitation.

The Role of Emodin in the Treatment of Bladder Cancer based on Network Pharmacology and Experimental Verification.

BACKGROUND AND PURPOSE: Emodin, a compound derived from rhubarb and various traditional Chinese medicines, exhibits a range of pharmacological actions, including antiinflammatory, antiviral, and anticancer properties. Nevertheless, its pharmacological impact on bladder cancer (BLCA) and the underlying mechanism are still unclear. This research aimed to analyze the pharmacological mechanisms of Emodin against BLCA using network pharmacology analysis and experimental verification. METHODS: Initially, network pharmacology was employed to identify core targets and associated pathways affected by Emodin in bladder cancer. Subsequently, the expression of key targets in normal bladder tissues and BLCA tissues was assessed by searching the GEPIA and HPA databases. The binding energy between Emodin and key targets was predicted using molecular docking. Furthermore, in vitro experiments were carried out to confirm the predictions made with network pharmacology. RESULTS: Our analysis identified 148 common genes targeted by Emodin and BLCA, with the top ten target genes including TP53, HSP90AA1, EGFR, MYC, CASP3, CDK1, PTPN11, EGF, ESR1, and TNF. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated a significant correlation between Emodin and the PI3KAKT pathway in the context of BLCA. Molecular docking investigations revealed a strong affinity between Emodin and critical target proteins. In vitro experiments demonstrated that Emodin inhibits T24 proliferation, migration, and invasion while inducing cell apoptosis. The findings also indicated that Emodin reduces both PI3K and AKT protein and mRNA expression, suggesting that Emodin may mitigate BLCA by modulating the PI3K-AKT signaling pathway. CONCLUSION: This study integrates network pharmacology with in vitro experimentation to elucidate the potential mechanisms underlying the action of Emodin against BLCA. The results of this research enhance our understanding of the pharmacological mechanisms by which Emodin may be employed in treating BLCA.

Effect of Body Mass Index on Cecal Intubation Time During Unsedated Colonoscopy: Variation Across the Learning Stages of an Endoscopist.

BACKGROUND Body mass index (BMI) and endoscopists' experiences can be associated with cecal intubation time (CIT), but such associations are controversial. This study aimed to clarify the association between BMI and CIT during unsedated colonoscopy at 3 learning stages of a single endoscopist. MATERIAL AND METHODS A total of 1500 consecutive patients undergoing unsedated colonoscopy by 1 endoscopist at our department from December 11, 2020, to August 21, 2022, were reviewed. They were divided into 3 learning stages according to the number of colonoscopies performed by 1 endoscopist, including intermediate (501-1000 colonoscopies), experienced (1001-1500 colonoscopies), and senior stages (1501-2000 colonoscopies). Variables that significantly correlated with CIT were identified by Spearman rank correlation analyses and then included in multiple linear regression analysis. RESULTS Overall, 1233 patients were included. Among them, 392, 420, and 421 patients were divided into intermediate, experienced, and senior stages, respectively. Median CIT was 7.83, 6.38, and 5.58 min at intermediate, experienced, and senior stages, respectively (P.

Supramolecular Chiral Binding Affinity-Achieved Efficient Synergistic Cancer Therapy.

Supramolecular chirality-mediated selective interaction among native assemblies is essential for precise disease diagnosis and treatment. Herein, to fully understand the supramolecular chiral binding affinity-achieved therapeutic efficiency, supramolecular chiral nanoparticles (WP5⊃D/L-Arg+DOX+ICG) with the chirality transfer from chiral arginine (D/L-Arg) to water-soluble pillar[5]arene (WP5) are developed through non-covalent interactions, in which an anticancer drug (DOX, doxorubicin hydrochloride) and a photothermal agent (ICG, indocyanine green) are successfully loaded. Interestingly, the WP5⊃D-Arg nanoparticles show 107 folds stronger binding capability toward phospholipid-composed liposomes compared with WP5⊃L-Arg. The enantioselective interaction further triggers the supramolecular chirality-specific drug accumulation in cancer cells. As a consequence, WP5⊃D-Arg+DOX+ICG exhibits extremely enhanced chemo-photothermal synergistic therapeutic efficacy (tumor inhibition rate of 99.4%) than that of WP5⊃L-Arg+DOX+ICG (tumor inhibition rate of 56.4%) under the same condition. This work reveals the breakthrough that supramolecular chiral assemblies can induce surprisingly large difference in cancer therapy, providing strong support for the significance of supramolecular chirality in bio-application.

