An Electrocatalytic Cascade Reaction for the Synthesis of Ketones Using CO2 as a CO Surrogate.

The construction of carbonyl compounds via carbonylation reactions using safe CO sources remains a long-standing challenge to synthetic chemists. Herein, we propose a catalyst cascade Scheme in which CO2 is used as a CO surrogate in the carbonylation of benzyl chlorides. Our approach is based on the cooperation between two coexisting catalytic cycles: the CO2-to-CO electroreduction cycle promoted by [Fe(TPP)Cl] (TPP=meso-tetraphenylporphyrin) and an electrochemical carbonylation cycle catalyzed by [Ni(bpy)Br2] (2,2'-bipyridine). As a proof of concept, this protocol allows for the synthesis of symmetric ketones from good to excellent yields in an undivided cell with non-sacrificial electrodes. The reaction can be directly scaled up to gram-scale and operates effectively at a CO2 concentration of 10 %, demonstrating its robustness. Our mechanistic studies based on cyclic voltammetry, IR spectroelectrochemistry and Density Functional Theory calculations suggest a synergistic effect between the two catalysts. The CO produced from CO2 reduction is key in the formation of the [Ni(bpy)(CO)2], which is proposed as the catalytic intermediate responsible for the C-C bond formation in the carbonylation steps.

Nanoparticles as an antidote for poisoned gold single-atom catalysts in sustainable propylene epoxidation.

The development of sustainable and anti-poisoning single-atom catalysts (SACs) is essential for advancing their research from laboratory to industry. Here, we present a proof-of-concept study on the poisoning of Au SACs, and the antidote of Au nanoparticles (NPs), with trace addition shown to reinforce and sustain propylene epoxidation. Multiple characterizations, kinetics investigations, and multiscale simulations reveal that Au SACs display remarkable epoxidation activity at a low propylene coverage, but become poisoned at higher coverages. Interestingly, Au NPs can synergistically cooperate with Au SACs by providing distinct active sites required for H2/O2 and C3H6 activations, as well as hydroperoxyl radical to restore poisoned SACs. The difference in reaction order between C3H6 and H2 (nC3H6-nH2) is identified as the descriptor for establishing the volcano curves, which can be fine-tuned by the intimacy and composition of SACs and NPs to achieve a rate-matching scenario for the formation, transfer, and consumption of hydroperoxyl. Consequently, only trace addition of Au NPs antidote (0.3% ratio of SACs) stimulates significant improvements in propylene oxide formation rate, selectivity, and H2 efficiency compared to SACs alone, offering a 56-fold, 3-fold, and 22-fold increase, respectively, whose performances can be maintained for 150 h.

(-)-Epicatechin ameliorates type 2 diabetes mellitus by reshaping the gut microbiota and Gut-Liver axis in GK rats.

As one of the most abundant plant polyphenols in the human diet, (-)-epicatechin (EC) can improve insulin sensitivity and regulate glucose homeostasis. However, the primary mechanisms involved in EC anti-T2DM benefits remain unclear. The present study explored the effects of EC on the gut microbiota and liver transcriptome in type 2 diabetes mellitus (T2DM) Goto-Kakizaki rats for the first time. The findings showed that EC protected glucose homeostasis, alleviated systemic oxidative stress, relieved liver damage, and increased serum insulin. Further investigation showed that EC reshaped gut microbiota structure, including inhibiting the proliferation of lipopolysaccharide (LPS)-producing bacteria and reducing serum LPS. In addition, transcriptome analysis revealed that the insulin signaling pathway may be the core pathway of the EC anti-T2DM effect. Therefore, EC may modulate the gut microbiota and liver insulin signaling pathways by the gut-liver axis to alleviate T2DM. As a diet supplement, EC has promising potential in T2DM prevention and treatment.

7.5F Mini Flexible Ureteroscope in Retrograde Intrarenal Surgery: Initial Results from a Multicenter Randomized Clinical Trial.

