Retrospective analysis of the clinical utility of multi-cytokine profiles in smear-negative pulmonary tuberculosis.

OBJECTIVES: To evaluate cytokine profiles and interferon-gamma release assay (IGRA) for their diagnostic capabilities in the differentiation of tuberculosis (TB) from non-TB conditions, as well as smear-negative pulmonary tuberculosis (SNPT) from smear-positive pulmonary tuberculosis (SPPT). METHODS: A total of 125 participants were included, 77 of whom had TB and 48 who didn't, and demographic, clinical, and laboratory data were collected, including cytokine levels and IGRA results. The TB patients were further divided into 2 subgroups: SNPT (n=42) and SPPT (n=35). RESULTS: Compared to non-TB, the TB group had lower BMI, higher WBC, neutrophils, monocytes, ESR and CRP (p<0.05). TB patients showed higher IL-2, IL-6, IFN-γ, IL-8 (p<0.001) and higher IGRA positivity (88.3% versus [vs.] 29.2%, p<0.001). Between SNPT and SPPT, moderate effect sizes were observed for IFN-α, IL-2, IL-10, IL-8 (Cohen's d 0.59-0.76), with lower IGRA positivity in SNPT (81.0% vs. 97.1%, p=0.015). ROC analysis indicated IFN-α, IL-2, IL-10, IL-8 had moderate accuracy for SNPT diagnosis (AUCs 0.668-0.734), and combining these improved accuracy (AUC 0.759, 80% sensitivity, 64.2% specificity). CONCLUSION: A multi-biomarker approach combining these cytokines demonstrates enhanced diagnostic accuracy for tuberculosis.

Serum cystatin C, monocyte/high-density lipoprotein-C ratio, and uric acid for the diagnosis of coronary heart disease and heart failure.

BACKGROUND: Coronary heart disease (CHD) and heart failure (HF) are the major causes of morbidity and mortality worldwide. Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis. However, conventional diagnostic methods such as electrocardiography, echocardiography, and cardiac biomarkers have certain limitations, such as low sensitivity, specificity, availability, and cost-effectiveness. Therefore, there is a need for simple, noninvasive, and reliable biomarkers to diagnose CHD and HF. AIM: To investigate serum cystatin C (Cys-C), monocyte/high-density lipoprotein cholesterol ratio (MHR), and uric acid (UA) diagnostic values for CHD and HF. METHODS: We enrolled 80 patients with suspected CHD or HF who were admitted to our hospital between July 2022 and July 2023. The patients were divided into CHD (n = 20), HF (n = 20), CHD + HF (n = 20), and control groups (n = 20). The serum levels of Cys-C, MHR, and UA were measured using immunonephelometry and an enzymatic method, respectively, and the diagnostic values for CHD and HF were evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Serum levels of Cys-C, MHR, and UA were significantly higher in the CHD, HF, and CHD + HF groups than those in the control group. The serum levels of Cys-C, MHR, and UA were significantly higher in the CHD + HF group than those in the CHD or HF group. The ROC curve analysis showed that serum Cys-C, MHR, and UA had good diagnostic performance for CHD and HF, with areas under the curve ranging from 0.78 to 0.93. The optimal cutoff values of serum Cys-C, MHR, and UA for diagnosing CHD, HF, and CHD+HF were 1.2 mg/L, 0.9 × 109, and 389 µmol/L; 1.4 mg/L, 1.0 × 109, and 449 µmol/L; and 1.6 mg/L, 1.1 × 109, and 508 µmol/L, respectively. CONCLUSION: Serum Cys-C, MHR, and UA are useful biomarkers for diagnosing CHD and HF, and CHD+HF. These can provide information for decision-making and risk stratification in patients with CHD and HF.

Optimizing Prediction of In-Hospital Mortality in Elderly Patients With Acute Myocardial Infarction: A Nomogram Approach Using the Age-Adjusted Charlson Comorbidity Index Score.

