Clinical Outcomes of Severe Rhinosinusitis Complicated with Cavernous Sinus Syndrome.

Background: Various diseases involving the cavernous sinus can cause a condition called cavernous sinus syndrome (CSS), which is characterized by ophthalmoplegia or sensory deficits over the face resulting from the compression effect of internal structure. While tumor compression is the most reported cause of CSS, statistical data on CSS caused by infections are limited. Its risk factors, treatment methods, and clinical outcomes are not well-documented. Methods: In this retrospective study, we reviewed the data of patients admitted to a tertiary medical center from 2015 to 2022 with a diagnosis of acute and chronic sinusitis and at least one diagnostic code for CSS symptoms. We manually reviewed whether patients were involved in two or more of the following cranial nerves (CN): CN III, CN IV, CN V, or CN VI, or at least one of these nerves with a neuroimaging-confirmed lesion in the cavernous sinus. Results: Nine patients were diagnosed with rhinosinusitis-related CSS. The most common comorbidity was type 2 diabetes, and the most common clinical manifestations were diplopia and blurred vision. The sphenoid sinus was the most affected sinus. One patient expired due to a severe brain abscess infection without surgery. The remaining patients underwent functional endoscopic sinus surgery, and 50% of the pathology reports indicated fungal infections. Staphylococcus spp. was the most cultured bacteria, and Amoxycillin/Clavulanate was the most used antibiotic. Only four patients had total recovery during the follow-up one year later. Conclusions: CSS is a rare but serious complication of rhinosinusitis. Patients with diabetes and the elderly may be at a higher risk for this complication. Even after treatment, some patients may still have neurological symptoms.

MCOLN1/TRPML1 in the lysosome: a promising target for autophagy modulation in diverse diseases.

MCOLN1/TRPML1 is a nonselective cationic channel specifically localized to the late endosome and lysosome. With its property of mediating the release of several divalent cations such as Ca2+, Zn2+ and Fe2+ from the lysosome to the cytosol, MCOLN1 plays a pivotal role in regulating a variety of cellular events including endocytosis, exocytosis, lysosomal biogenesis, lysosome reformation, and especially in Macroautophagy/autophagy. Autophagy is a highly conserved catabolic process that maintains cytoplasmic integrity by removing superfluous proteins and damaged organelles. Acting as the terminal compartments, lysosomes are crucial for the completion of the autophagy process. This review delves into the emerging role of MCOLN1 in controlling the autophagic process by regulating lysosomal ionic homeostasis, thereby governing the fundamental functions of lysosomes. Furthermore, this review summarizes the physiological relevance as well as molecular mechanisms through which MCOLN1 orchestrates autophagy, consequently influencing mitochondria turnover, cell apoptosis and migration. In addition, we have illustrated the implications of MCOLN1-regulated autophagy in the pathological process of cancer and myocardial ischemia-reperfusion (I/R) injury. In summary, given the involvement of MCOLN1-mediated autophagy in the pathogenesis of cancer and myocardial I/R injury, targeting MCOLN1 May provide clues for developing new therapeutic strategies for the treatment of these diseases. Exploring the regulation of MCOLN1-mediated autophagy in diverse diseases contexts will surely broaden our understanding of this pathway and offer its potential as a promising drug target.Abbreviation: CCCP:carbonyl cyanide3-chlorophenylhydrazone; CQ:chloroquine; HCQ: hydroxychloroquine;I/R: ischemia-reperfusion; MAP1LC3/LC3:microtubule associated protein 1 light chain 3; MCOLN1/TRPML1:mucolipin TRP cation channel 1; MLIV: mucolipidosis type IV; MTORC1:MTOR complex 1; ROS: reactive oxygenspecies; SQSTM1/p62: sequestosome 1.

Flexible molecular crystals for optoelectronic applications.