Objective: To report the initial results of an randomized clinical trail comparing the safety and efficacy between 7.5F and 9.2F flexible ureteroscope (FUS) in the management of renal calculi <2 cm. Materials and Methods: Eighty patients were enrolled and received retrograde intrarenal surgery (RIRS) with a different size FUS. The operation results and complications were compared. Results: Two cases in the 7.5F group and four cases in the 9.2F group failed to insert the 12/14F ureteral access sheath (UAS), respectively, and no significant difference (p = 0.396) was noted. However, 10/12F UAS was inserted in the 7.5F group, but not available in the 9.2F group, and thus, the 10/12F UAS inserting rate in the 7.5F group was higher than in the 9.2F group (100% vs 0%, p = 0.014), and the UAS insertion failure rate in 9.2F group was higher than in the 7.5F group (10% vs 0%, p = 0.040). The operation time in 7.5F group was shorter than the 9.2F group (35.60 ± 7.86 vs 41.05 ± 8.14, p = 0.003). Less irrigation was required in 7.5F group (813.93 ± 279.47 mL vs 1504.18 ± 385.31 mL, p = 0.000). The postoperative fever rate in 9.2F group was higher than 7.5F group (20% vs 5%, p = 0.043). There was no significant difference in sepsis (0% vs 2.5%, p = 0.314) between the two groups. No significant difference was noted in hospital stay (0.93 ± 0.49 days vs 1.14 ± 0.64 days, p = 0.099) between the two groups. The final stone-free rate (SFR) in 7.5F group was higher than 9.2F group (95% vs 80%, p = 0.043). Conclusion: The latest 7.5F mini FUS was a reliable instrument in RIRS to keep a good visualization with low requirement of irrigation, low postoperative infection complication, and also a high SFR when compared with the conventional 9.2F FUS. Clinical Trial Registration: NCT05231577.

Gut Microbiota Alterations in Adolescent Idiopathic Scoliosis Are Associated with Aberrant Bone Homeostasis.

OBJECTIVE: Low bone mineral density is the major prognostic factor for adolescent idiopathic scoliosis (AIS), but the underlying mechanisms remain unclear. Accumulating evidence suggests that gut microbiota (GM) have the potential to affect bone development, and the GM signatures are altered in AIS patients. However, the effect of GM alterations on aberrant bone homeostasis in AIS remains unclear. This study aims to investigate the GM profile in AIS patients with different bone mineral density (BMD) and explore the association between GM, osteopenia, and aberrant bone turnover. METHODS: A total of 126 patients with AIS who received surgical treatment were retrospectively included in this study. We analyzed the composition of the GM by 16S rRNA sequencing and BMD by dual X-ray absorptiometry. Based on the BMD of the femur neck, the patients were divided into the osteopenia group (OPN) if the Z score < -1, and the normal (NOR) group if the Z score ≥ -1 SD compared to the healthy control. For the 16S rRNA sequencing, the raw reads were filtered to remove low-quality reads, and operational taxonomic units were identified with the Uparse program. Weighted UniFrac distance matrix for the beta-diversity metrics and principal coordinate analysis (PCoA) was performed, and the statistical comparisons were made with permutational multivariate analysis of variance (PERMANOVA) and analysis of similarity (ANONISM). Linear discriminant analysis effect size (LEfSe) was used to identify the enriched species in two groups. The "Random forest" was applied to determine the optimal biomarker for OPN according to the mean decrease in Gini value. The metabolic function was predicted by the Tax4Fun analysis. The Pearson correlation coefficient was used to evaluate the associations between GM species, bone turnover markers, and BMD. RESULTS: The serum ß-CTX was increased in the OPN group (n = 67) compared to the NOR group (n = 59). Patients in OPN groups showed significantly decreased α diversity indicated by the Shannon index. Principal coordinate analysis (PCoA) analysis showed significant clustering of GM between OPN and NOR groups. At genus level, the Escherichia-Shigella and Faecalibacterium were significantly enriched in the OPN group compared to that in the NOR group (p < 0.05), whereas the abundance of Prevotella was significantly decreased (p = 0.0012). The relative abundance of Megamonas and Prevotella was positively correlated with the femur BMD. The abundance of Escherichia-Shigella was negatively correlated with femur BMD and positively correlated with serum ß-CTX levels. Functional analysis revealed significant differences in starch and sucrose metabolism, pyruvate and cysteine, and methionine metabolism between NOR and OPN groups. CONCLUSION: The alterations of GM in AIS patients are correlated with osteopenia. The association between enriched species, BMD, and bone turnover markers provides novel diagnostic and therapeutic targets for the clinical management of AIS.

An Anatomic Classification Scheme for Surgical Planning of Renal Artery Aneurysms.

