Selective Oxidative Cleavage of Benzyl C-N Bond under Metal-Free Electrochemical Conditions.

With the growing significance of green chemistry in organic synthesis, electrochemical oxidation has seen rapid development. Compounds undergo oxidation-reduction reactions through electron transfer at the electrode surface. This article proposes the use of electrochemical methods to achieve cleavage of the benzyl C-N bond. This method selectively oxidatively cleaves the C-N bond without the need for metal catalysts or external oxidants. Additionally, primary, secondary, and tertiary amines exhibit good adaptability under these conditions, utilizing water as the sole source of oxygen.

Iodophor-Catalyzed Disulfenylation of Amino Naphthalenes with Aryl Sulfonyl Hydrazines.

An iodophor-catalyzed direct disulfenylation of amino naphthalenes with aryl sulfonyl hydrazines in water was developed. A series of aryl sulfides were obtained in moderate to excellent yields. The advantages of this green protocol were the simple reaction conditions (metal-free, water as the solvent, under air), the odorless and easily available sulfur reagent, the broad substrate scope, and gram-scale synthesis. Moreover, the potential application of aryl sulfides was exemplified by further transformations.

Application value of artificial intelligence algorithm-based magnetic resonance multi-sequence imaging in staging diagnosis of cervical cancer.

The aim of this research is to explore the application value of Deep residual network model (DRN) for deep learning-based multi-sequence magnetic resonance imaging (MRI) in the staging diagnosis of cervical cancer (CC). This research included 90 patients diagnosed with CC between August 2019 and May 2021 at the hospital. After undergoing MRI examination, the clinical staging and surgical pathological staging of patients were conducted. The research then evaluated the results of clinical staging and MRI staging to assess their diagnostic accuracy and correlation. In the staging diagnosis of CC, the feature enhancement layer was added to the DRN model, and the MRI imaging features of CC were used to enhance the image information. The precision, specificity, and sensitivity of the constructed model were analyzed, and then the accuracy of clinical diagnosis staging and MRI staging were compared. As the model constructed DRN in this research was compared with convolutional neural network (CNN) and the classic deep neural network visual geometry group (VGG), the precision was 67.7, 84.9, and 93.6%, respectively. The sensitivity was 70.4, 82.5, and 91.2%, while the specificity was 68.5, 83.8, and 92.2%, respectively. The precision, sensitivity, and specificity of the model were remarkably higher than those of CNN and VGG models (P < 0.05). As the clinical staging and MRI staging of CC were compared, the diagnostic accuracy of MRI was 100%, while that of clinical diagnosis was 83.7%, showing a significant difference between them (P < 0.05). Multi-sequence MRI under intelligent algorithm had a high diagnostic rate for CC staging, deserving a good clinical application value.

Generation of an iPSC line from a 79-year-old female patient diagnosed with sporadic Parkinson's disease.

Parkinson's disease is a common neurodegenerative disorder. Here we present a human induced pluripotent stem cells (iPSCs) derived from peripheral blood mononuclear cells (PBMCs) of a 79-year-old female patient diagnosed with sporadic Parkinson's disease using the sendai virus. Generated iPSCs maintain normal karyotype, exhibit pluripotent stem cell markers, and possess differentiation potential. The iPSCs allows for differentiation into various cell subtypes, providing conditions for the research of the pathogenesis and drug development of Parkinson's disease.

Pathway to Approval of Innovative Radiopharmaceuticals in China.

Since the late 1950s, radiopharmaceuticals have been used for diagnosis and treatment in clinical nuclear medicine in China. Over the decades, China has successfully established a relatively sophisticated system for radiopharmaceutical production and management, supported by state-of-the-art facilities. With the rapid growth of the national economy, the radiopharmaceutical market in China is expanding at a remarkable pace. This burgeoning market has led to an escalating demand for clinical-stage radiopharmaceuticals, either produced domestically or imported. Despite this positive trajectory, the development and application of radiopharmaceuticals in China have been hindered by several challenges that persist, such as inadequate research, insufficient investment, limited availability of radionuclides, shortage of trained personnel in related fields, and imperfections in policies and regulations. In an exciting development, the regulation reforms implemented since 2015 have positively affected China's drug regulatory system. The introduction of the "Mid- and Long-Term Development Plan (2021-2035) for Medical Isotopes" created concurrently an opportune environment for the advancement of innovative radiopharmaceuticals. In this review, we aim to provide an overview of the approval process for novel radiopharmaceuticals by the National Medical Products Administration and the status of radiopharmaceuticals in research and development in China. Preclinical development and clinical translation of radiopharmaceuticals are undergoing rapid evolution in China. As practitioners in the field in China, we provide several practical suggestions to stimulate open discussions and thoughtful consideration.

