Kinetic Evaluation on Lithium Polysulfide in Weakly Solvating Electrolyte toward Practical Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are highly considered as next-generation energy storage techniques. Weakly solvating electrolyte with low lithium polysulfide (LiPS) solvating power promises Li anode protection and improved cycling stability. However, the cathodic LiPS kinetics is inevitably deteriorated, resulting in severe cathodic polarization and limited energy density. Herein, the LiPS kinetic degradation mechanism in weakly solvating electrolytes is disclosed to construct high-energy-density Li-S batteries. Activation polarization instead of concentration or ohmic polarization is identified as the dominant kinetic limitation, which originates from higher charge-transfer activation energy and a changed rate-determining step. To solve the kinetic issue, a titanium nitride (TiN) electrocatalyst is introduced and corresponding Li-S batteries exhibit reduced polarization, prolonged cycling lifespan, and high actual energy density of 381 Wh kg-1 in 2.5 Ah-level pouch cells. This work clarifies the LiPS reaction mechanism in protective weakly solvating electrolytes and highlights the electrocatalytic regulation strategy toward high-energy-density and long-cycling Li-S batteries.

Early prediction of acute gallstone pancreatitis severity: a novel machine learning model based on CT features and open access online prediction platform.

BACKGROUND: Early diagnosis of acute gallstone pancreatitis severity (GSP) is challenging in clinical practice. We aimed to investigate the efficacy of CT features and radiomics for the early prediction of acute GSP severity. METHODS: We retrospectively recruited GSP patients who underwent CT imaging within 48 h of admission from tertiary referral centre. Radiomics and CT features were extracted from CT scans. The clinical and CT features were selected by the random forest algorithm to develop the ML GSP model for the identification of severity of GSP (mild or severe), and its predictive efficacy was compared with radiomics model. The predictive performance was assessed by the area under operating characteristic curve. Calibration curve and decision curve analysis were performed to demonstrate the classification performance and clinical efficacy. Furthermore, we built a web-based open access GSP severity calculator. The study was registered with ClinicalTrials.gov (NCT05498961). RESULTS: A total of 301 patients were enrolled. They were randomly assigned into the training (n = 210) and validation (n = 91) cohorts at a ratio of 7:3. The random forest algorithm identified the level of calcium ions, WBC count, urea level, combined cholecystitis, gallbladder wall thickening, gallstones, and hydrothorax as the seven predictive factors for severity of GSP. In the validation cohort, the areas under the curve for the radiomics model and ML GSP model were 0.841 (0.757-0.926) and 0.914 (0.851-0.978), respectively. The calibration plot shows that the ML GSP model has good consistency between the prediction probability and the observation probability. Decision curve analysis showed that the ML GSP model had high clinical utility. CONCLUSIONS: We built the ML GSP model based on clinical and CT image features and distributed it as a free web-based calculator. Our results indicated that the ML GSP model is useful for predicting the severity of GSP.

ML GSP model based on machine learning has good severity discrimination in both training and validation cohorts (0.916 (0.872­0.958), 0.914 (0.851­0.978), respectively).We built an online user-friendly platform for the ML GSP model to help clinicians better identify the severity of GSP.

Screening and diagnosis of cardiovascular disease using artificial intelligence-enabled cardiac magnetic resonance imaging.

Cardiac magnetic resonance imaging (CMR) is the gold standard for cardiac function assessment and plays a crucial role in diagnosing cardiovascular disease (CVD). However, its widespread application has been limited by the heavy resource burden of CMR interpretation. Here, to address this challenge, we developed and validated computerized CMR interpretation for screening and diagnosis of 11 types of CVD in 9,719 patients. We propose a two-stage paradigm consisting of noninvasive cine-based CVD screening followed by cine and late gadolinium enhancement-based diagnosis. The screening and diagnostic models achieved high performance (area under the curve of 0.988 ± 0.3% and 0.991 ± 0.0%, respectively) in both internal and external datasets. Furthermore, the diagnostic model outperformed cardiologists in diagnosing pulmonary arterial hypertension, demonstrating the ability of artificial intelligence-enabled CMR to detect previously unidentified CMR features. This proof-of-concept study holds the potential to substantially advance the efficiency and scalability of CMR interpretation, thereby improving CVD screening and diagnosis.

