The safety and efficacy of indobufen or aspirin combined with clopidogrel in patients with acute myocardial infarction after percutaneous coronary intervention.

Currently, the standard treatment for patients who have undergone percutaneous coronary intervention (PCI) following acute myocardial infarction (MI) involves dual antiplatelet therapy (DAPT) with a combination of aspirin and a potent P2Y12 receptor inhibitor. However, the potential benefits of aspirin were partially constrained by the intolerance of some patients. The safety and efficacy of indobufen, an alternative antiplatelet agents to aspirin, in patients with AMI after PCI are yet to be thoroughly investigated.This retrospective study was conducted at a single center and utilized propensity score matching. The enrollment spanned from January 2019 to June 2022, incorporating patients with AMI after PCI. The participants were categorized into two groups based on discharged prescriptions: the aspirin DAPT group and the indobufen DAPT group. The primary endpoint focused on net adverse clinical event (NACE), defined as a composite outcome, including cardiac death, recurrence of MI, definite or probable stent thrombosis (ST), target lesion revascularization (TLR), ischemic stroke and Bleeding Academic Research Consortium (BARC) criteria type 2, 3, or 5. All the patients underwent a one-year follow-up period.A total of 1451 patients were enrolled in this study, with 258 assigned to the indobufen DAPT group and 1193 to the aspirin DAPT group. Following 1:1 propensity score matching, 224 patients were retained in each group. In the indobufen DAPT group, 58 individuals (25.9%) experienced the primary endpoint within one year, compared to 52 individuals (23.2%) in the aspirin DAPT group (HR 1.128, 95% CI 0.776-1.639, p = .527). Specifically, no significant differences were observed in either the efficacy endpoint (MACCE, 20.1% vs. 14.7%, HR 1.392, 95% CI 0.893-2.170, p = .146) or the safety endpoint (BARC 2,3 or 5, 8.04% vs. 10.30%, HR 0.779, p = .427). These findings remained consistent at 1, 3, or 6 months. Additionally, the incidence of gastrointestinal symptoms were significantly lower in indobufen DAPT group compared to the aspirin DAPT group (7.1% vs. 14.3%, p = .022).Our research reveals that the efficacy and safety of indobufen are comparable to aspirin in Chinese patients with AMI following PCI. Given the potential advantages of indobufen in alleviating gastrointestinal symptoms, we propose it as a viable alternative for individuals intolerant to aspirin.

What is the context? Currently, the standard treatment for patients who have undergone percutaneous coronary intervention following acute myocardial infarction involves dual antiplatelet therapy with a combination of aspirin and a potent P2Y12 receptor inhibitor.However, the potential benefits of aspirin were partially constrained by the intolerance of some patients.The safety and efficacy of indobufen, an alternative antiplatelet agents to aspirin, in patients with AMI after PCI are yet to be thoroughly investigated.What is new? While both American and European clinical guidelines recommend the use of indobufen as an alternative treatment for patients who cannot tolerate aspirin, there exists a limited body of research on this subject.Our research is the first to address this gap by comparing the efficacy and safety of indobufen and aspirin in patients with AMI.Our research reveals that the efficacy and safety of indobufen are comparable to aspirin in Chinese patients with AMI following PCI. Given the potential advantages of indobufen in alleviating gastrointestinal symptoms, we propose it as a viable alternative for individuals intolerant to aspirin.What is the impact? These findings might pave the way for further exploration of alternatives to aspirin in patients with AMI.

Clinical value of Tc-99m MDP SPECT/CT bone imaging for early diagnosis of Relapsing Polychondritis: a report of 5 cases.

BACKGROUND: Relapsing Polychondritis(RP) is a rare rheumatic immune disease. As with most diseases, if intervention is delayed, the patient's prognosis is worse. Currently, the diagnostic criteria used in clinical practice do not include CT, PET/CT, SPECT/CT and other new imaging examinations that have developed rapidly in recent years. However, these examinations have some special manifestations for RP, which can help clinicians diagnose RP earlier and distinguish it from other diseases. CASE PRESENTATION: These five RP patients all had respiratory symptoms such as cough and wheezing as the first symptom, which could not be diagnosed in time according to the previous diagnostic criteria. The clinical data of the five patients are listed in Table 1. The relatively specific manifestations of SPECT/CT examination provided clinicians with very valuable clues to help them advance the diagnosis time. CONCLUSIONS: The application of SPECT/CT bone imaging in early diagnosing RP proves to be effective, enabling clinicians to intervene promptly and enhance the overall well-being and quality of life for individuals affected by this condition.

