Precise GDP Spatialization and Analysis in Built-Up Area by Combining the NPP-VIIRS-like Dataset and Sentinel-2 Images.

Spatialization and analysis of the gross domestic product of second and tertiary industries (GDP23) can effectively depict the socioeconomic status of regional development. However, existing studies mainly conduct GDP spatialization using nighttime light data; few studies specifically concentrated on the spatialization and analysis of GDP23 in a built-up area by combining multi-source remote sensing images. In this study, the NPP-VIIRS-like dataset and Sentinel-2 multi-spectral remote sensing images in six years were combined to precisely spatialize and analyze the variation patterns of the GDP23 in the built-up area of Zibo city, China. Sentinel-2 images and the random forest (RF) classification method based on PIE-Engine cloud platform were employed to extract built-up areas, in which the NPP-VIIRS-like dataset and comprehensive nighttime light index were used to indicate the nighttime light magnitudes to construct models to spatialize GDP23 and analyze their change patterns during the study period. The results found that (1) the RF classification method can accurately extract the built-up area with an overall accuracy higher than 0.90; the change patterns of built-up areas varied among districts and counties, with Yiyuan county being the only administrative region with an annual expansion rate of more than 1%. (2) The comprehensive nighttime light index is a viable indicator of GDP23 in the built-up area; the fitted model exhibited an R2 value of 0.82, and the overall relative errors of simulated GDP23 and statistical GDP23 were below 1%. (3) The year 2018 marked a significant turning point in the trajectory of GDP23 development in the study area; in 2018, Zhoucun district had the largest decrease in GDP23 at -52.36%. (4) GDP23 gradation results found that Zhangdian district exhibited the highest proportion of high GDP23 (>9%), while the proportions of low GDP23 regions in the remaining seven districts and counties all exceeded 60%. The innovation of this study is that the GDP23 in built-up areas were first precisely spatialized and analyzed using the NPP-VIIRS-like dataset and Sentinel-2 images. The findings of this study can serve as references for formulating improved city planning strategies and sustainable development policies.

Association between TyG index and long-term prognosis of patients with ST-segment elevated myocardial infarction undergoing percutaneous coronary intervention: a retrospective cohort study.

OBJECTIVE: To assess the association between the serum triglyceride-glucose product index (TyG index) and the risk for all-cause mortality in patients with ST-segment elevated myocardial infarction (STEMI). DESIGN: Retrospective. SETTING AND PARTICIPANTS: This retrospective study included 896 patients with STEMI who underwent percutaneous coronary intervention (PCI) at a comprehensive university-affiliated hospital between January 2016 and January 2019. METHODS: Patients were equally divided into quartiles (Q1, Q2, Q3 and Q4 group) according to TyG index values. PRIMARY ENDPOINT: All-cause mortality. RESULTS: After a median follow-up of 3 years, 108 (17.1%) patients died. TyG index was independently associated with increased all-cause mortality (OR, 1.39; 95% CI, 1.22 to 1.58) after adjusting for age, sex, low-density lipoprotein cholesterol (LDL-c), cardiac troponin I, B-type natriuretic peptide, delayed PCI, post-PCI complications, medication and left ventricular ejection fraction. The adjusted OR was 1.31 (95% CI, 0.62 to 2.77) for Q2, 2.12 (95% CI, 1.01 to 4.53) for Q3 and 4.02 (95% CI, 1.90 to 8.78) for Q4 compared with the lowest quartile (Q1) (p for trend<0.001). In the restricted cubic spline regression model, the relationship between the TyG index and the risk of all-cause mortality was linear (p for non-linear=0.575). Each unit increase in the TyG index was associated with a 68% increase in the multivariate risk for all-cause mortality (OR 1.68; 95% CI, 1.20 to 2.38). In the subgroup analysis, there was an interaction between LDL-c and the TyG index on the risk of all-cause mortality (p for interaction=0.007). CONCLUSION: The TyG index was significantly associated with the long-term all-cause mortality among patients with STEMI who underwent PCI.

Role of LRP5/6/GSK-3ß/ß-catenin in the differences in exenatide- and insulin-promoted T2D osteogenesis and osteomodulation.