Case Report: A left ventricular pseudoaneurysm detected by cardiac magnetic resonance more than 1 year after a percutaneous transluminal coronary intervention.

Pseudoaneurysm is a rare but lethal complication of acute myocardial infarction. In this study, we present a unique case of a patient with left ventricular free wall rupture detected by cardiac magnetic resonance more than 1 year after a percutaneous transluminal coronary intervention.

Hybridization-based discovery of novel quinazoline-2-indolinone derivatives as potent and selective PI3Kα inhibitors.

INTRODUCTION: Phosphatidylinositol 3-kinases (PI3Ks) overexpression can elicit cellular homeostatic dysregulation, which further contributes to tumorigenesis, with PI3Kα emerging as the most prevalent mutant isoform kinase among PI3Ks. Therefore, selective inhibitors targeting PI3Kα have attracted considerable interest in recent years. Molecular hybridization, with the advantage of simplified pharmacokinetics and drug-drug interactions, emerged as one of the important avenues for discovering potential drugs. OBJECTIVES: This study aimed to construct PI3Kα inhibitors by hybridization and investigate their antitumor activity and mechanism. METHODS: 26 quinazoline-2-indolinone derivatives were obtained by molecular hybridization, and their structure-activity relationship was analyzed by MTT, in vitro kinase activity and molecular docking. The biological evaluation of compound 8 was performed by transwell, flow cytometry, laser scanning confocal microscopy, Western blot, CTESA and immunohistochemistry. RESULTS: Here, we employed molecular hybridization methods to construct a series of quinazoline-2-indolinone derivatives as PI3Kα selective inhibitors. Encouragingly, representative compound 8 exhibited a PI3Kα enzymatic IC50 value of 9.11 nM and 10.41/16.99/37.53-fold relative to the biochemical selectivity for PI3Kß/γ/δ, respectively. Moreover, compound 8 effectively suppressed the viability of B16, HCT116, MCF-7, H22, PC-3, and A549 cells (IC50 values: 0.2 µM âˆ¼ 0.98 µM), and dramatically inhibited the proliferation and migration of NSCLC cells, as well as induced mitochondrial apoptosis through the PI3K/Akt/mTOR pathway. Importantly, compound 8 demonstrated potent in vivo anti-tumor activity in non-small cell lung cancer mouse models without visible toxicity. CONCLUSIONS: This study presented a new avenue for the development of PI3Kα inhibitors and provided a solid foundation for novel QHIDs as potential future therapies for the treatment of NSCLC.

Improving Rate Performance of Encapsulating Lithium-Polysulfide Electrolytes for Practical Lithium-Sulfur Batteries.

The cycle life of high-energy-density lithium-sulfur (Li-S) batteries is severely plagued by the incessant parasitic reactions between Li metal anodes and reactive Li polysulfides (LiPSs). Encapsulating Li-polysulfide electrolyte (EPSE) emerges as an effective electrolyte design to mitigate the parasitic reactions kinetically. Nevertheless, the rate performance of Li-S batteries with EPSE is synchronously suppressed. Herein, the sacrifice in rate performance by EPSE is circumvented while mitigating parasitic reactions by employing hexyl methyl ether (HME) as a co-solvent. The specific capacity of Li-S batteries with HME-based EPSE is nearly not decreased at 0.1 C compared with conventional ether electrolytes. With an ultrathin Li metal anode (50 µm) and a high-areal-loading sulfur cathode (4.4 mgS cm-2 ), a longer cycle life of 113 cycles was achieved in HME-based EPSE compared with that of 65 cycles in conventional ether electrolytes at 0.1 C. Furthermore, both high energy density of 387 Wh kg-1 and stable cycle life of 27 cycles were achieved in a Li-S pouch cell (2.7 Ah). This work inspires the feasibility of regulating the solvation structure of LiPSs in EPSE for Li-S batteries with balanced performance.