Core-shell magnetic covalent organic polymer nanocomposites as an adsorbent for the extraction of flavonoids.

A novel 3D magnetic nanocomposite material based on covalent organic polymers was successfully synthesized and utilized as an efficient sorbent for magnetic solid-phase extraction. It exhibited a regular core-shell structure, large specific surface area, superior stability, and paramagnetism. To evaluate its extraction efficiency, six flavonoids were tested, demonstrating maximum adsorption capacities ranging from 90 to 218 mg/g. Additionally, the material exhibited remarkable reusability and mechanical stability, maintaining its original state over eight cycles with consistent recovery. An analytical strategy combining magnetic solid-phase extraction with high performance liquid chromatography and tandem mass spectrometry was developed for the determination of flavonoids in orange, honey, soybean, and Dioscorea bulbifera L. samples. The low limits of detection (0.01-0.1 ng/mL) and limits of quantification (0.05-0.5 ng/mL), as well as satisfactory recovery (80.4-114.8%), were obtained. The linear range started from the limits of quantification to 500 ng/mL with R2 ≥ 0.9929. These results suggest that the prepared adsorbent possesses excellent adsorption capabilities for flavonoids, highlighting its significant potential for detecting these compounds in complex sample matrices.

Genome-wide association analysis to search for new loci associated with stroke risk in Northwestern Chinese population.

BACKGROUND AND PURPOSE: Genetic factors play an important role in the pathogenesis of stroke(S). This study aimed to screen the loci associated with S risk in northwestern Chinese population by genome-wide association analysis (GWAS). METHODS: A total of 1394 subjects, including 682 S patients and 692 controls, were enrolled in this study. SPSS 25.0 software was used for statistical analysis, and the independent sample t-test as well as Chi-square test were used to analyze the differences in age and gender between the case and control groups. The Precision Medicine Diversity Array (PMDA) genotyping chip was used in this study. The genotyping platform was the Gene Titan multi-channel instrument, and the Axiom Analysis Suite 6.0 software was used for the data analyzing. Besides, the LASSO analysis, SNP-SNP and GO/KEGG analysis were conducted to analyze the association between significant loci and S risk. RESULTS: A total of 30 SNPs were found to be associated with the S risk based on additive model (p < 5 × 10-8). After the LASSO screening, 22 SNPs showed the diagnostic value in S. The SNPs interaction analysis further screened the SNP-SNP interaction groups associated with the S risk(p < 0.05). Finally, the GO/KEGG analysis discovered the suggestive significance loci could be involved in the S development mainly by immune-related functions and pathways. CONCLUSION: This study discovered 30 S related SNPs and analyzed the potential pathways associated with genes located on the 30 SNPs, which were beneficial for enriching the genetic mechanism analysis of S in northwestern Chinese population.

Synergistic Effects of Glutamine Deprivation and Metformin in Acute Myeloid Leukemia.

OBJECTIVE: The metabolic reprogramming of acute myeloid leukemia (AML) cells is a compensatory adaptation to meet energy requirements for rapid proliferation. This study aimed to examine the synergistic effects of glutamine deprivation and metformin exposure on AML cells. METHODS: SKM-1 cells (an AML cell line) were subjected to glutamine deprivation and/or treatment with metformin or bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES, a glutaminase inhibitor) or cytarabine. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay, and cell apoptosis and reactive oxygen species (ROS) by flow cytometry. Western blotting was conducted to examine the levels of apoptotic proteins, including cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP). Moreover, the human long noncoding RNA (lncRNA) microarray was used to analyze gene expression after glutamine deprivation, and results were confirmed with quantitative RT-PCR (qRT-PCR). The expression of metallothionein 2A (MT2A) was suppressed using siRNA. Cell growth and apoptosis were further detected by CCK-8 assay and flow cytometry, respectively, in cells with MT2A knockdown. RESULTS: Glutamine deprivation or treatment with BPTES inhibited cell growth and induced apoptosis in SKM-1 cells. The lncRNA microarray result showed that the expression of MT family genes was significantly upregulated after glutamine deprivation. MT2A knockdown increased apoptosis, while proliferation was not affected in SKM-1 cells. In addition, metformin inhibited cell growth and induced apoptosis in SKM-1 cells. Both glutamine deprivation and metformin enhanced the sensitivity of SKM-1 cells to cytarabine. Furthermore, the combination of glutamine deprivation with metformin exhibited synergistic antileukemia effects on SKM-1 cells. CONCLUSION: Targeting glutamine metabolism in combination with metformin is a promising new therapeutic strategy for AML.