Development of Recombinant High-Density Lipoprotein Platform with Innate Adipose Tissue-Targeting Abilities for Regional Fat Reduction.

As an escalating public health issue, obesity and overweight conditions are predispositions to various diseases and are exacerbated by concurrent chronic inflammation. Nonetheless, extant antiobesity pharmaceuticals (quercetin, capsaicin, catecholamine, etc.) manifest constrained efficacy alongside systemic toxic effects. Effective therapeutic approaches that selectively target adipose tissue, thereby enhancing local energy expenditure, surmounting the limitations of prevailing antiobesity modalities are highly expected. In this context, we developed a temperature-sensitive hydrogel loaded with recombinant high-density lipoprotein (rHDL) to achieve targeted delivery of resveratrol, an adipose browning activator, to adipose tissue. rHDL exhibits self-regulation on fat cell metabolism and demonstrates natural targeting toward scavenger receptor class B type I (SR-BI), which is highly expressed by fat cells, thereby achieving a synergistic effect for the treatment of obesity. Additionally, the dispersion of rHDL@Res in temperature-sensitive hydrogels, coupled with the regulation of their degradation and drug release rate, facilitated sustainable drug release at local adipose tissues over an extended period. Following 24 days' treatment regimen, obese mice exhibited improved metabolic status, resulting in a reduction of 68.2% of their inguinal white adipose tissue (ingWAT). Specifically, rHDL@Res/gel facilitated the conversion of fatty acids to phospholipids (PA, PC), expediting fat mobilization, mitigating triglyceride accumulation, and therefore facilitating adipose tissue reduction. Furthermore, rHDL@Res/gel demonstrated efficacy in attenuating obesity-induced inflammation and fostering angiogenesis in ingWAT. Collectively, this engineered local fat reduction platform demonstrated heightened effectiveness and safety through simultaneously targeting adipocytes, promoting WAT browning, regulating lipid metabolism, and controlling inflammation, showing promise for adipose-targeted therapy.

Coumarin Glycosides Reverse Enterococci-Facilitated Enteric Infections.

Commensal enterococci with pathogenic potential often facilitate the growth of diverse pathogens, thereby exacerbating infections. However, there are few effective therapeutic strategies to prevent and intervene in enterococci-mediated polymicrobial infections. Here, we find that enterococci at high density drive the expansion and pathogenicity of enteric Salmonella enterica serotype Typhimurium (S. Tm). Subsequently, we show that the driving role of enterococci in such infections is counteracted by dietary coumarin glycosides in vivo. Enterococci, which are tolerant of iron-deficient environments, produce ß-glucosidases to hydrolyze coumarin glycosides into bioactive aglycones, inhibiting S. Tm growth and ameliorating the severity of S. Tm-induced symptoms by inducing iron limitation. Overall, we demonstrate that coumarin glycosides as a common diet effectively reverse enterococci-facilitated enteric infections, providing an alternative intervention to combat polymicrobial infections.

Human Placental Mesenchymal Stem Cells-Exosomes Alleviate Endothelial Barrier Dysfunction via Cytoskeletal Remodeling through hsa-miR-148a-3p/ROCK1 Pathway.