[A preliminary study on compliance of supportive treatment of patients with periodontitis after implant restoration therapy].

OBJECTIVE: To find out factors influencing the compliance of supportive treatment of patients with periodontitis who have received implant restoration therapy. METHODS: Patients who had completed periodontal and implant restoration treatment for more than 5 years in Department of Periodontology, Peking University Hospital of Stomatology were subjected to inclusion between March 2022 and August 2023.A questionnaire was compiled to gather the information including patients ' basic information (gender, age, and educational background etc.), smoking habits, general health conditions, oral hygiene habits, willingness to undertake periodontal and dental implant supportive treatment, actual fact on supportive treatment recorded in medical records, whether medical advices were correctly remembered, and reasons affected them to implement supportive therapy. The questionnaires were handed out to the above patients and filled during the process of follow-up treatment. Chi-square test, univariate and multivariate analysis of Logistic regression were employed to explore the correlations of these factors and the patients' compliance. RESULTS: In the study, 92 patients and questionnaires were collected and analyzed. The results indicated that oral hygiene habits and whether medical advices were correctly remembered had significant correlation with compliance (P < 0.05). Time constraint (47.0%) and difficulty in appointment registration (24.8%) were the top 2 reasons obstructed them to undertake supportive treatment. Although the vast majority of the patients indicated willingness to perform follow-ups, 55.4% of them wouldn't come back until the dentist called them back. The results of our study also indicated that the patients placed significantly less importance on the health of natural teeth than implants. CONCLUSION: In order to improve the compliance of supportive treatment, we suggest that dentists should put more emphasis on oral hygiene instruction, and knowledge regarding periodontitis should also be added as part of patient education contents. In the early stages of treatment, the patient should develop the habit of regular follow-up checks, More attention and patience should be given to elderly patients and those with lower level of education; use language that is easy to understand and printed medical instructions to help them remember. Patients can memorize better from refined doctors' advice, reinforcing care knowledge and refining medical advices can promote better follow-up treatment results. Motivating patients based on their characteristics is critical to improving compliance.

Excellent Bowel Preparation Quality Is Not Superior to Good Bowel Preparation Quality for Improving Adenoma/Polyp Detection Rate.

Background: Adequate bowel preparation quality is essential for high-quality colonoscopy according to the current guidelines. However, the excellent effect of bowel preparation on adenoma/polyp detection rate (ADR/PDR) remained controversial. Methods: During the period from December 2020 to August 2022, a total of 1566 consecutive patients underwent colonoscopy by an endoscopist. Their medical records were reviewed. According to the Boston bowel preparation scale, patients were divided into excellent, good, and poor bowel preparation quality groups. ADR/PDR, diminutive ADR/PDR, small ADR/PDR, intermediate ADR/PDR, large ADR/PDR, and number of adenomas/polyps were compared among them. Logistic regression analyses were performed to identify the factors that were significantly associated with ADR/PDR. Results: Overall, 1232 patients were included, of whom 463, 636, and 133 were assigned to the excellent, good, and poor groups, respectively. The good group had a significantly higher ADR/PDR (63% vs 55%, P = .015) and a larger number of adenomas/polyps (2.5 ± 3.2 vs 2.0 ± 2.8, P = .030) than the poor group. Both ADR/PDR (63% vs 55%, P = .097) and number of adenomas/polyps (2.2 ± 2.8 vs 2.0 ± 2.8, P = .219) were not significantly different between excellent and poor groups. The excellent (9% vs 4%, P = .045) and good (9% vs 4%, P = .040) groups had a significantly higher intermediate ADR/PDR than the poor group. Logistic regression analyses showed that either good (odds ratio [OR] = 1.786, 95% CI = 1.046-3.047, P = .034) or excellent (OR = 2.179, 95% CI = 1.241-3.826, P = .007) bowel preparation quality was independently associated with a higher ADR/PDR compared with poor bowel preparation quality. Excellent (OR = 1.202, 95% CI = 0.848-1.704, P = .302) bowel preparation quality was not independently associated with a higher ADR/PDR compared with good bowel preparation quality. Conclusions: The pursuit of excellence in bowel preparation does not show an association with increased ADR/PDR and number of adenomas/polyps compared with a good level. In addition, our study further contributes to the existing evidence that poor bowel preparation compromises ADR/PDR and number of adenomas/polyps.