The cornerstones of the advancement of flexible optoelectronics are the design, preparation, and utilization of novel materials with favorable mechanical and advanced optoelectronic properties. Molecular crystalline materials have emerged as a class of underexplored yet promising materials due to the reduced grain boundaries and defects anticipated to provide enhanced photoelectric characteristics. An inherent drawback that has precluded wider implementation of molecular crystals thus far, however, has been their brittleness, which renders them incapable of ensuring mechanical compliance required for even simple elastic or plastic deformation of the device. It is perplexing that despite a plethora of reports that have in the meantime become available underpinning the flexibility of molecular crystals, the "discovery" of elastically or plastically deformable crystals remains limited to cases of serendipitous and laborious trial-and-error approaches, a situation that calls for a systematic and thorough assessment of these properties and their correlation with the structure. This review provides a comprehensive and concise overview of the current understanding of the origins of crystal flexibility, the working mechanisms of deformations such as plastic and elastic bending behaviors, and insights into the examples of flexible molecular crystals, specifically concerning photoelectronic changes that occur in deformed crystals. We hope this summary will provide a reference for future experimental and computational efforts with flexible molecular crystals aimed towards improving their mechanical behavior and optoelectronic properties, ultimately intending to advance the flexible optoelectronic technology.

Triphenylamine Spirofunctionalized Light-Emitting Conjugated Polymer with an Ultradeep-Blue Narrowband Emission for Large-Area Printed Display.

Emerging printed large-area polymer light-emitting diodes (PLEDs) are essential for manufacturing flat-panel displays and solid lighting devices. However, it is challenging to obtain large-area and stable ultradeep-blue PLEDs because of the lack of light-emitting conjugated polymers (LCPs) with robust deep-blue emissions, excellent morphological stabilities, and high charging abilities. Here, a novel unsymmetrically substituted polydiarylfluorene (POPSAF) is obtained with stable narrowband emission for large-area printed displays via triphenylamine (TPA) spirofunctionalization of LCPs. POPSAF films show narrowband and stable ultradeep-blue emission with a full width at half maximum (FWHM) of 36 nm, associated with their intrachain excitonic behavior without obvious polaron formation. Compared to controlled poly[4-(octyloxy)-9,9-diphenylfluoren-2,7-diyl]-co-[5-(octyloxy)-9,9-diphenylfluoren-2,7-diyl] (PODPF), excellent charge transport is observed in the POPSAF films because of the intrinsic hole transport ability of the TPA units. Large-area PLEDs are fabricated via blade-coating with an emission area of 9 cm2, which exhibit uniform ultradeep-blue emission with an FWHM of 36 nm and corresponding Commission internationale de l'éclairage (CIE) coordinates of (0.155, 0.072). These findings are attributed to the synergistic effects of robust emission, stable morphology, and printing capacity. Finally, preliminary printed passive matrix (PM) PLED displays with 20 × 20 pixels monochromes are fabricated, confirmed the effectiveness of spirofunctionalization in optoelectronics.

Cardiac magnetic resonance-based layer-specific strain in immune checkpoint inhibitor-associated myocarditis.