BACKGROUND AND PURPOSE: Insulin and exenatide are two hypoglycaemic agents that exhibit different osteogenic effects. This study compared the differences between exenatide and insulin in osseointegration in a rat model of Type 2 diabetes (T2D) and explored the mechanisms promoting osteogenesis in this model of T2D. EXPERIMENTAL APPROACH: In vivo, micro-CT was used to detect differences in the peri-implant bone microstructure in vivo. Histology, dual-fluorescent labelling, immunofluorescence and immunohistochemistry were used to detect differences in tissue, cell and protein expression around the implants. In vitro, RT-PCR and western blotting were used to measure the expression of osteogenesis- and Wnt signalling-related genes and proteins in bone marrow mesenchymal stromal cells (BMSCs) from rats with T2D (TBMSCs) after PBS, insulin and exenatide treatment. RT-PCR was used to detect the expression of Wnt bypass cascade reactions under Wnt inactivation. KEY RESULTS: Micro-CT and section staining showed exenatide extensively promoted peri-implant osseointegration. Both in vivo and in vitro experiments showed exenatide substantially increased the expression of osteogenesis-related and activated the LRP5/6/GSK-3ß/ß-catenin-related Wnt pathway. Furthermore, exenatide suppressed expression of Bmpr1a to inhibit lipogenesis and promoted expression of Btrc to suppress inflammation. CONCLUSION AND IMPLICATIONS: Compared to insulin, exenatide significantly improved osteogenesis in T2D rats and TBMSCs. In addition to its dependence on LRP5/6/GSK-3ß/ß-catenin signalling for osteogenic differentiation, exenatide-mediated osteomodulation also involves inhibition of inflammation and adipogenesis by BMPR1A and ß-TrCP, respectively.

SDH, a novel diarylheptane compound, alleviates dextran sulfate sodium (DSS)-induced colitis by reducing Th1/Th2/Th17 induction and regulating the gut microbiota in mice.

Ulcerative colitis, a chronic inflammatory condition affecting the rectum and colon to varying degrees, is linked to a dysregulated immune response and the microbiota. Sodium (aS,9R)-3-hydroxy-16,17-dimethoxy-15-oxidotricyclo[12.3.1.12,6]nonadeca-1(18),2,4,6(19),14,16-hexene-9-yl sulfate hydrate (SDH) emerges as a novel diarylheptane compound aimed at treating inflammatory bowel diseases. However, the mechanisms by which SDH modulates these conditions remain largely unknown. In this study, we assessed SDH's impact on the clinical progression of dextran sodium sulfate (DSS)-induced ulcerative colitis. Our results demonstrated that SDH significantly mitigated the symptoms of DSS-induced colitis, reflected in reduced disease activity index scores, alleviation of weight loss, shortening of the colorectum, and reduction in spleen swelling. Notably, SDH decreased the proportion of Th1/Th2/Th17 cells and normalized inflammatory cytokine levels in the colon. Furthermore, SDH treatment modified the gut microbial composition in mice with colitis, notably decreasing Bacteroidetes and Proteobacteria populations while substantially increasing Firmicutes, Actinobacteria, and Patescibacteria. In conclusion, our findings suggest that SDH may protect the colon from DSS-induced colitis through the regulation of Th1/Th2/Th17 cells and gut microbiota, offering novel insights into SDH's therapeutic potential.

Expedient Access to 18F-Fluoroheteroarenes via Deaminative Radiofluorination of Aniline-Derived Pyridinium Salts.

Herein, we disclose that pyridinium salts derived from abundant (hetero)anilines represent a novel precursor class for nucleophilic aromatic substitution reactions with [18F]fluoride. The value of this new 18F-fluorodeamination is demonstrated with the synthesis of over 30 structurally diverse and complex heteroaryl 18F-fluorides, several derived from scaffolds that were yet to be labelled with fluorine-18. The protocol tolerates heteroarenes and functionalities commonly found in drug discovery libraries, and is amenable to scale-up and automation on a commercial radiosynthesiser.

The Impact of Valve Surgery on the Safety and Cardiac Function of Patients with Valvular Heart Disease Complicated by Pulmonary Arterial Hypertension.

