OMGMed: Advanced System for Ocular Myasthenia Gravis Diagnosis via Eye Image Segmentation.

This paper presents an eye image segmentation-based computer-aided system for automatic diagnosis of ocular myasthenia gravis (OMG), called OMGMed. It provides great potential to effectively liberate the diagnostic efficiency of expert doctors (the scarce resources) and reduces the cost of healthcare treatment for diagnosed patients, making it possible to disseminate high-quality myasthenia gravis healthcare to under-developed areas. The system is composed of data pre-processing, indicator calculation, and automatic OMG scoring. Building upon this framework, an empirical study on the eye segmentation algorithm is conducted. It further optimizes the algorithm from the perspectives of "network structure" and "loss function", and experimentally verifies the effectiveness of the hybrid loss function. The results show that the combination of "nnUNet" network structure and "Cross-Entropy + Iou + Boundary" hybrid loss function can achieve the best segmentation performance, and its MIOU on the public and private myasthenia gravis datasets reaches 82.1% and 83.7%, respectively. The research has been used in expert centers. The pilot study demonstrates that our research on eye image segmentation for OMG diagnosis is very helpful in improving the healthcare quality of expert doctors. We believe that this work can serve as an important reference for the development of a similar auxiliary diagnosis system and contribute to the healthy development of proactive healthcare services.

Enhancing CO2 Electroreduction to C2 Products on Metal-Nitrogen Sites by Regulating H2O Dissociation.

Water dissociation remarkably affects the CO2 reduction to CO and HCOOH, but whether it is effective for two-carbon product formation on M-Nx-containing catalysts is still ambiguous. Herein, by using a fluorinated metal phthalocyanine (MPc-F) as the M-N4-based model electrocatalyst, experimental and theoretical results reveal that the H2O-dissociation-induced active H species decrease the overpotential of the *CO hydrogenation to *CHO and facilitate the C-C coupling between *CHO and neighboring CO. Such an effect is strengthened by an increase in the *CO binding strength on the metal center. By introducing CuPc as the H2O dissociation catalyst into MPc-F (MPc-F/CuPc) to accurately regulate the H2O dissociation, the faradic efficiency of C2 products on FePc-F/CuPc and MnPc-F/CuPc increases from 0% (FePc-F and MnPc-F) to 26 and 36%, respectively. This work develops a novel strategy for enhancing the selectivity of M-Nx-containing catalysts to C2 products and reveals the correlation between H2O dissociation and C2 product formation.

Revealing a Double-Volcano-Like Structure-Activity Relationship for Substitution-Functionalized Metal-Phthalocyanine Catalysts toward Electrochemical CO2 Reduction.

Electron-donating/-withdrawing groups (EDGs/EWGs) substitution is widely used to regulate the catalytic performance of transition-metal phthalocyanine (MPc) toward electrochemical CO2 reduction, but the corresponding structure-activity relationships and regulation mechanisms are still ambiguous. Herein, by investigating a series of substitution-functionalized MPc (MPc-X), this work reveals a double-volcano-like relationship between the electron-donating/-withdrawing abilities of the substituents and the catalytic activities of MPc-X. The weak-EDG/-EWG substitution enhances whereas the strong-EDG/-EWG substitution mostly lowers the CO selectivity of MPc. Experimental and calculation results demonstrate that the electronic properties of the substituents influence the symmetry and energy of the highest occupied molecular orbitals of MPc-X, which in turn determine the CO2 adsorption/activation and lead to diverse CO2 reduction pathways on the EWG or EDG substituted MPc via different CO2 adsorption modes. This work provides mechanism insights that could be guidance for the design and regulation of molecular catalysts.

Cross-cultural adaptation for international nursing students from the Belt and Road Initiative in China: A follow-up survey study.