AIMS: To assess the different imaging characteristics between corticosteroid-sensitive (CS) and corticosteroid-refractory (CR) immune checkpoint inhibitor-associated myocarditis (ICIaM) with cardiac magnetic resonance (CMR) and the potential CMR parameters in the early detection of CR ICIaM. METHODS AND RESULTS: Thirty-five patients diagnosed with ICIaM and 30 age and gender-matched cancer patients without a history of ICI treatment were enrolled. CMR with contrast was performed within 2 days of clinical suspicion. Left ventricular ejection fraction (LVEF) and late gadolinium enhancement (LGE) were assessed by CMR. LV sub-endocardial (GLSendo) and sub-epicardial (GLSepi) global longitudinal strains were quantified by offline feature tracking analysis. CS and CR ICIaM were defined based on the trend of Troponin I and clinical course during corticosteroid treatment. All 35 patients presented with non-fulminant symptoms upon initial assessment. Twenty patients (57.14%) were sensitive, and 15 (42.86%) were refractory to corticosteroids. Compared with controls, 22 patients (62.86%) with ICIaM developed LGE. LVEF decreased in CR ICIaM compared with the CS group and controls. GLSendo (-14.61 ± 2.67 vs. -18.50 ± 2.53, P < 0.001) and GLSepi (-14.75 ± 2.53 vs. -16.68 ± 2.05, P < 0.001) significantly increased in patients with CR ICIaM compared with the CS ICIaM. In patients with CS ICIaM, although GLSepi (-16.68 ± 2.05 vs. -19.31 ± 1.80, P < 0.001) was impaired compared with the controls, GLSendo was preserved. There was no difference in CMR parameters between LGE-positive and negative groups. LVEF, GLSendo, and GLSepi were predictors of CR ICIaM. When LVEF, GLSendo, and GLSepi were included in multivariate analysis, only GLSendo remained an independent predictor of CR ICIaM (OR: 2.170, 95% CI: 1.189-3.962, P = 0.012). A GLSendo of ≥-17.10% (sensitivity, 86.7%; specificity, 80.0%; AUC, 0.860; P < 0.001) could predict CR ICIaM in the ICIaM cohort. Kaplan-Meier analysis showed that in patients with impaired GLSendo of ≥-17.10%, cardiovascular adverse events (CAEs) occurred much earlier than in patients with preserved GLSendo of <-17.10% (Log-rank test P = 0.017). CONCLUSIONS: CR and CS ICIaM demonstrated different functional and morphological characteristics in different myocardial layers. An impaired GLSendo could be a helpful parameter in early identifying corticosteroid-refractory individuals in the ICIaM population.

A Holistic Review of C = C Crosslinkable Conjugated Molecules in Solution-Processed Organic Electronics: Insights into Stability, Processibility, and Mechanical Properties.

Solution-processable organic conjugated molecules (OCMs) consist of a series of aromatic units linked by σ-bonds, which present a relatively freedom intramolecular motion and intermolecular re-arrangement under external stimulation. The cross-linked strategy provides an effective platform to obtain OCMs network, which allows for outstanding optoelectronic, excellent physicochemical properties, and substantial improvement in device fabrication. An unsaturated double carbon-carbon bond (C = C) is universal segment to construct crosslinkable OCMs. In this review, the authors will set C = C cross-linkable units as an example to summarize the development of cross-linkable OCMs for solution-processable optoelectronic applications. First, this review provides a comprehensive overview of the distinctive chemical, physical, and optoelectronic properties arising from the cross-linking strategies employed in OCMs. Second, the methods for probing the C = C cross-linking reaction are also emphasized based on the perturbations of chemical structure and physicochemical property. Third, a series of model C = C cross-linkable units, including styrene, trifluoroethylene, and unsaturated acid ester, are further discussed to design and prepare novel OCMs. Furthermore, a concise overview of the optoelectronic applications associated with this approach is presented, including light-emitting diodes (LEDs), solar cells (SCs), and field-effect transistors (FETs). Lastly, the authors offer a concluding perspective and outlook for the improvement of OCMs and their optoelectronic application via the cross-linking strategy.

SARS-CoV-2 NSP2 as a Potential Delivery Vehicle for Proteins.

The development of biomolecule delivery systems is essential for the treatment of various diseases such as cancer, immunological diseases, and metabolic disorders. For the first time, we found that SARS-CoV-2-encoded nonstructural protein 2 (NSP2) can be secreted from the cells, where it is synthesized. Brefeldin A and H89, inhibitors of ER/Golgi secretion pathways, did not inhibit NSP2 secretion. NSP2 is likely secreted via an unconventional secretory pathway. Moreover, both secreted and purified NSP2 proteins were able to traverse the plasma membrane barrier and enter both immortalized human umbilical vein endothelial cells and tumor cell lines. After entry, the NSP2 protein was localized in only the cytoplasm. Cytochalasin D, a potent inhibitor of actin polymerization, inhibited the entry of NSP2. NSP2 can carry other molecules into cells. Burkholderia lethal factor 1, a monomeric toxin from the intracellular pathogen Burkholderia pseudomallei, has demonstrated antitumor activity by targeting host eukaryotic initiation translation factor 4A. An NSP2-BLF1 fusion protein was translocated across the cellular membranes of Huh7 cells and mediated cell killing. By using different approaches, including protein purification, chemical inhibition, and cell imaging, we confirm that NSP2 is able to deliver heterologous proteins into cells. NSP2 can act as a potential delivery vehicle for proteins.