Objective: This study evaluates the effects of valve surgery on safety and cardiac function in patients with valvular heart disease complicated by pulmonary arterial hypertension (PAH), focusing on postoperative outcomes influenced by age, heart function grade, and PAH severity. Methods: A retrospective analysis was conducted on 307 valve surgery patients from April 2017 to April 2022. The cohort had a mean age of 57.6 years, with 56.9% males, and was stratified by NYHA functional class II-IV. Outcomes assessed included mortality, complication rates, left ventricular ejection fraction (LVEF), and pulmonary artery systolic pressure (PASP), with statistical analysis performed using t-tests and chi-square tests for continuous and categorical data, respectively. Results: Postoperative outcomes varied significantly with age, NYHA class, and PASP grade. Patients aged ≤60 exhibited an average PASP reduction of 44.46% in the male group and 44.44% in the female group and an LVEF improvement of 5.28% in the male group and 5.80% in the female group. However, these patients showed a higher risk of postoperative complications, such as renal failure, arrhythmia, low cardiac output syndrome, respiratory insufficiency, (23.31%), and a higher mortality rate (13.53%)(P < .05). Higher NYHA classes correlated with increased postoperative risks of complications and mortality rates, and elevated PASP grades were associated with larger improvements in PASP and LVEF but also higher postoperative risks. Conclusion: Valve surgery in valvular heart disease with PAH is influenced by patient age, functional status, and PAH severity. Despite advances in surgical techniques, there remains a notable gap in understanding the nuanced interplay between these conditions and the variable outcomes of valve surgery. This study addresses this research gap, offering comprehensive insights into how age, heart function, and PAH severity influence postoperative outcomes. These findings are crucial for clinicians, providing a more informed basis for tailored treatment strategies, and ultimately enhancing patient care in this complex clinical scenario.Healthcare providers should consider the age-specific benefits and risks of valve surgery in patients with valvular heart disease and pulmonary arterial hypertension. Tailored decision-making, particularly for those aged ≤60, higher NYHA classes, or severe PAH, is essential for optimizing individual outcomes.

Inhibition of PTEN promotes osteointegration of titanium implants in type 2 diabetes by enhancing anti-inflammation and osteogenic capacity of adipose-derived stem cells.

Background: The low osteogenic differentiation potential and attenuated anti-inflammatory effect of adipose-derived stem cells (ADSCs) from animals with type 2 diabetes mellitus (T2DM) limits osseointegration of the implant. However, the underlying mechanisms are not fully understood. Methods: Western blotting and qRT-PCR analyses were performed to investigate the effects of PTEN on the osteogenic capacity of ADSCs of T2DM rats (TADSCs). We conducted animal experiments in T2DM-Sprague Dawley (SD) rats to evaluate the osteogenic capacity of modified TADSC sheets in vivo. New bone formation was assessed by micro-CT and histological analyses. Results: In this study, adipose-derived stem cells of T2DM rats exhibited an impaired osteogenic capacity. RNA-seq analysis showed that PTEN mRNA expression was upregulated in TADSCs, which attenuated the osteogenic capacity of TADSCs by inhibiting the AKT/mTOR/HIF-1α signaling pathway. miR-140-3p, which inhibits PTEN, was suppressed in TADSCs. Overexpression or inhibition of PTEN could correspondingly reduce or enhance the osteogenic ability of TADSCs by regulating the AKT/mTOR/HIF-1α signaling pathway. TADSCs transfected with PTEN siRNA resulted in higher and lower expressions of genes encoded in M2 macrophages (Arg1) and M1 macrophages (iNOS), respectively. In the T2DM rat model, PTEN inhibition in TADSC sheets promoted macrophage polarization toward the M2 phenotype, attenuated inflammation, and enhanced osseointegration around implants. Conclusion: Upregulation of PTEN, which was partially due to the inhibition of miR-140-3p, is important for the attenuated osteogenesis by TADSCs owing to the inhibition of the AKT/mTOR/HIF-1α signaling pathway. Inhibition of PTEN significantly improves the anti-inflammatory effect and osteogenic capacity of TADSCs, thus promoting peri-implant bone formation in T2DM rats. Our findings offer a potential therapeutic approach for modifying stem cells derived from patients with T2DM to enhance osseointegration.

Model-Based Optimization of Superconducting Qubit Readout.

Measurement is an essential component of quantum algorithms, and for superconducting qubits it is often the most error prone. Here, we demonstrate model-based readout optimization achieving low measurement errors while avoiding detrimental side effects. For simultaneous and midcircuit measurements across 17 qubits, we observe 1.5% error per qubit with a 500 ns end-to-end duration and minimal excess reset error from residual resonator photons. We also suppress measurement-induced state transitions achieving a leakage rate limited by natural heating. This technique can scale to hundreds of qubits and be used to enhance the performance of error-correcting codes and near-term applications.

Clinical study of reoperation for acute type A aortic dissection.