Polyvinylpyrrolidone-Coated Cubic Hollow Nanocages of PdPt3 and PdIr3 as Highly Efficient Self-Cascade Uricase/Peroxidase Mimics.

Uricase-catalyzed uric acid (UA) degradation has been applied for hyperuricemia therapy, but this medication is limited by H2O2 accumulation, which can cause oxidative stress of cells, resulting in many other health issues. Herein, we report a robust cubic hollow nanocage (HNC) system based on polyvinylpyrrolidone-coated PdPt3 and PdIr3 to serve as highly efficient self-cascade uricase/peroxidase mimics to achieve the desired dual catalysis for both UA degradation and H2O2 elimination. These HNCs have hollow cubic shape with average wall thickness of 1.5 nm, providing desired synergy to enhance catalyst's activity and stability. Density functional theory calculations suggest the PdIr3 HNC surface tend to promote OH*/O* desorption for better peroxidase-like catalysis, while the PdPt3 HNC surface accelerates the UA oxidation by facilitating O2-to-H2O2 conversion. The dual catalysis power demonstrated by these HNCs in cell studies suggests their great potential as a new type of nanozyme for treating hyperuricemia.

Differential Gene Expression and Immune Cell Infiltration in Patients with Steroid-induced Necrosis of the Femoral Head.

OBJECTIVE: The study aimed to study the differential gene expression and immune cell infiltration in patients with steroid-induced necrosis of the femoral head (SANFH), identify the key genes and immune cells of SANFH, and explore the relationship between immune cells and SANFH. METHODS: The high-throughput gene chip dataset GSE123568 was downloaded from the GEO database, and the differential gene expression was analyzed with the R language. The STRING database and Cytoscape software were used to analyze the protein interaction network and screen key genes, and enrichment analysis was carried out on key genes. The infiltration of immune cells in SANFH patients was analyzed and verified by immunohistochemistry. RESULTS: EP300, TRAF6, STAT1, JAK1, CASP8, and JAK2 are key genes in the pathogenesis of SANFH, which mainly involve myeloid cell differentiation, cytokine-mediated signaling pathway, tumor necrosis factor-mediated signaling pathway, and cellular response to tumor necrosis factor through JAK-STAT, NOD-like receptor, toll-like receptor, and other signaling pathways, leading to the occurrence of diseases; immune infiltration and immunohistochemical results have shown the expression of memory B cells and activated dendritic cells as reduced in SANFH patients, while in the same SANFH samples, M1 macrophages have been positively correlated with monocytes, and neutrophils have been negatively correlated with monocytes expression. CONCLUSION: EP300, TRAF6, STAT1, JAK1, CASP8, and JAK2 have exhibited significant differences in SANFH (spontaneous osteonecrosis of the femoral head). Memory B cells, activated dendritic cells, M1 macrophages, monocytes, and neutrophils have shown abnormal expression in SANFH.

Triphenyl phosphate exposure impairs colorectal health by altering host immunity and colorectal microbiota.

Colorectal diseases such as colorectal cancer (CRC) and inflammatory bowel disease (IBD) have become one of the most common public health concerns worldwide due to the increasing incidence. Environmental factors are one of the important causes of colorectal diseases, as they can affect the intestinal barrier function, immune response and microbiota, causing intestinal inflammation and tumorigenesis. Triphenyl phosphate (TPHP), a widely used organophosphorus flame retardant that can leach and accumulate in various environmental media and biota, can enter the human intestine through drinking water and food. However, the effects of TPHP on colorectal health have not been well understood. In this study, we investigated the adverse influence of TPHP exposure on colorectal cells (in vitro assay) and C57BL/6 mice (in vivo assay), and further explored the potential mechanism underlying the association between TPHP and colorectal disease. We found that TPHP exposure inhibited cell viability, increased apoptosis and caused G1/S cycle arrest of colorectal cells. Moreover, TPHP exposure damaged colorectal tissue structure, changed immune-related gene expression in the colorectal transcriptome, and disrupted the composition of colorectal microbiota. Importantly, we found that TPHP exposure upregulated chemokine CXCL10, which was involved in colorectal diseases. Our study revealed that exposure to TPHP had significant impacts on colorectal health, which may possibly stem from alterations in host immunity and the structure of the colorectal microbial community.