A Chinese individual with DEL phenotype caused by a novel RHD allele.

BACKGROUND: RhD variants are categorized into partial D, weak D, and DEL. The detection of DEL can only be achieved through the adsorption and elution method or molecular techniques. Here, we report a case of DEL phenotypes associated with a novel allele in a Chinese individual. STUDY DESIGN AND METHODS: We used serological methods such as saline, indirect anti-human globulin, and adsorption-elution. The RHD genotype was determined by the PCR-sequence specific primer (PCR-SSP) method as well as the Sanger dideoxy sequencing. RESULTS: RBCs of the sample were found to be DEL phenotype by serological testing, with negative reactions in the saline and indirect anti-human globulin tests while positive reactions by the absorption-elution method. The genotyping results revealed a hemizygous (RHDc .1127 T>G/RHD-). The novel allele sequence has been submitted to GenBank (Accession number: OR608456). CONCLUSION: Our study demonstrates a case of a Chinese individual with DEL phenotype caused by a novel allele RHD c .1127 T > G. It expands the database of the DEL variant.

Robust detection of a rotational Doppler shift with randomly fluctuated light.

The complex external environment, such as obstruction and turbulence, poses significant limitations on the applications of rotational Doppler detection. The active manipulation of randomly fluctuated light has been proven effective in mitigating external environmental perturbations. Here, as an example, a partially coherent source with petal-like focal (or far) field distribution is constructed specifically for detecting rotational Doppler frequency shifts. The experiment involved conducting rotational Doppler detection under obstruction or turbulence conditions, and the results are compared with the fully coherent counterpart. The results demonstrate that the use of a partially coherent source can address the frequency-shift broadening problem due to the obstruction-induced beam information loss and mitigate it due to the turbulence-induced beam misalignment. These advantages make the proposed approach applicable to velocity metrology in complex environments.

Association of serum uric acid to serum creatinine ratio with 1-year stroke outcomes in patients with acute ischemic stroke: A multicenter observational cohort study.

BACKGROUND AND PURPOSE: Considering the reliance of serum uric acid (SUA) levels on renal clearance function, its role in stroke outcomes remains controversial. This study investigated the association of renal function-normalized SUA (SUA to serum creatinine ratio, SUA/SCr), a novel renal function index, with the 1-year outcomes in patients with acute ischemic stroke (AIS). METHODS: This is a prospective, multicenter observational study. Renal function-normalized SUA levels were determined by calculating the ratio of SUA to SCr. One-year outcomes included stroke recurrence, all-cause mortality, and poor prognosis. Multivariable Cox regression analyses and restriction cubic splines for curve fitting were used to evaluate SUA/SCr's association with 1-year stroke outcomes. RESULTS: Among 2294 enrolled patients, after adjustment for potential confounders, multivariable Cox regression analyses showed that each one-unit increase in SUA/SCr corresponded to a 19% decrease in 1-year stroke recurrence in patients with AIS. SUA/SCr was analyzed as a continuous variable and categorized into quartiles (Q1-Q4). Compared with the Q1 reference group, Q2, Q3, and Q4 showed significantly lower 1-year stroke recurrence risks. The trend test indicated significant differences in the 1-year stroke recurrence trend from Q1 to Q4. In these patients, SUA/SCr did not show a significant association with poor prognosis or all-cause mortality. Curve fitting revealed SUA/SCr had a negative but nonlinear association with 1-year stroke recurrence. CONCLUSIONS: In patients with AIS, low SUA/SCr may be an independent risk factor for 1-year stroke recurrence. Changes in SUA/SCr had no significant impact on 1-year poor prognosis and all-cause mortality.

Revealing the dual impact of VOCs on recycled rubber workers: Health risk and odor perception.