Objective: The initial operation for type A aortic dissection has limitations, and there may be a need for reoperation in cases such as giant pseudoaneurysm formation and reduced blood supply to the distal vessels. In this study, we collected case data of patients who underwent cardiac major vascular surgery at our hospital to analyze the effectiveness of reoperation treatment options for type A aortic dissection and to summarize our treatment experience. Method: Between June 2018 and December 2022, 62 patients with type A aortic dissection (TAAD) underwent reoperation after previous surgical treatment. Of these, 49 patients (45 males) underwent endovascular aortic repair (EVAR) with a mean age of (49.69 ± 10.21) years (30-75 years), and 13 patients (11 males) underwent thoracoabdominal aortic replacement (TAAR) with a mean age of (41.00 ± 11.18) years (23-66 years). In this study, we retrospectively analyzed the recorded data of 62 patients. In addition, we summarized and analyzed their Computed Tomographic Angiography (CTA) results and perioperative complications. Outcome: In the EVAR group, 47 patients (95.92%) were successfully implanted with overlapping stents, and 2 patients died in the perioperative period. Postoperative complications included cerebral infarction (4.08%), acute renal insufficiency (30.61%), pulmonary insufficiency and need for ventilator (6.12%), poor wound healing (2.04%), postoperative reoperation (16.33%), and lower limb ischemia (2.04%). In the TAAR group, 12 patients (92.31%) were successfully revascularized and 1 patient died in the perioperative period. Postoperative complications included cerebral infarction (7.69%), acute kidney injury (46.15%), pulmonary insufficiency and need for ventilator (15.38%), poor wound healing (30.77%) and postoperative reoperation (15.38%). Conclusion: According to the results of the study, compared with TAAR, EVAR was less invasive, faster recovery, and offered a better choice for some high-risk and high-age patients with comorbid underlying diseases. However, the rate of revascularization was higher after EVAR than TAAR due to vascular lesions. Compared with the use of ascending aortic replacement + hemi-aortic arch replacement for acute type A aortic dissection in many countries and regions, the use of ascending aortic replacement + aortic arch replacement + elephant trunk stent is more traumatic in China, but facilitates reoperation. For young patients, the choice of treatment should be individualized combining vascular lesions and long-term quality of life.

Optimizing quantum gates towards the scale of logical qubits.

A foundational assumption of quantum error correction theory is that quantum gates can be scaled to large processors without exceeding the error-threshold for fault tolerance. Two major challenges that could become fundamental roadblocks are manufacturing high-performance quantum hardware and engineering a control system that can reach its performance limits. The control challenge of scaling quantum gates from small to large processors without degrading performance often maps to non-convex, high-constraint, and time-dynamic control optimization over an exponentially expanding configuration space. Here we report on a control optimization strategy that can scalably overcome the complexity of such problems. We demonstrate it by choreographing the frequency trajectories of 68 frequency-tunable superconducting qubits to execute single- and two-qubit gates while mitigating computational errors. When combined with a comprehensive model of physical errors across our processor, the strategy suppresses physical error rates by ~3.7× compared with the case of no optimization. Furthermore, it is projected to achieve a similar performance advantage on a distance-23 surface code logical qubit with 1057 physical qubits. Our control optimization strategy solves a generic scaling challenge in a way that can be adapted to a variety of quantum operations, algorithms, and computing architectures.

A radiogenomic multimodal and whole-transcriptome sequencing for preoperative prediction of axillary lymph node metastasis and drug therapeutic response in breast cancer: a retrospective, machine learning and international multicohort study.