BACKGROUND: To study the age-adjusted Charlson comorbidity index (ACCI) scale, which is a comprehensive quantification of multimorbidity coexistence, for the assessment of the risk of acute myocardial infarction death in elderly people. METHODS AND RESULTS: A total of 502 older patients with acute myocardial infarction were studied at Qilu Hospital from September 2017 to March 2022. They were categorized on the basis of ACCI into low (≤5), intermediate (6, 7), and high (≥8) risk groups. Hospitalization duration was observed, with death as the end point. least absolute shrinkage and selection operator regression was used to screen variables, 10-fold cross-validation was performed to validate the screened variables, a Cox regression nomogram predicting the risk of patient death was prepared, hazard ratio with 95% CI was calculated, a nomogram calibration curve was constructed, and a receiver operating characteristic curve, decision curve analysis, and a clinical impact curve were established. From 62 potential factors in a least absolute shrinkage and selection operator regression, 12 were selected via 10-fold cross-validation. Retain variables with significant statistical differences in the Cox regression. A nomogram of the risk of death from acute infarction was constructed, and risk factors included ventricular tachycardia/fibrillation, atrial fibrillation, nicorandil, angiotensin-converting enzyme inhibitors/angiotensin-converting enzyme inhibitors, ß blockers, and ACCI score, carbon dioxide combining power, and blood calcium concentration. CONCLUSIONS: The ACCI score effectively assesses multimorbidity in the older patients. As ACCI rises, the death risk from acute myocardial infarction grows. The study's nomogram is valid and clinically applicable.

eIF6 Promotes Gastric Cancer Proliferation and Invasion by Regulating Cell Cycle.

OBJECTIVE: To investigate the role and function of eIF6 in gastric cancer (GC). METHODS: The expression level of eIF6 in GC tissues and normal tissues was detected in different high-throughput sequencing cohorts. Survival analysis, gene differential analysis, and enrichment analysis were performed in the TCGA cohort. Biological networks centered on eIF6 were constructed through two different databases. Immunohistochemistry (IHC) and Western blot were used to detect protein expression of eIF6, and qRT-PCR was used to detect eIF6 mRNA expression. The correlation between the expression of eIF6 in GC tissues and clinicopathological parameters of GC was analyzed. siRNA knockout of eIF6 was used to study the proliferation, migration, and invasion. The effects of eIF6 on cell cycle and Cyclin B1 were detected by flow cytometry and Western blot. RESULTS: eIF6 was significantly overexpressed in GC tissues and predicted poor prognosis. In addition, 113 differentially expressed genes were detected in cancer-related biological pathways and functions by differential analysis. Biological networks revealed interactions of genes and proteins with eIF6. The expression intensity of eIF6 in cancer tissues was higher than that in adjacent tissues (P = 0.0001), confirming the up-regulation of eIF6 expression in GC tissues. The expression level of eIF6 was statistically significant with pTNM stage (P = 0.006). siRNA knockout of eIF6 significantly reduced the proliferation, colony formation, migration, and invasion ability of GC cells. Silencing of eIF6 also inhibited the cell cycle of GC cells in G2/M phase and decreased the expression level of CyclinB1. CONCLUSION: Our study suggests that eIF6 is up-regulated in GC and may promote the proliferation, migration, and invasion of GC by regulating cell cycle.

Aggravating effect of abnormal low-density protein cholesterol level on coronary atherosclerotic plaque in type 2 diabetes mellitus patients assessed by coronary computed tomography angiography.

BACKGROUND: The abnormal low-density protein cholesterol (LDL-C) level in the development of atherosclerosis is often comorbid in individuals with type 2 diabetes mellitus(T2DM). This study aimed to investigate the aggravating effect of abnormal LDL-C levels on coronary artery plaques assessed by coronary computed tomography angiography (CCTA) in T2DM. MATERIALS AND METHODS: This study collected 3439 T2DM patients from September 2011 to February 2022. Comparative analysis of differences in coronary plaque characteristics was performed for the patients between the normal LDL-C level group and the abnormal LDL-C level group. Factors with P < 0.1 in the univariable linear regression analyses were included in the multivariable linear stepwise regression. RESULTS: A total of 2820 eligible T2DM patients were included and identified as the normal LDL-C level group (n = 973) and the abnormal LDL-C level group (n = 1847). Compared with the normal LDL-C level group, both on a per-patient basis and per-segment basis, patients with abnormal LDL-C level showed more calcified plaques, partially calcified plaques, low attenuation plaques, positive remodellings, and spotty calcifications. Multivessel obstructive disease (MVD), nonobstructive stenosis (NOS), obstructive stenosis (OS), plaque involvement degree (PID), segment stenosis score (SSS), and segment involvement scores (SIS) were likely higher in the abnormal LDL-C level group than that in the normal LDL-C level group (P < 0.001). In multivariable linear stepwise regression, the abnormal LDL-C level was validated as an independent positive correlation with high-risk coronary plaques and the degree and extent of stenosis caused by plaques (low attenuation plaque: ß = 0.116; positive remodelling: ß = 0.138; spotty calcification: ß = 0.091; NOS: ß = 0.427; OS: ß = 0.659: SIS: ß = 1.114; SSS: ß = 2.987; PID: ß = 2.716, all P value < 0.001). CONCLUSIONS: Abnormal LDL-C levels aggravate atherosclerotic cardiovascular disease (ASCVD) in patients with T2DM. Clinical attention deserves to be caught by the tailored identification of cardiovascular risk categories in T2DM individuals and the achievement of the corresponding LDL-C treatment goal.