Background: and Purpose: As the number of international students from Belt and Road Initiative countries continues to increase in China, it is essential to find methods to improve cross-cultural adaptation in the host country, a crucial aspect of the experiences of international nursing students. Therefore, this study aimed to investigate the change in cross-cultural adaptation of international nursing students during the first year in China. Methods: Data collection was conducted for international nursing students (n = 108) between September 2019 and August 2020, focusing on sociocultural adaptation, academic adaptation, and academic performance of international nursing students using validated questionnaires. Results: The mean score at the follow-up time verified an increased level of sociocultural and academic adaptation and academic performance. Academic adaptation is a complete mediator between sociocultural adaptation and academic performance at two-time points, and the size of the mediation effect accounted for 95.9 % of the total effect in six months and 99.0 % in one year. Conclusions: The findings emphasized the importance of sociocultural and academic adaptation in cross-cultural adaptation and suggest that educational institutions should provide learning environments supporting these factors to ensure academic success.

The Role of Proton in High Power Density Vanadium Redox Flow Batteries.

To design high-performance vanadium redox flow batteries (VRFBs), the influence of proton on electrocatalysts cannot be neglected considering the abundance of proton in a highly acidic electrolyte. Herein, the impact of proton on metal oxide-based electrocatalysts in VRFBs is investigated, and a proton-incorporating strategy is introduced for high power density VRFBs, in addition to unraveling the catalytic mechanism. This study discloses that the metal oxide-based electrocatalyst (WO3) undergoes in situ surface reconstruction by forming H0.5WO3 after incorporating proton. Experimental and theoretical results precisely disclose the catalytic active sites. The battery with H0.5WO3 designed by a proton-incorporating strategy achieves an attractive power density of 1.12 W cm-2 and sustains more than 900 cycles without an obvious decay, verifying the outstanding electrochemical performance of H0.5WO3. This work not only sheds light on the influence of proton on electrocatalysts for rational design of advanced VRFBs catalysts but also provides guidelines for the fundamental understanding of the reaction mechanism, which is highly important for the application of VRFBs.

Singlet Oxygen Induced Site-Specific Etching Boosts Nitrogen-Carbon Sites for High-Efficiency Oxygen Reduction.

Targeted construction of carbon defects near the N dopants is an intriguing but challenging way to boost the electrocatalytic activity of N-doped carbon toward oxygen reduction reaction (ORR). Here, we report a novel site-specific etching strategy that features targeted anchoring of singlet oxygen (1 O2 ) on the N-adjacent atoms to directionally construct topological carbon defects neighboring the N dopants in N-doped carbon (1 O2 -N/C). This 1 O2 -N/C exhibits the highest ORR half-wave potential of 0.915 VRHE among all the reported metal-free carbon catalysts. Pyridinic-N bonded with a carbon pentagon of the neighboring topological carbon defects is identified as the primary active configuration, rendering enhanced adsorption of O2 , optimized adsorption energy of the ORR intermediates, and a significantly decreased total energy barrier for ORR. This 1 O2 -induced site-specific etching strategy is also applicable to different precursors, showing a tremendous potential for targeted construction of high-efficiency active sites in carbon-based materials.

Weakly Supervised Collaborative Learning for Airborne Pollen Segmentation and Classification from SEM Images.

Existing pollen identification methods heavily rely on the scale and quality of pollen images. However, there are many impurities in real-world SEM images that should be considered. This paper proposes a collaborative learning method to jointly improve the performance of pollen segmentation and classification in a weakly supervised manner. It first locates pollen regions from the raw images based on the detection model. To improve the classification performance, we segmented the pollen grains through a pre-trained U-Net using unsupervised pollen contour features. The segmented pollen regions were fed into a deep convolutional neural network to obtain the activation maps, which were used to further refine the segmentation masks. In this way, both segmentation and classification models can be collaboratively trained, supervised by just pollen contour features and class-specific information. Extensive experiments on real-world datasets were conducted, and the results prove that our method effectively avoids impurity interference and improves pollen identification accuracy (86.6%) under the limited supervision (around 1000 images with image-level labels).

Simulation Palynologists for Pollinosis Prevention: A Progressive Learning of Pollen Localization and Classification for Whole Slide Images.

