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The understanding on the growth mechanism of complex gold nanostructures both experimentally and theoretically can guide their design and fabrication toward various applications. In this work, we report a cysteine-directed overgrowth of penta-twinned nanorod seeds into jagged gold bipyramids with discontinuous stepped {hhk} facets. By monitoring the growth process, we find that {hhk} facets with large k/h values (∼7) are formed first at two ends of the nanorods, followed by the protrusion of the middle section exposing {hhk} facets with smaller indices (k/h ∼ 2–3). Molecular dynamics simulations indicate that the strong adsorption of cysteine molecules on {110} facets is likely responsible for the formation of stepped {hhk} facets, and the stronger adsorption of cysteine molecules on {hhk} facets with smaller k/h compared to that on {hhk} facets with larger k/h is a possible cause of the discontinuity of {hhk} facets at the middle of gold bipyramids. The obtained jagged gold bipyramids display large field enhancement under illumination due to their sharp nanostructures, demonstrating their application potentials in surface-enhanced spectroscopy and catalysis. [ABSTRACT FROM AUTHOR]

Worldwide, over 800 million people are affected by kidney disease, yet its pathogenesis remains elusive, hindering the development of novel therapeutics. In this study, we used kidney-specific expression of quantitative traits and single-nucleus open chromatin analysis to show that genetic variants linked to kidney dysfunction on chromosome 20 target the acyl-CoA synthetase short-chain family 2 (ACSS2). By generating ACSS2-KO mice, we demonstrated their protection from kidney fibrosis in multiple disease models. Our analysis of primary tubular cells revealed that ACSS2 regulated de novo lipogenesis (DNL), causing NADPH depletion and increasing ROS levels, ultimately leading to NLRP3-dependent pyroptosis. Additionally, we discovered that pharmacological inhibition or genetic ablation of fatty acid synthase safeguarded kidney cells against profibrotic gene expression and prevented kidney disease in mice. Lipid accumulation and the expression of genes related to DNL were elevated in the kidneys of patients with fibrosis. Our findings pinpoint ACSS2 as a critical kidney disease gene and reveal the role of DNL in kidney disease., Introduction Over 800 million people in the world have chronic kidney disease (CKD) (1). CKD is a major cause of cardiovascular death and if left untreated leads to end-stage kidney [...]

High-strength engineered cementitious composites (HS-ECCs) have garnered significant attention for their superior mechanical properties and ductility. However, their high autogenous shrinkage, caused by a low water-to-binder ratio, high cementitious content, and lack of coarse aggregate, often results in early-age cracking, limiting their broader use in civil engineering. Incorporating iron sand in HS-ECCs has enhanced their mechanical properties, reduced the carbon footprint, and moderately decreased shrinkage strain compared to traditional silica sand; however, the shrinkage strain remains substantial. This study aims to reduce the autogenous shrinkage of HS-ECCs further by incorporating united expanding admixtures (UEAs)—calcium oxide-based (CEA) and magnesium oxide-based (MEA) expansive agents—in varying amounts (3% to 10% by mass of cement). This study also examines the impact of these admixtures on the workability and mechanical properties of HS-ECCs. The results show that increasing the UEA content significantly reduces autogenous shrinkage strain, achieving a 40.66% reduction at 10% UEA, from 1007.31 με to 647.18 με. While higher UEA content decreases workability, as indicated by lower fluidity and penetration depth, the compressive strength remains largely unaffected. The tensile strength peaks at 12.38 MPa with 3% UEA but declines at higher contents, with higher UEA content effectively minimizing crack formation. The novelty of this research lies in the combined use of waste iron sand and UEA, optimizing the balance between workability, mechanical properties, and autogenous shrinkage reduction in HS-ECCs. These findings support the broader application of HS-ECCs in civil engineering projects requiring high mechanical properties and low shrinkage. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to explore the effects of long noncoding RNA (lncRNA) H19 knockdown on angiogenesis and blood–brain barrier (BBB) integrity following cerebral ischemia/reperfusion (I/R) and elucidate their underlying regulatory mechanisms. Methods: A middle cerebral artery occlusion/reperfusion model was used to induce cerebral I/R injury. The cerebral infarct volume and neurological impairment were assessed using 2,3,5‐triphenyl‐tetrazolium chloride staining and neurobehavioral tests, respectively. Relevant proteins were evaluated using western blotting and immunofluorescence staining. Additionally, a bioinformatics website was used to predict the potential target genes of lncRNA H19. Finally, a rescue experiment was conducted to confirm the potential mechanism. Results: Silencing of H19 significantly decreased the cerebral infarct volume, enhanced the recovery of neurological function, mitigated BBB damage, and stimulated endothelial cell proliferation following ischemic stroke. Insulin‐like growth factor 2 mRNA‐binding protein 2 (IMP2) is predicted to be a potential target gene for lncRNA H19. H19 knockdown increased IMP2 protein expression and IMP2 inhibition reversed the protective effects of H19 inhibition. Conclusion: Downregulation of H19 enhances angiogenesis and mitigates BBB damage by regulating IMP2, thereby alleviating cerebral I/R injury. [ABSTRACT FROM AUTHOR]

