Natural short-lived halogens exert an indirect cooling effect on climate.

Observational evidence shows the ubiquitous presence of ocean-emitted short-lived halogens in the global atmosphere1-3. Natural emissions of these chemical compounds have been anthropogenically amplified since pre-industrial times4-6, while, in addition, anthropogenic short-lived halocarbons are currently being emitted to the atmosphere7,8. Despite their widespread distribution in the atmosphere, the combined impact of these species on Earth's radiative balance remains unknown. Here we show that short-lived halogens exert a substantial indirect cooling effect at present (-0.13 ± 0.03 watts per square metre) that arises from halogen-mediated radiative perturbations of ozone (-0.24 ± 0.02 watts per square metre), compensated by those from methane (+0.09 ± 0.01 watts per square metre), aerosols (+0.03 ± 0.01 watts per square metre) and stratospheric water vapour (+0.011 ± 0.001 watts per square metre). Importantly, this substantial cooling effect has increased since 1750 by -0.05 ± 0.03 watts per square metre (61 per cent), driven by the anthropogenic amplification of natural halogen emissions, and is projected to change further (18-31 per cent by 2100) depending on climate warming projections and socioeconomic development. We conclude that the indirect radiative effect due to short-lived halogens should now be incorporated into climate models to provide a more realistic natural baseline of Earth's climate system.

Anthropogenic short-lived halogens increase human exposure to mercury contamination due to enhanced mercury oxidation over continents.

Mercury (Hg) is a contaminant of global concern, and an accurate understanding of its atmospheric fate is needed to assess its risks to humans and ecosystem health. Atmospheric oxidation of Hg is key to the deposition of this toxic metal to the Earth's surface. Short-lived halogens (SLHs) can provide halogen radicals to directly oxidize Hg and perturb the budget of other Hg oxidants (e.g., OH and O3). In addition to known ocean emissions of halogens, recent observational evidence has revealed abundant anthropogenic emissions of SLHs over continental areas. However, the impacts of anthropogenic SLHs emissions on the atmospheric fate of Hg and human exposure to Hg contamination remain unknown. Here, we show that the inclusion of anthropogenic SLHs substantially increased local Hg oxidation and, consequently, deposition in/near Hg continental source regions by up to 20%, thereby decreasing Hg export from source regions to clean environments. Our modeling results indicated that the inclusion of anthropogenic SLHs can lead to higher Hg exposure in/near Hg source regions than estimated in previous assessments, e.g., with increases of 8.7% and 7.5% in China and India, respectively, consequently leading to higher Hg-related human health risks. These results highlight the urgent need for policymakers to reduce local Hg and SLHs emissions. We conclude that the substantial impacts of anthropogenic SLHs emissions should be included in model assessments of the Hg budget and associated health risks at local and global scales.

Overlooked significance of iodic acid in new particle formation in the continental atmosphere.

New particle formation (NPF) substantially affects the global radiation balance and climate. Iodic acid (IA) is a key marine NPF driver that recently has also been detected inland. However, its impact on continental particle nucleation remains unclear. Here, we provide molecular-level evidence that IA greatly facilitates clustering of two typical land-based nucleating precursors: dimethylamine (DMA) and sulfuric acid (SA), thereby enhancing particle nucleation. Incorporating this mechanism into an atmospheric chemical transport model, we show that IA-induced enhancement could realize an increase of over 20% in the SA-DMA nucleation rate in iodine-rich regions of China. With declining anthropogenic pollution driven by carbon neutrality and clean air policies in China, IA could enhance nucleation rates by 1.5 to 50 times by 2060. Our results demonstrate the overlooked key role of IA in continental NPF nucleation and highlight the necessity for considering synergistic SA-IA-DMA nucleation in atmospheric modeling for correct representation of the climatic impacts of aerosols.

Pharmacology of hydrogen sulfide and its donors in cardiometabolic diseases.