Senescent endothelial cells promote liver metastasis of uveal melanoma in single-cell resolution.

BACKGROUND: Uveal melanoma (UM), the most common adult intraocular tumor, is characterized by high malignancy and poor prognosis in advanced stages. Angiogenesis is critical for UM development, however, not only the role of vascular endothelial dysfunction in UM remains unknown, but also their analysis at the single-cell level has been lacking. A comprehensive analysis is essential to clarify the role of the endothelium in the development of UM. METHODS: By using single-cell RNA transcriptomics data of 11 cases of primary and liver metastasis UM, we analyzed the endothelial cell status. In addition, we analyzed and validated ECs in the in vitro model and collected clinical specimens. Subsequently, we explored the impact of endothelial dysfunction on UM cell migration and explored the mechanisms responsible for the endothelial cell abnormalities and the reasons for their peripheral effects. RESULTS: UM metastasis has a significantly higher percentage of vascular endothelial cells compared to in situ tumors, and endothelial cells in metastasis show significant senescence. Senescent endothelial cells in metastatic tumors showed significant Krüppel-like factor 4 (KLF4) upregulation, overexpression of KLF4 in normal endothelial cells induced senescence, and knockdown of KLF4 in senescent endothelium inhibited senescence, suggesting that KLF4 is a driver gene for endothelial senescence. KLF4-induced endothelial senescence drove tumor cell migration through a senescence-associated secretory phenotype (SASP), of which the most important component of the effector was CXCL12 (C-X-C motif chemokine ligand 12), and participated in the composition of the immunosuppressive microenvironment. CONCLUSION: This study provides an undesirable insight of senescent endothelial cells in promoting UM metastasis.

Elevated expression of ECT2 as a diagnostic marker and prognostic indicator in endometrial cancer.

OBJECTIVES: The study aimed to investigate the genes linked with the progression of Endometrial cancer (EC) and discover promising new biomarkers for early detection. METHODS: Based on the analysis of differentially expressed genes (DEGs), Series test of cluster (STC) and protein-protein interaction, potential hub genes involved in EC development were identified. The expression pattern, prognostic value, and diagnostic potential of ECT2 were investigated using clinical samples. RESULTS: The DEGs showing an upward trend were significantly enriched in cancer-related processes and pathways. Through validations conducted across additional databases, eight potential hub genes for EC were identified: ASPM, ATAD2, BUB1B, ECT2, KIF14, NUF2, NCAPG, and SPAG5. Particularly, ECT2 exhibited the highest diagnostic efficacy. The expression levels of ECT2 varied significantly across different clinical stages, pathological grades, and metastasis statuses in UCEC. ECT2 mRNA was upregulated in the p53abn group, indicating a poorer prognosis, while it was lower in the MMRd and NSMP groups, indicating a moderate prognosis. In clinical samples, ECT2 showed an increasing trend from normal endometria and endometrial hyperplasia without atypia (EH) to atypical endometrial hyperplasia (AH) and EC. ECT2 effectively distinguished between Normal/EH and AH/EC. Patients with high expression of ECT2 had a more unfavourable prognosis. CONCLUSIONS: The expression of ECT2 is significantly increased in cases of AH and EC. It has shown impressive accuracy in distinguishing between non-malignant and malignant endometria. These findings suggest that ECT2 has the potential to serve as a valuable biomarker for diagnosing endometrial neoplasia and as a prognostic indicator in EC.

Efficient removal of Chromium(VI) from wastewater based on magnetic multiwalled carbon nanotubes coupled with deep eutectic solvents.

Industrial wastewater containing heavy metal Cr(VI) seriously affects the health of organisms and may even lead to cancer. Developing efficient adsorbents that can quickly separate heavy metals is crucial for treating wastewater. In this study, magnetic multiwalled carbon nanotubes (MMWCNTs) with moderate particle size and abundant surface active sites were prepared by coating multiwalled carbon nanotubes with magnetic nanoparticles. The results of FTIR, XRD, TG, VSM, BET, and EDS showed MWCNTs completely encapsulated on the surface of the magnetic nanoparticles, with a particle size of approximately 30 nm. Oxygenated groups provided abundant surface active sites and formed numerous mesopores. The response surface methodology was used to optimize the adsorbent dose, adsorption contact time and adsorption temperature, and the removal rate of Cr(VI) was more than 95%. The quasi-second order kinetics and Freundlich adsorption isotherm model explained the adsorption process to Cr(VI). MMWCNTs interacted with Cr(VI) through electrostatic attraction, reduction reactions, complexation, and other means. The extensive hydrogen bonding of the green solvent deep eutectic solvent (DES) was employed to desorb the MMWCNTs and desorption rate exceed 90%. Even after five adsorption-regeneration cycles, the adsorbent maintained a high capacity. In conclusion, these novel MMWCNTs, as efficient adsorbents paired with DES desorption, hold broad potential for application in the treatment of Cr(VI)-contaminated wastewater.