Background: Endothelial barrier disruption of human pulmonary vascular endothelial cells (HPVECs) is an important pathogenic factor for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Mesenchymal stem cells-exosome (MSCs-Exo) represents an ideal carrier for cell-free therapy. The therapeutic implication and underlying mechanism of human placental MSCs-Exo (HPMSCs-Exo) in ALI/ARDS need to be further explored. Materials and Methods: HPMSCs-Exo was extracted from HPMSCs and characterized. Then, the therapeutic effects of exosomes were evaluated in ALI mice and HPVECs. RNA-sequencing was applied to reveal the miRNA profile of HPMSCs-Exo and differentially expressed genes (DEGs) in HPMSCs-Exo-pretreated HPVECs. The targets of miRNAs were predicted by bioinformatics methods and correlated to DEGs. Finally, the role of hsa-miR-148a-3p/ROCK1 pathway in HPVECs has been further discussed. Results: The results showed that HPMSCs-Exo could downregulate Rho-associated coiled-coil-containing protein kinase 1 (ROCK1), upregulate the expression of zonula occludens-1 (ZO-1) and F-actin, promote HPVECs migration and tube formation, reduce cytoskeletal disorders and cell permeability, and thus improve ALI/ARDS. RNA-sequencing revealed the DEGs were mainly enriched in cell junction, angiogenesis, inflammation, and energy metabolism. HPMSCs-Exo contains multiple miRNAs which are associated with cytoskeletal function; the expression abundance of hsa-miR-148a-3p is the highest. Bioinformatic analysis identified ROCK1 as a target of hsa-miR-148a-3p. The overexpression of hsa-miR-148a-3p in HPMSCs-Exo promoted the migration and tube formation of HPVECs and reduced ROCK1 expression. However, the overexpression of ROCK1 on HPVECs reduced the therapeutic effect of HPMSCs-Exo. Conclusions: HPMSCs-Exo represents a protective regimen against endothelial barrier disruption of HPVECs in ALI/ARDS, and the hsa-miR-148a-3p/ROCK1 pathway plays an important role in this therapeutics implication.

BnaABF3 and BnaMYB44 regulate the transcription of zeaxanthin epoxidase genes in carotenoid and abscisic acid biosynthesis.

Zeaxanthin epoxidase (ZEP) is a key enzyme that catalyzes the conversion of zeaxanthin to violaxanthin in the carotenoid and abscisic acid (ABA) biosynthesis pathways. The rapeseed (Brassica napus) genome has 4 ZEP (BnaZEP) copies that are suspected to have undergone subfunctionalization, yet the 4 genes' underlying regulatory mechanisms remain unknown. Here, we genetically confirmed the functional divergence of the gene pairs BnaA09.ZEP/BnaC09.ZEP and BnaA07.ZEP/BnaC07.ZEP, which encode enzymes with tissue-specific roles in carotenoid and ABA biosynthesis in flowers and leaves, respectively. Molecular and transgenic experiments demonstrated that each BnaZEP pair is transcriptionally regulated via ABA-responsive element-binding factor 3 s (BnaABF3s) and BnaMYB44s as common and specific regulators, respectively. BnaABF3s directly bound to the promoters of all 4 BnaZEPs and activated their transcription, with overexpression of individual BnaABF3s inducing BnaZEP expression and ABA accumulation under drought stress. Conversely, loss of BnaABF3s function resulted in lower expression of several genes functioning in carotenoid and ABA metabolism and compromised drought tolerance. BnaMYB44s specifically targeted and repressed the expression of BnaA09.ZEP/BnaC09.ZEP but not BnaA07.ZEP/BnaC07.ZEP. Overexpression of BnaA07.MYB44 resulted in increased carotenoid content and an altered carotenoid profile in petals. Additionally, RNA-seq analysis indicated that BnaMYB44s functions as a repressor in phenylpropanoid and flavonoid biosynthesis. These findings provide clear evidence for the subfunctionalization of duplicated genes and contribute to our understanding of the complex regulatory network involved in carotenoid and ABA biosynthesis in B. napus.

Diagnosis and prognosis of abnormal cardiac scintigraphy uptake suggestive of cardiac amyloidosis using artificial intelligence: a retrospective, international, multicentre, cross-tracer development and validation study.