BACKGROUND: Axillary lymph nodes (ALN) status serves as a crucial prognostic indicator in breast cancer (BC). The aim of this study was to construct a radiogenomic multimodal model, based on machine learning and whole-transcriptome sequencing (WTS), to accurately evaluate the risk of ALN metastasis (ALNM), drug therapeutic response and avoid unnecessary axillary surgery in BC patients. METHODS: In this study, conducted a retrospective analysis of 1078 BC patients from The Cancer Genome Atlas (TCGA), The Cancer Imaging Archive (TCIA), and Foshan cohort. These patients were divided into the TCIA cohort ( N =103), TCIA validation cohort ( N =51), Duke cohort ( N =138), Foshan cohort ( N =106), and TCGA cohort ( N =680). Radiological features were extracted from BC radiological images and differentially expressed gene expression was calibrated using technology. A support vector machine model was employed to screen radiological and genetic features, and a multimodal model was established based on radiogenomic and clinical pathological features to predict ALNM. The accuracy of the model predictions was assessed using the area under the curve (AUC) and the clinical benefit was measured using decision curve analysis. Risk stratification analysis of BC patients was performed by gene set enrichment analysis, differential comparison of immune checkpoint gene expression, and drug sensitivity testing. RESULTS: For the prediction of ALNM, rad-score was able to significantly differentiate between ALN- and ALN+ patients in both the Duke and Foshan cohorts ( P <0.05). Similarly, the gene-score was able to significantly differentiate between ALN- and ALN+ patients in the TCGA cohort ( P <0.05). The radiogenomic multimodal nomogram demonstrated satisfactory performance in the TCIA cohort (AUC 0.82, 95% CI: 0.74-0.91) and the TCIA validation cohort (AUC 0.77, 95% CI: 0.63-0.91). In the risk sub-stratification analysis, there were significant differences in gene pathway enrichment between high and low-risk groups ( P <0.05). Additionally, different risk groups may exhibit varying treatment responses ( P <0.05). CONCLUSION: Overall, the radiogenomic multimodal model employs multimodal data, including radiological images, genetic, and clinicopathological typing. The radiogenomic multimodal nomogram can precisely predict ALNM and drug therapeutic response in BC patients.

Total-body PET/CT with half-dose [68 Ga]Ga-PSMA-11 for biochemical recurrent prostate cancer: comparable diagnostic value to short axial field-of-view PET/CT with full-dose [68 Ga]Ga-PSMA-11.

PURPOSE: The objective of this study was to evaluate the diagnostic performance and image quality of total-body positron emission tomography/computed tomography (PET/CT) imaging using a half-dose of [68 Ga]Ga-prostate specific membrane antigen ([68 Ga]Ga-PSMA) radiotracer, compared to conventional short axial field-of-view PET/CT imaging using a full dose of [68 Ga]Ga-PSMA. METHODS: This retrospective study enrolled 52 patients with biochemical recurrent (BCR) prostate cancer after radical prostatectomy who underwent total-body PET/CT with a half-dose (0.9-1.1 MBq/kg) of [68 Ga]Ga-PSMA. These patients were matched by baseline characteristics to another 52 BCR patients after prostatectomy who underwent conventional PET/CT with a full dose (1.8-2.2 MBq/kg) of [68 Ga]Ga-PSMA. The half-dose group was further divided into 5-min (G5) and 2-min (G2) acquisition subgroups. Image quality was assessed through subjective analysis using a 5-point scale and objective measurements of standard uptake value maximum (SUVmax), standard uptake value mean (SUVmean), background variation (BV) of the liver, blood pool, and parotid glands. Additionally, SUVmax and tumor-to-background ratio (TBR) were calculated for lesions. RESULTS: No significant difference in subjective image quality was found between the G2 and full-dose groups (p > 0.05). PET/CT image quality was significantly higher for the G5 versus G2 (p < 0.001) and full-dose groups (p < 0.001). TBR did not differ between the G2 and full-dose groups (4.23 ± 5.21 vs 4.22 ± 3.97, p = 0.99). Liver BV was significantly lower for G2 versus full-dose groups (0.16 ± 0.03 vs 0.20 ± 0.05, p < 0.001). CONCLUSIONS: Total-body PET/CT with a half-dose [68 Ga]Ga-PSMA yields image quality superior or comparable to that of conventional PET/CT. The utilization of total-body [68 Ga]Ga-PSMA PET/CT meets the diagnostic demands of BCR patients, particularly those who exhibit reduced tolerance to prolonged horizontal positioning and scan durations, while simultaneously reducing radiation exposure for the subjects.

A tool kit of highly selective and sensitive genetically encoded neuropeptide sensors.

Neuropeptides are key signaling molecules in the endocrine and nervous systems that regulate many critical physiological processes. Understanding the functions of neuropeptides in vivo requires the ability to monitor their dynamics with high specificity, sensitivity, and spatiotemporal resolution. However, this has been hindered by the lack of direct, sensitive, and noninvasive tools. We developed a series of GRAB (G protein-coupled receptor activation‒based) sensors for detecting somatostatin (SST), corticotropin-releasing factor (CRF), cholecystokinin (CCK), neuropeptide Y (NPY), neurotensin (NTS), and vasoactive intestinal peptide (VIP). These fluorescent sensors, which enable detection of specific neuropeptide binding at nanomolar concentrations, establish a robust tool kit for studying the release, function, and regulation of neuropeptides under both physiological and pathophysiological conditions.