Ultraviolet Organic Laser from Rhombus Microcrystal: Benefits of Single-Molecule Emission from Twisted Structure.

Light-emitting molecular crystals with efficient emission behavior are crucial for fabricating low-threshold ultraviolet organic lasers. Herein, we demonstrated a rhombus microcrystal from a fluorene-based conjugated molecule (CL-1) with robust emission behavior for an ultraviolet organic laser. Due to the synergistic effect of twisted intramolecular conformation and weak π-interaction, the CL-1 single crystal showed an extremely high photoluminescence quantum yield (PLQY) of ∼82%, due to their single-molecule excitonic behavior. Considering the diverse noncovalent interactions, CL-1 molecules easily self-assembled into the rhombus microcrystals. Finally, a low-threshold ultraviolet organic laser was fabricated with a sharp emission at 379 nm, attributed to the 0-1 vibration band of a single CL-1 molecule, also further confirming the single twisted-molecule emission in crystal states. Precisely controlling the intramolecular twisted structure and intermolecular interaction of organic conjugated molecules is a precondition to obtain robust ultraviolet emission for optoelectronic applications.

Coplanar Conformational Structure of π-Conjugated Polymers for Optoelectronic Applications.

Hierarchical structure of conjugated polymers is critical to dominating their optoelectronic properties and applications. Compared to nonplanar conformational segments, coplanar conformational segments of conjugated polymers (CPs) demonstrate favorable properties for applications as a semiconductor. Herein, recent developments in the coplanar conformational structure of CPs for optoelectronic devices are summarized. First, this review comprehensively summarizes the unique properties of planar conformational structures. Second, the characteristics of the coplanar conformation in terms of optoelectrical properties and other polymer physics characteristics are emphasized. Five primary characterization methods for investigating the complanate backbone structures are illustrated, providing a systematical toolbox for studying this specific conformation. Third, internal and external conditions for inducing the coplanar conformational structure are presented, offering guidelines for designing this conformation. Fourth, the optoelectronic applications of this segment, such as light-emitting diodes, solar cells, and field-effect transistors, are briefly summarized. Finally, a conclusion and outlook for the coplanar conformational segment regarding molecular design and applications are provided.

Nanocrystal Array Engineering and Optoelectronic Applications of Organic Small-Molecule Semiconductors.

Organic small-molecule semiconductor materials have attracted extensive attention because of their excellent properties. Due to the randomness of crystal orientation and growth location, however, the preparation of continuous and highly ordered organic small-molecule semiconductor nanocrystal arrays still face more challenges. Compared to organic macromolecules, organic small molecules exhibit better crystallinity, and therefore, they exhibit better semiconductor performance. The formation of organic small-molecule crystals relies heavily on weak interactions such as hydrogen bonds, van der Waals forces, and π-π interactions, which are very sensitive to external stimuli such as mechanical forces, high temperatures, and organic solvents. Therefore, nanocrystal array engineering is more flexible than that of the inorganic materials. In addition, nanocrystal array engineering is a key step towards practical application. To resolve this problem, many conventional nanocrystal array preparation methods have been developed, such as spin coating, etc. In this review, the typical and recent progress of nanocrystal array engineering are summarized. It is the typical and recent innovations that the array of nanocrystal array engineering can be patterned on the substrate through top-down, bottom-up, self-assembly, and crystallization methods, and it can also be patterned by constructing a series of microscopic structures. Finally, various multifunctional and emerging applications based on organic small-molecule semiconductor nanocrystal arrays are introduced.