Volatile organic compounds (VOCs) pose potential hazards to human health and contribute significantly to odor pollution. This study examined VOC emissions from a representative recycled rubber industry, evaluating the occupational health risks for frontline workers in various workshops. Variables such as gender and workshop-specific concentration variations were considered using Monte Carlo simulation methods. Employees in the five production workshops and office areas face noncarcinogenic health risks with hazard indices (HIs) greater than 1, with the rubber compounding phase presenting the highest risk. Acetaldehyde is identified as the primary noncarcinogenic health risk substance, with hazard quotient (HQ) values exceeding 1 in all workshops. Carcinogenic health risks vary by area, with the highest risks found in compounding and refining workshops. Formaldehyde poses the greatest risk in rubber grinding workshops and offices, with cumulative weights exceeding unacceptable levels of M80.58 % and W77.56 % in grinding and M94.98 % and W92.24 % in the office. Male workers face 4-7 % greater noncarcinogenic VOC health risks than females and 5-14 % greater carcinogenic risks from individual VOCs, increasing their susceptibility to health risks caused by VOCs. Additionally, our analysis of odor identification and intensity classification revealed that 53 VOCs are capable of causing odor pollution, with several substances reaching odor levels of 2 or higher. The predominant perceived odors, as reflected in the odor wheel, include categories such as "solvent/aromatic" and "sweet/fruit," with aldehydes being the primary odor-causing substances. In summary, emissions of VOCs from rubber industrial processes not only pose substantial health risks to workers but also contribute significantly to odor pollution. Consequently, enterprises must prioritize optimizing workplace conditions to ensure the occupational health and well-being of their employees.

PANDA-3D: protein function prediction based on AlphaFold models.

Previous protein function predictors primarily make predictions from amino acid sequences instead of tertiary structures because of the limited number of experimentally determined structures and the unsatisfying qualities of predicted structures. AlphaFold recently achieved promising performances when predicting protein tertiary structures, and the AlphaFold protein structure database (AlphaFold DB) is fast-expanding. Therefore, we aimed to develop a deep-learning tool that is specifically trained with AlphaFold models and predict GO terms from AlphaFold models. We developed an advanced learning architecture by combining geometric vector perceptron graph neural networks and variant transformer decoder layers for multi-label classification. PANDA-3D predicts gene ontology (GO) terms from the predicted structures of AlphaFold and the embeddings of amino acid sequences based on a large language model. Our method significantly outperformed a state-of-the-art deep-learning method that was trained with experimentally determined tertiary structures, and either outperformed or was comparable with several other language-model-based state-of-the-art methods with amino acid sequences as input. PANDA-3D is tailored to AlphaFold models, and the AlphaFold DB currently contains over 200 million predicted protein structures (as of May 1st, 2023), making PANDA-3D a useful tool that can accurately annotate the functions of a large number of proteins. PANDA-3D can be freely accessed as a web server from http://dna.cs.miami.edu/PANDA-3D/ and as a repository from https://github.com/zwang-bioinformatics/PANDA-3D.

Optimization of concentrations of different n-3PUFAs on antioxidant capacity in mouse hepatocytes.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), mainly including α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), possess antioxidant properties and play a crucial role in growth and development. However, the combined effects of ALA, EPA, and DHA at different concentrations have rarely been reported. This work explored the effects of EPA, ALA, and DHA on the viability and antioxidant capacity of mouse hepatocytes, with the objective of enhancing the antioxidant capacity. Within the appropriate concentration range, cell viability and the activity of glutathione S-transferase, superoxide dismutase, and catalase were increased, while the oxidation products of malondialdehyde and the level of intracellular reactive oxygen species were obviously reduced. Thus, oxidative stress was relieved, and cellular antioxidant levels were improved. Finally, response surface optimization was carried out for EPA, ALA, and DHA, and the model was established. The antioxidant capacity of the cells was highest at EPA, ALA, and DHA concentrations of 145.46, 405.05, and 551.52 µM, respectively. These findings lay the foundation for further exploration of the interactive mechanisms of n-3 PUFAs in the body, as well as their applications in nutraceutical food.

Mst1-mediated phosphorylation of FoxO1 and C/EBP-ß stimulates cell-protective mechanisms in cardiomyocytes.