Multi-omics analysis in IgM monoclonal gammopathies reveals epigenetic influence on oncogenesis via DNA methylation.

Currently, the role of DNA methylation in the IgM-monoclonal gammopathy disease spectrum remains poorly understood. In the present study, a multi-omics prospective analysis was conducted integrating DNA methylation, RNA-seq and WES data in 34 subjects [23 WM, 6 IgM-MGUS, 5 normal controls]. Analysis was focused on defining differences between IgM-gammopathies (WM/IgM-MGUS) compared to controls, and specifically between WM and IgM-MGUS. Between groups, genome-wide DNA methylation analysis demonstrated a significant number of differentially methylated regions which were annotated according to genomic region. Next, integration of RNA-seq data was performed to identify potentially epigenetically deregulated pathways. We found that pathways involved in cell cycle, metabolism, cytokine/immune signaling, cytoskeleton, tumor microenvironment, and intracellular signaling were differentially activated and potentially epigenetically regulated. Importantly, there was a positive enrichment of CXCR4 signaling pathway along with several interleukin (IL-6, IL-8, IL15) signaling pathways in WM compared to IgM-MGUS. Further assessment of known tumor suppressor genes and oncogenes uncovered differential promoter methylation of several targets with concordant change in gene expression, including CCND1 and CD79B. Overall, this report defines how aberrant DNA methylation in IgM-gammopathies may play a critical role in the epigenetic control of oncogenesis and key cellular functions.

Glutathione-activated biotin-targeted dual-modal imaging probe with improved PDT/PTT synergistic therapy.

BACKGROUND: Glutathione (GSH), a highly abundant thiol compound within cells, plays a critical role in physiological processes and exhibits close correlation with cancer. Among molecular imaging technologies, most probes have relatively short emission wavelengths and lack photoacoustic imaging (PA) capability, resulting in the inability to obtain tissue images with high penetration depth. The presence of GSH in the tumor microenvironment neutralizes ROS, diminishing the therapeutic effect of PDT, thus resulting in often unsatisfactory therapeutic efficacy. Therefore, it is imperative to develop a dual-modal probe for the detection of GSH and the diagnosis and treatment of cancer. RESULTS: In this study, we synthesized a novel dual-modal probe, Cy-Bio-GSH, utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging techniques for GSH detection. The probe integrates cyanine dye as the fluorophore, nitroazobenzene as the recognition moiety, and biotin as the tumor-targeting moiety. Upon reacting with GSH, the probe emits NIR fluorescence at 820 nm and generates a PA signal. Significantly, this reaction activates the photodynamic and photothermal properties of the probe. By depleting GSH and employing a synergistic photothermal therapy (PTT) treatment, the therapeutic efficacy of photodynamic therapy (PDT) is remarkably enhanced. In-vivo experiments confirm the capability of the probe to detect GSH via NIRF and PA imaging. Notably, the combined tumor-targeting ability and PDT/PTT synergistic therapy enhance therapeutic outcomes for tumors and facilitate their ablation. SIGNIFICANCE: A novel tumor-targeting and dual-modal imaging probe (Cy-Bio-GSH) is synthesized, exhibiting remarkable sensitivity and selectivity to GSH, enabling the visualization of GSH in cells and the differentiation between normal and cancer cells. Cy-Bio-GSH enhances PDT/PTT with effective killing of cancer cells and makes the ablation of tumors in mice. This work represents the first tumor-targeting probe for GSH detection, and provides crucial tool for cancer diagnosis and treatment by dual-modal imaging with improved PDT/PTT synergistic therapy.

Comparison of an Affibody-based Molecular Probe and 18F-FDG for Detecting HER2-Positive Breast Cancer at PET/CT.