Impact of left atrial diameter on all-cause mortality of patients with STEMI undergoing primary percutaneous coronary intervention.

OBJECTIVES: To evaluating the predictive significance of the left atrial diameter in acute ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). METHODS: The STEMI population came from 2 retrospective cohorts with 1097 patients, cohorts A (YongChuan Hospital) and cohorts B (Taizhou First People's Hospital). Within 3 days (cohort A) or 5 days (cohort B) post-PCI, patients underwent ultrasound evaluations. Cohort A was segmented into quartile categories based on eft atrial diameter (LAd) (Q1 to Q4). The odds ratios (ORs) for overall mortality were assessed using logistic regression. Cohort B was used for sensitivity analysis. RESULTS: During follow-up period, 226 (20.6%) patients experienced endpoint. In cohort A, univariable odds ratios were 2.68 (95%CI 1.11~6.89), 5.32 (95%CI 2.46~12.83) and 11.92 (95%CI 5.78~27.92), while multivariate ORs were 2.25 (95%CI 0.82~6.55), 5.09 (95%CI 2.12~13.56), and 15.05 (95%CI 6.58~39.09) in Q2 to Q4 group, respectively, compared with Q1 group (p for trend <0.001). Upon subgroup evaluation, the correlation between LAd and the likelihood of overall mortality was more pronounced in patients having a left ventricular ejection fraction (LVEF) between 40% and 50%, and those with LVEF ≥50%, in contrast to those with LVEF <40% (p for interaction <0.001). CONCLUSION: Left atrial diameter is indicative of the long-term overall mortality risk in STEMI patients post-PCI, particularly in those with an LVEF ≥ 40%.

Insulin-like growth factor binding protein 2: a core biomarker of left ventricular dysfunction in dilated cardiomyopathy.

BACKGROUND: RNA modifications, especially N6-methyladenosine, N1-methyladenosine and 5-methylcytosine, play an important role in the progression of cardiovascular disease. However, its regulatory function in dilated cardiomyopathy (DCM) remains to be undefined. METHODS: In the study, key RNA modification regulators (RMRs) were screened by three machine learning models. Subsequently, a risk prediction model for DCM was developed and validated based on these important genes, and the diagnostic efficiency of these genes was assessed. Meanwhile, the relevance of these genes to clinical traits was explored. In both animal models and human subjects, the gene with the strongest connection was confirmed. The expression patterns of important genes were investigated using single-cell analysis. RESULTS: A total of 4 key RMRs were identified. The risk prediction models were constructed basing on these genes which showed a good accuracy and sensitivity in both the training and test set. Correlation analysis showed that insulin-like growth factor binding protein 2 (IGFBP2) had the highest correlation with left ventricular ejection fraction (LVEF) (R = -0.49, P = 0.00039). Further validation expression level of IGFBP2 indicated that this gene was significantly upregulated in DCM animal models and patients, and correlation analysis validation showed a significant negative correlation between IGFBP2 and LVEF (R = -0.87; P = 6*10-5). Single-cell analysis revealed that this gene was mainly expressed in endothelial cells. CONCLUSION: In conclusion, IGFBP2 is an important biomarker of left ventricular dysfunction in DCM. Future clinical applications could possibly use it as a possible therapeutic target.

Association between urinary metabolites of volatile organic compounds and cardiovascular disease in the general population from NHANES 2011-2018.

