Single-cell sequencing of immune cells from the coronary sinus reveals immune mechanisms of the progression of persistent atrial fibrillation.

Identifying the atlas of immune cells from coronary sinus circulation (CSC) of patients with persistent atrial fibrillation (PerAF) may provide new insights into the role of immune cells in the progression of AF. Single-cell sequencing revealed substantial alterations in immune cells from CSCs of patients with PerAF, especially a markedly elevated abundance of T cells, after which we identified a T cell subset: FGFBP2(+)TRDC(-)CD4(-) T cells (Ftc-T cells), which can promote the proliferation of cardiac fibroblasts (CFs),and the proportion of Ftc-T had a positive linear with AF recurrence post catheter ablation (CA). Moreover, IFI27 was found to be highly enriched in Ftc-T cells and promoted CFs proliferation and collagen expression. Altogether, our findings represent a unique resource providing in-depth insights into the heterogeneity of the immune cell from CSC of patients with PerAF and highlight the potential role of Ftc-T cells and IFI27 for AF progression.

Identifying Associations between Small Nucleolar RNAs and Diseases via Graph Convolutional Network and Attention Mechanism.

Research has shown that small nucleolar RNAs (snoRNAs) play crucial roles in various biological processes, and understanding disease pathogenesis by studying their relationship with diseases is beneficial. Currently, known associations are insufficient, and conventional biological experiments are costly and time-consuming. Therefore, developing efficient computational methods is crucial for identifying potential snoRNA-disease associations. In this paper, a method to identify snoRNA-disease associations based on graph convolutional network and multi-view graph attention mechanism (GCASDA) is proposed. Firstly, the similarity matrices of snoRNAs and diseases are calculated based on biological entity-related information, and the weights of the edges between the snoRNA nodes and the disease nodes are supplemented by random forest. Then two homogeneous graphs and one heterogeneous graph are constructed. Subsequently, different types of embedded features are extracted from the graphs using specific graph convolutional network structure and integrated through a multi-view graph attention mechanism to obtain node embedded feature representations. Finally, for each pair of nodes, in addition to their global features, node interaction features are passed together to a multilayer perceptron neural network (MLP) to identify snoRNA-disease associations. Experimental results show that GCASDA achieves 0.9356 and 0.9294 in AUC and AUPR, respectively, and significantly outperformed other state-of-the-art methods on the basis of different evaluation metrics. Furthermore, the case study could further demonstrate the realistic feasibility of GCASDA.

W-Shaped π-Extended Double Undecabenzo[7]helicene.

A chiral W-shaped fully π-extended double [7]helicene (ED7H) has been synthesized and fully characterized. It displays fluorescence emission (λem = 636 nm) with a quantum yield (Φf) of 0.10. In comparison to its X-shaped and monomict π-extended [7]helicene analogues, enantiopure W-shaped ED7H exhibited superior chiral optical characteristics, including distinct circular dichroism signals from 400 to 650 nm, a good dissymmetric emission factor |glum| of 4 × 10-3, and a circularly polarized luminescence brightness value BCPL of 42 M-1 cm-1.

New Clerodane Diterpenoids from Tinospora capillipes with Antibacterial and Anti-Inflammatory Properties.

Four new clerodane diterpenoids, namely tinocapills A-D (1-4), and one known analogue (5) were isolated from the roots of Tinospora capillipes in the present study. The structures of these new compounds, including their absolute configurations, were determined through a combination of detailed spectroscopic analysis and theoretical statistical approaches, including electronic circular dichroism (ECD) analyses and quantum mechanical (QM)-NMR methods. Additionally, the stereostructure of 5 was confirmed via X-ray diffraction analysis. Furthermore, all these isolates were evaluated for their antibacterial and anti-inflammatory activities. Compounds 1, 2 and 5 demonstrated antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with MICs ranging from 4 to 64 µg/mL, and compounds 3 and 4 exhibited potential anti-inflammatory effects by suppressing LPS-induced TNF-α and NO releases in RAW264.7 cells.