Objective To analyze the genetic evolution and molecular characteristics of the H5N6 avian influenza virus A/Changsha/1/2022(H5N6) in a human infection case in Changsha City, providing insights for the prevention and control of H5N6 avian influenza transmission to humans. Methods The sample underwent whole-genome sequencing on a third-generation sequencing platform. Reference sequences were downloaded from the NCBI and GISAID databases for comparison. The phylogenetic tree was constructed and key amino acid mutation sites were analyzed using MEGA7 software. Results The sequence analysis results revealed that the strain studied belongs to the H5 subtype Clade 2.3.4.4b branch. The PB1 gene shared 99.69% homology with the H5N6 virus A/duck/Hunan/S40199/2021(H5N6) from Hunan Province; PB2 had 98.58% homology with A/Whooper swan/Sanmenxia/Y36/2020(H5N8); and other sequences showed high homology with the strain A/Guangdong/1/2021(H5N6) discovered in Guangzhou in 2021. These results indicate that an infection with a recombinant H5N6 subtype avian influenza virus caused the case. The amino acid composition of the cleavage site was RERRRKR ↓GLF, consistent with high-pathogenicity avian influenza characteristics. The HA sequence showed no mutations at the Q226L and G228S sites, indicating the preservation of characteristics binding to avian receptors. However, mutations at the S127P, S137A, T160A, T192R, and A267T sites increased the virus's affinity for humans. A deletion found in positions 59-70 of the NA protein stalk implies enhanced viral virulence in mammals. Mutations were noted in the internal genes; S622G in PB1, K389R and V598T in PB2, N409S in PA, N30D and T215A in M1, and P42S in NS1, which may enhance the virulence of avian influenza virus in infecting mice. Conclusions The H5N6 virus strain detected in a human case in Changsha City in this study is highly pathogenic, prone to bind to avian receptors, but numerous mutations at key amino acid sites facilitate infection in humans. Continuous monitoring and research on H5N6 avian influenza virus should be strengthened [ABSTRACT FROM AUTHOR]