Luteolin, a flavone ingredient: Anticancer mechanisms, combined medication strategy, pharmacokinetics, clinical trials, and pharmaceutical researches.

Current pharmaceutical research is energetically excavating the pharmacotherapeutic role of herb-derived ingredients in multiple malignancies' targeting. Luteolin is one of the major phytochemical components that exist in various traditional Chinese medicine or medical herbs. Mounting evidence reveals that this phytoconstituent endows prominent therapeutic actions on diverse malignancies, with the underlying mechanisms, combined medication strategy, and pharmacokinetics elusive. Additionally, the clinical trial and pharmaceutical investigation of luteolin remain to be systematically delineated. The present review aimed to comprehensively summarize the updated information with regard to the anticancer mechanism, combined medication strategies, pharmacokinetics, clinical trials, and pharmaceutical researches of luteolin. The survey corroborates that luteolin executes multiple anticancer effects mainly by dampening proliferation and invasion, spurring apoptosis, intercepting cell cycle, regulating autophagy and immune, inhibiting inflammatory response, inducing ferroptosis, and pyroptosis, as well as epigenetic modification, and so on. Luteolin can be applied in combination with numerous clinical anticarcinogens and natural ingredients to synergistically enhance the therapeutic efficacy of malignancies while reducing adverse reactions. For pharmacokinetics, luteolin has an unfavorable oral bioavailability, it mainly persists in plasma as glucuronides and sulfate-conjugates after being metabolized, and is regarded as potent inhibitors of OATP1B1 and OATP2B1, which may be messed with the pharmacokinetic interactions of miscellaneous bioactive substances in vivo. Besides, pharmaceutical innovation of luteolin with leading-edge drug delivery systems such as host-guest complexes, nanoparticles, liposomes, nanoemulsion, microspheres, and hydrogels are beneficial to the exploitation of luteolin-based products. Moreover, some registered clinical trials on luteolin are being carried out, yet clinical research on anticancer effects should be continuously promoted.

Bromocriptine protects perilesional spinal cord neurons from lipotoxicity after spinal cord injury.

Recent studies have revealed that lipid droplets accumulate in neurons after brain injury and evoke lipotoxicity, damaging the neurons. However, how lipids are metabolized by spinal cord neurons after spinal cord injury remains unclear. Herein, we investigated lipid metabolism by spinal cord neurons after spinal cord injury and identified lipid-lowering compounds to treat spinal cord injury. We found that lipid droplets accumulated in perilesional spinal cord neurons after spinal cord injury in mice. Lipid droplet accumulation could be induced by myelin debris in HT22 cells. Myelin debris degradation by phospholipase led to massive free fatty acid production, which increased lipid droplet synthesis, ß-oxidation, and oxidative phosphorylation. Excessive oxidative phosphorylation increased reactive oxygen species generation, which led to increased lipid peroxidation and HT22 cell apoptosis. Bromocriptine was identified as a lipid-lowering compound that inhibited phosphorylation of cytosolic phospholipase A2 by reducing the phosphorylation of extracellular signal-regulated kinases 1/2 in the mitogen-activated protein kinase pathway, thereby inhibiting myelin debris degradation by cytosolic phospholipase A2 and alleviating lipid droplet accumulation in myelin debris-treated HT22 cells. Motor function, lipid droplet accumulation in spinal cord neurons and neuronal survival were all improved in bromocriptine-treated mice after spinal cord injury. The results suggest that bromocriptine can protect neurons from lipotoxic damage after spinal cord injury via the extracellular signal-regulated kinases 1/2-cytosolic phospholipase A2 pathway.

Tissue Identification of Intervertebral Disc Anatomy Using Forward-oriented Ultrasound Endoscopic System: A Feasibility Study.