Background Human epidermal growth factor receptor 2 (HER2) affibody-based tracers could be an alternative to nonspecific radiotracers for noninvasive detection of HER2 expression in breast cancer lesions at PET/CT. Purpose To compare an affibody-based tracer, Al18F-NOTA-HER2-BCH, and fluorine 18 (18F) fluorodeoxyglucose (FDG) for detecting HER2-positive breast cancer lesions on PET/CT images. Materials and Methods In this prospective study conducted from June 2020 to July 2023, participants with HER2-positive breast cancer underwent both Al18F-NOTA-HER2-BCH and 18F-FDG PET/CT. HER2 positivity was confirmed with pathologic assessment (immunohistochemistry test results of 3+, or 2+ followed by fluorescence in situ hybridization, indicated HER2 amplification). Two independent readers visually assessed the uptake of tracers on images. Lesion uptake was quantified using the maximum standardized uptake value (SUVmax) and target to background ratio (TBR) and compared using a general linear mixed model. Results A total of 42 participants (mean age, 56.3 years ± 10.1 [SD]; 41 female) with HER2-positive breast cancer were included; 42 (100%) had tumors that were detected with Al18F-NOTA-HER2-BCH PET/CT and 40 (95.2%) had tumors detected with 18F-FDG PET/CT. Primary tumors in two of 21 participants, lymph node metastases in four of 21 participants, bone metastases in four of 15 participants, and liver metastases in three of nine participants were visualized only with Al18F-NOTA-HER2-BCH. Lung metastasis in one of nine participants was visualized only with 18F-FDG. Al18F-NOTA-HER2-BCH enabled depiction of more suspected HER2-positive primary tumors (26 vs 21) and lymph node (170 vs 130), bone (92 vs 66), and liver (55 vs 27) metastases than 18F-FDG. The SUVmax and TBR values of primary tumors and lymph node, bone, and liver metastases were all higher on Al18F-NOTA-HER2-BCH images than on 18F-FDG images (median SUVmax range, 10.4-13.5 vs 3.4-6.2; P value range, <.001 to .02; median TBR range, 2.7-17.6 vs 1.2-7.8; P value range, <.001 to .001). No evidence of differences in the SUVmax and TBR for chest wall or lung metastases was observed between Al18F-NOTA-HER2-BCH and 18F-FDG (P value range, .06 to .53). Conclusion PET/CT with the affibody-based tracer Al18F-NOTA-HER2-BCH enabled detection of more primary lesions and lymph node, bone, and liver metastases than PET/CT using 18F-FDG. ClinicalTrials.gov Identifier: NCT04547309 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Ulaner in this issue.

Preclinical Evaluation and Pilot Clinical Study of 18F-Labeled Inhibitor Peptide for Noninvasive Positron Emission Tomography Mapping of Angiotensin Converting Enzyme 2.

Angiotensin-converting enzyme 2 (ACE2) is the main molecular target for coronavirus SARS-CoV-2 to enter cells. Molecularly specific tracers that bind to ACE2 with high affinity can be used to determine the tissue distribution of this important receptor, noninvasively. A novel targeting PET imaging probe, [18F]AlF-DX600-BCH, was developed to detect the in vivo expression of ACE2 and monitor response to therapy. Preclinical experiments, including biodistribution, PET imaging, and tissue section analysis, were conducted after tests of in vitro and in vivo stability and pharmacokinetics. The agent was advanced to clinical evaluation in 10 volunteers who received [18F]AlF-DX600-BCH PET/CT at 1 and 2 h after injection (NCT04542863). Preclinical results of both biodistribution and PET demonstrated [18F]AlF-DX600-BCH accumulation in rat kidney (standardized uptake value; SUVkidney/normal > 50), along with specific uptake in testes (SUVtestis/normal > 10) tissues. Kidney, gastrointestinal, and bronchial cell labeling were correlated to ACE2 positive by immunohistochemistry (IHC) staining. In clinical imaging, significant tracer accumulation was predominantly observed in the urinary and reproductive system (SUVrenal cortex = 32.00, SUVtestis = 4.56), and the conjunctiva and nasal mucosa saw elevated uptake in several cases. This work is the first report of a radioisotope probe, [18F]AlF-DX600-BCH, targeting ACE2 with promising preliminary preclinical and translational outlook, thereby demonstrating the potential of noninvasive mapping of ACE2.

Responses of Soil C, N, P and Enzyme Activities to Biological Soil Crusts in China: A Meta-Analysis.