Intrinsically Stretchable and Efficient Fully Π-Conjugated Polymer via Internal Plasticization for Flexible Deep-Blue Polymer Light-Emitting Diodes with CIEy = 0.08.

Intrinsically stretchable polymeric semiconductors are essential to flexible polymer light-emitting diodes (PLEDs) owing to their excellent strain tolerance capacity under long-time deformation operation. Obtaining intrinsic stretchability, robust emission properties, and excellent charge-transport behavior simultaneously from fully π-conjugated polymers (FCPs) is difficult, particularly for applications in deep-blue PLEDs. Herein, an internal plasticization strategy is proposed to introduce a phenyl-ester plasticizer into polyfluorenes (PF-MC4, PF-MC6, and PF-MC8) for narrowband deep-blue flexible PLEDs. Compared with controlled poly[4-(octyloxy)-9,9-diphenylfluoren-2,7-diyl]-co-[5-(octyloxy)-9,9-diphenylfluoren-2,7-diyl] (PODPFs) (2.5%), the freestanding PF-MC8 thin film shows a fracture strain of >25%. The three stretchable films exhibit stable and efficient deep-blue emission (PLQY > 50%) because of the encapsulation of π-conjugated backbone via pendant phenyl-ester plasticizers. The PF-MC8-based PLEDs show deep-blue emission, which corresponds to CIE and EQE values of (0.16, 0.10) and 1.06%, respectively. Finally, the narrowband deep-blue electroluminescence (FWHM of ≈25 nm; CIE coordinates: (0.15, 0.08)) and performance of the transferred PLEDs based on the PF-MC8 stretchable film are independent of the tensile ratio (up to 45%); however, they show a maximum brightness of 1976 cd m-2 at a ratio of 35%. Therefore, internal plasticization is a promising approach for designing intrinsically stretchable FCPs for flexible electronics.

Validation of an Automated Cardiothoracic Ratio Calculation for Hemodialysis Patients.

Cardiomegaly is associated with poor clinical outcomes and is assessed by routine monitoring of the cardiothoracic ratio (CTR) from chest X-rays (CXRs). Judgment of the margins of the heart and lungs is subjective and may vary between different operators. METHODS: Patients aged > 19 years in our hemodialysis unit from March 2021 to October 2021 were enrolled. The borders of the lungs and heart on CXRs were labeled by two nephrologists as the ground truth (nephrologist-defined mask). We implemented AlbuNet-34, a U-Net variant, to predict the heart and lung margins from CXR images and to automatically calculate the CTRs. RESULTS: The coefficient of determination (R2) obtained using the neural network model was 0.96, compared with an R2 of 0.90 obtained by nurse practitioners. The mean difference between the CTRs calculated by the nurse practitioners and senior nephrologists was 1.52 ± 1.46%, and that between the neural network model and the nephrologists was 0.83 ± 0.87% (p < 0.001). The mean CTR calculation duration was 85 s using the manual method and less than 2 s using the automated method (p < 0.001). CONCLUSIONS: Our study confirmed the validity of automated CTR calculations. By achieving high accuracy and saving time, our model can be implemented in clinical practice.

Selenide-doped bismuth sulfides (Bi2S3-xSex) and their hierarchical heterostructure with ReS2for sodium/potassium-ion batteries.

In this work, selenide-doped bismuth sulfides (Bi2S3-xSex) was successfully prepared through Se doping Bi2S3 Se to improve the electronic conductivity and increase the interlayer spacing. Then the anisotropic ReS2 nanosheet arrays were grown on the surface of Bi2S3-xSex to form a hierarchical heterostructure (Bi2S3-xSex@ReS2). The doping and construction of heterostructure processes can greatly improve the electrochemical conductivity of electrode materials and relieve the volume expansion during the continuous charge/discharge processes. While applied as SIBs anode, the specific capacity of 330 mAh g-1 was maintained after 450 cycles at the current density of 1.0 A g-1. It can also keep 200 mAh g-1 specific capacity after 900 cycles at 1.0 A g-1 for the anode of PIBs. This heterogeneous engineering and doping dual strategies could provide a good idea for the synthesis of new bimetallic sulfides with outstanding battery performance for SIBs and PIBs.