BACKGROUND: The diagnosis of cardiac amyloidosis can be established non-invasively by scintigraphy using bone-avid tracers, but visual assessment is subjective and can lead to misdiagnosis. We aimed to develop and validate an artificial intelligence (AI) system for standardised and reliable screening of cardiac amyloidosis-suggestive uptake and assess its prognostic value, using a multinational database of 99mTc-scintigraphy data across multiple tracers and scanners. METHODS: In this retrospective, international, multicentre, cross-tracer development and validation study, 16 241 patients with 19 401 scans were included from nine centres: one hospital in Austria (consecutive recruitment Jan 4, 2010, to Aug 19, 2020), five hospital sites in London, UK (consecutive recruitment Oct 1, 2014, to Sept 29, 2022), two centres in China (selected scans from Jan 1, 2021, to Oct 31, 2022), and one centre in Italy (selected scans from Jan 1, 2011, to May 23, 2023). The dataset included all patients referred to whole-body 99mTc-scintigraphy with an anterior view and all 99mTc-labelled tracers currently used to identify cardiac amyloidosis-suggestive uptake. Exclusion criteria were image acquisition at less than 2 h (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, 99mTc-hydroxymethylene diphosphonate, and 99mTc-methylene diphosphonate) or less than 1 h (99mTc-pyrophosphate) after tracer injection and if patients' imaging and clinical data could not be linked. Ground truth annotation was derived from centralised core-lab consensus reading of at least three independent experts (CN, TT-W, and JN). An AI system for detection of cardiac amyloidosis-associated high-grade cardiac tracer uptake was developed using data from one centre (Austria) and independently validated in the remaining centres. A multicase, multireader study and a medical algorithmic audit were conducted to assess clinician performance compared with AI and to evaluate and correct failure modes. The system's prognostic value in predicting mortality was tested in the consecutively recruited cohorts using cox proportional hazards models for each cohort individually and for the combined cohorts. FINDINGS: The prevalence of cases positive for cardiac amyloidosis-suggestive uptake was 142 (2%) of 9176 patients in the Austrian, 125 (2%) of 6763 patients in the UK, 63 (62%) of 102 patients in the Chinese, and 103 (52%) of 200 patients in the Italian cohorts. In the Austrian cohort, cross-validation performance showed an area under the curve (AUC) of 1·000 (95% CI 1·000-1·000). Independent validation yielded AUCs of 0·997 (0·993-0·999) for the UK, 0·925 (0·871-0·971) for the Chinese, and 1·000 (0·999-1·000) for the Italian cohorts. In the multicase multireader study, five physicians disagreed in 22 (11%) of 200 cases (Fleiss' kappa 0·89), with a mean AUC of 0·946 (95% CI 0·924-0·967), which was inferior to AI (AUC 0·997 [0·991-1·000], p=0·0040). The medical algorithmic audit demonstrated the system's robustness across demographic factors, tracers, scanners, and centres. The AI's predictions were independently prognostic for overall mortality (adjusted hazard ratio 1·44 [95% CI 1·19-1·74], p<0·0001). INTERPRETATION: AI-based screening of cardiac amyloidosis-suggestive uptake in patients undergoing scintigraphy was reliable, eliminated inter-rater variability, and portended prognostic value, with potential implications for identification, referral, and management pathways. FUNDING: Pfizer.

Novel PET Imaging Probe for Quantitative Detection of Senescence In Vivo.

Real-time detection of cellular senescence remains a clinical challenge. Here, we aimed to develop a positron emission tomography (PET) imaging probe targeting senescence-associated ß-galactosidase (SA-ß-Gal), the most widely used biomarker of cellular senescence, and investigate its performance for real-time in vivo quantitative detection of cellular senescence. A stable PET imaging agent [68Ga]Ga-BGal was obtained with a high labeling yield (90.0 ± 4.3%) and a radiochemical purity (>95%). [68Ga]Ga-BGal displayed high sensitivity and specificity for ß-Gal both in vitro and in vivo. The reaction and uptake of the probe correlated with the ß-Gal concentration and reaction time. In PET imaging, high ß-Gal-expressing CT26.CL25 tumors and doxorubicin-treated HeLa tumors showed high signals from [68Ga]Ga-BGal, while a low signal was observed in CT26.WT and untreated HeLa tumors. In summary, we showcased successful PET imaging of senescence in preclinical models using probe [68Ga]Ga-BGal. This finding holds the potential for translating senescence imaging into clinical applications.

Clinical effect analysis of different treatment schemes for children with ulnar and radial double fractures.