Biological soil crusts (BSCs) are often referred to as the "living skin" of arid regions worldwide. Yet, the combined impact of BSCs on soil carbon (C), nitrogen (N), phosphorus (P), and enzyme activities remains not fully understood. This study identified, screened and reviewed 71 out of 2856 literature sources to assess the responses of soil C, N, P and enzyme activity to BSCs through a meta-analysis. The results indicated that BSC presence significantly increased soil C, N, P and soil enzyme activity, and this increasing effect was significantly influenced by the types of BSCs. Results from the overall effect showed that soil organic carbon (SOC), total nitrogen (TN), available nitrogen (AN), total phosphorus (TP), and available phosphorus (AP) increased by 107.88%, 84.52%, 45.43%, 27.46%, and 54.71%, respectively, and four soil enzyme activities (Alkaline Phosphatase, Cellulase, Sucrase, and Urease) increased by 93.65-229.27%. The highest increases in SOC, TN and AN content occurred in the soil covered with lichen crusts and moss crusts, and significant increases in Alkaline Phosphatase and Cellulase were observed in the soil covered with moss crusts and mixed crusts, suggesting that moss crusts can synergistically enhance soil C and N pool and enzyme activity. Additionally, variations in soil C, N, P content, and enzyme activity were observed under different environmental settings, with more pronounced improvements seen in coarse and medium-textured soils compared to fine-textured soils, particularly at a depth of 5 cm from the soil surface. BSCs in desert ecosystems showed more significant increases in SOC, TN, AN, and Alkaline Phosphatase compared to forest and grassland ecosystems. Specifically, BSCs at low altitude (≤500 m) with an annual average rainfall of 0-400 mm and an annual average temperature ≤ 10 °C were the most conducive to improving soil C, N, and P levels. Our results highlight the role of BSCs and their type in increasing soil C, N, P and enzyme activities, with these effects significantly impacted by soil texture, ecosystem type, and climatic conditions. The implications of these findings are crucial for soil enhancement, ecosystem revitalization, windbreak, and sand stabilization efforts in the drylands of China.

Type 2 diabetes mellitus aggravates coronary atherosclerosis in hypertensive individuals based on coronary CT angiography: a retrospective propensity score-based study.

Background: The effect of type 2 diabetes mellitus (T2DM) on coronary atherosclerosis detected on coronary computed tomography angiography (CCTA) in hypertensive patients has attracted increasing attention. This study investigated the relationships of T2DM with coronary artery plaque characteristics and semiquantitative CCTA scores in hypertensive patients. Materials and methods: In this single-center study, 1,700 hypertensive patients, including 850 T2DM [HT(T2DM+)] and 850 non-T2DM [HT(T2DM-)] individuals, were retrospectively analyzed after propensity matching. Plaque type, extent, coronary stenosis, segment involvement score (SIS), segment stenosis score (SSS), and CT-based Leaman score (CT-LeSc) based on CCTA were assessed and compared between the two groups. Results: HT(T2DM+) patients had more coronary segments with calcified plaque (2.08 ± 2.20 vs. 1.40 ± 1.91), mixed plaque (2.90 ± 2.87 vs. 2.50 ± 2.66), nonobstructive stenosis (4.23 ± 2.44 vs. 3.62 ± 2.42), and obstructive stenosis (1.22 ± 2.18 vs. 0.78 ± 1.51), a lower proportion of 1-vessel disease (15.3% vs. 25.5%), a higher proportion of 3-vessel disease (59.6% vs. 46.7%), and higher SIS (5.5 ± 3.1 vs. 4.4 ± 3.0), SSS (10.3 ± 8.5 vs. 7.7 ± 7.1), and CT-LeSc (9.4 ± 5.6 vs. 7.9 ± 5.2) than HT(T2DM-) patients (all P-values <0.05). Multivariable analysis revealed that T2DM was an independent risk factor for calcified plaque [odds ratio (OR) = 2.213], obstructive coronary artery disease (CAD) (OR = 1.271), multivessel disease (OR = 1.838), SIS > 4 (OR = 1.910), SSS > 6 (OR = 1.718), and CT-LeSc > 5 (OR = 1.584) in hypertension population (all P-values <0.05). Conclusion: T2DM was independently associated with the presence of calcified coronary artery plaque and increased the risk of obstructive CAD, multivessel disease, and CT-LeSc > 5 in hypertensive patients. More attention should be given to the assessment and management for coronary atherosclerosis in hypertensive patients with T2DM, as this population may have a higher risk of cardiovascular events.

Breast metastasis from lung adenocarcinoma: a case report and review of the literature.

Lung cancer (LC) is one of the most lethal and most prevalent malignant tumors, and lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer. Breast cancer (BC) is the most common cancer worldwide, but metastases to the breast from extramammary neoplasms are rare, especially from the lung. Early diagnosis and differentiation of primary from metastatic breast carcinoma are essential. Here, we present a case of metastases to the breast from lung adenocarcinoma, the treatment options varied according to disease progression.

Enantioselective synthesis of chiral amides by carbene insertion into amide N-H bond.