Photoexcitation dynamics and energy engineering in supramolecular doping of organic conjugated molecules.

Doping and blending strategies are crucial means to precisely control the excited states and energy level in conjugated molecular systems. However, effective models and platforms are rarely proposed to systematically explore the effects of the formation of trapped doped centers on heterogeneous structures, energy level and ultrafast photophysical process. Herein, for deeply understanding the impact of molecular doping in film energy levels and photoexcitation dynamics, we set a supramolecular N-B coordination composed by the conjugated molecules of pyridine functionalized diarylfluorene (host material), named as ODPF-Phpy and ODPF-(Phpy)2, and the molecule of tris(perfluorophenyl)borane (BCF) (guest material). The generation of the molecular-level coordination bond increased the binding energy of N atoms and tuned the band-gap, leading to a new fluorescent emission center with longer excitation wavelength and emission wavelength. The intermolecular Förster resonance energy transfer (FRET) in blending films make it present inconsistent fluorescent behaviors compared to that in solution. The charge transfer (CT) state of N-B coordinated compounds and the changed dielectric constant of blending films resulted in a large PL spectra red-shift with the increased dopant ratio, causing a wide-tunable fluorescent color. The excited state behaviors of two compounds in blending system was further investigated by the transient absorption (TA) spectroscopy. Finally, we found supramolecular coordination blending can effectively improve the films' photoluminescence quantum yield (PLQY) and conductivity. We believe this exploration in the internal coordination mechanisms would deepen the insights about doped semiconductors and is helpful in developing novel high-efficient fluorescent systems.

Large-Area Blade-Coated Deep-Blue Polymer Light-Emitting Diodes with a Narrowband and Uniform Emission.

Large-area polymer light-emitting diodes (PLEDs) manufactured by printing are required for flat-panel lighting and displays. Nevertheless, it remains challenging to fabricate large-area and stable deep-blue PLEDs with narrowband emission due to the difficulties in precisely tuning film uniformity and obtaining single-exciton emission. Herein, efficient and stable large-area deep-blue PLEDs with narrowband emission are prepared from encapsulated polydiarylfluorene. Encapsulated polydiarylfluorenes presented an efficient and stable deep-blue emission (peak: 439 nm; full width at half maximum (FWHM): 39 nm) in the solid state due to their single-chain emission behavior without inter-backbone chain aggregation. Large-area uniform blade-coated films (16 cm2 ) are also fabricated with excellent smoothness and morphology. Benefitting from efficient emission and excellent printed capacity, the blade-coated PLEDs with a device area of 9 mm2 realized uniform deep-blue emission (FWHM: 38 nm; CIE: 0.153, 0.067), with a corresponding maximum external quantum efficiency and the brightness comparable to those of devices based on spin-coated films. Finally, considering the essential role of deep-blue LEDs, a preliminary patterned PLED array with a pixel size of 800 × 1000 µm2 and a monochrome display is fabricated, highlighting potential full-color display applications.

Applying quantitative CMR parameters for detecting myocardial lesion in immune checkpoint inhibitors-associated myocarditis.