PURPOSE: Renal artery aneurysm (RAA) is a rare disease. This study proposed and evaluated a new classification for RAA to assist in surgical decision-making. MATERIALS AND METHODS: Single-center data of 105 patients with RAAs from the vascular department of vascular surgery were collected retrospectively. A new classification scheme was proposed. Type I aneurysms arise from the main trunk, accessory branch, or first-order branches away from any bifurcation. Type II aneurysms arise from the first bifurcation with narrow necks (defined as dome-to-neck ratio >2) or from intralobular branches. Type III aneurysms with a wide neck arise from the first bifurcation and affect 2 or more branches that cannot be sacrificed without significant infarction of the kidney. RESULTS: There was 50 (47.62%) type I, 33 (31.43%) type II, and 22 (20.95%) type III aneurysms. The classification assigned endovascular repair as first-line treatment (for type I or II), while open techniques were conducted if anatomically suitable (for type III). A kappa level of 0.752 was achieved by the classification compared with a level of 0.579 from the classic Rundback classification. Technical primary success was achieved in 100% and 96.05%, and symptoms were completely resolved in 100% and 84.85%, while hypertension was relieved in 84.21% and 72.92% of patients receiving open surgery or endovascular repair, respectively. No significant difference was observed for perioperative or long-term complications among the 3 classification types. CONCLUSION: The new classification proved to be a convenient and effective method for facilitating choice of intervention for RAAs. CLINICAL IMPACT: This study proposed and evaluated a new classification scheme for renal artery aneurysms, which proved to be a convenient and effective method for facilitating surgical decision-making. Coil embolization was the first-line treatment if suitable, while aneurysm resection and reconstruction with vein graft were conducted for some complex lesions. The safety and efficacy of both open and endovascular methods were validated.

Endovascular repair with a physician-modified fenestrated endograft to treat abdominal aortic pseudoaneurysm with Behcet's disease: a case report.

BACKGROUND: Aortic involvement in patients with Behcet's disease (BD) is rare, but it is one of the most severe manifestations. Open surgical repair of aortic aneurysm is challenging considering the high risk of postoperative recurrent anastomotic pseudoaneurysms and is associated with a much higher mortality rate. Recently, endovascular treatment has proven to be a feasible, less invasive alternative to surgery for these patients. CASE PRESENTATION: We report a total endovascular repair of a paravisceral abdominal aortic pseudoaneurysm in a 25-year-old male patient with BD. The pseudoaneurysm was successfully excluded, and the blood supply of visceral arteries was preserved with a physician-modified three-fenestration endograft under 3D image fusion guidance. Immunosuppressive therapy was continued for 1 year postoperatively. At 18 months, the patient was asymptomatic without abdominal pain. Computed tomography angiography demonstrated the absence of pseudoaneurysm recurrence, good patency of visceral vessels. DISCUSSION AND CONCLUSIONS: Endovascular repair using physician-modified fenestrated endografts is a relatively safe and effective approach for treating paravisceral aortic pseudoaneurysm in BD patients. This technique enables the preservation of the visceral arteries and prevents aneurysm recurrence at the proximal and distal landing zones, which are common complications of open surgical repair in these patients. Furthermore, we emphasize the importance of adequate immunosuppressive therapy before and after surgical repair in BD patients, which is a major risk factor for recurrence and poor prognosis.

Electromagnetic interference shielding of flexible carboxymethyl cellulose/MWCNT@Fe3O4 composite film with ultralow reflection loss.

Nowadays, various high-performance electromagnetic interference (EMI) shielding materials have enormous application potential in electronic field. However, traditional EMI shielding materials often have high conductivity, resulting in the serious mismatch between the impedance of the material surface and the free space, which will cause a large amount of reflection of electromagnetic (EM) waves, leading to secondary reflection pollution. In this paper, we report a novel flexible EMI shielding composite film with extremely low reflection loss and efficient EM wave absorption, which was prepared by assisted self-assembly based on simple vacuum filtration using carboxymethyl cellulose as the matrix and MWCNT@Fe3O4 synthesized by chemical coprecipitation as the composite functional filler. By adjusting the Fe3O4 coating degree of MWCNTs in the filler, the composite film achieved the construction of a conductive network with high Fe3O4 content. Benefit by the good adaptability of conductivity and magnetic permeability, the composite film has good impedance matching ability and microwave absorption performance. The reflection loss of the composite film with the thickness of 28 µm in the X-band was only 0.23 dB, accounting for 1.7 % of the total loss. This work provides new insights for the development of EMI materials and effective mitigation secondary EM wave reflection pollution.