Chiral amides are important structure in many natural products and pharmaceuticals, yet their efficient synthesis from simple amide feedstock remains challenge due to its weak Lewis basicity. Herein, we describe our study of the enantioselective synthesis of chiral amides by N-alkylation of primary amides taking advantage of an achiral rhodium and chiral squaramide co-catalyzed carbene N-H insertion reaction. This method features mild condition, rapid reaction rate (in all cases 1 min) and a wide substrate scope with high yield and excellent enantioselectivity. Further product transformations show the synthetic potential of this reaction. Mechanistic studies reveal that the non-covalent interactions between the catalyst and reaction intermediate play a critical role in enantiocontrol.

Transforming crystal structures of cobalt molybdate to generate electron-rich sites for electrochemical detection of Pb(II).

BACKGROUND: Most of the investigations on distinct crystal structures of catalysts are individually focused on the difference of surface functional groups or adsorption properties, but rarely explore the changes of active sites to affect the electrocatalytic performance. Catalysts with diverse crystal structures had been applied to modified electrodes in different electrocatalytic reactions. However, there is currently a lack of an essential understanding for the role of real active sites in catalysts with crystalline structures in electroanalysis, which is crucial for designing highly sensitive sensing interfaces. RESULTS: Herein, cobalt molybdate with divergent crystal structures (α-CoMoO4 and ß-CoMoO4) were synthesized by adjusting the calcination temperature, indicating that α-CoMoO4 (800 °C) (60.00 µA µM-1) had the highest catalytic ability than ß-CoMoO4 (700 °C) (38.68 µA µM-1) and α-CoMoO4 (900 °C) (29.55 µA µM-1) for the catalysis of Pb(II). It was proved that the proportion of Co(II) and Mo(IV) as electron-rich sites in α-CoMoO4 (800 °C) were higher than ß-CoMoO4 (700 °C) and α-CoMoO4 (900 °C), possessing more electrons to participate in the valence cycles of Co(II)/Co(III) and Mo(IV)/Mo(VI) to boost the catalytic reduction of Pb(II). Specifically, Co(II) transferred a part of electrons to Mo(VI), promoting the formation of Mo(IV). Co(II) and Mo(IV), as the electron-rich sites, providing electrons to Pb(II), further accelerating the conversion of Pb(II) into Pb(0). SIGNIFICANCE: In the process of detecting Pb(II), the CoMoO4 structures under different temperatures have distinct content of electron-rich sites Co(II) and Mo(IV). α-CoMoO4 (800 °C), with the highest content are benefited to detect Pb(II). This work is conducive to understanding the effect of the changes of active sites resulting from crystal transformation on the electrocatalytic performance, and provides a way to construct sensitive electrochemical interfaces of distinct active sites.

Fine hippocampal morphology analysis with a multi-dataset cross-sectional study on 2911 subjects.

CA1 subfield and subiculum of the hippocampus contain a series of dentate bulges, which are also called hippocampus dentation (HD). There have been several studies demonstrating an association between HD and brain disorders. Such as the number of hippocampal dentation correlates with temporal lobe epilepsy. And epileptic hippocampus have a lower number of dentation compared to contralateral hippocampus. However, most studies rely on subjective assessment by manual searching and counting in HD areas, which is time-consuming and labor-intensive to process large amounts of samples. And to date, only one objective method for quantifying HD has been proposed. Therefore, to fill this gap, we developed an automated and objective method to quantify HD and explore its relationship with neurodegenerative diseases. In this work, we performed a fine-scale morphological characterization of HD in 2911 subjects from four different cohorts of ADNI, PPMI, HCP, and IXI to quantify and explore differences between them in MR T1w images. The results showed that the degree of right hippocampal dentation are lower in patients with Alzheimer's disease than samples in mild cognitive impairment or cognitively normal, whereas this change is not significant in Parkinson's disease progression. The innovation of this paper that we propose a quantitative, robust, and fully automated method. These methodological innovation and corresponding results delineated above constitute the significance and novelty of our study. What's more, the proposed method breaks through the limitations of manual labeling and is the first to quantitatively measure and compare HD in four different brain populations including thousands of subjects. These findings revealed new morphological patterns in the hippocampal dentation, which can help with subsequent fine-scale hippocampal morphology research.