The molecular mechanisms by which FoxO transcription factors mediate diametrically opposite cellular responses, namely death and survival, remain unknown. Here we show that Mst1 phosphorylates FoxO1 Ser209/Ser215/Ser218/Thr228/Ser232/Ser243, thereby inhibiting FoxO1-mediated transcription of proapoptotic genes. On the other hand, Mst1 increases FoxO1-C/EBP-ß interaction and activates C/EBP-ß by phosphorylating it at Thr299, thereby promoting transcription of prosurvival genes. Myocardial ischemia/reperfusion injury is larger in cardiac-specific FoxO1 knockout mice than in control mice. However, the concurrent presence of a C/EBP-ß T299E phospho-mimetic mutation reduces infarct size in cardiac-specific FoxO1 knockout mice. The C/EBP-ß phospho-mimetic mutant exhibits greater binding to the promoter of prosurvival genes than wild type C/EBP-ß. In conclusion, phosphorylation of FoxO1 by Mst1 inhibits binding of FoxO1 to pro-apoptotic gene promoters but enhances its binding to C/EBP-ß, phosphorylation of C/EBP-ß, and transcription of prosurvival genes, which stimulate protective mechanisms in the heart.

Left Atrial Electrophysiological Properties after Pulmonary Vein Isolation Predict the Recurrence of Atrial Fibrillation: A Cohort Study.

Background: The aim of this work was to investigate left atrial electrophysiological properties for their ability to predict the recurrence of atrial fibrillation (AF) following pulmonary vein isolation (PVI). Methods: The study comprised 53 patients with AF [62 (interquartile range (IQR): 52-68) years old; 47.2% females]. High-density, three-dimensional electro-anatomic mapping using PentaRay was conducted during sinus rhythm in the left atrium (LA) immediately after PVI. LA conduction time, conduction velocity in predefined anterior and posterior routes, low voltage area percentage and distribution were assessed. Results: The AF recurrence group had longer LA conduction time compared to the non-recurrence group [11 (IQR: 10-12) ms vs. 9 (IQR: 8-10) ms, p = 0.001). The percent low voltage area was greater in the recurrence group than the non-recurrence group [31.2 (IRQ: 7.1-49.3)% vs. 7.7 (IQR: 4.3-15.2)%, p = 0.008]. Multivariate Cox regression revealed that LA conduction time independently predicted AF recurrence following ablation over a median follow-up of 235 days [IQR: 154-382 days; hazard ratio (HR): 2.37, 95% confidence interval (CI): 1.08-5.23, p = 0.031]. The optimal cut-off for LA conduction time was 98 ms [area under curve (AUC): 0.926, sensitivity: 0.833, specificity: 0.894, p < 0.01]. Kaplan-Meier analysis revealed that patients with a conduction time > 98 ms had a higher rate of AF recurrence following ablation (p < 0.001). Conclusions: Patients with longer LA conduction time after PVI had more frequent AF recurrence.

The Restriction Activity Investigation of Rv2528c, an Mrr-like Modification-Dependent Restriction Endonuclease from Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb), as a typical intracellular pathogen, possesses several putative restriction-modification (R-M) systems, which restrict exogenous DNA's entry, such as bacterial phage infection. Here, we investigate Rv2528c, a putative Mrr-like type IV restriction endonuclease (REase) from Mtb H37Rv, which is predicted to degrade methylated DNA that contains m6A, m5C, etc. Rv2528c shows significant cytotoxicity after being expressed in Escherichia coli BL21(DE3)pLysS strain. The Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assay indicates that Rv2528c cleaves genomic DNA in vivo. The plasmid transformation efficiency of BL21(DE3)pLysS strain harboring Rv2528c gene was obviously decreased after plasmids were in vitro methylated by commercial DNA methyltransferases such as M.EcoGII, M.HhaI, etc. These results are consistent with the characteristics of type IV REases. The in vitro DNA cleavage condition and the consensus cleavage/recognition site of Rv2528c still remain unclear, similar to that of most Mrr-family proteins. The possible reasons mentioned above and the potential role of Rv2528c for Mtb were discussed.

Unique Plant Resources and Distribution Patterns in the Valley Forest of the Irtysh River Basin.