BACKGROUND: Volatile organic compounds (VOCs) contain hundreds of chemicals and human exposure to VOCs is pervasive. However, most studies have considered only a single chemical or a class of similar chemicals. OBJECTIVE: We aimed to investigate the association between urinary volatile organic compound metabolites (mVOCs) and the risk of cardiovascular disease (CVD) in the general population. METHODS: The data in this study were collected from the National Health and Nutrition Examination Survey in 2011-2018. Eligible patients were aged ≥20 years for whom complete data for 20 types of urinary mVOCs and CVD outcomes were available. Multivariate logistic regression models were used to elucidate the association between mVOCs and CVD. Generalized additive models were used to examine the nonlinear relationships between mVOCs and CVD. RESULTS: 6814 indiviuals were included in the final analysis, of whom 508 had CVD. Higher urinary concentrations of N-acetyl-S-(2-carboxyethyl)-L-cysteine (CEMA) and N-Acetyl-S-(2-cyanoethyl)-l-cysteine (CYMA) and a lower urinary concentration of 2-aminothiazoline-4-carboxylic acid (ATCA) were associated with CVD outcomes after the adjustment for potential confounding factors. A nonlinear relationship and a threshold effect were only observed between N-acetyl-S-(N-methylcarbamoyl)-l-cysteine (AMCC) and CVD among 20 types of mVOCs. There was a significantly positive correlation between AMCC and CVD when AMCC concentration was >2.32 g/mL. CONCLUSION: The findings of this study suggested a significant correlation between urinary VOC metabolites and CVD. Urinary mVOCs may indicate hazardous exposure or distinct metabolic traits in patients with CVD.

[123I]CC1: A PARP-Targeting, Auger Electron-Emitting Radiopharmaceutical for Radionuclide Therapy of Cancer.

Poly(adenosine diphosphate ribose) polymerase (PARP) has emerged as an effective therapeutic strategy against cancer that targets the DNA damage repair enzyme. PARP-targeting compounds radiolabeled with an Auger electron-emitting radionuclide can be trapped close to damaged DNA in tumor tissue, where high ionizing potential and short range lead Auger electrons to kill cancer cells through the creation of complex DNA damage, with minimal damage to surrounding normal tissue. Here, we report on [123I]CC1, an 123I-labeled PARP inhibitor for radioligand therapy of cancer. Methods: Copper-mediated 123I iododeboronation of a boronic pinacol ester precursor afforded [123I]CC1. The level and specificity of cell uptake and the therapeutic efficacy of [123I]CC1 were determined in human breast carcinoma, pancreatic adenocarcinoma, and glioblastoma cells. Tumor uptake and tumor growth inhibition of [123I]CC1 were assessed in mice bearing human cancer xenografts (MDA-MB-231, PSN1, and U87MG). Results: In vitro and in vivo studies showed selective uptake of [123I]CC1 in all models. Significantly reduced clonogenicity, a proxy for tumor growth inhibition by ionizing radiation in vivo, was observed in vitro after treatment with as little as 10 Bq [123I]CC1. Biodistribution at 1 h after intravenous administration showed PSN1 tumor xenograft uptake of 0.9 ± 0.06 percentage injected dose per gram of tissue. Intravenous administration of a relatively low amount of [123I]CC1 (3 MBq) was able to significantly inhibit PSN1 xenograft tumor growth but was less effective in xenografts that expressed less PARP. [123I]CC1 did not cause significant toxicity to normal tissues. Conclusion: Taken together, these results show the potential of [123I]CC1 as a radioligand therapy for PARP-expressing cancers.

HIF-1α increases the osteogenic capacity of ADSCs by coupling angiogenesis and osteogenesis via the HIF-1α/VEGF/AKT/mTOR signaling pathway.

BACKGROUND: Stabilization and increased activity of hypoxia-inducible factor 1-α (HIF-1α) can directly increase cancellous bone formation and play an essential role in bone modeling and remodeling. However, whether an increased HIF-1α expression in adipose-derived stem cells (ADSCs) increases osteogenic capacity and promotes bone regeneration is not known. RESULTS: In this study, ADSCs transfected with small interfering RNA and HIF-1α overexpression plasmid were established to investigate the proliferation, migration, adhesion, and osteogenic capacity of ADSCs and the angiogenic ability of human umbilical vein endothelial cells (HUVECs). Overexpression of HIF-1α could promote the biological functions of ADSCs, and the angiogenic ability of HUVECs. Western blotting showed that the protein levels of osteogenesis-related factors were increased when HIF-1α was overexpressed. Furthermore, the influence of upregulation of HIF-1α in ADSC sheets on osseointegration was evaluated using a Sprague-Dawley (SD) rats implant model, in which the bone mass and osteoid mineralization speed were evaluated by radiological and histological analysis. The overexpression of HIF-1α in ADSCs enhanced bone remodeling and osseointegration around titanium implants. However, transfecting the small interfering RNA (siRNA) of HIF-1α in ADSCs attenuated their osteogenic and angiogenic capacity. Finally, it was confirmed in vitro that HIF-1α promotes osteogenic differentiation and the biological functions in ADSCs via the VEGF/AKT/mTOR pathway. CONCLUSIONS: This study demonstrates that HIF-1α has a critical ability to promote osteogenic differentiation in ADSCs by coupling osteogenesis and angiogenesis via the VEGF/AKT/mTOR signaling pathway, which in turn increases osteointegration and bone formation around titanium implants.