Minimally invasive surgery is widely used for spine surgery, however the commonly used optical endoscopes cannot identity tissues under surface. In this study, a forward-oriented ultrasound endoscopic system was proposed to detect and identity different types of tissues for surgical approaches. A total of 150 ultrasound image data were collected from 6 types of intervertebral disc tissue using a custom-developed endoscopic probe. The gray-level co-occurrence matrix (GLCM) properties including energy (angular second moment, ASM), contrast, entropy, and homogeneity (inverse difference moment, IDM) were calculated on the acquired ultrasound images, and the single-parameter and combined parameter were applied for tissue classification. The classification accuracies of fibrous ring, nerve roots and bone were 100%, and the overall accuracy for all tissues was 73.33%. The results indicated that the combined parameter method provided more accurate classification output. It demonstrated that the proposed endoscopic ultrasonography system had the potential of identifying different tissues under surface during the endoscopic spine surgery.Clinical Relevance-This study establishes that the forward-oriented ultrasound endoscopic system was feasible to identify different types of tissues under surface during the endoscopic spine surgery.

Correlating Polysulfide Solvation Structure with Electrode Kinetics towards Long-Cycling Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are promising due to ultrahigh theoretical energy density. However, their cycling lifespan is crucially affected by the electrode kinetics of lithium polysulfides. Herein, the polysulfide solvation structure is correlated with polysulfide electrode kinetics towards long-cycling Li-S batteries. The solvation structure derived from strong solvating power electrolyte induces fast anode kinetics and rapid anode failure, while that derived from weak solvating power electrolyte causes sluggish cathode kinetics and rapid capacity loss. By contrast, the solvation structure derived from medium solvating power electrolyte balances cathode and anode kinetics and improves the cycling performance of Li-S batteries. Li-S coin cells with ultra-thin Li anodes and high-S-loading cathodes deliver 146 cycles and a 338 Wh kg-1 pouch cell undergoes stable 30 cycles. This work clarifies the relationship between polysulfide solvation structure and electrode kinetics and inspires rational electrolyte design for long-cycling Li-S batteries.

An MRI-based machine learning radiomics can predict short-term response to neoadjuvant chemotherapy in patients with cervical squamous cell carcinoma: A multicenter study.

BACKGROUND AND PURPOSE: Neoadjuvant chemotherapy (NACT) has become an essential component of the comprehensive treatment of cervical squamous cell carcinoma (CSCC). However, not all patients respond to chemotherapy due to individual differences in sensitivity and tolerance to chemotherapy drugs. Therefore, accurately predicting the sensitivity of CSCC patients to NACT was vital for individual chemotherapy. This study aims to construct a machine learning radiomics model based on magnetic resonance imaging (MRI) to assess its efficacy in predicting NACT susceptibility among CSCC patients. METHODS: This study included 234 patients with CSCC from two hospitals, who were divided into a training set (n = 180), a testing set (n = 20), and an external validation set (n = 34). Manual radiomic features were extracted from transverse section MRI images, and feature selection was performed using the recursive feature elimination (RFE) method. A prediction model was then generated using three machine learning algorithms, namely logistic regression, random forest, and support vector machines (SVM), for predicting NACT susceptibility. The model's performance was assessed based on the area under the receiver operating characteristic curve (AUC), accuracy, and sensitivity. RESULTS: The SVM approach achieves the highest scores on both the testing set and the external validation set. In the testing set and external validation set, the AUC of the model was 0.88 and 0.764, and the accuracy was 0.90 and 0.853, the sensitivity was 0.93 and 0.962, respectively. CONCLUSIONS: Machine learning radiomics models based on MRI images have achieved satisfactory performance in predicting the sensitivity of NACT in CSCC patients with high accuracy and robustness, which has great significance for the treatment and personalized medicine of CSCC patients.