Cardiometabolic diseases (CMDs) are major contributors to global mortality, emphasizing the critical need for novel therapeutic interventions. Hydrogen sulfide (H2S) has garnered enormous attention as a significant gasotransmitter with various physiological, pathophysiological, and pharmacological impacts within mammalian cardiometabolic systems. In addition to its roles in attenuating oxidative stress and inflammatory response, burgeoning research emphasizes the significance of H2S in regulating proteins via persulfidation, a well-known modification intricately associated with the pathogenesis of CMDs This review seeks to investigate recent updates on the physiological actions of endogenous H2S and the pharmacological roles of various H2S donors in addressing diverse aspects of CMDs across cellular, animal, and clinical studies. Of note, advanced methodologies including multi-omics, intestinal microflora analysis, organoid and single-cell sequencing techniques are gaining traction due to their ability to offer comprehensive insights into biomedical research. These emerging approaches hold promise in characterizing the pharmacological roles of H2S in health and diseases. We will critically assesse the current literatures to clarify the roles of H2S in diseases while also delineating the opportunities and challenges they present in H2S-based pharmacotherapy for CMDs. Significance Statement The comprehensive review covers recent developments in H2S biology and pharmacology in CMDs. Endogenous H2S and its donors show great promise for the management of CMDs by regulating numerous proteins and signaling pathways. The emergence of new technologies will considerably advance the pharmacological research and clinical translation of H2S.

17ß-estradiol promotes extracellular vesicle release and selective miRNA loading in ERα-positive breast cancer.

The causes and consequences of abnormal biogenesis of extracellular vesicles (EVs) are not yet well understood in malignancies, including in breast cancers (BCs). Given the hormonal signaling dependence of estrogen receptor-positive (ER+) BC, we hypothesized that 17ß-estradiol (estrogen) might influence EV production and microRNA (miRNA) loading. We report that physiological doses of 17ß-estradiol promote EV secretion specifically from ER+ BC cells via inhibition of miR-149-5p, hindering its regulatory activity on SP1, a transcription factor that regulates the EV biogenesis factor nSMase2. Additionally, miR-149-5p downregulation promotes hnRNPA1 expression, responsible for the loading of let-7's miRNAs into EVs. In multiple patient cohorts, we observed increased levels of let-7a-5p and let-7d-5p in EVs derived from the blood of premenopausal ER+ BC patients, and elevated EV levels in patients with high BMI, both conditions associated with higher levels of 17ß-estradiol. In brief, we identified a unique estrogen-driven mechanism by which ER+ BC cells eliminate tumor suppressor miRNAs in EVs, with effects on modulating tumor-associated macrophages in the microenvironment.

Rational Design of 2D Metal Halide Perovskites with Low Congruent Melting Temperature and Large Melt-Processable Window.

Metal halide perovskites (MHPs) have garnered significant attention due to their distinctive optical and electronic properties, coupled with excellent processability. However, the thermal characteristics of these materials are often overlooked, which can be harnessed to cater to diverse application scenarios. We showcase the efficacy of lowering the congruent melting temperature (Tm) of layered 2D MHPs by employing a strategy that involves the modification of flexible alkylammonium through N-methylation and I-substitution. Structural-property analysis reveals that the N-methylation and I-substitution play pivotal roles in reducing hydrogen bond interactions between the organic components and inorganic parts, lowering the rotational symmetry number of the cation and restricting the residual motion of the cations. Additional I···I interactions enhance intermolecular interactions and lead to improved molten stability, as evidenced by a higher viscosity. The 2D MHPs discussed in this study exhibit low Tm and wide melt-processable windows, e.g., (DMIPA)2PbI4 showcasing a low Tm of 98 °C and large melt-processable window of 145 °C. The efficacy of the strategy was further validated when applied to bromine-substituted 2D MHPs. Lowering the Tm and enhancing the molten stability of the MHPs hold great promise for various applications, including glass formation, preparation of high-quality films for photodetection, and fabrication of flexible devices.

Transcription factor TaNF-YB2 interacts with partners TaNF-YA7/YC7 and transcriptionally activates distinct stress-defensive genes to modulate drought tolerance in T. Aestivum.