Existing API approaches usually independently leverage detection or classification models to distinguish allergic pollens from Whole Slide Images (WSIs). However, palynologists tend to identify pollen grains in a progressive learning manner instead of the above one-stage straightforward way. They generally focus on two pivotal problems during pollen identification. (1) Localization: where are the pollen grains located? (2) Classification: which categories do these pollen grains belong to? To perfectly mimic the manual observation process of the palynologists, we propose a progressive method integrating pollen localization and classification to achieve allergic pollen identification from WSIs. Specifically, data preprocessing is first used to cut WSIs into specific patches and filter out blank background patches. Subsequently, we present the multi-scale detection model to locate coarse-grained pollen regions (targeting at "pollen localization problem") and the multi-classifiers combination to determine the fine-grained category of allergic pollens (targeting at "pollen classification problem"). Extensive experimental results have demonstrated the feasibility and effectiveness of our proposed method.

HLA-B*27 Heavy Chain Homo-Oligomers Promote the Cytotoxicity of NK Cells via Activation of PI3K/AKT Signaling.

Background and Objectives: Ankylosing spondylitis (AS) is a chronic inflammatory disease and is highly linked with the expression of the human leukocytic antigen-B*27 (HLA-B*27) genotype. HLA-B*27 heavy chain (B*27-HC) has an innate characteristic to slowly fold, resulting in the accumulation of the misfolded B*27-HC and the formation of homo-oligomeric B*27-HC molecules. The homo-oligomeric B*27-HC can act as a ligand of KIR3DL2. Interaction of the homo-oligomeric B*27-HC molecules with KIR3DL2 will trigger the survival and activation of KIR3DL2-positive NK cells. However, the effects of homo-oligomeric B*27-HC molecules associated with KIR3DL2 on the cytotoxic activity of NK cells and their cytokine expressions remain unknown. Materials and Methods: HLA-B*-2704-HC was overexpressed in the HMy2.C1R (C1R) cell line. Western blotting and quantitative RT-PCR were used to analyze the protein expression and cytokine expression, respectively, when C1R-B*-2704 cells that overexpress B*2704-HC were co-cultured with NK-92MI cells. Flow cytometry was used to analyze the cytotoxicity mediated by NK-92MI cells. Results: Our results revealed that NK-92MI cells up-regulated the expression of perforin and enhanced the cytotoxic activity via augmentation of PI3K/AKT signaling after co-culturing with C1R-B*2704 cells. Suppression of the dimerized B*27-HC formation or treatment with an inhibitor of PI3K, LY294002, or with an anti-B*27-HC monoclonal antibody can reduce the perforin expression of NK-92MI after co-culturing with C1R-B*-2704. Co-culturing with C1R-B*-2704 cells suppressed the TNF-α and IL6 expressions of NK-92MI cells. Conclusion: Stimulation of NK cell-mediated cytotoxicity by homo-oligomeric B*27-HC molecules may contribute to the pathogenesis of AS.

Pentacyclic triterpene oleanolic acid protects against cardiac aging through regulation of mitophagy and mitochondrial integrity.

Advanced aging exhibits altered cardiac geometry and function involving mitochondrial anomaly. Natural compounds display promises in the regulation of cardiac homeostasis via governance of mitochondrial integrity in aging. This study examined the effect of oleanolic acid (OA), a natural pentacyclic triterpenoid with free radical scavenging and P450 cyclooxygenase-regulating properties, on cardiac aging and mechanisms involved with a focus on mitophagy. Young (4-5 month-old) and old (22-24 month-old) mice were treated with OA for 6 weeks prior to assessment of cardiac function, morphology, ultrastructure, mitochondrial integrity, cell death and autophagy. Our data revealed that OA treatment alleviated aging-induced changes in myocardial remodeling (increased heart weight, chamber size, cardiomyocyte area and interstitial fibrosis), contractile function and intracellular Ca2+ handling, apoptosis, necroptosis, inflammation, autophagy and mitophagy (LC3B, p62, TOM20 and FUNDC1 but not BNIP3 and Parkin). OA treatment rescued aging-induced anomalies in mitochondrial ultrastructure (loss of myofilament alignment, swollen mitochondria, increased circularity), mitochondrial biogenesis and O2- production without any notable effect at young age. Interestingly, OA-offered benefit against cardiomyocyte aging was nullified by deletion of the mitophagy receptor FUNDC1 using FUNDC1 knockout mice, denoting an obligatory role for FUNDC1 in OA-elicited preservation of mitophagy. OA reconciled aging-induced changes in E3 ligase MARCH5 but not FBXL2, and failed to affect aging-induced rises in IP3R3. Taken together, our data indicated a beneficial role for OA in attenuating cardiac remodeling and contractile dysfunction in aging through a FUNDC1-mediated mechanism.