Cathode Kinetics Evaluation in Lean-Electrolyte Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries afford great promise on achieving practical high energy density beyond lithium-ion batteries. Lean-electrolyte conditions constitute the prerequisite for achieving high-energy-density Li-S batteries but inevitably deteriorates battery performances, especially the sulfur cathode kinetics. Herein, the polarizations of the sulfur cathode are systematically decoupled to identify the key kinetic limiting factor in lean-electrolyte Li-S batteries. Concretely, an electrochemical impedance spectroscopy combined galvanostatic intermittent titration technique method is developed to decouple the cathodic polarizations into activation, concentration, and ohmic parts. Therein, activation polarization during lithium sulfide nucleation emerges as the dominant polarization as the electrolyte-to-sulfur ratio (E/S ratio) decreases, and the sluggish interfacial charge transfer kinetics is identified as the main reason for degraded cell performances under lean-electrolyte conditions. Accordingly, a lithium bis(fluorosulfonyl)imide electrolyte is proposed to decrease activation polarization, and Li-S batteries adopting this electrolyte provide a discharge capacity of 985 mAh g-1 under a low E/S ratio of 4 µL mg-1 at 0.2 C. This work identifies the key kinetic limiting factor of lean-electrolyte Li-S batteries and provides guidance on designing rational promotion strategies to achieve advanced Li-S batteries.

Improved Dynamic Event-Triggered Robust Control for Flexible Robotic Arm Systems with Semi-Markov Jump Process.

In this paper, we investigate the problem of a dynamic event-triggered robust controller design for flexible robotic arm systems with continuous-time phase-type semi-Markov jump process. In particular, the change in moment of inertia is first considered in the flexible robotic arm system, which is necessary for ensuring the security and stability control of special robots employed under special circumstances, such as surgical robots and assisted-living robots which have strict lightweight requirements. To handle this problem, a semi-Markov chain is conducted to model this process. Furthermore, the dynamic event-triggered scheme is used to solve the problem of limited bandwidth in the network transmission environment, while considering the impact of DoS attacks. With regard to the challenging circumstances and negative elements previously mentioned, the adequate criteria for the existence of the resilient H∞ controller are obtained using the Lyapunov function approach, and the controller gains, Lyapunov parameters and event-triggered parameters are co-designed. Finally, the effectiveness of the designed controller is demonstrated via numerical simulation using the LMI toolbox in MATLAB.

Electrolyte Design for Improving Mechanical Stability of Solid Electrolyte Interphase in Lithium-Sulfur Batteries.

Practical lithium-sulfur (Li-S) batteries are severely plagued by the instability of solid electrolyte interphase (SEI) formed in routine ether electrolytes. Herein, an electrolyte with 1,3,5-trioxane (TO) and 1,2-dimethoxyethane (DME) as co-solvents is proposed to construct a high-mechanical-stability SEI by enriching organic components in Li-S batteries. The high-mechanical-stability SEI works compatibly in Li-S batteries. TO with high polymerization capability can preferentially decompose and form organic-rich SEI, strengthening mechanical stability of SEI, which mitigates crack and regeneration of SEI and reduces the consumption rate of active Li, Li polysulfides, and electrolytes. Meanwhile, DME ensures high specific capacity of S cathodes. Accordingly, the lifespan of Li-S batteries increases from 75 cycles in routine ether electrolyte to 216 cycles in TO-based electrolyte. Furthermore, a 417 Wh kg-1 Li-S pouch cell undergoes 20 cycles. This work provides an emerging electrolyte design for practical Li-S batteries.

Identification and functional analysis of a novel de novo missense mutation located in the initiation codon of LAMP2 associated with early onset female Danon disease.

BACKGROUND: Danon disease is characterized by the failure of lysosomal biogenesis, maturation, and function due to a deficiency of lysosomal membrane structural protein (LAMP2). METHODS: The current report describes a female patient with a sudden syncope and hypertrophic cardiomyopathy phenotype. We identified the pathogenic mutations in patients by whole-exon sequencing, followed by a series of molecular biology and genetic approaches to identify and functional analysis of the mutations. RESULTS: Suggestive findings by cardiac magnetic resonance (CMR), electrocardiogram (ECG), and laboratory examination suggested Danon disease which was confirmed by genetic testing. The patient carried a novel de novo mutation, LAMP2 c.2T>C located at the initiation codon. The quantitative polymerase chain reaction (qPCR) and Western blot (WB) analysis of peripheral blood leukocytes from the patients revealed evidence of LAMP2 haploinsufficiency. Labeling of the new initiation codon predicted by the software with green fluorescent protein followed by fluorescence microscopy and Western blotting showed that the first ATG downstream from the original initiation codon became the new translational initiation codon. The three-dimensional structure of the mutated protein predicted by alphafold2 revealed that it consisted of only six amino acids and failed to form a functional polypeptide or protein. Overexpression of the mutated LAMP2 c.2T>C showed a loss of function of the protein, as assessed by the dual-fluorescence autophagy indicator system. The mutation was confirmed to be null, AR experiments and sequencing results confirmed that 28% of the mutant X chromosome remained active. CONCLUSION: We propose possible mechanisms of mutations associated with haploinsufficiency of LAMP2: (1) The inactivation X chromosome carrying the mutation was not significantly skewed. However, it decreased in the mRNA level and the expression ratio of the mutant transcripts; (2) The identified mutation is null, and the active mutant transcript fails to translate into the normal LAMP2 proteins. The presence of haploinsufficiency in LAMP2 and the X chromosome inactivation pattern were crucial factors contributing to the early onset of Danon disease in this female patient.