BACKGROUND: Drought stress limits significantly the crop productivity. However, plants have evolved various strategies to cope with the drought conditions by adopting complex molecular, biochemical, and physiological mechanisms. Members of the nuclear factor Y (NF-Y) transcription factor (TF) family constitute one of the largest TF classes and are involved in plant responses to abiotic stresses. RESULTS: TaNF-YB2, a NY-YB subfamily gene in T. aestivum, was characterized in this study focusing on its role in mediating plant adaptation to drought stress. Yeast two-hybrid (Y-2 H), biomolecular fluoresence complementation (BiFC), and Co-immunoprecipitation (Co-IP) assays indicated that TaNF-YB2 interacts with the NF-YA member TaNF-YA7 and NF-YC family member TaNF-YC7, which constitutes a heterotrimer TaNF-YB2/TaNF-YA7/TaNF-YC7. The TaNF-YB2 transcripts are induced in roots and aerial tissues upon drought signaling; GUS histochemical staining analysis demonstrated the roles of cis-regulatory elements ABRE and MYB situated in TaNF-YB2 promoter to contribute to target gene response to drought. Transgene analysis on TaNF-YB2 confirmed its functions in regulating drought adaptation via modulating stomata movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis. TaNF-YB2 possessed the abilities in transcriptionally activating TaP5CS2, the P5CS family gene involving proline biosynthesis and TaSOD1, TaCAT5, and TaPOD5, the genes encoding antioxidant enzymes. Positive correlations were found between yield and the TaNF-YB2 transcripts in a core panel constituting 45 wheat cultivars under drought condition, in which two types of major haplotypes including TaNF-YB2-Hap1 and -Hap2 were included, with the former conferring more TaNF-YB2 transcripts and stronger plant drought tolerance. CONCLUSIONS: TaNF-YB2 is transcriptional response to drought stress. It is an essential regulator in mediating plant drought adaptation by modulating the physiological processes associated with stomatal movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis, depending on its role in transcriptionally regulating stress response genes. Our research deepens the understanding of plant drought stress underlying NF-Y TF family and provides gene resource in efforts for molecular breeding the drought-tolerant cultivars in T. aestivum.

Parathyroid hormone receptor-1 signaling aggravates hepatic fibrosis through upregulating cAMP response element-binding protein-like 2.

BACKGROUND AND AIMS: Parathyroid hormone receptor-1 (PTH1R) is a class B G protein-coupled receptor central to skeletal development, bone turnover, and calcium homeostasis. However, the role of PTH1R signaling in liver fibrosis is largely unknown. Here, the role of PTH1R signaling in the activation of HSCs and hepatic fibrosis was examined. APPROACH AND RESULTS: PTH1R was highly expressed in activated HSCs and fibrotic liver by using human liver specimens or carbon tetrachloride (CCl 4 )-treated or methionine and choline-deficient diet (MCD)-fed C57/BL6 mice. The mRNA level of hepatic PTH1R was positively correlated to α-smooth muscle actin in patients with liver cirrhosis. Mice with HSCs-specific PTH1R deletion were protected from CCl 4 , MCD, or western diet, plus low-dose CCl 4 -induced liver fibrosis. Conversely, parathyroid hormone (PTH) aggravated liver fibrosis in CCl 4 -treated mice. Mouse primary HSCs and LX2 cell lines were used for in vitro experiments. Molecular analyses by luciferase reporter assays and chromatin immunoprecipitation assays in combination with mRNA sequencing in HSCs revealed that cAMP response element-binding protein-like 2 (Crebl2), a novel regulator in HSCs treated by PTH that interacted with mothers against decapentaplegic homolog 3 (SMAD3) and increased the transcription of TGFß in activating HSCs and collagen deposition. In agreement, HSCs-specific Crebl2 deletion ameliorated PTH-induced liver fibrosis in CCl 4 -treated mice. CONCLUSIONS: In both mouse and human models, we found that PTH1R was highly expressed in activated HSCs and fibrotic liver. PTH1R signaling regulated collagen production in the HSCs through Crebl2/SMAD3/TGFß regulatory circuits. Blockade of PTH1R signaling in HSCs might help mitigate the development of liver fibrosis.