Setd2 deficiency promotes gastric tumorigenesis through inhibiting the SIRT1/FOXO pathway.

Gastric cancer (GC) is the fifth most common cancer and the second leading cause of cancer death globally. SETD2 is a histone methyltransferase catalyzing tri-methylation of H3K36 (H3K36me3) and has been shown to participate in diverse biological processes and human tumors. However, the mechanism of SETD2 in GC remains unclear. Here, we reported that Setd2 deficiency predicts poor prognosis of gastric cancer. SETD2 loss facilitated H. felis/MNU and c-Myc-induced gastric tumorigenesis, respectively. The mouse model of stomach-specific Setd2 depletion together with c-MYC overexpression (AMS) developed high-grade epithelial defects, intestinal metaplasia and dysplasia at only 10-12 weeks of age. Mechanistically, Setd2 depletion resulted in impaired epigenetic regulation of Sirt1, thus inhibiting the SIRT1/FOXO pathway. Moreover, the agonists of FOXO signaling or overexpression of SIRT1 significantly rescued the enhanced cell proliferation and migration caused by Setd2 deficiency in SGC7901 cells. Together, our findings highlight an epigenetic mechanism by which SETD2 regulates gastric tumorigenesis through SIRT1/FOXO pathway. It may also pave the way for the development of targeted, patient-tailored therapies for GC patients with Setd2 deficiency.

Effects of Mulberry Leaf Fu Tea on the Intestines and Intestinal Flora of Goto-Kakizaki Type 2 Diabetic Rats.

Type 2 diabetes mellitus is a disease caused by hyperglycemia, an imbalance in the intestinal flora and disruption of the endocrine system. At present, it is primarily controlled through drug treatment and an improved diet. Mulberry leaf and fu brick tea were considered to have excellent hypoglycemic effects. This study used mulberry leaves and fu brick tea as raw materials to develop a dietary regulator that can assist in the prevention and alleviation of diabetes. The experiment used the Goto-Kakizaki (GK) rat model to investigate the hypoglycemic effect of mulberry leaf fu tea (MFT) and its influence on the intestinal flora of diabetic rats through methods including ELISA, tissue section observation and 16S RNA microbial sequencing. The results showed that, compared with the GK group, the intervention of mulberry leaf fu tea significantly reduced the activities of α-glucosidase (p < 0.05) and α-amylase (p < 0.05) in the duodenum of GK diabetic rats. The height of the duodenal villi was significantly reduced (p < 0.001), leading to decreased intestinal sugar absorption. At the same time, MFT alleviates the imbalance of intestinal flora caused by high blood sugar, promotes the growth of beneficial bacteria (Lactobacillus, Bifidobacterium, etc.), and inhibits the reproduction of harmful bacteria (Blautia, Klebsiella, Helicobacter, Alistipes, etc.). MFT helps reduce the secretion of toxic substances (lipopolysaccharide, p < 0.001), decreases oxidative stress and inflammation, mitigates organ damage, and improves symptoms of diabetes. Finally, the random blood glucose value of GK rats dropped from 22.79 mmol/L to 14.06 mmol/L. In summary, mulberry leaf fu tea can lower sugar absorption in diabetic rats, reduce the body's oxidative stress and inflammatory response, regulate intestinal flora, and reduce blood sugar levels in GK rats. It is hinted that mulberry leaf fu tea could be used as a functional drink to help prevent the occurrence of diabetes.

Loss of SETD2 aggravates colorectal cancer progression caused by SMAD4 deletion through the RAS/ERK signalling pathway.