An Organodiselenide Comediator to Facilitate Sulfur Redox Kinetics in Lithium-Sulfur Batteries with Encapsulating Lithium Polysulfide Electrolyte.

Lithium-sulfur (Li-S) batteries are regarded as promising high-energy-density energy storage devices. However, the cycling stability of Li-S batteries is restricted by the parasitic reactions between Li metal anodes and soluble lithium polysulfides (LiPSs). Encapsulating LiPS electrolyte (EPSE) can efficiently suppress the parasitic reactions but inevitably sacrifices the cathode sulfur redox kinetics. To address the above dilemma, a redox comediation strategy for EPSE is proposed to realize high-energy-density and long-cycling Li-S batteries. Concretely, dimethyl diselenide (DMDSe) is employed as an efficient redox comediator to facilitate the sulfur redox kinetics in Li-S batteries with EPSE. DMDSe enhances the liquid-liquid and liquid-solid conversion kinetics of LiPS in EPSE while maintains the ability to alleviate the anode parasitic reactions from LiPSs. Consequently, a Li-S pouch cell with a high energy density of 359 Wh kg-1 at cell level and stable 37 cycles is realized. This work provides an effective redox comediation strategy for EPSE to simultaneously achieve high energy density and long cycling stability in Li-S batteries and inspires rational integration of multi-strategies for practical working batteries.

Paeonol Promotes Reendothelialization After Vascular Injury Through Activation of c-Myc/VEGFR2 Signaling Pathway.

Purpose: Dysfunction of endothelium is associated with multiple pathological vascular diseases. However, how to regulate reendothelialization after vascular injury is not well defined. This study aims to determine whether and how Paeonol controls reendothelialization following artery injury. Methods: The endothelium of murine carotid artery was denuded by catheter guide wires injury. H&E staining and IF staining were performed to determine whether Paeonol is critical for reendothelialization. BRDU Incorporation Assay, Boyden Chamber Migration Assay, Tube Formation Assay, and Spheroid Sprouting Assay were used to investigate whether Paeonol is involved in regulating proliferation and migration of endothelial cells. The underlying mechanism of how Paeonol regulates reendothelialization was determined by Molecular docking simulation and CO-IP Assay. Results: Paeonol treatment significantly inhibits neointima formation in carotid artery ligation model by promoting proliferation and migration of endothelial cells. Mechanistically, Paeonol enhances c-Myc expression, consequently interacts with VEGFR2 results in activating VEGF signaling pathway, and eventually promotes reendothelialization after vascular injury. Conclusion: Our data demonstrated that Paeonol plays a critical role in regulating vascular reendothelialization, which may be therapeutically used for treatment of pathological vascular diseases.

Characteristics of cervical intervertebral disc signal intensity: an analysis of T2-weighted magnetic resonance imaging in 5843 asymptomatic Chinese subjects.