Detection of SARS-CoV-2 virus in middle ear effusions and its association with otitis media with effusion.

A large-scale outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) occurred in Shanghai, China, in early December 2022. To study the incidence and characteristics of otitis media with effusion (OME) complicating SARS-CoV-2, we collected 267 middle ear effusion (MEE) samples and 172 nasopharyngeal (NP) swabs from patients. The SARS-CoV-2 virus was detected by RT-PCR targeting. The SARS-CoV-2 virus, angiotensin-converting enzyme 2 (ACE2), and transmembrane serine protease 2 (TMPRSS2) expression in human samples was examined via immunofluorescence. During the COVID-19 epidemic in 2022, the incidence of OME (3%) significantly increased compared to the same period from 2020 to 2022. Ear symptoms in patients with SARS-CoV-2 complicated by OME generally appeared late, even after a negative NP swab, an average of 9.33 ± 6.272 days after COVID-19 infection. The SARS-CoV-2 virus was detected in MEE, which had a higher viral load than NP swabs. The insertion rate of tympanostomy tubes was not significantly higher than in OME patients in 2019-2022. Virus migration led to high viral loads in MEE despite negative NP swabs, indicating that OME lagged behind respiratory infections but had a favorable prognosis. Furthermore, middle ear tissue from adult humans coexpressed the ACE2 receptor for the SARS-CoV-2 virus and the TMPRSS2 cofactors required for virus entry.

Axial clearance measurement method based on wavelength division multiplexing with all-fiber microwave photonic mixing.

Rotor-stator axial clearance plays a pivotal role in ensuring the safety and efficiency of major rotating machinery. This paper introduces an innovative clearance measurement method based on wavelength division multiplexing (WDM) combined with all-fiber microwave photonic mixing. The method is distinguished by large measurement range, high accuracy and low drift. The WDM-based common optical path structure is established. A comprehensive theoretical model of axial clearance drift determined by wavelength and temperature is developed based on the thermo-optic effect of optical fiber material. To efficiently separate measurement and reference light at the probe, the optical design for a compact optical bandpass filter (OBPF) fiber sensor probe is proposed. The performance of the method is substantiated by simulations and experiments. The results demonstrate an accuracy of better than 2.8µm over a 23.5 mm range, surpassing existing methods. The method's capability to mitigate temperature-induced drift is further confirmed through high-temperature drift and comparative experiments.

Parameters estimation-based calibration method for rotational axis of line-structured light 3D reconstruction.

Rotation is a critical component in 3D reconstruction systems, where accurate calibration of rotation axis parameters is essential for 3D stitching. In this study, what we believe to be a novel parameters estimation-based method for calibrating rotation axis parameters using 2D planar targets is proposed. Compared to traditional circle fitting methods, this method takes both orientation and position information into account, resulting in better precision performance. By leveraging the transmission of spatial pose relationships, the parameters estimation-based calibration method also effectively mitigates the impact of noise for more accurate calibration of rotation axis parameters. Error validation and 3D reconstruction experiments proved the superior performance of the proposed method. The experiment results demonstrate the effectiveness and applicability of the approach in enhancing the calibration of rotation axis parameters for 3D reconstruction systems.

Deficiency of neutral cholesterol ester hydrolase 1 (NCEH1) impairs endothelial function in diet-induced diabetic mice.