BACKGOUND: Colorectal cancer (CRC) is a complex, multistep disease that arises from the interplay genetic mutations and epigenetic alterations. The histone H3K36 trimethyltransferase SET domain-containing 2 (SETD2), as an epigenetic signalling molecule, has a 5% mutation rate in CRC. SETD2 expression is decreased in the development of human CRC and mice treated with Azoxymethane /Dextran sodium sulfate (AOM/DSS). Loss of SETD2 promoted CRC development. SMAD Family member 4 (SMAD4) has a 14% mutation rate in CRC, and SMAD4 ablation leads to CRC. The co-mutation of SETD2 and SMAD4 predicted advanced CRC. However, little is known on the potential synergistic effect of SETD2 and SMAD4. METHODS: CRC tissues from mice and SW620 cells were used as research subjects. Clinical databases of CRC patients were analyzed to investigate the association between SETD2 and SMAD4. SETD2 and SMAD4 double-knockout mice were established to further investigate the role of SETD2 in SMAD4-deficient CRC. The intestinal epithelial cells (IECs) were isolated for RNA sequencing and chromatin immunoprecipitation sequencing (ChIP-seq) to explore the mechanism and the key molecules resulting in CRC. Molecular and cellular experiments were conducted to analyze the role of SETD2 in SMAD4-deficient CRC. Finally, rescue experiments were performed to confirm the molecular mechanism of SETD2 in the development of SMAD4-dificient CRC. RESULTS: The deletion of SETD2 promotes the malignant progression of SMAD4-deficient CRC. Smad4Vil-KO ; Setd2Vil-KO mice developed a more severe CRC phenotype after AOM/DSS induction, with a larger tumour size and a more vigorous epithelial proliferation rate. Further mechanistic findings revealed that the loss of SETD2 resulted in the down-regulation of DUSP7, which is involved in the inhibition of the RAS/ERK signalling pathway. Finally, the ERK1/2 inhibitor SCH772984 significantly attenuated the progression of CRC in Smad4Vil-KO ;Setd2Vil-KO mice, and overexpression of DUSP7 significantly inhibited the proliferation rates of SETD2KO ; SMAD4KO SW620 cells. CONCLUSIONS: Our results demonstrated that SETD2 inhibits the RAS/ERK signaling pathway by facilitating the transcription of DUSP7 in SMAD4-deficient CRC, which could provide a potential therapeutic target for the treatment of advanced CRC.

Implications for TB control among migrants in large cities in China: A prospective population-based genomic epidemiology study in Shenzhen.

Internal migrants are a challenge for TB control in large Chinese cities and understanding this epidemiology is crucial for designing effective control and prevention strategies. We conducted a prospective genomic epidemiological study of culture-positive TB patients diagnosed between June 1, 2018 and May 31, 2021 in the Longhua District of Shenzhen. Treatment status was obtained from local and national TB registries and all isolates were sequenced. Genomic clusters were defined as strains differing by ≤12 SNPs. Risk factors for clustering were identified with multivariable analysis and then Bayesian models and TransPhylo were used to infer the timing of transmission within clusters. Of the 2277 culture-positive patients, 70.1% (1596/2277) were migrants: 72.1% (1043/1446) of the migrants patients developed TB within two years of arriving in Longhua; 38.8% within 6 months of arriving; and 12.3% (104/843) had TB symptoms when they arrived. Only 15.4% of Longhua strains were in genomic clusters. More than one third (33.6%) of patients were not treated in Shenzhen but were involved in nearly one third of the recent transmission events. Clustering was associated with migrants not treated in Shenzhen, males, and teachers/trainers. TB in Longhua is prinicipally due to reactivation of infections in migrants, but a proportion may have had clinical or incipient TB upon arrival in the district. Patients diagnosed but not treated in Longhua were involved in recent local TB transmission. Controlling TB in Shenzhen will require strategies to comprehensively diagnose and treat active TB in the internal migrant population.

Effects of pile-fermentation on the aroma quality of dark tea from a single large-leaf tea variety by GC × GC-QTOFMS and electronic nose.

Aroma is one of the significant quality factors of dark tea (DT). However, for a single large-leaf tea variety, there are few studies analyzing the effect of pile-fermentation on the aroma quality of DT. The GC × GC-QTOFMS, electronic nose (E-nose) and GC-olfactometry (GC-O) techniques were employed to analysis the difference of tea products before and after pile-fermentation. A total of 149 volatile metabolites (VMs) were identified, with 92 VMs exhibiting differential characteristics. Among these, 31 VMs with OAV > 1.0 were found to be correlated with E-nose results (|r| > 0.8). Additionally, GC-O analysis validated seven major differential metabolites. Notably, naphthalene, 2-methylnaphthalene, and dibenzofuran were found to enhance the woody aroma, while (Z)-4-heptenal, 2-nonenal and 1-hexanol were associated with an increase in mushroom, fatty and sweet odors, respectively. Moreover, 1-octen-3-ol was linked to reducing pungent fishy smell. These findings could provide a certain theoretical basis for understanding the influence of pile-fermentation on the aroma quality of dark tea.