A Sulfonated Polyimide/Nafion Blend Membrane with High Proton Selectivity and Remarkable Stability for Vanadium Redox Flow Battery.

A sulfonated polyimide (SPI)/Nafion blend membrane composed of a designed and synthesized SPI polymer and the commercial Nafion polymer is prepared by a facile solution casting method for vanadium redox flow battery (VRFB). Similar molecular structures of both SPI and Nafion provide good compatibility and complementarity of the blend membrane. ATR-FTIR, 1H-NMR, AFM, and SEM are used to gain insights on the chemical structure and morphology of the blend membrane. Fortunately, the chemical stability of the SPI/Nafion blend membrane is effectively improved compared with reported SPI-based membranes for VRFB applications. In cycling charge-discharge tests, the VRFB with the as-prepared SPI/Nafion blend membrane shows excellent battery efficiencies and operational stability. Above results indicate that the SPI/Nafion blend membrane is a promising candidate for VRFB application. This work opens up a new possibility for fabricating high-performance SPI-based blend membrane by introduction of a polymer with a similar molecular structure and special functional groups into the SPI polymer.

Copper (II) Ion-Modified Gold Nanoclusters as Peroxidase Mimetics for the Colorimetric Detection of Pyrophosphate.

Copper (II) ions have been shown to greatly improve the chemical stability and peroxidase-like activity of gold nanoclusters (AuNCs). Since the affinity between Cu2+ and pyrophosphate (PPi) is higher than that between Cu2+ and AuNCs, the catalytic activity of AuNCs-Cu2+ decreases with the introduction of PPi. Based on this principle, a new colorimetric detection method of PPi with high sensitivity and selectivity was developed by using AuNCs-Cu2+ as a probe. Under optimized conditions, the detection limit of PPi was 0.49 nM with a linear range of 0.51 to 30,000 nM. The sensitivity of the method was three orders of magnitude higher than that of a fluorescence method using AuNCs-Cu2+ as the probe. Finally, the AuNCs-Cu2+ system was successfully applied to directly determine the concentration of PPi in human urine samples.

FUNDC1 insufficiency sensitizes high fat diet intake-induced cardiac remodeling and contractile anomaly through ACSL4-mediated ferroptosis.