BACKGROUND: Neutral cholesterol ester hydrolase 1 (NCEH1) plays a critical role in the regulation of cholesterol ester metabolism. Deficiency of NCHE1 accelerated atherosclerotic lesion formation in mice. Nonetheless, the role of NCEH1 in endothelial dysfunction associated with diabetes has not been explored. The present study sought to investigate whether NCEH1 improved endothelial function in diabetes, and the underlying mechanisms were explored. METHODS: The expression and activity of NCEH1 were determined in obese mice with high-fat diet (HFD) feeding, high glucose (HG)-induced mouse aortae or primary endothelial cells (ECs). Endothelium-dependent relaxation (EDR) in aortae response to acetylcholine (Ach) was measured. RESULTS: Results showed that the expression and activity of NCEH1 were lower in HFD-induced mouse aortae, HG-exposed mouse aortae ex vivo, and HG-incubated primary ECs. HG exposure reduced EDR in mouse aortae, which was exaggerated by endothelial-specific deficiency of NCEH1, whereas NCEH1 overexpression restored the impaired EDR. Similar results were observed in HFD mice. Mechanically, NCEH1 ameliorated the disrupted EDR by dissociating endothelial nitric oxide synthase (eNOS) from caveolin-1 (Cav-1), leading to eNOS activation and nitric oxide (NO) release. Moreover, interaction of NCEH1 with the E3 ubiquitin-protein ligase ZNRF1 led to the degradation of Cav-1 through the ubiquitination pathway. Silencing Cav-1 and upregulating ZNRF1 were sufficient to improve EDR of diabetic aortas, while overexpression of Cav-1 and downregulation of ZNRF1 abolished the effects of NCEH1 on endothelial function in diabetes. Thus, NCEH1 preserves endothelial function through increasing NO bioavailability secondary to the disruption of the Cav-1/eNOS complex in the endothelium of diabetic mice, depending on ZNRF1-induced ubiquitination of Cav-1. CONCLUSIONS: NCEH1 may be a promising candidate for the prevention and treatment of vascular complications of diabetes.

Association between endometrial thickness and birthweight of singletons from vitrified-warmed cycles: a retrospective cohort study.

RESEARCH QUESTION: What is the association between endometrial thickness (EMT) and the birthweight of singleton infants born from frozen-thawed embryo transfer cycles? DESIGN: This retrospective cohort study was conducted from January 2016 to December 2019. Participants were categorized into a natural cycle (NC, n = 8132) group and hormone replacement therapy (HRT, n = 4975) group. Only singleton deliveries were included. The primary outcomes were measures of birthweight and relevant indexes. Multivariable logistic regression and multivariable-adjusted linear regression models that incorporated restricted cubic splines were used. RESULTS: In the HRT group, the risk of delivering a small for gestational age (SGA) infant was increased in women with an EMT <8.0 mm (adjusted odds ratio [aOR] 1.85, 95% confidence interval [CI] 1.17-2.91) compared with women with an EMT of 8.0 to <12.0 mm, and increased with an EMT ≥12.0 mm (aOR 1.85, 95% CI 1.03-3.33). An inverted U-shaped relationship was found between EMT and birthweight in women with HRT. No significant differences were shown in birthweight z-score, or being SGA or large for gestational age, in singletons among the three EMT groups in the natural cycles. CONCLUSIONS: A thinner endometrium seen in women undergoing HRT cycles was associated with a lower birthweight z-score, as well as a higher risk of SGA. However, no significant association was observed between EMT and birthweight z-score or SGA in the NC group. It is noteworthy that a thicker endometrium was not associated with a higher birthweight in frozen-thawed embryo transfer (FET) cycles. Women with a thin endometrium who achieve pregnancy require specialized attention, particularly if they are undergoing FET with HRT cycles.

Rh(III)-Catalyzed C7-Alkylation of Isatogens with Malonic Acid Diazoesters.

Rh(III)-catalyzed C7-alkylation of isatogens (indolin-3-one N-oxides) with malonic acid diazoesters has been developed. This strategy utilizes oxygen anion on the N-oxide group of isatogens as a directing group and successfully achieves the synthesis of a series of C7-alkylated isatogens with moderate to good yields (48-86% yields). Moreover, the N-oxides of isatogens can not only serve as the simple directing group for C7-H bond cleavage but also be deoxidized for easy removal.

Application of digital pathology-based advanced analytics of tumour microenvironment organisation to predict prognosis and therapeutic response.