Thioproline-Based Oxidation Strategy for Direct Preparation of N-Terminal Thiazolidine-Containing Peptide Thioesters from Peptide Hydrazides.

We describe a simple and robust oxidation strategy for preparing N-terminal thiazolidine-containing peptide thioesters from peptide hydrazides. We find for the first time that l-thioproline can be used as a protective agent to prevent the nitrosation of N-terminal thiazolidine during peptide hydrazide oxidation. The thioproline-based oxidation strategy has been successfully applied to the chemical synthesis of CC chemokine ligand-2 (69aa) and omniligase-C (113aa), thereby demonstrating its utility in hydrazide-based native chemical ligation.

Synthesis and biological evaluation of novel 1,2,3,4-tetrahydro-ß-carboline derivatives as potential antibacterial agents.

The quest for novel antibacterial agents is imperative in the face of escalating antibiotic resistance. Naturally occurring tetrahydro-ß-carboline (THßC) alkaloids have been highlighted due to their significant biological derivatives. However, these structures have been little explored for antibacterial drugs development. In this study, a series of 1,2,3,4-THßC derivatives were synthesized and assessed for their antibacterial prowess against both gram-positive and gram-negative bacteria. The compounds exhibited moderate to good antibacterial activity, with some compounds showing superior efficacy against gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), to that of Gentamicin. Among these analogs, compound 3k emerged as a hit compound, demonstrating rapid bactericidal action and a significant post-antibacterial effect, with significant cytotoxicity towards human LO2 and HepG2 cells. In addition, compound 3k (10 mg/kg) showed comparable anti-MRSA efficacy to Ciprofloxacin (2 mg/kg) in a mouse model of abdominal infection. Overall, the present findings suggested that THßC derivatives based on the title compounds hold promising applications in the development of antibacterial drugs.

Hyperactivation of SREBP induces pannexin-1-dependent lytic cell death.

Sterol-regulatory element binding proteins (SREBPs) are a conserved transcription factor family governing lipid metabolism. When cellular cholesterol level is low, SREBP2 is transported from the endoplasmic reticulum to the Golgi apparatus where it undergoes proteolytic activation to generate a soluble N-terminal fragment, which drives the expression of lipid biosynthetic genes. Malfunctional SREBP activation is associated with various metabolic abnormalities. In this study, we find that overexpression of the active nuclear form SREBP2 (nSREBP2) causes caspase-dependent lytic cell death in various types of cells. These cells display typical pyroptotic and necrotic signatures, including plasma membrane ballooning and release of cellular contents. However, this phenotype is independent of the gasdermin family proteins or mixed lineage kinase domain-like (MLKL). Transcriptomic analysis identifies that nSREBP2 induces expression of p73, which further activates caspases. Through whole-genome CRISPR-Cas9 screening, we find that Pannexin-1 (PANX1) acts downstream of caspases to promote membrane rupture. Caspase-3 or 7 cleaves PANX1 at the C-terminal tail and increases permeability. Inhibition of the pore-forming activity of PANX1 alleviates lytic cell death. PANX1 can mediate gasdermins and MLKL-independent cell lysis during TNF-induced or chemotherapeutic reagents (doxorubicin or cisplatin)-induced cell death. Together, this study uncovers a noncanonical function of SREBPs as a potentiator of programmed cell death and suggests that PANX1 can directly promote lytic cell death independent of gasdermins and MLKL.

[Coupling Mechanisms of Eco-environmental Quality and Human Activities in China and Their Influencing Factors].