PURPOSE: Sparse researches evaluated the quantitative cardiovascular magnetic resonance (CMR) parameters for immune checkpoint inhibitors (ICI)-associated myocarditis. We aimed to apply quantitative CMR mappings and late gadolinium enhancement (LGE) extent for detecting ICI-associated myocarditis. METHOD: The retrospective study included patients with ICI-associated myocarditis and CMR examination from August 2018 to August 2021 in our hospital. ICI-associated myocarditis was clinically diagnosed based on the clinical criteria by European Society of Cardiology guidelines. The multiparametric CMR images including T2 mapping and black blood T2-weighted images were used to evaluate myocardial edema. The myocardial edema ratio (ER) ≥ 2.0 was applied for determining myocardial edema on T2-weighted images. RESULTS: 56 patients with ICI-associated myocarditis were included. The global T2 value and native T1 value of patients with ICI-associated myocarditis were significantly higher than the reference ranges in our hospital (p < 0.05). The rate of elevated global T2 value (92%) was significantly higher than those of abnormal native T1 value (73%), ER (52%) and LGE presence (68%) in patients with ICI-associated myocarditis (p < 0.05). The LGE extent and left ventricular ejection fraction of patients with ICI-associated myocarditis were 10.38 ± 9.64% and 56.42 ± 8.54%, respectively. LGE extent inversely correlated with left ventricular ejection fraction (r = -0.38, p = 0.004) but positively correlated with native T1 value (r = 0.28, p < 0.04) and extracellular volume (r = 0.50, p = 0.001). CONCLUSIONS: T2 mapping could detect higher rate of patients with ICI-associated myocarditis than native T1 mapping, ER and LGE presence. LGE extent inversely correlated with left ventricular ejection fraction but positively correlated with native T1 value and extracellular volume in patients with ICI-associated myocarditis.

Inferior Vena Cava as a Trigger for Paroxysmal Atrial Fibrillation: Incidence, Characteristics, and Implications.

BACKGROUND: Identifying nonpulmonary vein triggers during atrial fibrillation (AF) ablation is of great importance. Currently, there are limited data on AF triggered by the inferior vena cava (IVC). OBJECTIVES: This study was performed to investigate the incidence, characteristics, and implications of IVC triggers for AF. METHODS: A total of 661 patients who underwent initial paroxysmal AF ablation were included. After pulmonary vein isolation, ectopic beats that triggered AF were further studied. Activation mapping and angiography were performed to confirm the location of ectopic origin. Electrocardiographic analysis of the ectopic P-wave (P'-wave) was performed. RESULTS: Six patients (0.91%) with AF triggered by the IVC were confirmed. The mean distance from the earliest activation site to the IVC ostium was 6.8 ± 2.5 mm (5.2 to 11.2 mm). Furthermore, the arrhythmogenic foci within the IVC were all located at the apical hemisphere of the IVC (3 at the septal side and 3 at the anterior side). A total of 2.3 ± 0.5 applications of radiofrequency energy were delivered to eliminate IVC triggers. The mean duration of the P' wave was 91.2 ± 11.2 milliseconds (81 to 108 milliseconds), which was narrower than that of the sinus P-wave (115.2 ± 19.3 milliseconds [87 to 139 milliseconds]; P = 0.002). Moreover, the configuration of all P' waves in the inferior leads was negative. During a mean follow-up period of 25.5 ± 7.3 months, all 6 patients remained arrhythmia free without antiarrhythmic drugs. CONCLUSIONS: IVC trigger, a rare but latent source of paroxysmal AF, could be identified and safely eliminated by focal radiofrequency ablation. Ectopic beats originating from the IVC presented with narrow P'-wave duration and negative P' waves in all inferior leads.

Improving the Intrinsic Stretchability of Fully Conjugated Polymer for Deep-Blue Polymer Light-Emitting Diodes with a Narrow Band Emission: Benefits of Self-Toughness Effect.

It is challenging to construct the intrinsically stretchable active layer of rigid conjugated polymers (CPs) toward flexible deep-blue light-emitting diodes (FLEDs). Inspired by the self-toughness effect, sacrificial hydrogen bonding (H-bonding) and a cross-linked network synergistically enabled polydiarylfluorene (PFs-NH) films to present efficient deep-blue emission and excellent intrinsic stretchability. In particular, a cross-linked network structure presenting viscoelasticity behaviors, which was successfully inherited into postprocessed films with interchain interpenetration and a crystallinity domain and behaved as energy absorption and dissipation centers, was induced by the interchain H-bonding interaction in toluene (Tol) precursor solutions where the storage moduli (G') gradually exceeded the loss moduli (G″). Subsequently, intrinsic stretchable films with a tensile rate of 30% were prepared from Tol solutions, different from the brittle films from polar solvents. Eventually, narrow band, deep-blue PLEDs showed a maximum EQE of 1.28% and a full width half-maximum (fwhm) of 28 nm. Therefore, the self-toughness effect induced by hierarchical structures will be feasible to obtain high-performance FLEDs.