In recent years, the application of advanced analytics, especially artificial intelligence (AI), to digital H&E images, and other histological image types, has begun to radically change how histological images are used in the clinic. Alongside the recognition that the tumour microenvironment (TME) has a profound impact on tumour phenotype, the technical development of highly multiplexed immunofluorescence platforms has enhanced the biological complexity that can be captured in the TME with high precision. AI has an increasingly powerful role in the recognition and quantitation of image features and the association of such features with clinically important outcomes, as occurs in distinct stages in conventional machine learning. Deep-learning algorithms are able to elucidate TME patterns inherent in the input data with minimum levels of human intelligence and, hence, have the potential to achieve clinically relevant predictions and discovery of important TME features. Furthermore, the diverse repertoire of deep-learning algorithms able to interrogate TME patterns extends beyond convolutional neural networks to include attention-based models, graph neural networks, and multimodal models. To date, AI models have largely been evaluated retrospectively, outside the well-established rigour of prospective clinical trials, in part because traditional clinical trial methodology may not always be suitable for the assessment of AI technology. However, to enable digital pathology-based advanced analytics to meaningfully impact clinical care, specific measures of 'added benefit' to the current standard of care and validation in a prospective setting are important. This will need to be accompanied by adequate measures of explainability and interpretability. Despite such challenges, the combination of expanding datasets, increased computational power, and the possibility of integration of pre-clinical experimental insights into model development means there is exciting potential for the future progress of these AI applications. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Impact of Molecular Chlorine Production from Aerosol Iron Photochemistry on Atmospheric Oxidative Capacity in North China.

Elevated levels of atmospheric molecular chlorine (Cl2) have been observed during the daytime in recent field studies in China but could not be explained by the current chlorine chemistry mechanisms in models. Here, we propose a Cl2 formation mechanism initiated by aerosol iron photochemistry to explain daytime Cl2 formation. We implement this mechanism into the GEOS-Chem chemical transport model and investigate its impacts on the atmospheric composition in wintertime North China where high levels of Cl2 as well as aerosol chloride and iron were observed. The new mechanism accounts for more than 90% of surface air Cl2 production in North China and consequently increases the surface air Cl2 abundances by an order of magnitude, improving the model's agreement with observed Cl2. The presence of high Cl2 significantly alters the oxidative capacity of the atmosphere, with a factor of 20-40 increase in the chlorine radical concentration and a 20-40% increase in the hydroxyl radical concentration in regions with high aerosol chloride and iron loadings. This results in an increase in surface air ozone by about 10%. This new Cl2 formation mechanism will improve the model simulation capability for reactive chlorine abundances in the regions with high emissions of chlorine and iron.

Yin Yang 1 facilitates the activation, inflammation, and extracellular matrix deposition of hepatic stellate cells in hepatic fibrosis.

Chronic hepatic diseases often involve fibrosis as a pivotal factor in their progression. This study investigates the regulatory mechanisms of Yin Yang 1 (YY1) in hepatic fibrosis. Our data reveal that YY1 binds to the prolyl hydroxylase domain 1 (PHD1) promoter. Rats treated with carbon tetrachloride (CCl4) display heightened fibrosis in liver tissues, accompanied by increased levels of YY1, PHD1, and the fibrosis marker alpha-smooth muscle actin (α-SMA). Elevated levels of YY1, PHD1, and α-SMA are observed in the liver tissues of CCl4-treated rats, primary hepatic stellate cells (HSCs) isolated from fibrotic liver tissues, and transforming growth factor beta-1 (TGF-ß1)-induced HSCs. The human HSC cell line LX-2, upon YY1 overexpression, exhibits enhanced TGF-ß1-induced activation, leading to increased expression of extracellular matrix (ECM)-related proteins and inflammatory cytokines. YY1 silencing produces the opposite effect. YY1 exerts a positive regulatory effect on the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and PHD1 expression. PHD1 silencing rescues the promotion of YY1 in cell activation, ECM-related protein expression, and inflammatory cytokine production in TGF-ß1-treated LX-2 cells. Overall, our findings propose a model wherein YY1 facilitates TGF-ß1-induced HSC activation, ECM-related protein expression, and inflammatory cytokine production by promoting PHD1 expression and activating the PI3K/AKT signaling pathway. This study positions YY1 as a promising therapeutic target for hepatic fibrosis.

A Stepwise Interventional Strategy for the Removal of Adherent Totally Implanted Central Venous Access Port Catheters.