In the context of sustainable development, it is important to thoroughly investigate the coupling mechanism between China's eco-environmental quality and human activities, as well as identify the influencing factors, in order to provide scientific references for achieving sustainable development goals in China. This study applied trend analysis, coupling coordination degree, LMDI, and optimal parameter geographic detector models to explore and evaluate the coupling mechanism between China's eco-environmental quality and human activities. The findings of the study were as follows:① During the research period, there was a growth trend in China's coupling coordination degree, human activities, and eco-environmental quality. Human activities and coupling coordination degree exhibited a spatial differentiation pattern with the Hu Line as the boundary, showing an "east high, west low" distribution. The eco-environmental quality demonstrated a "south high, north low" differentiation pattern. ② The overall trend of China's coupling coordination type transformation was shifting from lower-level to higher-level coordination types. ③ Based on the geographic detector and LMDI models, the dominant factors influencing the coupling coordination degree in most provinces east of the Hu Line were social and economic factors, as well as the comprehensive coordination index. In contrast, the dominant factors in most provinces west of the Hu Line were natural environmental factors and coupling degree. ④ The evaluation of the impact of changes in human activities on eco-environmental quality revealed that the regions east of the Hu Line were mainly characterized by favorable development and effective protection, whereas the regions west of the line were mainly characterized by destructive development and ineffective protection. It is suggested that the regions on both sides of the Hu Line should prioritize development based on local prerequisites influencing the coupling coordination degree and the relative relationship between human activities and eco-environmental quality. It is crucial to actively adjust development strategies and pursue a sustainable development path towards the high-level coordination between eco-environmental quality and human activities.

Cynanchum paniculatum (Bunge) Kitag. ex H.Hara inhibits pancreatic cancer progression by inducing caspase-dependent apoptosis and suppressing TGF-ß-mediated epithelial-mesenchymal transition.

Background: Cynanchum paniculatum (Bunge) Kitag. ex H.Hara, a member of the Asclepiadaceae family, has a rich history as a traditional Chinese medicinal plant used to treat digestive disorders. However, its potential anti-cancer effects in pancreatic cancer remain largely unexplored. Aim: This study delves into the intricate anti-pancreatic cancer mechanisms of C. paniculatum (Bunge) Kitag. ex H.Hara aqueous extract (CPAE) by elucidating its role in apoptosis induction and the inhibition of invasion and migration. Methods: A comprehensive set of methodologies was employed to assess CPAE's impact, including cell viability analyses using MTT and colony formation assays, flow cytometry for cell cycle distribution and apoptosis assessment, scratch-wound and Matrigel invasion assays for migration and invasion capabilities, and immunoblotting to measure the expression levels of key proteins involved in apoptosis and metastasis. Additionally, a murine xenograft model was established to investigate CPAE's in vivo anti-cancer potential. Results: CPAE exhibited time- and dose-dependent suppression of proliferation and colony formation in pancreatic cancer cells. Notably, CPAE induced apoptosis and G2/M phase arrest, effectively activating the caspase-dependent PARP pathway. At non-cytotoxic doses, CPAE significantly curtailed the metastatic abilities of pancreatic cells, effectively suppressing epithelial-mesenchymal transition (EMT) and downregulating the TGF-ß1/Smad2/3 pathway. In vivo experiments underscored CPAE's ability to inhibit tumor proliferation. Conclusion: This study illuminates the multifaceted anti-proliferative, pro-apoptotic, anti-invasive, and anti-migratory effects of CPAE, both in vitro and in vivo. CPAE emerges as a promising herbal medicine for pancreatic cancer treatment, with its potential mediated through apoptosis induction via the caspase-dependent PARP pathway and MET suppression via the TGF-ß1/Smad2/3 signaling pathway at non-cytotoxic doses. These findings advocate for further exploration of CPAE's therapeutic potential in pancreatic cancer.

Systematic proteomics analysis revealed different expression of laminin interaction proteins in breast cancer: lower in luminal subtype and higher in claudin-low subtype.