PURPOSE: The study aimed to observe cervical intervertebral discs (IVDs) in asymptomatic subjects and to explore the factors associated with cervical intervertebral disc degeneration (IVDD). METHODS: Cervical spine MRI of 5843 subjects was retrospectively analyzed. On the sagittal T2-weighted MR images, the mean signal intensities of the nucleus pulposus were obtained. Standard signal intensity (SSI) of intervertebral discs was defined as the ratio of mean disc signal intensity to mean CSF signal intensity. RESULTS: In subjects under 70 years old, the SSI of IVD was lowest at the C5/6 level. In those over 70, the SSI of IVD was similar among the disc levels from C2/3 to C7/T1. The disc SSI decreased significantly with age in both genders. In subjects under 70 years old, the SSI of the discs at each level was higher in females than in males. In those over 70 years old, no difference was found in disc SSI between two genders at most disc levels. Logistic regression analysis showed that kyphotic and straight cervical spine, obesity and older age were associated with higher risk of having lower disc SSI. CONCLUSION: To our knowledge, this is the largest cross-sectional study using MRI-based quantitative assessment to characterize cervical IVDD in asymptomatic subjects. Cervical IVDD was shown to progress with age and significantly correlated with gender, BMI and cervical alignment. Early intervention of related factors may help delay cervical IVDD and prevent future neck and shoulder pain.

Isolation, identification, and pathogenicity analysis of newly emerging gosling astrovirus in South China.

Goose astroviruses (GoAstV) cause fatal gout and decrease product performance in the waterfowl industry across the world. Since no effective vaccines are available, studies on the epidemiology of the virus are necessary for vaccine development. In this study, we collected 94 gout samples from goose farms in the Guangdong Province of South China. Among them, 87 samples (92.6%) tested positive for GoAstV, out of which five GoAstV strains were isolated after four generations of blind transmission through healthy 13-day-old goose embryos. The whole genome of the isolates was sequenced and further analyzed by comparing the sequences with published sequences from China and other parts of the world. The results of the alignment analysis showed that nucleotide sequence similarities among the five GoAstV isolates were around 97.4-98.8%, 98.6-100%, 98.1-99.8%, and 96.7-100% for the whole genome, ORF1a, ORF1b, and ORF2, respectively. These results showed that the GoAstV isolates were highly similar to each other, although they were prevalent in five different regions of the Guangdong Province. The results of the phylogenetic analysis showed that the whole genome, along with the ORF1a, ORF1b, and ORF2 genes of the isolates, were clustered on a single branch, along with the recently published GoAstV-2, and were very distinct from the DNA sequences of the GoAstV-1 virus. In this study, we also reproduced the clinical symptoms of natural infection using the GoAstV-GD2101 isolates, confirming that the gout-causing pathogen in goslings was the goose astrovirus. These findings provided new insights into the pathogenicity and genetic evolution of GoAstV and laid the foundation for effectively controlling the disease.

Andrographolide suppresses hypoxia-induced embryonic hyaloid vascular system development through HIF-1a/VEGFR2 signaling pathway.

Introduction: Ocular abnormalities and the development of retinal vasculature may cause postnatal retinopathy. In the past decade, tremendous progress has been made in identifying the mechanisms that regulate retina vasculature. However, the means of regulating embryonic hyaloid vasculature development is largely unknown. This study aims to determine whether and how andrographolide regulates embryonic hyaloid vasculature development. Methods: Murine embryonic retinas were used in this study. Whole mount isolectin B4 (IB4) staining, hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and immunofluorescence staining (IF) were performed to determine whether andrographolide is critical for embryonic hyaloid vasculature development. BrdU incorporation assay, Boyden chamber migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay were performed to evaluate whether andrographolide regulates the proliferation and migration of vascular endothelial cells. Molecular docking simulation and Co-immunoprecipitation assay were used to observe protein interaction. Results: Hypoxia conditions exist in murine embryonic retinas. Hypoxia induces HIF-1a expression; high-expressed HIF-1a interacts with VEGFR2, resulting in the activation of the VEGF signaling pathway. Andrographolide suppresses hypoxia-induced HIF-1a expression and, at least in part, interrupts the interaction between HIF-1a and VEGFR2, causing inhibiting endothelial proliferation and migration, eventually inhibiting embryonic hyaloid vasculature development. Conclusion: Our data demonstrated that andrographolide plays a critical role in regulating embryonic hyaloid vasculature development.