OBJECTIVE: Ferroptosis is indicated in cardiovascular diseases. Given the prominent role of mitophagy in the governance of ferroptosis and our recent finding for FUN14 domain containing 1 (FUNDC1) in obesity anomalies, this study evaluated the impact of FUNDC1 deficiency in high fat diet (HFD)-induced cardiac anomalies. METHODS AND MATERIALS: WT and FUNDC1-/- mice were fed HFD (45% calorie from fat) or low fat diet (LFD, 10% calorie from fat) for 10 weeks in the presence of the ferroptosis inhibitor liproxstatin-1 (LIP-1, 10 mg/kg, i.p.). RESULTS: RNAseq analysis for differentially expressed genes (DEGs) reported gene ontology term related to ferroptosis and mitophagy in obese rat hearts, which was validated in obese rodent and human hearts. Although 10-week HFD intake did not alter global metabolism, cardiac geometry and function, ablation of FUNDC1 unmasked metabolic derangement, pronounced cardiac remodeling, contractile, intracellular Ca2+ and mitochondrial anomalies upon HFD challenge, the effects of which with exception of global metabolism were attenuated or mitigated by LIP-1. FUNDC1 ablation unmasked HFD-evoked rises in fatty acid synthase ACSL4, necroptosis, inflammation, ferroptosis, mitochondrial O2- production, and mitochondrial injury as well as dampened autophagy and DNA repair enzyme 8-oxoG DNA glycosylase 1 (OGG1) but not apoptosis, the effect of which except ACSL4 and its regulator SP1 was reversed by LIP-1. In vitro data noted that arachidonic acid, an ACSL4 substrate, provoked cytochrome C release, cardiomyocyte defect, and lipid peroxidation under FUNDC1 deficiency, the effects were interrupted by inhibitors of SP1, ACSL4 and ferroptosis. CONCLUSIONS: These data suggest that FUNDC1 deficiency sensitized cardiac remodeling and dysfunction with short-term HFD exposure, likely through ACSL4-mediated regulation of ferroptosis.

Fe induction strategy for hollow porous N-doped carbon with superior performance in oxygen reduction.

An Fe induction strategy is introduced to achieve template-free synthesis of Co,Fe dual-metal N-codoped hollow porous carbon from zeolitic imidazole frameworks, which is beneficial for the exposure of highly dispersed metal (M)-Nx active sites and enhancement of mass transport, thereby exhibiting a superior electrocatalytic activity (E1/2, 0.86 VRHE).

Dual Substitution Strategy in Co-Free Layered Cathode Materials for Superior Lithium Ion Batteries.

A dual substitution strategy is introduced to Co-free layered material LiNi0.5Mn0.5O2 by partially replacing Li and Ni with Na and Al, respectively, to achieve a superior cathode material for lithium ion batteries. Na+ ion functions as a "pillar" and a " cationic barrier" in the lithium layer while Al3+ ion plays an auxiliary role in stabilizing structure and lattice oxygen to improve the electrochemical performance and safety. The stability of lattice oxygen comes from the binding energy between the Ni and O, which is larger due to higher valences of Ni ions, along with a stronger Al-O bond in the crystal structure and the "cationic barrier" effect of Na+ ion at the high-charge. The more stable lattice oxygen reduces the cation disorder in cycling, and Na+ in the Li layer squeezes the pathway of the transition metal from the LiM2 (M = metal) layer to the Li layer, stabilizing the layered crystal structure by inhibiting the electrochemical-driven cation disorder. Moreover, the cathode with Na-Al dual-substitution displays a smaller volume change, yielding a more stable structure. This study unravels the influence of Na-Al dual-substitution on the discharge capacity, midpoint potential, and cyclic stability of Co-free layered cathode materials, which is crucial for the development of lithium ion batteries.

Down-Regulation of LOC645166 in T Cells of Ankylosing Spondylitis Patients Promotes the NF-κB Signaling via Decreasingly Blocking Recruitment of the IKK Complex to K63-Linked Polyubiquitin Chains.

Ankylosing spondylitis (AS) is a chronic inflammatory disease that mainly affects the spine. AS is highly associated with the expression of HLA-B27. Up to 95% AS patients are HLA-B27-positive. However, only 1%-2% of the HLA-B27-positive carriers suffer from AS, implying that other factors may also govern the development of AS. Long non-coding RNAs (lncRNAs) can regulate the immune response via their binding proteins. In the present study, we have identified that the levels of lncRNA, LOC645166, in T cells of AS patients were reduced. Overexpression of LOC645166 in Jurkat cells down-regulated the IL-23p19 expression and suppressed the JAK2/STAT3 signaling in response to stimulation by phorbol 12-myristate 13-acetate. Suppression of STAT3 activation by LOC645166 was also observed when Jurkat cells or T cells of AS patient were treated with anti-CD3/CD28 antibodies. In order to explore the role of LOC645166 in the pathogenesis of AS, RNA pull-down assay plus proteomic approach and western blotting were performed and identified that LOC645166 prefers binding the K63-linked polyubiquitin chains. LOC645166 can suppress recruitment of the IKK complex to K63-linked polyubiquitin chains and diminish IKK2 activation, leading to down-regulation of NF-κB activation. Down-regulation of LOC645166 expression in T cells of AS patients up-regulates NF-kB activation via decreasingly impeding recruitment of the IKK complex to K63-linked polyubiquitin chains, allowing AS patients to exhibit more sensitivity to stimulation by the proinflammatory cytokines or by TLR ligands.