Background: Breast cancer is a major public health concern. Proteomics enables identification of proteins with aberrant properties. Here, we identified proteins with abnormal expression levels in breast cancer tissues and systematically analyzed and validated the data to locate potential diagnostic and therapeutic targets. Methods: Protein expression level in breast cancer tissues and para-carcinoma tissues were detected by Isobaric Tags for Relative and Absolute Quantification (iTRAQ) technology and further screened through Gene Expression Profiling Interactive Analysis (GEPIA) database. Cellular components, protein domain and Reactome pathway analysis were performed to screen functional targets. Abnormal expression levels of functional targets were validated by Oncomine database, quantitative real time polymerase chain reaction (qRT-PCR) and proteomics detection. Protein correlation analysis was performed to explain the abnormal expression levels of potential targets in breast cancer. Results: Overall, 207 and 207 proteins were up- and down-regulated, respectively, in breast cancer tissues, and approximately 50% were also detected in the GEPIA database. The overlapping proteins were mainly extracellular proteins containing epidermal growth factor-like domain in leukocyte adhesion molecule (EGF-Lam) domain and enriched in laminin interaction pathway. Moreover, the downregulated laminin interaction proteins could be functional targets, which were also validated through Oncomine-Richardson and Oncomine-Curtis database. However, the lower expression level of laminin interaction proteins only fit for luminal breast cancer cells with no or low metastasis ability because the proteins achieved higher expression level in more invasive claudin-low breast cancer cells. In addition, when compared with corresponding in situ carcinoma tissues, above-mentioned proteins also showed higher expression levels in invasive carcinoma tissues. Finally, we have revealed the negative correlation between the laminin interaction proteins and the claudins. Conclusions: The laminin interaction protein, especially for laminins with ß1 and γ1 subunits and their integrin receptors with α1 and α6 subunits, showed lower expression levels in luminal breast cancer with no or lower metastatic ability, but showed higher expression levels in claudin-low breast cancer with higher metastatic ability; and their higher expression could be related to the low claudin expression.

[Single mini-incision combined with honeycomb titanium plate in treatment of acute acromioclavicular joint dislocation].

OBJECTIVE: To explore clinical effect of single small incision with honeycomb titanium plate in treating acute acromioclavicular dislocation. METHODS: The clinical data of 40 patients with acute acromioclavicular dislocation admitted from December 2019 to December 2021 were retrospectively analyzed and divided into two groups according to different surgical methods. Among them, 20 patients were fixed with single small incision with honeycomb titanium plate (titanium plate group), including 11 males and 9 females, aged from 23 to 65 years old with an average of (47.40±12.58) years old;12 patients on the left side, 8 patients on the right side;11 patients with type Ⅲ, 3 patients with type Ⅳ, and 6 patients with type Ⅴ according to Rockwood classification. Twenty patients were fixed with clavicular hook plate (clavicular hook group), including 8 males and 12 females, aged from 24 to 65 years old with an average of (48.40±12.08) years old;12 patients on the left side, 8 patients on the right side;10 patients with type Ⅲ, 2 patients with type Ⅳ, and 8 patients with type Ⅴ according to Rockwood classification. Operative time, incision length, intraoperative blood loss, hospital stay, visual analogue scale (VAS) and Constant-Murley score of shoulder joint function were compared between two groups. Anteroposterior radiographs of the affected shoulder joint were recorded before, immediately and 6 months after surgery, and the coracoclavicular distance was measured and compared. RESULTS: Both groups of patients were successfully completed operation without serious complications. All patients were followed up for 6 to 15 months with an average of (11.9±4.8) months. There were no incisional infection, internal plant fracture or failure, bone tunnel fracture and other complications occurred. The incision length of titanium plate group (35.90±3.14) mm was significantly shorter than that of clavicular hook group (49.30±3.79) mm (P<0.05). There were no significant difference in operative time, intraoperative blood loss and hospital stay between two groups (P>0.05). At 1 and 3 months after operation, VAS of titanium plate group was lower than that of clavicular hook group (P<0.05). Connstant-Murley scores in titanium plate group at 1, 3 and 6 months after operation were (86.80±1.36), (91.60±2.32) and (94.90±2.22), respectively;and in clavicular hook group were (78.45±5.47), (85.55±2.01) and (90.25±1.92), which were higher than that of clavicular hook group (P<0.05). There was no significant difference in coracoclavicular distance between two groups immediately and 6 months after operation(P>0.05). CONCLUSION: For the treatment of acute acromioclavicular joint dislocation, single small incision combined with honeycomb titanium plate have advantages of shorter incision, fast recovery of shoulder joint function without the second operation, and has good satisfaction of patient.