SETD2 deficiency accelerates sphingomyelin accumulation and promotes the development of renal cancer.

Patients with polycystic kidney disease (PKD) encounter a high risk of clear cell renal cell carcinoma (ccRCC), a malignant tumor with dysregulated lipid metabolism. SET domain-containing 2 (SETD2) has been identified as an important tumor suppressor and an immunosuppressor in ccRCC. However, the role of SETD2 in ccRCC generation in PKD remains largely unexplored. Herein, we perform metabolomics, lipidomics, transcriptomics and proteomics within SETD2 loss induced PKD-ccRCC transition mouse model. Our analyses show that SETD2 loss causes extensive metabolic reprogramming events that eventually results in enhanced sphingomyelin biosynthesis and tumorigenesis. Clinical ccRCC patient specimens further confirm the abnormal metabolic reprogramming and sphingomyelin accumulation. Tumor symptom caused by Setd2 knockout is relieved by myriocin, a selective inhibitor of serine-palmitoyl-transferase and sphingomyelin biosynthesis. Our results reveal that SETD2 deficiency promotes large-scale metabolic reprogramming and sphingomyelin biosynthesis during PKD-ccRCC transition. This study introduces high-quality multi-omics resources and uncovers a regulatory mechanism of SETD2 on lipid metabolism during tumorigenesis.

SETD2 deficiency promotes renal fibrosis through the TGF-ß/Smad signalling pathway in the absence of VHL.

BACKGROUND: Renal fibrosis is the final development pathway and the most common pathological manifestation of chronic kidney disease. Epigenetic alteration is a significant intrinsic factor contributing to the development of renal fibrosis. SET domain-containing 2 (SETD2) is the sole histone H3K36 trimethyltransferase, catalysing H3K36 trimethylation. There is evidence that SETD2-mediated epigenetic alterations are implicated in many diseases. However, it is unclear what role SETD2 plays in the development of renal fibrosis. METHODS: Kidney tissues from mice as well as HK2 cells were used as research subjects. Clinical databases of patients with renal fibrosis were analysed to investigate whether SETD2 expression is reduced in the occurrence of renal fibrosis. SETD2 and Von Hippel-Lindau (VHL) double-knockout mice were used to further investigate the role of SETD2 in renal fibrosis. Renal tubular epithelial cells isolated from mice were used for RNA sequencing and chromatin immunoprecipitation sequencing to search for molecular signalling pathways and key molecules leading to renal fibrosis in mice. Molecular and cell biology experiments were conducted to analyse and validate the role of SETD2 in the development of renal fibrosis. Finally, rescue experiments were performed to determine the molecular mechanism of SETD2 deficiency in the development of renal fibrosis. RESULTS: SETD2 deficiency leads to severe renal fibrosis in VHL-deficient mice. Mechanically, SETD2 maintains the transcriptional level of Smad7, a negative feedback factor of the transforming growth factor-ß (TGF-ß)/Smad signalling pathway, thereby preventing the activation of the TGF-ß/Smad signalling pathway. Deletion of SETD2 leads to reduced Smad7 expression, which results in activation of the TGF-ß/Smad signalling pathway and ultimately renal fibrosis in the absence of VHL. CONCLUSIONS: Our findings reveal the role of SETD2-mediated H3K36me3 of Smad7 in regulating the TGF-ß/Smad signalling pathway in renal fibrogenesis and provide an innovative insight into SETD2 as a potential therapeutic target for the treatment of renal fibrosis.

Drug-coated balloon for treatment of non-atherosclerotic renal artery stenosis-a multi-center study.

INTRODUCTION: Renal artery stenosis (RAS) is a significant reason for secondary hypertension. Impaired renal function and subsequent cardiopulmonary dysfunction could also occur. Patients of non-atherosclerotic RAS has a relatively young age and long life expectancy. Revascularization with percutaneous transluminal angioplasty (PTA) is a viable treatment option. However, restenosis is unavoidable which limits its use. Drug-coated balloon (DCB) has been proven to be effective in restenosis prevention in femoropopliteal arterial diseases and in patients with renal artery stenosis. And PTA for Renal artery fibromuscular dysplasia is safe and clinically successful. Therefore, we could speculate that DCB might have potential efficacy in non-atherosclerotic RAS treatment. METHODS AND ANALYSIS: This will be a randomized multi-center-controlled trial. Eighty-four eligible participants will be assigned randomly in a 1:1 ratio to the control group (plain old balloon, POB) and the experimental group (DCB). Subjects in the former group will receive balloon dilatation alone, and in the latter group will undergo the DCB angioplasty. The DCB used in this study will be a paclitaxel-coated balloon (Orchid, Acotec Scientific Holdings Limited, Beijing, China). Follow-up visits will be scheduled 1, 3, 6, 9, and 12 months after the intervention. Primary outcomes will include controlled blood pressure and primary patency in the 9-month follow-up. Secondary outcomes will include technical success rate, complication rate, and bail-out stenting rate. TRIAL REGISTRATION: ClinicalTrials.gov (number NCT05858190). Protocol version V.4 (3 May 2023).