Three new compounds (1–2, 4) along with ten known ones (3, 5–13), were isolated from the whole plant of Erigeron breviscapus. Compounds 1 and 2, two novel C10 acetylenic acids and compound 4, a jasmone glucoside were elucidated by the detailed analysis of 1D and 2D NMR, HRESIMS spectra, and experimental and calculated electronic circular dichroism (ECD). Compounds 1–3 represent the first example of acetylenic acids incorporating C10 skeleton from E. breviscapus. In addition, the antioxidant effects of all compounds were evaluated by ferric reducing power, 2,2′-Azinobis-(3-ethylbenzthiazoline-6-sulphonate acid) (ABTS) and 2.2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays. Our results indicated the significant antioxidant activity of caffeoylquinic acids. Additionally, compounds 10–11 and 13 played protective role on alcoholic liver injury cells in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Background: To analyze the clinical efficacy of K-wire placement guided technology in paediatric supracondylar humerus fractures. Methods: A retrospective study was conducted in 105 patients who underwent closed reduction and percutaneous pinning surgeries in our hospital from June 2019 to August 2022. 54 patients treated with a assisted reduction fixation device to assist in closed reduction and percutaneous K-wire cross-fixation were allocated into the Non-guided group, and 51 patients with K-wire placement guided technology to guide K-wire placement were assigned into the Guided group. The operation duration, number of disposable K-wire placement, intraoperative fluoroscopy frequency, Baumann angle, carrying angle, fracture healing time and Flynn score of elbow joint function at the final follow-up were compared between two groups. The postoperative complications of two groups were recorded. Results: There were significant differences between two groups in terms of operation duration, intraoperative fluoroscopy frequency, and disposable K-wire placement rate (p < 0. 05), while no significant differences of Baumann angle, carrying angle and the fracture healing time between two groups were observed (p > 0. 05). In the control group, ulnar nerve injury in 2 case, pin site infection in 4 cases, mild cubitus varus in 2 cases and loss of reduction in 4 cases were detected. In the study group, ulnar nerve injury in 1 case, pin site infection in 2 cases and loss of reduction in 1 case was observed. There was no significant difference in Flynn scores between two groups. Conclusion: K-wire placement guided technology is simple and convenient. The application of K-wire placement guided technology could relatively improved disposable K-wire placement rate, shorten the intraoperative fluoroscopy frequencies and reduce complication rates. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 72-year-old woman with pigmented villonodular synovitis (PVNS), a rare benign disorder of the synovium. The woman underwent a [68Ga]Ga-fibroblast activation protein inhibitor (FAPI)-04 PET/CT scan, which revealed intense and inhomogeneous FAPI uptake in both knees, indicating PVNS. The study highlights the potential value of [68Ga]Ga-FAPI in detecting PVNS, although further research is needed to determine its specificity. The article emphasizes the need to consider other bone or joint diseases in the differential diagnosis. [Extracted from the article]

Background: Fibrosis after nephrotoxic injury is common. Activation of the paraventricular nucleus (PVN) renin-angiotensin system (RAS) and sympathetic nervous system (SNS) are common mechanism of renal fibrosis. However, there have limited knowledge about which brain regions are most affected by Angiotensin II (Ang II) after nephrotoxic injury, what role does Angiotensin II type 1a receptors (AT1R) signaling play and how this affects the outcomes of the kidneys., Methods: In nephrotoxic folic acid-induced chronic kidney disease (FA-CKD) mouse models, we have integrated retrograde tracer techniques with studies on AT1afl/fl mice to pinpoint an excessively active central pathway that connects the paraventricular nucleus (PVN) to the rostral ventrolateral medulla (RVLM). This pathway plays a pivotal role in determining the kidney's fibrotic response following injury induced by folic acid., Results: FA-CKD ( vs sham) had increased in the kidney SNS activity and Ang II expression in the central PVN. The activation of Ang II in the PVN triggers the activation of the PVN-RVLM pathway, amplifies SNS output, thus facilitating fibrosis development in FA-CKD mouse. Blocking sympathetic traffic or deleting AT1a in the PVN alleviated renal fibrosis in FA-CKD mice., Conclusions: The FA-CKD mice have increased the expression of Ang II in PVN, thereby activating AT1a-positive PVN neurons project to the RVLM, where SNS activity is engaged to initiate fibrotic processes. The Ang II in PVN may contribute to the development of kidney fibrosis after nephrotoxic folic acid-induced kidney injury., Competing Interests: The authors declare there are no competing interests., (©2024 Wan et al.)

Background: This first-in-human study evaluated HRS-1780, an oral selective non-steroidal mineralocorticoid receptor antagonist, in healthy men., Research Design and Methods: In single ascending dose (SAD) part, 10 participants for each dose cohort (5, 10, 20, 40, 60, and 80 mg) were randomized (8:2) to HRS-1780 or placebo. In multiple ascending dose part, 12 participants for each dose (10, 20, and 40 mg) were randomized (9:3) to HRS-1780 or placebo once daily for 7 days. The primary endpoint was safety and tolerability., Results: HRS-1780 was well tolerated with all adverse events being mild. In the steady state, the median time to maximum concentration (T max ) was 0.750 h and mean half-life was 1.76-1.96 h. High-fat/high-calorie meal prolonged T max but did not affect exposure. Multiple dosing of HRS-1780 at 40 mg showed a decreasing trend in systolic blood pressure compared with placebo. Changes in plasma aldosterone and norepinephrine with HRS-1780 were higher compared to placebo. Upper bounds of two-sided 90% confidence interval of placebo-adjusted change-from-baseline QTcF were below 10 msec at the maximum concentration in SAD. The trial had limited sample size and short study duration., Conclusions: HRS-1780 had favorable safety and pharmacokinetic profiles and did not cause clinically meaningful QTcF prolongation., Trial Registration: ClinicalTrials.gov (NCT05638126).