The activator protein-1 complex governs a vascular degenerative transcriptional programme in smooth muscle cells to trigger aortic dissection and rupture.

BACKGROUND AND AIMS: Stanford type A aortic dissection (AD) is a degenerative aortic remodelling disease marked by an exceedingly high mortality without effective pharmacologic therapies. Smooth muscle cells (SMCs) lining tunica media adopt a range of states, and their transformation from contractile to synthetic phenotypes fundamentally triggers AD. However, the underlying pathomechanisms governing this population shift and subsequent AD, particularly at distinct disease temporal stages, remain elusive. METHODS: Ascending aortas from nine patients undergoing ascending aorta replacement and five individuals undergoing heart transplantation were subjected to single-cell RNA sequencing. The pathogenic targets governing the phenotypic switch of SMCs were identified by trajectory inference, functional scoring, single-cell regulatory network inference and clustering, regulon, and interactome analyses and confirmed using human ascending aortas, primary SMCs, and a ß-aminopropionitrile monofumarate-induced AD model. RESULTS: The transcriptional profiles of 93 397 cells revealed a dynamic temporal-specific phenotypic transition and marked elevation of the activator protein-1 (AP-1) complex, actively enabling synthetic SMC expansion. Mechanistically, tumour necrosis factor signalling enhanced AP-1 transcriptional activity by dampening mitochondrial oxidative phosphorylation (OXPHOS). Targeting this axis with the OXPHOS enhancer coenzyme Q10 or AP-1-specific inhibitor T-5224 impedes phenotypic transition and aortic degeneration while improving survival by 42.88% (58.3%-83.3% for coenzyme Q10 treatment), 150.15% (33.3%-83.3% for 2-week T-5224), and 175.38% (33.3%-91.7% for 3-week T-5224) in the ß-aminopropionitrile monofumarate-induced AD model. CONCLUSIONS: This cross-sectional compendium of cellular atlas of human ascending aortas during AD progression provides previously unappreciated insights into a transcriptional programme permitting aortic degeneration, highlighting a translational proof of concept for an anti-remodelling intervention as an attractive strategy to manage temporal-specific AD by modulating the tumour necrosis factor-OXPHOS-AP-1 axis.

Chiral cysteine-copper ion-based assemblies for improved phototherapy.

Phototherapy, encompassing photothermal therapy and photodynamic therapy, is gaining attention as an appealing cancer treatment modality. To enhance its clinical implementation, a comprehensive exploration of the pivotal factors influencing phototherapy is warranted. In this study, the L/d-cysteine (Cys)-copper ion (Cu2+) chiral nanoparticles, through the assembly of L/d-Cys-Cu2+ coordination complexes, were constructed. We found that these nanoparticles interacted with chiral liposomes in a chirality-dependent manner, with d-Cys-Cu2+ nanoparticles exhibiting more than three times stronger binding affinity than l-Cys-Cu2+ nanoparticles. Furthermore, we demonstrated that the d-Cys-Cu2+ nanoparticles were more efficiently internalized by Hela cells in contrast with l-Cys-Cu2+. On this basis, indocyanine green (ICG), acting as both photothermal and photodynamic agent, was encapsulated into L/d-Cys-Cu2+ nanoparticles. Experimental results showed that the l-Cys-Cu2+-ICG and d-Cys-Cu2+-ICG nanoparticles displayed almost identical photothermal performance and singlet oxygen (1O2) generation capability in aqueous solution. However, upon laser irradiation, the d-Cys-Cu2+-ICG nanoparticles achieved enhanced anti-tumor effects compared to l-Cys-Cu2+-ICG due to their chirality-promoted higher cellular uptake efficiency. These findings highlight the crucial role of chirality in phototherapy and provide new perspectives for engineering cancer therapeutic agents.