Glycosylation-Engineered Platelet Membrane-Coated Interleukin 10 Nanoparticles for Targeted Inhibition of Vascular Restenosis.

Purpose: The purpose of this study was to improve the immune compatibility and targeting abilities of IL10 nanoparticles coated with platelet membrane (IL10-PNPs) by glycosylation engineering in order to effectively reduce restenosis after vascular injury. Materials and Methods: In this study, we removed sialic acids and added α (1,2)-fucose and α (1,3)-fucose to platelet membrane glycoprotein, thus engineering the glycosylation of IL10-PNPs (IL10-GE-PNPs). In vitro and in vivo experiments were conducted to evaluate the targeting and regulatory effects of IL10-GE-PNPs on macrophage polarization, as well as the influence of IL10-GE-PNPs on the phenotypic transformation, proliferation, and migration of smooth muscle cells, and its potential in promoting the repair function of endothelial cells within an inflammatory environment. In order to assess the distribution of IL10-GE-PNP in different organs, in vivo imaging experiments were conducted. Results: IL10-GE-PNPs were successfully constructed and demonstrated to effectively target and regulate macrophage polarization in both in vitro and in vivo settings. This regulation resulted in reduced proliferation and migration of smooth muscle cells and promoted the repair of endothelial cells in an inflammatory environment. Consequently, restenosis after vascular injury was reduced. Furthermore, the deposition of IL10-GE-PNPs in the liver and spleen was significantly reduced compared to IL10-PNPs. Conclusion: IL10-GE-PNPs emerged as a promising candidate for targeting vascular injury and exhibited potential as an innovative drug delivery system for suppressing vascular restenosis. The engineered glycosylation of IL10-PNPs improved their immune compatibility and targeting abilities, making them an excellent therapeutic option.

Cosmetic evaluation in type II congenital scoliosis with long-spanned curve: a case-matched comparison with adolescent idiopathic scoliosis.

Background: There is an acknowledged discrepancy between radiographic and cosmetic parameters for patients with adolescent idiopathic scoliosis (AIS). However, no study has specifically evaluated cosmesis in patients with congenital scoliosis (CS). Therefore, the purpose of this study was to identify the cosmetic differences between patients with CS and case-matched patients with AIS and to investigate the correlation between radiological measurements and clinical cosmetic assessment indices. Methods: A total of 37 adolescents with CS and 37 sex-, age-, and curve magnitude-matched patients with AIS were included. Cobb angle, shoulder height difference (SHD), coronal balance (CB), T1 tilt, first rib angle (FRA), clavicle angle (CA), clavicle-rib cage intersection (CRCI), and apical vertebra translation (AVT) were measured in the full X-ray of the spine. Shoulder area index 1 (SAI1), shoulder area index 2 (SAI2), shoulder angle (SA), axilla angle (AA), thoracolumbar area index (TLAI), and right and left waist angle difference (RLWAD) were measured on the clinical images from a posterior view. Hump index (HI) was measured in the forward bending photography. All patients completed the Scoliosis Research Society-22 (SRS-22) questionnaire. Results: No significant difference was noted in the radiographic parameters between the AIS and CS groups (P>0.05). However, patients with CS exhibited significantly lower SAI1 (0.91 vs. 0.98; P=0.002) and SAI2 (0.85 vs. 0.95; P=0.001) than did the patients with AIS. The SRS-22 scores for self-image and mental health in patients with CS were significantly lower than those in patients with AIS (P<0.05). The correlation coefficients with statistical significance between radiographic and cosmetic measurements in patients with CS and those with AIS ranged from -0.493 to 0.534 and from -0.653 to 0.717, respectively. None of the correlation coefficients exceeded 0.8, indicating that the current radiological indices only exhibited a limited level of consistency with patients' cosmesis. Conclusions: As compared with age-, gender-, and curve pattern-matched patients with AIS, patients with CS exhibited worse cosmesis and had clinically significantly lower SRS-22 scores despite having relatively small clinical differences. Although the radiographic parameters may not always align with clinical presentation, this discrepancy could be observed in both patients with CS and those with AIS.