This study explored the mechanism of Huangbai liniment (HB) for the treatment of oral lichen planus (OLP) through network pharmacology and molecular docking techniques. The study identified HB' active ingredients, therapeutic targets for OLP, and associated signaling pathways. The chemical composition of HB was screened using the HERB database. The disease targets of OLP were obtained through the GeneCards and OMIM databases. A protein-protein interactions network was constructed with the String platform. Topological analysis was performed using Cytoscape software to identify core targets. Gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using the Hiplot database, and the active ingredients and core targets were verified by molecular docking. Date analysis showed that the active composition of HB in the treatment of OLP were quercetin, wogonin, kaempferol, and luteolin. This survey identified 10 potential therapeutic targets, including TNF, CXCL8, IL-6, IL1B, PIK3R1, ESR1, JUN, AKT1, PIK3CA, and CTNNB1. Molecular docking revealed stable interactions between OLP' key targets and HB. These key targets were predominantly involved in the PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, TNF signaling pathway, and HIF-1 signaling pathway. HB plays a crucial role in the treatment of OLP, acting on multiple targets and pathways, particularly the PI3K-Akt signaling pathway. It regulated biological processes like the proliferation of epithelial cells and lymphocytes and mediates the expression of transcription factors, cytokines, and chemokines. Therefore, this study provides a theoretical basis for the clinical trial and application of HB in the therapy of OLP., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Linear-array endoscopic ultrasound (EUS) and narrow-band imaging (NBI) are both used to estimate the invasion depth of nonpedunculated rectal lesions (NPRLs). However, it is unclear which procedure is more accurate. This randomized controlled trial aimed to compare the diagnostic accuracy of linear EUS and NBI for estimating the invasion depth of NPRLs., Methods: This study is a single-center, randomized, tandem trial. Eligible patients with NPRLs were randomly assigned to A group (assessment with EUS followed by NBI) or B group (assessment with NBI followed by EUS). The invasion depth of each lesion was independently measured by each procedure and categorized as mucosal to slight submucosal (M-SM s , invasion depth <1,000 μm) or deep submucosal (SM d , invasion depth ≥1,000 μm) invasion, with postoperative pathology as the standard of measurement. The primary outcome was diagnostic accuracy, and secondary outcomes included sensitivity, specificity, and procedure time., Results: Eighty-six patients with NPRLs were enrolled, and 79 patients were finally analyzed, including 39 cases in the A group and 40 cases in the B group. Comparable diagnostic accuracies were observed between EUS and NBI (96.2% vs 93.7%, P = 0.625). EUS identified lesions with deep submucosal invasion with 81.8% sensitivity while that of NBI was 63.6% ( P = 0.500). The specificity of both EUS and NBI was 98.5%. The procedure time was also similar between EUS and NBI (5.90 ± 3.44 vs 6.4 ± 3.94 minutes, P = 0.450). Furthermore, the combined use of EUS and NBI did not improve diagnostic accuracy compared with EUS or NBI alone (94.9% vs 96.2% vs 93.7%, P = 0.333)., Discussion: Linear EUS and NBI measure the invasion depth of NPRLs with comparable accuracy. The combination of the 2 methods does not improve the diagnostic accuracy. Single NBI should be preferred, considering its simplicity and convenience in clinical practice., (Copyright © 2024 by The American College of Gastroenterology.)

Three new compounds ( 1 - 2 , 4 ) along with ten known ones ( 3, 5 - 13 ), were isolated from the whole plant of Erigeron breviscapus . Compounds 1 and 2 , two novel C 10 acetylenic acids and compound 4 , a jasmone glucoside were elucidated by the detailed analysis of 1D and 2D NMR, HRESIMS spectra, and experimental and calculated electronic circular dichroism (ECD). Compounds 1 - 3 represent the first example of acetylenic acids incorporating C 10 skeleton from E. breviscapus . In addition, the antioxidant effects of all compounds were evaluated by ferric reducing power, 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate acid) (ABTS) and 2.2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays. Our results indicated the significant antioxidant activity of caffeoylquinic acids. Additionally, compounds 10-11 and 13 played protective role on alcoholic liver injury cells in a dose-dependent manner.