Objective: The objective of the study is to evaluate the safety and efficacy of three different treatment methods for pediatric ulnar and radial double fractures. Methods: 120 children with ulnar and radial double fractures were included in the study. According to the different treatment plans, children were divided into three groups: manual reduction, splint external fixation, double elastic intramedullary fixation, and double plate fixation. Surgical indicators, radiological results, clinical efficacy, and complications were evaluated and compared among the groups. Results: The average hospital stay and operation time were significantly longer in the double plate internal fixation group compared to the other two groups. The double elastic intramedullary nailing group showed a higher fracture healing rate at 3 months compared to the other groups. There were no significant differences in clinical efficacy among the three groups. Complications were observed in all groups but did not show significant statistical differences. Conclusion: Double elastic intramedullary nailing fixation demonstrated favorable outcomes in terms of surgical indicators and fracture healing rates for pediatric ulnar and radial double fractures.

Objetivo: Evaluar la seguridad y eficacia de tres métodos de tratamiento diferentes para las fracturas dobles cubital y radial pediátricas. Métodos: Se incluyeron en el estudio 120 niños con fracturas dobles de cúbito y radio. Según los diferentes planes de tratamiento, los niños se dividieron en tres grupos: reducción manual, fijación externa con férula, fijación intramedular doble elástica y fijación con doble placa. Se evaluaron y compararon entre los grupos indicadores quirúrgicos, resultados radiológicos, eficacia clínica y complicaciones. Resultados: La estancia hospitalaria promedio y el tiempo de operación fueron significativamente más prolongados en el grupo de fijación interna con doble placa en comparación con los otros dos grupos. El grupo de clavo intramedular elástico doble mostró una mayor tasa de curación de la fractura a los 3 meses en comparación con los otros grupos. No hubo diferencias significativas en la eficacia clínica entre los tres grupos. Se observaron complicaciones en todos los grupos pero no mostraron diferencias estadísticas significativas. Conclusión: La fijación con clavo intramedular elástico doble demostró resultados favorables en términos de indicadores quirúrgicos y tasas de curación de fracturas pediátricas dobles cubital y radial.

A Comparative Analysis of the Antibacterial Spectrum of Ultrasmall Manganese Ferrite Nanozymes with Varied Surface Modifications.

Bacterial infectious diseases pose a significant global challenge. However, conventional antibacterial agents exhibit limited therapeutic effectiveness due to the emergence of drug resistance, necessitating the exploration of novel antibacterial strategies. Nanozymes have emerged as a highly promising alternative to antibiotics, owing to their particular catalytic activities against pathogens. Herein, we synthesized ultrasmall-sized MnFe2O4 nanozymes with different charges (MnFe2O4-COOH, MnFe2O4-PEG, MnFe2O4-NH2) and assessed their antibacterial capabilities. It was found that MnFe2O4 nanozymes exhibited both antibacterial and antibiofilm properties attributed to their excellent peroxidase-like activities and small sizes, enabling them to penetrate biofilms and interact with bacteria. Moreover, MnFe2O4 nanozymes effectively expedite wound healing within 12 days and facilitate tissue repair and regeneration while concurrently reducing inflammation. MnFe2O4-COOH displayed favorable antibacterial activity against Gram-positive bacteria, with 80% bacterial removal efficiency against MRSA by interacting with phosphatidylglycerol (PG) and cardiolipin (CL) of the membrane. By interacting with negatively charged bacteria surfaces, MnFe2O4-NH2 demonstrated the most significant and broad-spectrum antibacterial activity, with 95 and 85% removal efficiency against methicillin-resistant Staphylococcus aureus (MRSA) and P. aeruginosa, respectively. MnFe2O4-PEG dissipated membrane potential and reduced ATP levels in MRSA and P. aeruginosa, showing relatively broad-spectrum antibacterial activity. To conclude, MnFe2O4 nanozymes offer a promising therapeutic approach for treating wound infections.

High-quality genomes of Bombax ceiba and Ceiba pentandra provide insights into the evolution of Malvaceae species and differences in their natural fiber development.