FANCD2 and RAD51 recombinase directly inhibit DNA2 nuclease at stalled replication forks and FANCD2 acts as a novel RAD51 mediator in strand exchange to promote genome stability.

FANCD2 protein, a key coordinator and effector of the interstrand crosslink repair pathway, is also required to prevent excessive nascent strand degradation at hydroxyurea-induced stalled forks. The RAD51 recombinase has also been implicated in regulation of resection at stalled replication forks. The mechanistic contributions of these proteins to fork protection are not well understood. Here, we used purified FANCD2 and RAD51 to study how each protein regulates DNA resection at stalled forks. We characterized three mechanisms of FANCD2-mediated fork protection: (1) The N-terminal domain of FANCD2 inhibits the essential DNA2 nuclease activity by directly binding to DNA2 accounting for over-resection in FANCD2 defective cells. (2) Independent of dimerization with FANCI, FANCD2 itself stabilizes RAD51 filaments to inhibit multiple nucleases, including DNA2, MRE11 and EXO1. (3) Unexpectedly, we uncovered a new FANCD2 function: by stabilizing RAD51 filaments, FANCD2 acts to stimulate the strand exchange activity of RAD51. Our work biochemically explains non-canonical mechanisms by which FANCD2 and RAD51 protect stalled forks. We propose a model in which the strand exchange activity of FANCD2 provides a simple molecular explanation for genetic interactions between FANCD2 and BRCA2 in the FA/BRCA fork protection pathway.

Diabetes mellitus and adverse outcomes after carotid endarterectomy: A systematic review and meta-analysis.

BACKGROUND: There is still uncertainty regarding whether diabetes mellitus (DM) can adversely affect patients undergoing carotid endarterectomy (CEA) for carotid stenosis. The aim of the study was to assess the adverse impact of DM on patients with carotid stenosis treated by CEA. METHODS: Eligible studies published between 1 January 2000 and 30 March 2023 were selected from the PubMed, EMBASE, Web of Science, CENTRAL, and ClinicalTrials databases. The short-term and long-term outcomes of major adverse events (MAEs), death, stroke, the composite outcomes of death/stroke, and myocardial infarction (MI) were collected to calculate the pooled effect sizes (ESs), 95% confidence intervals (CIs), and prevalence of adverse outcomes. Subgroup analysis by asymptomatic/symptomatic carotid stenosis and insulin/noninsulin-dependent DM was performed. RESULTS: A total of 19 studies (n = 122,003) were included. Regarding the short-term outcomes, DM was associated with increased risks of MAEs (ES = 1.52, 95% CI: [1.15-2.01], prevalence = 5.1%), death/stroke (ES = 1.61, 95% CI: [1.13-2.28], prevalence = 2.3%), stroke (ES = 1.55, 95% CI: [1.16-1.55], prevalence = 3.5%), death (ES = 1.70, 95% CI: [1.25-2.31], prevalence =1.2%), and MI (ES = 1.52, 95% CI: [1.15-2.01], prevalence = 1.4%). DM was associated with increased risks of long-term MAEs (ES = 1.24, 95% CI: [1.04-1.49], prevalence = 12.2%). In the subgroup analysis, DM was associated with an increased risk of short-term MAEs, death/stroke, stroke, and MI in asymptomatic patients undergoing CEA and with only short-term MAEs in the symptomatic patients. Both insulin- and noninsulin-dependent DM patients had an increased risk of short-term and long-term MAEs, and insulin-dependent DM was also associated with the short-term risk of death/stroke, death, and MI. CONCLUSIONS: In patients with carotid stenosis treated by CEA, DM is associated with short-term and long-term MAEs. DM may have a greater impact on adverse outcomes in asymptomatic patients after CEA. Insulin-dependent DM may have a more significant impact on post-CEA adverse outcomes than noninsulin-dependent DM. Whether DM management could reduce the risk of adverse outcomes after CEA requires further investigation.