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Background: Several epidemiological studies have reported the protective role of caffeine on health outcomes; however, it remained debatable on caffeine consumption and brain amyloid positivity. Objective: We aimed to determine the relationship between caffeine consumption and brain amyloid pathology in cognitively normal older adults. Methods: The dataset used for analysis in this cross-sectional study was selected from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) Study. Multivariable logistic regression analyses were performed to explore the association between caffeine consumption and amyloid positivity using odds ratios (ORs) and 95% confidence intervals (CIs). Results: In total, 4,394 participants were included in the final analysis. No significant association between caffeine consumption and amyloid positivity was observed in the whole participants (OR, 0.95; 95% CI, 0.78–1.14; p = 0.558). Subgroup analysis showed that caffeine intake was significantly associated with decreased amyloid positivity in males (OR, 0.72; 95% CI, 0.54–0.97; p = 0.032) but not in females (OR, 1.14; 95% CI, 0.90–1.46; p = 0.280), and the association between caffeine and amyloid positivity was not affected by age or APOE genotypes. In addition, different levels of caffeine were not associated with amyloid positivity. Conclusion: The findings suggest that caffeine consumption was not significantly associated with amyloid positivity in the whole sample. However, caffeine consumption may be inversely associated with amyloid positivity among males but not females. More studies are needed to explore the mechanisms underlying caffeine consumption and brain amyloid positivity.

Vascular smooth muscle cell (VSMC) plasticity is tightly associated with the pathological process of vasculopathy. Blood vessel epicardial substance (Bves) has emerged as an important regulator of intracardiac vasculogenesis and organ homeostasis. However, the involvement and role of Bves in VSMC plasticity and neointimal lesion development remain unclear.We used an in vivo rat model of graft arteriosclerosis and in vitro PDGF-treated VSMCs and identified the novel VSMC contractile phenotype-related gene Bves using a transcriptomic analysis and literature search. In vitro knockdown and overexpression approaches were used to investigate the mechanisms underlying VSMC phenotypic plasticity. In vivo, VSMC-specific Bves overexpression in rat aortic grafts was generated to assess the physiological function of Bves in neointimal lesion development.Here, we found that Bves expression was negatively regulated in aortic allografts in vivo and PDGF-treated VSMCs in vitro. The genetic knockdown of Bves dramatically inhibited, whereas Bves overexpression markedly promoted, the VSMC contractile phenotype. Furthermore, RNA sequencing unraveled a positive correlation between Bves and dual-specificity protein phosphatase 1 (Dusp1) expression in VSMCs. We found that Bves knockdown restrained Dusp1 expression, but enhanced p38MAPK and ERK1/2 activation, resulting in the loss of the VSMC contractile phenotype. In vivo, an analysis of a rat graft model confirmed that VSMC-specific Bves and Dusp1 overexpression in aortic allografts significantly attenuated neointimal lesion formation.Bves maintains the VSMC contractile phenotype through Dusp1-dependent p38MAPK and ERK1/2 signaling, and protects against neointimal formation, underscoring the important role of Bves in preventing transplant vasculopathy.

Background Uveal melanoma (UM) is adults’ most common primary intraocular malignant tumor, prone to metastasis and high mortality. Eyeball enucleation commonly used in the clinic will lead to permanent blindness and mental disorders. Thus, new methods are urgently needed to diagnose and treat UM early to preserve patients’ vision. Methods and results Herein, multifunctional nanoparticles (NPs) were synthesized by loading chlorin e6 (Ce6) in poly-lactic-co-glycolic acid (PLGA) NPs and wrapping FeIII-tannic acid (FeIII-TA) on the outside (FeIII-TA/PLGA/Ce6, designated as FTCPNPs). Then, the synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) antitumor effects of FTCPNPs excited by near-infrared (NIR) laser were evaluated. Moreover, we verified the mechanism of synergistic PTT/PDT leading to mitochondrial dysfunction and inducing tumor cell apoptosis. Additionally, FTCPNPs can be used as excellent magnetic resonance (MR)/photoacoustic (PA) imaging contrast agents, enabling imaging-guided cancer treatment. Finally, The NPs have good biological safety. Conclusion This noninvasive NIR light-triggered cooperative phototherapy can easily penetrate eye tissue and overcome the disadvantage of limited penetration of phototherapy. Therefore, cooperative phototherapy is expected to be used in fundus tumors. This treatment model is applied to UM for the first time, providing a promising strategy and new idea for integrating the diagnosis and treatment of UM.