The river valley forests of the Irtysh River Basin are a germplasm bank of Salicaceae species and rare plant resources in China, and the distribution varies with the river and is highly distinctive. However, there is a dearth of systematic research on the characteristics of plant resources. In this study, a comprehensive investigation was conducted in the trunk stream and six tributaries with valley forest distribution in the Irtysh River Basin, and 244 quadrats were set up. The analysis focused on the composition of the flora and resource characteristics. The results reveal the following: (1) The valley forests of the Irtysh River Basin contain 256 species of plants belonging to 57 families and 178 genera, among which 19 species of trees, 23 species of shrubs, and 214 species of herbs were investigated. (2) Among the identified species, 226 (88.67%) were recognized as resource plants, with medicinal plants being the most abundant (176 species, 68.75% of the total). (3) The distribution patterns of trees, shrubs, and herbs of each resource type vary across rivers. Elevation drop, river length, and river distance all significantly affect the number of specie. This study elucidated the current status and distributional characteristics of plant resources in the valley forests of the Irtysh River Basin, which is essential for both biodiversity conservation and sustainable resource utilization.

New Electrocardiographic Score for Predicting the Site of Coronary Artery Occlusion in Inferior Wall Acute Myocardial Infarction.

Background: An electrocardiogram (ECG) was used to determine the type of acute myocardial infarction (MI) and locate the culprit vessel. Inferior wall myocardial infarction (IWMI) patients with the right coronary artery (RCA) as the culprit vessel may have a worse clinical prognosis than the left circumflex artery (LCx). We aimed to develop a new, simple, accurate scoring system to localize the RCA. Methods: From January 2018 to January 2020, patients were admitted to the Department of Cardiology of TEDA International Cardiovascular Hospital and the Second Hospital of Tianjin Medical University due to IWMI and coronary angiography confirmed that the infarct-related vessel was a single RCA or LCx. ECG of patients before percutaneous coronary intervention (PCI) was collected to quantitatively analyze the characteristics of ST-segment deviation in non-inferior wall leads (N-IWL) and establish the RCA score in N-IWL. Results: 149 patients were enrolled, including 83 in the RCA group and 66 in the LCx group. Finally, ST-segment depression (ST↓) lead I, aVR, V1, and V6, and ST↓≥ 1mm in lead V4 were found to be associated with the location of the RCA. The sensitivity, specificity, and area under the curve (AUC) of the N-IWL RCA scoring system were 77.1%, 72.7%, and 0.83, respectively. The diagnostic ability of the scoring system was better than that of other algorithms and scoring systems. Conclusion: ECG helps identify the RCA in patients with IWMI before PCI. The N-IWL RCA score may help identify the culprit vessel as the RCA in patients with IWMI.

Idiopathic ventricular arrhythmia originating from the vicinity of lateral tricuspid annulus: the precise origin and anatomical concerns.

BACKGROUND: Although the electrcardiographic and electrophysiological properties of ventricular arrhythmias (VA) from the vicinity of lateral tricuspid annulus (TA) have been reported in previous studies, their precise site of origin have not been addressed. OBJECTIVE: To describe the precise origin of lateral TA-VA and the relevant anatomy. METHODS: Consecutive patients with idiopathic lateral TA-VAs were reviewed and analyzed. Three-dimensional mapping system combined with intracardiac echocardiography (ICE) was used for anatomical reconstruction, mapping, and ablation. RESULTS: During the study period, 63 patients with lateral TA-VAs were included. Under ICE view, a prominent enfoldment structure was observed under the valve along lateral TA. The muscular bundle was documented in all patients (100%) within the sub-valvular enfoldment with an average number and diameter of 4±2 and 4.10±0.73mm, respectively. Initial ablation was attempted via the antegrade approach in 15 patients but succeeded in none. To reach the ventricular side of TA, the catheter needed to enter ventricular chamber and retroflexed toward the atrial side with a reverse curve. The earliest activation site was found at the valvular end of muscular bundles in 51 of the 63 (80.9%) patients with a local activation time of -26.78±4.63ms. The VAs were eliminated after an average of 4±2 seconds of ablations. CONCLUSION: The ventricular adjacent to the lateral TA exhibits a sub-valvular enfoldment-like structure, which is rich in muscular bundles and serves as the origin of TA-VAs in most patients. To reach the origins, a reverse technique is required.

Molecular insights into degron recognition by CRL5ASB7 ubiquitin ligase.