Discovery of Aurovertin B as a Potent Metastasis Inhibitor against Triple-Negative Breast Cancer: Elucidating the Complex Role of the ATF3-DUSP1 Axis.

Triple-negative breast cancer (TNBC) is characterized by high mortality rates primarily due to its propensity for metastasis. Addressing this challenge necessitates the development of effective antimetastatic therapies. This study aimed to identify natural compounds with potential antimetastatic properties mainly based on the high-throughput phenotypic screening system. This system, utilizing luciferase reporter gene assays combined with scratch wound assays, evaluates compounds based on their influence on the epithelial-mesenchymal transition (EMT) marker E-cadherin. Through this approach, aurovertin B (AVB) was revealed to have significant antimetastatic capability. Notably, AVB exhibited substantial metastasis suppression in many TNBC cell lines, including MDA-MB-231, HCC1937 and 4T1. Also, its remarkable antimetastatic activity was demonstrated in vivo via the orthotopic breast cancer mouse model. Further exploration revealed a pronounced association between AVB-induced upregulation of DUSP1 (dual-specificity phosphatase 1) and its inhibitory effect on TNBC metastasis. Additionally, microarray analysis conducted to elucidate the underlying mechanism of the AVB-DUSP1 interaction identified ATF3 (activating transcription factor 3) as a critical transcription factor instrumental in DUSP1 transcriptional activation. This discovery, coupled with observations of enhanced ATF3-DUSP1 expression and consequent reduction in TNBC metastatic foci in response to AVB, provides novel insights into the molecular mechanisms driving metastasis in TNBC. Significance Statement We construct a high-throughput phenotypic screening system utilizing EMT marker E-cadherin promoter luciferase reporter gene combined with scratch wound assays. Aurovertin B was revealed to possess significant antimetastatic activity through this approach, which was further demonstrated via in vivo and in vitro experiments. The discovery of the regulatory role of the ATF3-DUSP1 pathway enriches our understanding of TNBC metastasis mechanism and suggests the potential of ATF3 and DUSP1 as biomarkers for diagnosing TNBC metastasis.

Haplotype analysis on association between C-reactive protein gene and susceptibility to type 2 diabetes mellitus in Chinese Han population : CRP gene and type 2 diabetes mellitus.

AIMS: We aimed to evaluate the impact of C-reactive protein (CRP) gene polymorphism, additional gene-gene interaction, and haplotypes on susceptibility to type 2 diabetes mellitus (T2DM). METHODS: SNPstats online software ( https://www.snpstats.net/start.htm ) was employed to evaluate the association between CRP gene and T2DM risk. High-order interactions among SNPs was tested using generalized multifactor dimensionality reduction, and the testing balanced accuracy, training balanced accuracy and cross-validation consistency were calculated. The SHEsisPlus ( http://shesisplus.bio-x.cn/SHEsis.html ) online software was used for haplotype analysis. RESULTS: A total of 730 T2DM patients and 765 controls were enrolled. The T allele of rs1205 is associated with increased susceptibility to T2DM, OR (95% CI) were 1.51 (1.13-2.01), 1.44 (1.10-1.89) and 1.25 (1.01-1.54) for codominant, dominant and over-dominant models, respectively. We also found that minor allele of rs2794521 is associated with decreased susceptibility to T2DM under codominant and recessive models, OR (95%CI) were 0.38 (0.18-0.79) and 0.37 (0.16-0.80) for codominant and recessive models, respectively. No significant gene-gene interaction existed among CRP gene SNPs, all interaction p- values were more than 0.05. Haplotype analyses suggested the CGCA haplotype containing rs1205-C, rs1130864-G, rs2794521- C and rs3093059- A allele was associated with decreased risk of T2DM, OR (95% CI) = 0.83 (0.68-0.98), P = 0.047. CONCLUSIONS: Minor allele of rs1205 was associated with increased T2DM risk. Minor allele of rs2794521 and the CGCA haplotype were associated with decreased T2DM risk.

Risk factors of non-arteritic anterior ischaemic optic neuropathy and central retinal artery occlusion.