Identification of phostensin in association with Eps 15 homology domain-containing protein 1 (EHD1) and EHD4.

Phostensin (PTS) encoded by KIAA1949 is a protein phosphatase 1 (PP1)-binding protein. In order to explore the cellular functions of PTS, we have searched PTS-binding proteins by using co-immunoprecipitation in combination with shotgun proteomics. Here, we report two novel PTS-binding proteins, Eps 15 homology domain-containing protein 1 (EHD1) and EHD4. PTS associated with EHD proteins was also observed in GST pull-down assays. Immunofluorescence microscopy demonstrated that the complex was co-localized at the endocytic vesicles. EHD proteins have been known to play a critical role in regulation of endocytic transport. Overexpression of PTS-ß can attenuate the endocytic trafficking of transferrin.

Fiber Optic Particle Plasmon Resonance Biosensor for Label-Free Detection of Nucleic Acids and Its Application to HLA-B27 mRNA Detection in Patients with Ankylosing Spondylitis.

We developed a label-free, real-time, and highly sensitive nucleic acid biosensor based on fiber optic particle plasmon resonance (FOPPR). The biosensor employs a single-strand deoxyoligonucleotides (ssDNA) probe, conjugated to immobilized gold nanoparticles on the core surface of an optical fiber. We explore the steric effects on hybridization affinity and limit of detection (LOD), by using different ssDNA probe designs and surface chemistries, including diluent molecules of different lengths in mixed self-assembled monolayers, ssDNA probes of different oligonucleotide lengths, ssDNA probes in different orientations to accommodate target oligonucleotides with a hybridization region located unevenly in the strand. Based on the optimized ssDNA probe design and surface chemistry, we achieved LOD at sub-nM level, which makes detection of target oligonucleotides as low as 1 fmol possible in the 10-mL sensor chip. Additionally, the FOPPR biosensor shows a good correlation in determining HLA-B27 mRNA, in extracted blood samples from patients with ankylosing spondylitis (AS), with the clinically accepted real-time reverse transcription-polymerase chain reaction (RT-PCR) method. The results from this fundamental study should guide the design of ssDNA probe for anti-sense sensing. Further results through application to HLA-B27 mRNA detection illustrate the feasibility in detecting various nucleic acids of chemical and biological relevance.

Two-dimensional metal-organic frameworks and their derivatives for electrochemical energy storage and electrocatalysis.

Two-dimensional (2D) metal-organic frameworks (MOFs) and their derivatives with excellent dimension-related properties, e.g. high surface areas, abundantly accessible metal nodes, and tailorable structures, have attracted intensive attention as energy storage materials and electrocatalysts. A major challenge on the road toward the commercialization of 2D MOFs and their derivatives is to achieve the facile and controllable synthesis of 2D MOFs with high quality and at low cost. Significant developments have been made in the synthesis and applications of 2D MOFs and their derivatives in recent years. In this review, we first discuss the state-of-the-art synthetic strategies (including both top-down and bottom-up approaches) for 2D MOFs. Subsequently, we review the most recent application progress of 2D MOFs and their derivatives in the fields of electrochemical energy storage (e.g., batteries and supercapacitors) and electrocatalysis (of classical reactions such as the HER, OER, ORR, and CO2RR). Finally, the challenges and promising strategies for the synthesis and applications of 2D MOFs and their derivatives are addressed for future development.