Tripartite motif 25 ameliorates doxorubicin-induced cardiotoxicity by degrading p85α.

Doxorubicin (DOX)-based chemotherapy is widely used to treat malignant tumors; however, the cardiotoxicity induced by DOX restricts its clinical usage. A therapeutic dose of DOX can activate ubiquitin-proteasome system. However, whether and how ubiquitin-proteasome system brings out DOX-induced cardiotoxicity remains to be investigated. Here we conducted a proteomics analysis of a DOX-induced cardiotoxicity model to screen the potentially ubiquitination-related molecules. Dysregulated TRIM25 was found to contribute to the cardiotoxicity. In vivo and in vitro cardiotoxicity experiments revealed that TRIM25 ameliorated DOX-induced cardiotoxicity. Electron microscopy and endoplasmic reticulum stress markers revealed that TRIM25 mitigated endoplasmic reticulum stress and apoptosis in DOX-induced cardiomyocytes. Mechanistically, the Co-immunoprecipitation assays and CHX pulse-chase experiment determined that TRIM25 affected p85α stability and promoted its ubiquitination and degradation. This leads to increase of nuclear translocation of XBP-1s, which mitigates endoplasmic reticulum stress. These findings reveal that TRIM25 may have a therapeutic role for DOX-induced cardiotoxicity.

The prognostic value of global myocardium strain by CMR-feature tracking in immune checkpoint inhibitor-associated myocarditis.

OBJECTIVES: Immune checkpoint inhibitor (ICI)-associated myocarditis is a potentially fatal complication. Sparse published researches evaluated the prognostic value of cardiovascular magnetic resonance feature tracking (CMR-FT) for ICI-associated myocarditis. METHODS: In the single-center retrospective study, 52 patients with ICI-associated myocarditis and CMR were included from August 2018 to July 2021. The ICI-associated myocarditis was diagnosed by using the clinical criteria of the European Society of Cardiology guidelines. Major adverse cardiovascular events (MACE) were comprised of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. RESULTS: During a median follow-up of 171 days, 14 (27%) patients developed MACE. For patients with MACE, the global circumferential strain (GCS), global radial strain (GRS), global longitudinal strain (GLS), and left ventricular ejection fraction (LVEF) were significantly worse and native T1 values and late gadolinium enhancement (LGE) extent were significantly increased, compared with patients without MACE (p < 0.05). The GLS remained the independent factor associated with a higher risk of MACE (hazard ratio (HR): 2.115; 95% confidence interval (CI): 1.379-3.246; p = 0.001) when adjusting for LVEF, LGE extent, age, sex, body mass index, steroid treatment, and prior cardiotoxic chemotherapy or radiation. After adjustment for LVEF, the GLS remained the independent risk factor associated with a higher rate of MACE among patients with a preserved LVEF (HR: 1.358; 95% CI: 1.007-1.830; p = 0.045). CONCLUSIONS: GLS could provide independent prognostic value over GCS, GRS, traditional CMR features, and clinical features in patients with ICI-associated myocarditis. KEY POINTS: • The global circumferential strain (GCS), global radial strain (GRS), and global longitudinal strain (GLS) by cardiovascular magnetic resonance feature tracking were significantly impaired in patients with an immune checkpoint inhibitor (ICI)-associated myocarditis. • GLS was still significantly impaired in patients with preserved left ventricular ejection fraction. • The worse GLS was an independent risk factor over GCS, GRS, traditional CMR features, and clinical features for predicting major adverse cardiovascular events in patients with ICI-associated myocarditis.