AIM: To investigate the difference in risk factors between non-arteritic anterior ischaemic optic neuropathy (NAION) and central retinal artery occlusion (CRAO) and develop a predictive diagnostic nomogram. METHODS: The study included 37 patients with monocular NAION, 20 with monocular CRAO, and 24 with hypertension. Gender, age, and systemic diseases were recorded. Blood routine, lipids, hemorheology, carotid and brachial artery doppler ultrasound, and echocardiography were collected. The optic disc area, cup area, and cup-to-disc ratio (C/D) of the unaffected eye in the NAION and CRAO group and the right eye in the hypertension group were measured. RESULTS: The carotid artery intimal medial thickness (C-IMT) of the affected side of the CRAO group was thicker (P=0.039) and its flow-mediated dilation (FMD) was lower (P=0.049) than the NAION group. Compared with hypertension patients, NAION patients had higher whole blood reduced viscosity low-shear (WBRV-L) and erythrocyte aggregation index (EAI; P=0.045, 0.037), and CRAO patients had higher index of rigidity of erythrocyte (IR) and erythrocyte deformation index (EDI; P=0.004, 0.001). The optic cup and the C/D of the NAION group were smaller than the other two groups (P<0.0001). The diagnostic prediction model showed high diagnostic specificity (83.7%) and sensitivity (85.6%), which was highly related to hypertension, the C-IMT of the affected side, FMD, platelet (PLT), EAI, and C/D. CONCLUSION: CRAO patients show thicker C-IMT and worse endothelial function than NAION. NAION and CRAO may be related to abnormal hemorheology. A small cup and small C/D may be involved in NAION. The diagnostic nomogram can be used to preliminarily identify NAION and CRAO.

CD40L-Activated DC Promotes Th17 Differentiation and Inhibits Th2 Differentiation in Sepsis-Induced Lung Injury via cGAS-STING Signaling.

Immune hemostasis due to an infection plays a vital role in sepsis-induced multiple organ dysfunction. Dendritic cells (DC) and T helper (Th) cells are the key members of the immune system maintaining immune homeostasis. This study aimed to explore the effect and mechanism of CD40L on the activation of DC and activated DC-induced Th2/Th17 differentiation. A CD40L knockout and cecal ligation and puncture (CLP) mouse model was established via cecal ligation. HE staining was used to evaluate the pathological changes. The gene expressions were studied using quantitative real-time polymerase chain reaction (qRT-PCR), while a transwell system was used to perform the co-culture of DC and T-cells. Flow cytometry was performed to detect the subtype of T and DC cells. ELISA was used to assess the amount of inflammatory factors. CD40L was highly expressed in the plasma of CLP mice. Knock out of CD40L inhibited the activation of DC cell and Th17 differentiation while promoting the Th2 differentiation. The mechanistic investigations revealed that CD40L promoted the activation of cGAS-STING pathway. Rescue experiments indicated that CD40L mediated DC activation via cGAS-STING signaling. Moreover, co-culturing of CD and CD+4 T-cells demonstrated that silencing of CD40L in DC suppressed the DC activation and inhibited Th17 differentiation while promoting Th2 differentiation. These findings revealed a relationship between CD40L, DC activation, and Th2/Th17 differentiation balance in sepsis-induced acute lung injury for the first time. These findings are envisaged to provide novel molecular targets for sepsis-induced lung injury treatment.

Exploring the Synthesis of Self-Organization and Active Motion.

Proteins, genetic material, and membranes are fundamental to all known organisms, yet these components alone do not constitute life. Life emerges from the dynamic processes of self-organization, assembly, and active motion, suggesting the existence of similar artificial systems. Against this backdrop, our Perspective explores a variety of chemical phenomena illustrating how nonequilibrium self-organization and micromotors contribute to life-like behavior and functionalities. After explaining key terms, we discuss specific examples including enzymatic motion, diffusiophoretic and bubble-driven self-propulsion, pattern-forming reaction-diffusion systems, self-assembling inorganic aggregates, and hierarchically emergent phenomena. We also provide a roadmap for combining self-organization and active motion and discuss possible outcomes through biological analogs. We suggest that this research direction, deeply rooted in physical chemistry, offers opportunities for further development with broad impacts on related sciences and technologies.