Members of the Malvaceae family, including Corchorus spp., Gossypium spp., Bombax spp., and Ceiba spp., are important sources of natural fibers. In the past decade, the genomes of several Malvaceae species have been assembled; however, the evolutionary history of Malvaceae species and the differences in their fiber development remain to be clarified. Here, we report the genome assembly and annotation of two natural fiber plants from the Malvaceae, Bombax ceiba and Ceiba pentandra, whose assembled genome sizes are 783.56 Mb and 1575.47 Mb, respectively. Comparative analysis revealed that whole-genome duplication and Gypsy long terminal repeat retroelements have been the major causes of differences in chromosome number (2n = 14 to 2n = 96) and genome size (234 Mb to 2676 Mb) among Malvaceae species. We also used comparative genomic analyses to reconstruct the ancestral Malvaceae karyotype with 11 proto-chromosomes, providing new insights into the evolutionary trajectories of Malvaceae species. MYB-MIXTA-like 3 is relatively conserved among the Malvaceae and functions in fiber cell-fate determination in the epidermis. It appears to perform this function in any tissue where it is expressed, i.e. in fibers on the endocarp of B. ceiba and in ovule fibers of cotton. We identified a structural variation in a cellulose synthase gene and a higher copy number of cellulose synthase-like genes as possible causes of the finer, less spinnable, weaker fibers of B. ceiba. Our study provides two high-quality genomes of natural fiber plants and offers insights into the evolution of Malvaceae species and differences in their natural fiber formation and development through multi-omics analysis.

A comparison of the performance of 68Ga-Pentixafor PET/CT versus adrenal vein sampling for subtype diagnosis in primary aldosteronism.

Objective: To investigate the diagnostic efficiency and prognostic value of 68Ga-Pentixafor PET/CT in comparison with adrenal vein sampling (AVS) for functional lateralization in primary aldosteronism (PA). Histology and long-term clinical follow-up normally serve as the gold standard for such diagnosis. Methods: We prospectively recruited 26 patients diagnosed with PA. All patients underwent 68Ga-Pentixafor PET/CT and AVS. Postsurgical biochemical and clinical outcomes of patients with unilateral primary aldosteronism (UPA), as diagnosed by PET/CT or AVS, were assessed by applying standardized Primary Aldosteronism Surgical Outcome (PASO) criteria. Immunohistochemistry (IHC) was performed to detect the expression of aldosterone synthase (CYP11B2) and CXCR4. Results: On total, 19 patients were diagnosed with UPA; of these, 13 patients were lateralized by both PET/CT and AVS, four patients were lateralized by PET-only, and two by AVS-only. Seven subjects with no lateralization on AVS and PET received medical therapy. All patients achieved complete biochemical success except one with nodular hyperplasia lateralized by AVS alone. The consistency between PET/CT and AVS outcomes was 77% (20/26). Moreover, CYP11B2-positive nodules were all CXCR4-positive and showed positive findings on PET. Patients who achieved complete biochemical and clinical success had a higher uptake on PET as well as stronger expression levels of CXCR4 and CYP11B2. Conclusion: Our analysis showed that 68Ga-Pentixafor PET/CT could enable non-invasive diagnosis in most patients with PA and identify additional cases of unilateral and surgically curable PA which could not be classified by AVS. 68Ga-Pentixafor PET/CT should be considered as a first-line test for the future classification of PA.

A Programmable DNAzyme for the Sensitive Detection of Nucleic Acids.

Nucleic acids in biofluids are emerging biomarkers for the molecular diagnostics of diseases, but their clinical use has been hindered by the lack of sensitive detection assays. Herein, we report the development of a sensitive nucleic acid detection assay named SPOT (sensitive loop-initiated DNAzyme biosensor for nucleic acid detection) by rationally designing a catalytic DNAzyme of endonuclease capability into a unified one-stranded allosteric biosensor. SPOT is activated once a nucleic acid target of a specific sequence binds to its allosteric module to enable continuous cleavage of molecular reporters. SPOT provides a highly robust platform for sensitive, convenient and cost-effective detection of low-abundance nucleic acids. For clinical validation, we demonstrated that SPOT could detect serum miRNAs for the diagnostics of breast cancer, gastric cancer and prostate cancer. Furthermore, SPOT exhibits potent detection performance over SARS-CoV-2 RNA from clinical swabs with high sensitivity and specificity. Finally, SPOT is compatible with point-of-care testing modalities such as lateral flow assays. Hence, we envision that SPOT may serve as a robust assay for the sensitive detection of a variety of nucleic acid targets enabling molecular diagnostics in clinics.

Performance of 99mTc-PYP scintigraphy in the diagnosis of hereditary transthyretin cardiac amyloidosis.