The ankyrin (ANK) SOCS box (ASB) family, encompassing ASB1-18, is the largest group of substrate receptors of cullin 5 Ring E3 ubiquitin ligase. Nonetheless, the mechanism of substrate recognition by ASB family proteins has remained largely elusive. Here we present the crystal structure of ASB7-Elongin B-Elongin C ternary complex bound to a conserved helical degron. ASB7 employs its ANK3-6 to form an extended groove, effectively interacting with the internal α-helix-degron through a network of side-chain-mediated electrostatic and hydrophobic interactions. Our structural findings, combined with biochemical and cellular analyses, identify the key residues of the degron motif and ASB7 required for their recognition. This will facilitate the identification of additional physiological substrates of ASB7 by providing a defined degron motif for screening. Furthermore, the structural insights provide a basis for the rational design of compounds that can specifically target ASB7 by disrupting its interaction with its cognate degron.

Construction and validation of a risk score system for diagnosing invasive adenocarcinoma presenting as pulmonary pure ground-glass nodules: a multi-center cohort study in China.

Background: Anxiety-driven clinical interventions have been queried due to the nondeterminacy of pure ground-glass nodules (pGGNs). Although radiomics and radiogenomics aid diagnosis, standardization and reproducibility challenges persist. We aimed to assess a risk score system for invasive adenocarcinoma in pGGNs. Methods: In a retrospective, multi-center study, 772 pGGNs from 707 individuals in The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital were grouped into training (509 patients with 558 observations) and validation (198 patients with 214 observations) sets consecutively from January 2017 to November 2021. An additional test set of 143 observations in Hainan Cancer Hospital was analyzed in the same period. Computed tomography (CT) signs and clinical features were manually collected, and the quantitative parameters were achieved by artificial intelligence (AI). The positive cutoff score was ≥3. Risk scores system 3 combined carcinoma history, chronic obstructive pulmonary disease (COPD), maximum diameters, nodule volume, mean CT values, type II or III vascular supply signs, and other radiographic characteristics. The evaluation included the area under the curves (AUCs), accuracy, sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) for both the risk score systems 1, 2, 3 and the AI model. Results: The risk score system 3 [AUC, 0.840; 95% confidence interval (CI): 0.789-0.890] outperformed the AI model (AUC, 0.553; 95% CI: 0.487-0.619), risk score system 1 (AUC, 0.802; 95% CI: 0.754-0.851), and risk score system 2 (AUC, 0.816; 95% CI: 0.766-0.867), with 88.0% (0.850-0.904) accuracy, 95.6% (0.932-0.972) PPV, 0.620 (0.535-0.702) NPV, 89.6% (0.864-0.920) sensitivity, and 80.6% (0.717-0.872) specificity in the training sets. In the validation and test sets, risk score system 3 performed best with AUCs of 0.769 (0.678-0.860) and 0.801 (0.669-0.933). Conclusions: An AI-based risk scoring system using quantitative image parameters, clinical features, and radiographic characteristics effectively predicts invasive adenocarcinoma in pulmonary pGGNs.

Sol-gel transition effect based on konjac glucomannan thermosensitive hydrogel for photo-assisted uranium extraction.

Exploiting the intelligent photocatalysts capable of phase separation provides a promising solution to the removal of uranium, which is expected to solve the difficulty in separation and the poor selectivity of traditional photocatalysts in carbonate-containing uranium wastewater. In this paper, the γ-FeOOH/konjac glucomannan grafted with phenolic hydroxyl groups/poly-N-isopropylacrylamide (γ-FeOOH/KGM(Ga)/PNIPAM) thermosensitive hydrogel is proposed as the photocatalysts for extracting uranium from carbonate-containing uranium wastewater. The dynamic phase transformation is demonstrated to confirm the arbitrary transition of γ-FeOOH/KGM(Ga)/PNIPAM thermosensitive hydrogel from a dispersed state with a high specific surface area at low temperatures to a stable aggregated state at high temperatures. Notably, the γ-FeOOH/KGM(Ga)/PNIPAM thermosensitive hydrogel achieves a remarkably high rate of 92.3% in the removal of uranium from the wastewater containing carbonates and maintains the efficiency of uranium removal from uranium mine wastewater at over 90%. Relying on electron spin resonance and free radical capture experiment, we reveal the adsorption-reduction-nucleation-crystallization mechanism of uranium on γ-FeOOH/KGM(Ga)/PNIPAM thermosensitive hydrogel. Overall, this strategy provides a promising solution to treating uranium-contaminated wastewater, showing a massive potential in water purification.