A novel improved total variation algorithm for the elimination of scratch-type defects in high-voltage cable cross-sections.

In the quality inspection process of high-voltage cables, several commonly used indicators include cable length, insulation thickness, and the number of conductors within the core. Among these factors, the count of conductors holds particular significance as a key determinant of cable quality. Machine vision technology has found extensive application in automatically detecting the number of conductors in cross-sectional images of high-voltage cables. However, the presence of scratch-type defects in cut high-voltage cable cross-sections can significantly compromise the precision of conductor count detection. To address this problem, this paper introduces a novel improved total variation (TV) algorithm, marking the first-ever application of the TV algorithm in this domain. Considering the staircase effect, the direct use of the TV algorithm is prone to cause serious loss of image edge information. The proposed algorithm firstly introduces multimodal features to effectively mitigate the staircase effect. While eliminating scratch-type defects, the algorithm endeavors to preserve the original image's edge information, consequently yielding a noteworthy enhancement in detection accuracy. Furthermore, a dataset was curated, comprising images of cross-sections of high-voltage cables of varying sizes, each displaying an assortment of scratch-type defects. Experimental findings conclusively demonstrate the algorithm's exceptional efficiency in eradicating diverse scratch-type defects within high-voltage cable cross-sections. The average scratch elimination rate surpasses 90%, with an impressive 96.15% achieved on cable sample 4. A series of conducted ablation experiments in this paper substantiate a significant enhancement in cable image quality. Notably, the Edge Preservation Index (EPI) exhibits an improvement of approximately 20%, resulting in a substantial boost to conductor count detection accuracy, thus effectively enhancing the quality of high-voltage cable production.

Structural features and substrate engagement in peptide-modifying radical SAM enzymes.

In recent years, the biological significance of ribosomally synthesized, post-translationally modified peptides (RiPPs) and the intriguing chemistry catalyzed by their tailoring enzymes has garnered significant attention. A subgroup of bacterial radical S-adenosylmethionine (rSAM) enzymes can activate C-H bonds in peptides, which leads to the production of a diverse range of RiPPs. The remarkable ability of these enzymes to facilitate various chemical processes, to generate and harbor high-energy radical species, and to accommodate large substrates with a high degree of flexibility is truly intriguing. The wide substrate scope and diversity of the chemistry performed by rSAM enzymes raise one question: how does the protein environment facilitate these distinct chemical conversions while sharing a similar structural fold? In this review, we discuss recent advances in the field of RiPP-rSAM enzymes, with a particular emphasis on domain architectures and substrate engagements identified by biophysical and structural characterizations. We provide readers with a comparative analysis of six examples of RiPP-rSAM enzymes with experimentally characterized structures. Linking the structural elements and the nature of rSAM-catalyzed RiPP production will provide insight into the functional engineering of enzyme activity to harness their catalytic power in broader applications.

Treatment discontinuation in older people with multiple sclerosis.

PURPOSE OF REVIEW: The aim of this review was to examine the evidence for disease-modifying therapies (DMTs) discontinuation in older people with multiple sclerosis (MS). We first summarized aging-associated biological changes that influence MS progression and DMT effectiveness, and then summarized recent evidence in evaluating clinical outcomes of discontinuing DMTs in older people with MS. RECENT FINDINGS: Recent findings provide mixed evidence regarding the outcomes of DMT discontinuation in older people with MS. Retrospective observational studies suggested older age and longer stable duration on DMT before DMT discontinuation were associated with lower risk of relapse in people with MS. However, one randomized clinical trial did not demonstrate the noninferiority of DMT discontinuation. SUMMARY: The available clinical evidence examining DMT discontinuation in older people with MS remains inconclusive. More robust evidence from clinical trials and real-world data will be necessary to guide clinical decisions regarding DMT discontinuation in older people with MS.