OBJECTIVE: Most reported research has primarily investigated wild-type transthyretin cardiac amyloidosis (ATTRwt-CA). However, the application of bone scintigraphy for hereditary transthyretin cardiac amyloidosis (ATTRv-CA) has not been systematically investigated. Therefore, in this study, we aimed to evaluate the diagnostic value of 99mTc-PYP scintigraphy in ATTRv-CA. METHODS: Fifty-four patients were enrolled in a highly suspected cardiac amyloidosis cohort. Transthyretin (TTR) gene characteristics were summarized in the ATTRv-CA group. In 99mTc-PYP scintigraphy, the diagnostic efficiency of the visual score (VGS) and heart-to-contralateral chest (H/CL) ratio were evaluated. Furthermore, the interobserver consistency among the diagnosticians was investigated. RESULTS: Twenty-eight patients were diagnosed with ATTRv-CA with eight genotypes. The Ala97Ser genotype accounts for 46% (n = 13) with a mean age of disease onset, definite diagnosis, and interval of 61.6 ± 1.9, 66.5 ± 1.3, and 4.0 (3.0, 6.2) years, respectively. Their VGS is Grade 3, and their H/CL ratio is higher than that of the non-Ala97Ser group, but no statistical significance exists (mean H/CL: 1.95 ± 0.06 vs. 1.87 ± 0.02, p = 0.844). Additionally, ATTRv-CA patients showed VGS ≥ 2, and mean H/CL ratio of 2.09 ± 0.06. The sensitivity and specificity of VGS were 100% and 65%, respectively. And the interobserver consistency analysis of VGS showed the intraclass correlation coefficient is 0.522. The best cutoff value of H/CL ratio was 1.51 (AUC = 0.996), and the diagnostic consistency of H/CL (bias: 0.018) was high. CONCLUSIONS: Ala97Ser is the most common genotype in ATTRv-CA in our cohort, with characteristics of later onset and rapid progression, but delayed diagnosis and extensive 99mTc-PYP uptake. Overall, ATTRv-CA patients showed moderate-to-extensive myocardial 99mTc-PYP uptake. Additionally, VGS carries subjectivity, low specialty and interobserver consistency. But H/CL exhibit high diagnostic efficacy and interobserver consistency. The H/CL ratio is more useful than VGS.

The value of 18F-FDG PET/CT in Langerhans cell histiocytosis.

OBJECTIVE: To investigate the value of 18F-FDG PET/CT in diagnosis and disease evaluation of Langerhans cell histiocytosis (LCH). METHODS: A retrospective analysis of 31 patients with LCH confirmed by histopathology was performed. A systematic analysis of the PET/CT imaging manifestations of LCH was performed, recording patients who were treated and receiving PET/CT for efficacy evaluation. In addition, clinical and laboratory data of LCH patients were collected, and the correlation between these data and PET/CT metabolic parameters was initially investigated. RESULTS: Of the 31 patients, thirty had at least 1 PET/CT positive lesions (96.7%), and one had only skin damage without abnormalities on PET/CT. Of 31 patients, fifteen (48.4%) had single system (SS) disease (9 cases with a single site and 6 cases with multiple sites) and 16 (51.6%) had multisystem (MS) disease (6 low risk and 10 high risk cases). The incidence of LCH lesions in the bone, lymphatic system, pituitary gland, liver, soft tissue, thyroid gland, thymus, and lungs was 20 cases (64.5%), 12 cases (38.7%), 3 cases (9.7%), 2 cases (6.5%), 2 cases (6.5%), 1 case (3.2%), 1 case (3.2%), and 8 cases (25.8%), respectively. A total of 21 PET/CT follow-up scanning were performed in 13 patients receiving chemotherapy, with 13 (61.9%) partial metabolic remission (PMR), 6 (28.6%) progressive metabolic disease (PMD), and 2 (9.5%) stable metabolic disease (SMD), according to PET Response Evaluation Criteria in Solid Tumors (PRECIST) 1.0. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and Lactic Dehydrogenase (LDH) were positively correlated with TTLG (total TLG) (R2 = 0.3256, 0.2409, 0.4205, P < 0.05). The Re-examine SUVmax is positively correlated with re-examine LDH (R2 = 0.7285, P < 0.05). CONCLUSIONS: 18F-FDG PET/CT is an effective way to diagnose and evaluate LCH. PET metabolic parameters were associated with laboratory inflammatory markers, suggesting that 18F-FDG PET/CT may be helpful in evaluating disease activity of LCH.