Ferrostatin-1 improves neurological impairment induced by ischemia/reperfusion injury in the spinal cord through ERK1/2/SP1/GPX4.

Spinal cord ischemia/reperfusion injury (SCIRI) induced by artificial aortic occlusion for a while during aortic surgery is a serious complication, leading to paraplegia and even death. Ferroptosis in the nervous system has been confirmed to contribute to neuronal death induced by SCIRI. Therefore, we investigated the therapeutic benefits of ferrostatin-1 (Fer-1, a ferroptosis inhibitor) and explored the mechanism and target of Fer-1 in SCIRI. Our results demonstrate that intrathecal injection of Fer-1 had a strong anti-SCIRI effect, improved ferroptosis-related indices, increased neurological function scores and motor neuron counts, and reduced BSCB leakage and neuroinflammation levels in the anterior horn. We found that SCIRI significantly elevated the levels of several important proteins, including SP1, p-ERK1/2/ERK1/2, COX2, TFR1, SLC40A1, SLC7A11, cleaved Caspase 3, GFAP, and Iba1, while reducing FTH1 and GPX4 protein expression, with no effect on ACSL4 expression. Fer-1 effectively ameliorated the ferroptosis-related changes in these proteins induced by SCIRI. However, for p-ERK1/2 and SP1, Fer-1 not only failed to reduce their expression but also significantly enhanced it. Fer-1 was injected into sham operation rats, abnormal increases in p-ERK1/2/ERK1/2 and SP1 were observed, along with an increase in GPX4. Fluorescent double labeling revealed that SP1 and GPX4 were expressed in neurons and astrocytes. Inhibitors of the ERK pathway (SCH772984) and siRNA against SP1 (AV-sh-SP1) significantly decreased the increase in SP1 and GPX4 protein levels, fluorescent density of SP1 and GPX4 in neurons, and the number of SP1-positive and GPX4-positive neurons induced by Fer-1. SCH772984 but not AV-sh-SP1 significantly reversed the decrease in GFAP and Iba1 induced by Fer-1. In conclusion, our results indicate that Fer-1 inhibited ferroptosis in spinal cord anterior horn neurons, improving neurological impairment and BSCB damage after SCIRI through the ERK1/2/SP1/GPX4 signaling pathway in rats.

KIF20A Promotes CRC Progression and the Warburg Effect through the C-Myc/HIF-1α Axis.

BACKGROUND: Colorectal cancer (CRC) is a prevalent form of cancer globally, characterized by a high mortality rate. Therefore, discovering effective therapeutic approaches for CRC treatment is critical. METHODS: The levels of KIF20A in CRC clinical samples were determined using Western Blot and immunofluorescence assay. SW480 cells were transfected with siRNA targeting KIF20A, while HT-29 cells were transfected with a KIF20A overexpression vector. Cell viability and apoptosis of CRC cells were assessed using CCK-8 and TUNEL analysis. Migration ability was investigated using Transwell. The levels of pyruvate, lactate and ATP were determined through corresponding assay kits. Western Blot was applied to confirm the level of proteins associated with glycolysis, cMyc, HIF-1α, PKM2 and LDHA. Subsequently, functional rescue experiments were conducted to investigate further the regulatory relationship between KIF20A, c-Myc, and HIF-1α in colorectal cancer (CRC), employing the c-Myc inhibitor 10058-F4 and c-Myc overexpression plasmids. RESULTS: KIF20A was up-regulated in vivo and in vitro in CRC. KIF20A knockdown inhibited cell viability and migration while promoting cell apoptosis in SW480 cells. Conversely, overexpression of KIF20A yielded contrasting effects in HT-29 cells. Moreover, inhibition of KIF20A restrained the pyruvate, lactate production and ATP level, whereas overexpression of KIF20A enhanced the Warburg effect. Western Blot indicated that knockdown KIF20A attenuated the levels of c-Myc, HIF-1α, PKM2 and LDHA. In addition, rescue experiments further verified that KIF20A enhanced the Warburg effect by the KIF20A/c-Myc/HIF-1α axis in CRC. CONCLUSION: KIF20A, being a crucial regulator in the progression of CRC, has the potential to be a promising therapeutic target for the treatment of CRC.