Assessment of subclinical LV myocardial dysfunction in T2DM patients with diabetic peripheral neuropathy: a cardiovascular magnetic resonance study.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most prevalent complication of diabetes, and has been demonstrated to be independently associated with cardiovascular events and mortality. This aim of this study was to investigate the subclinical left ventricular (LV) myocardial dysfunction in type 2 diabetes mellitus (T2DM) patients with and without DPN. METHODS: One hundred and thirty T2DM patients without DPN, 61 patients with DPN and 65 age and sex-matched controls who underwent cardiovascular magnetic resonance (CMR) imaging were included, all subjects had no symptoms of heart failure and LV ejection fraction ≥ 50%. LV myocardial non-infarct late gadolinium enhancement (LGE) was determined. LV global strains, including radial, circumferential and longitudinal peak strain (PS) and peak systolic and diastolic strain rates (PSSR and PDSR, respectively), were evaluated using CMR feature tracking and compared among the three groups. Multivariable linear regression analyses were performed to determine the independent factors of reduced LV global myocardial strains in T2DM patients. RESULTS: The prevalence of non-infarct LGE was higher in patients with DPN than those without DPN (37.7% vs. 19.2%, p = 0.008). The LV radial and longitudinal PS (radial: 36.60 ± 7.24% vs. 33.57 ± 7.30% vs. 30.72 ± 8.68%; longitudinal: - 15.03 ± 2.52% vs. - 13.39 ± 2.48% vs. - 11.89 ± 3.02%), as well as longitudinal PDSR [0.89 (0.76, 1.05) 1/s vs. 0.80 (0.71, 0.93) 1/s vs. 0.77 (0.63, 0.87) 1/s] were decreased significantly from controls through T2DM patients without DPN to patients with DPN (all p < 0.001). LV radial and circumferential PDSR, as well as circumferential PS were reduced in both patient groups (all p < 0.05), but were not different between the two groups (all p > 0.05). Radial and longitudinal PSSR were decreased in patients with DPN (p = 0.006 and 0.003, respectively) but preserved in those without DPN (all p > 0.05). Multivariable linear regression analyses adjusting for confounders demonstrated that DPN was independently associated with LV radial and longitudinal PS (ß = - 3.025 and 1.187, p = 0.014 and 0.003, respectively) and PDSR (ß = 0.283 and - 0.086, p = 0.016 and 0.001, respectively), as well as radial PSSR (ß = - 0.266, p = 0.007). CONCLUSIONS: There was more severe subclinical LV dysfunction in T2DM patients complicated with DPN than those without DPN, suggesting further prospective study with more active intervention in this cohort of patients.

Impact of Functional Mitral Regurgitation on Left Ventricular Strain in Nonischemic Dilated Cardiomyopathy Patients with Type 2 Mellitus Diabetes: A Magnetic Resonance Feature Tracking Study.

BACKGROUND: The impact of functional mitral regurgitation and type 2 mellitus diabetes (T2DM) on left ventricular (LV) strain in nonischemic dilated cardiomyopathy (NIDCM) patients remains unclear. PURPOSE: To evaluate the impact of mitral regurgitation severity on LV strain, and explore additive effect of T2DM on LV function across varying mitral regurgitation severity levels in NIDCM patients. STUDY TYPE: Retrospective. POPULATION: 352 NIDCM (T2DM-) patients (49.1 ± 14.6 years, 67% male) (207, 85, and 60 no/mild, moderate, and severe mitral regurgitation) and 96 NIDCM (T2DM+) patients (55.2 ± 12.4 years, 77% male) (47, 30, and 19 no/mild, moderate, and severe mitral regurgitation). FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession sequence. ASSESSMENT: LV geometric parameters and strain were measured and compared among groups. Determinants of LV strain were investigated. STATISTICAL TEST: Student's t-test, Mann-Whitney U test, one-way ANOVA, Kruskal-Wallis test, univariable and multivariable linear regression. P < 0.05 was considered statistically significant. RESULTS: LV GLPS and longitudinal PDSR decreased gradually with increasing mitral regurgitation severity in NIDCM patients with T2DM(GLPS: -5.7% ± 2.1% vs. -4.3% ± 1.6% vs. -2.6% ± 1.3%; longitudinal PDSR:0.5 ± 0.2 sec-1 vs. 0.4 ± 0.2 sec-1 vs. 0.3 ± 0.1 sec-1). NIDCM (T2DM+) demonstrated decreased GCPS and GLPS in the no/mild subgroup, reduced LV GCPS, GLPS, and longitudinal PDSR in the moderate subgroup, and reduced GRPS, GCPS, GLPS, and longitudinal PDSR in the severe subgroup compared with NIDCM (T2DM-) patients. Multivariable regression analysis identified that mitral regurgitation severity (ß = -0.13, 0.15, and 0.25 for GRPS, GCPS, and GLPS) and the presence of T2DM (ß = 0.14 and 0.13 for GCPS and GLPS) were independent determinants of LV strains in NIDCM patients. DATA CONCLUSION: Increased mitral regurgitation severity is associated with reduced LV strains in NIDCM patients with T2DM. The presence of T2DM exacerbated the decline of LV function across various mitral regurgitation levels in NIDCM patients, resulting in reduced LV strains. TECHNICAL EFFICACY: Stage 3.