Development of a novel 18F-labeled small molecule probe for PET imaging of mesenchymal epithelial transition receptor expression.

The mesenchymal epithelial transition factor (c-Met) is frequently overexpressed in numerous cancers and has served as a validated anticancer target. Inter- and intra-tumor heterogeneity of c-Met, however, challenges the use of anti-MET therapies, highlighting an urgent need to develop an alternative tool for visualizing whole-body c-Met expression quantitatively and noninvasively. Here we firstly reported an 18F labeled, small-molecule quinine compound-based PET probe, 1-(4-(5-amino-7-(trifluoromethyl) quinolin-3-yl) piperazin-1-yl)-2-(fluoro-[18F]) propan-1-one, herein referred as [18F]-AZC. METHODS: [18F]-AZC was synthesized via a one-step substitution reaction and characterized by radiochemistry methods. [18F]-AZC specificity and affinity toward c-Met were assessed by cell uptake assay, with or without cold compound [19F]-AZC or commercial c-Met inhibitor blocking. MicroPET/CT imaging and biodistribution studies were conducted in subcutaneous murine xenografts of glioma. Additionally, [18F]-AZC was then further evaluated in orthotopic glioma xenografts, by microPET/CT imaging accompanied with MRI and autoradiography for co-registration of the tumor. Immunofluorescence staining was also carried out to qualitatively evaluate the c-Met expression in tumor tissue, co-localizes with H&E staining. RESULTS: This probe shows easy radiosynthesis, high stability in vitro and in vivo, high targeting affinity, and favorable lipophilicity and brain transport coefficient. [18F]-AZC demonstrates excellent tumor imaging properties in vivo and can delineate c-Met positive glioma specifically at 1 h after intravenous injection of the probe. Moreover, favorable correlation was observed between the [18F]-AZC accumulation and the amount of c-Met expression in tumor. CONCLUSION: This novel imaging probe could be applied as a valuable tool for management of anti-c-Met therapies in patients in the future.

Associations between Short-Term Exposure to Ambient Air Pollution and Influenza: An Individual-Level Case-Crossover Study in Guangzhou, China.

BACKGROUND: Influenza imposes a heavy burden on public health. Little is known, however, of the associations between detailed measures of exposure to ambient air pollution and influenza at an individual level. OBJECTIVE: We examined individual-level associations between six criteria air pollutants and influenza using case-crossover design. METHODS: In this individual-level time-stratified case-crossover study, we linked influenza cases collected by the Guangzhou Center for Disease Control and Prevention from 1 January 2013 to 31 December 2019 with individual residence-level exposure to particulate matter (PM2.5 and PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3) and carbon monoxide (CO). The exposures were estimated for the day of onset of influenza symptoms (lag 0), 1-7 d before the onset (lags 1-7), as well as an 8-d moving average (lag07), using a random forest model and linked to study participants' home addresses. Conditional logistic regression was developed to investigate the associations between short-term exposure to air pollution and influenza, adjusting for mean temperature, relative humidity, public holidays, population mobility, and community influenza susceptibility. RESULTS: N=108,479 eligible cases were identified in our study. Every 10-µg/m3 increase in exposure to PM2.5, PM10, NO2, and CO and every 5-µg/m3 increase in SO2 over 8-d moving average (lag07) was associated with higher risk of influenza with a relative risk (RR) of 1.028 (95% CI: 1.018, 1.038), 1.041 (95% CI: 1.032, 1.049), 1.169 (95% CI: 1.151, 1.188), 1.004 (95% CI: 1.003, 1.006), and 1.134 (95% CI: 1.107, 1.163), respectively. There was a negative association between O3 and influenza with a RR of 0.878 (95% CI: 0.866, 0.890). CONCLUSIONS: Our findings suggest that short-term exposure to air pollution, except for O3, is associated with greater risk for influenza. Further studies are necessary to decipher underlying mechanisms and design preventive interventions and policies. https://doi.org/10.1289/EHP12145.