Characterization of tumor microenvironment infiltration and therapeutic responses of cell cycle-related genes' signature in breast cancer.

BACKGROUND: It is unknown how the cell cycle plays a role in breast cancer (BC). This study aimed to establish a clinically applicable predictive model to predict the therapeutic responses and overall survival in BC patients. MATERIALS AND METHODS: Cell cycle-related genes (CCGs) were identified within the Cancer Genome Atlas cohort (n is equal to 1001) and the Gene Expression Omnibus cohort (n is equal to 3265). An analysis of univariate and multivariate Cox was then conducted to develop a nomogram based on CCGs. After validating the nomogram, risk cohort stratification was established and the predictive value was examined. Finally, immune cell infiltration and therapeutic responses were analysed. RESULTS: Based on 15 CCGs, 4 prognostic predictors were identified and entered into the nomogram. According to the curves of calibration, the estimated and observed value of the nomogram is in optimal agreement. Subsequently, stratification into two risk cohorts showed that the predictive value, immune cell infiltration and overall survival were better among patients with low risk. Immune checkpoint expression in patients with BC at higher risk was downregulated. Furthermore, the results of the study revealed that doxorubicin, paclitaxel, docetaxel, cisplatin and vinorelbine all had higher IC50 values in patients with high-risk BC. CONCLUSION: The nomogram based on CCG could assess tumour immune micro-environment regulation and therapeutic responses of immunotherapy in BC. Moreover, it may provide novel information on the control of immune micro-environment infiltration in BC and aid in the development of targeted immunotherapy.

Feasibility of acquisitions using total-body PET/CT with a half-dose [68Ga]Ga-FAPI-04 activity in oncology patients.

BACKGROUND: [68Ga]Ga-FAPI-04 (gallium-68-labeled fibroblast activation protein inhibitor-04) PET/CT has been widely used in diagnosing malignant tumors. Total-body PET/CT has a long axial field of view and provides higher sensitivity compared to traditional PET/CT. However, whether the reduced injected dose of [68Ga]Ga-FAPI-04 could obtain qualified imaging has not been evaluated. PURPOSE: To explore the effect of half-dose [68Ga]Ga-FAPI-04 on image quality and tumor detectability in oncology patients. METHODS: A total of twenty-seven patients with tumors or clinically suspected tumors were included, and all patients were scanned with total-body PET/CT after an injected dose of 0.84-1.14 MBq/kg [68Ga]Ga-FAPI-04. All patients obtained superior image quality with 300 s original acquisition time. Images were reconstructed using 180 s, 120 s, 60 s, 40 s, 30 s, 20 s scanning duration by ordered subset expectation maximization algorithm. The subjective image quality of all patients in each time group was scored using 5-point Likert scale. Mediastinal blood pool, liver, spleen, and muscle were analyzed as background using semi-quantitative parameters maximum standardized uptake values (SUVmax), mean standardized uptake values (SUVmean), standard deviation (SD), and signal to noise ratio (SNR). The lesion detection rate, SUVmax, and tumor-to-background ratio (TBR) were calculated for tumors confirmed by pathology. RESULTS: The subjective image quality score decreased with the shortening of scanning time; however, both 180 s and 120 s images met the diagnostic requirements in terms of overall quality, lesion conspicuity, and image noise. The SUVmax of background increased with the reduction of scanning time, while the SUVmean was relatively stable. With the shortening of scanning time, the SD gradually increased, and the SNR gradually decreased, which was consistent with subjective image quality scores. In 180 s and 120 s images, all 11 primary lesions and 79 metastatic lesions were detected. The SUVmax of tumor focus showed an increasing trend as same as the background. Compared with 300 s, the TBR muscle had no statistical difference in 180 s and 120 s. CONCLUSIONS: Half-dose [68Ga]Ga-FAPI-04 in total-body PET/CT imaging can shorten the acquisition time to 120 s with acceptable subjective image quality and 100% tumor detection rate. Total-body PET/CT imaging with a half-dose [68Ga]Ga-FAPI-04 and reduced acquisition time can be used in radiation-sensitive and poor tolerant to prolong horizontal positioning and waiting time populations such as children and gravidas.