BACKGROUND: To evaluate the safety and effectiveness of a stepwise interventional strategy for the removal of adherent totally implanted central venous access port catheters, consisting of a guidewire support, antegrade coaxial separation, and retrograde coaxial separation with increasing technical complexity. METHODS: This study has a retrospective design. Thirty-two patients who had failed routine removal of the port catheter and were then transferred to interventional radiology between November 2017 and December 2023 were reviewed. The technical success and complication rates were recorded. RESULTS: All adherent catheters were successfully removed without catheter fragmentation, using guidewire support (n = 21), antegrade coaxial separation (n = 5), and retrograde coaxial separation (n = 6). The technical success rate was 100%, and no complications occurred. CONCLUSIONS: The proposed stepwise interventional strategy successfully removed adherent port catheters, with good safety and high effectiveness. It appeared to reduce the incidence of catheter fracture during the removal of adherent totally implantable central venous access port catheters.

Diagnostic performance of coronary computed tomography angiography stenosis score for coronary stenosis.

BACKGROUND: Coronary computed tomography angiography stenosis score (CCTA-SS) is a proposed diagnosis score that considers the plaque characteristics, myocardial function, and the diameter reduction rate of the lesions. This study aimed to evaluate the diagnostic performance of the CCTA-SS in seeking coronary artery disease (CAD). METHODS: The 228 patients with suspected CAD who underwent CCTA and invasive coronary angiography (ICA) procedures were under examination. The diagnostic performance was evaluated with the receiver operating curve (ROC) for CCTA-SS in detecting CAD (defined as a diameter reduction of ≥ 50%) and severe CAD (defined as a diameter reduction of ≥ 70%). RESULTS: The area under ROC (AUC) of CCTA-SS was 0.909 (95% CI: 0.864-0.943), which was significantly higher than that of CCTA (AUC: 0.826; 95% CI: 0.771-0.873; P = 0.0352) in diagnosing of CAD with a threshold of 50%. The optimal cutoff point of CCTA-SS was 51% with a sensitivity of 90.66%, specificity of 95.65%, positive predictive value of 98.80%, negative predictive value of 72.13%, and accuracy of 91.67%, whereas the optimal cutoff point of CCTA was 55%, and the corresponding values were 87.36%, 93.48%, 98.15%, 65.15%, and 88.60%, respectively. With a threshold of 70%, the performance of CCTA-SS with an AUC of 0.927 (95% CI: 0.885-0.957) was significantly higher than that of CCTA with an AUC of 0.521 (95% CI: 0.454-0.587) (P < 0.0001). CONCLUSIONS: CCTA-SS significantly improved the diagnostic accuracy of coronary stenosis, including CAD and severe CAD, compared with CCTA.

circZNF532 promotes endothelial-to-mesenchymal transition in diabetic retinopathy by recruiting TAF15 to stabilize PIK3CD.

Endothelial-to-mesenchymal transition (EndMT) is a pivotal event in diabetic retinopathy (DR). This study explored the role of circRNA zinc finger protein 532 (circZNF532) in regulating EndMT in DR progression. Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) to induce the DR cell model. Actinomycin D-treated HRMECs were used to confirm the mRNA stability of phosphoinositide-3 kinase catalytic subunit δ (PIK3CD). The interaction between TATA-box-binding protein-associated factor 15 (TAF15) and circZNF532/PIK3CD was subsequently analyzed using RNA immunoprecipitation (RIP), RNA pull-down. It was found that HG treatment accelerated EndMT process, facilitated cell migration and angiogenesis, and enhanced PIK3CD and p-AKT levels in HRMECs, whereas si-circZNF532 transfection neutralized these effects. Further data showed that circZNF532 recruited TAF15 to stabilize PIK3CD, thus elevating PIK3CD expression. Following rescue experiments suggested that PIK3CD overexpression partially negated the inhibitory effect of circZNF532 silencing on EndMT, migration, and angiogenesis of HG-treated HRMECs. In conclusion, our results suggest that circZNF532 recruits TAF15 to stabilize PIK3CD, thereby facilitating EndMT in DR.