The proliferation and migration of vascular smooth muscle cells (VSMCs) are fundamental hallmarks of vasculopathy. Transforming growth factor β-activated kinase-1 (TAK1) plays a crucial role in mediating cellular functions, including autophagy, which has been recently linked to the regulation of VSMC functions and the development of vasculopathy. This study aims to better dissect how TAK1 controls VSMC proliferation and migration.A rat model of graft arteriosclerosis was employed to explore the influence of TAK1 signaling activation on VSMC proliferation, migration, autophagy, and neointima formation in vivo. Knockdown and pharmacological inhibition of TAK1 were utilized in cultured VSMCs to investigate the mechanisms underlying the progression of VSMC proliferation and migration.Increased phosphorylation of TAK1 (Thr-184/Thr-187) was examined in SMα-actin positive cells in the medial and neointimal lesions of aortic allografts. Lentivirus-mediated Tak1 shRNA transfection of aortic allografts robustly suppressed neointimal formation and lumen stenosis, as well as autophagy and cell proliferative responses. In cultured PDGF-BB-incubated VSMCs, genetic and pharmacological inhibition of TAK1 markedly attenuated autophagy activation, and blocked the progression of cell cycle, proliferation, and migration responses.Activation of TAK1 in VSMCs in the setting of aortic transplantation is an early and critical event in VSMC proliferation and migration, as well as neointima formation, because it controls autophagy activation, constituting a potential molecular mechanism and target for preventing transplant vasculopathy.

This paper proposes a novel Neural Lyapunov method-based transient stability assessment framework for power electronics-interfaced networked microgrids. The assessment framework aims to determine the large-signal stability of the networked microgrids and to characterize the disturbances that can be tolerated by the networked microgrids. The challenge of such assessment is how to construct a behavior-summary function for the nonlinear networked microgrids. By leveraging strong representation power of neural network, the behavior-summary function, i.e., a Neural Lyapunov function, is learned in the state space. A stability region is estimated based on the learned Neural Lyapunov function, and it is used for characterizing disturbances that the networked microgrids can tolerate. The proposed method is tested and validated in a grid-connected microgrid, three networked microgrids with mixed interface dynamics, and the IEEE 123-node feeder. Case studies suggest that the proposed method can address networked microgrids with heterogeneous interface dynamics, and in comparison with conventional methods that are based on quadratic Lyapunov functions, it can characterize the stability regions with much less conservativeness.

Polymeric hydrogels have extraordinary potential to be utilized for biomedical applications. Recently, sprayable hydrogels have received increasing attention for their biocompatibility, degradability, tunable mechanical properties and rapid spray-filming abilities. In this review, hydrogel-based biomaterials, especially those based on natural polymers, such as polysaccharides and proteins, have been explained. The focus of this review lies on illuminating recent advances in sprayable hydrogel systems and highlighting the properties and applications of sprayable hydrogels, such as wound management, postoperative adhesion and cancer therapeutics. In addition, future research directions and challenges are also discussed.

BACKGROUND: The aim was to retrospectively analyze the ultrasonographic and clinical characteristics of focal inflammatory masses and malignant masses of salivary gland by using B-mode ultrasound (US) and contrast-enhanced ultrasound (CEUS) for differential analysis. METHODS: The features of US and CEUS were retrospectively analyzed for 19 cases of focal salivary inflammatory masses and 45 cases of malignant salivary masses. All cases were confirmed by pathohistological examination. RESULTS: On B-mode US, the incidence of expansive growth patterns of malignant salivary masses (44.4%, 20/45) was significantly higher than that of focal salivary inflammatory masses (15.8%, 3/19) (p = 0.029). The rate of lymphadenopathy surrounding salivary glands of malignant salivary masses (42.2%, 19/45) was significantly higher than that of focal salivary inflammatory masses (15.8%, 3/19) (p = 0.042). On CEUS, clear enhancement margins were more common in malignant salivary masses (44.4%, 20/45) compared to focal salivary inflammatory masses (15.8%, 3/19) (p = 0.029); Rapid washout was more common in malignant salivary masses (82.2%, 37/45) than focal salivary inflammatory masses (31.6%, 6/19) (p

ObjectiveThe aim of this study was to evaluate whether a predictive model based on a contrast enhanced ultrasound (CEUS)-based nomogram and clinical features (Clin) could differentiate Her-2-overexpressing breast cancers from other breast cancers.MethodsA total of 152 pathology-proven breast cancers including 55 Her-2-overexpressing cancers and 97 other cancers from two units that underwent preoperative CEUS examination, were included and divided into training (n = 102) and validation cohorts (n = 50). Multivariate regression analysis was utilized to identify independent indicators for developing predictive nomogram models. The area under the receiver operating characteristic (AUC) curve was also calculated to establish the diagnostic performance of different predictive models. The corresponding sensitivities and specificities of different models at the cutoff nomogram value were compared.ResultsIn the training cohort, 7 clinical features (menstruation, larger tumor size, higher CA153 level, BMI, diastolic pressure, heart rate and outer upper quarter (OUQ)) + enlargement in CEUS with P < 0.2 according to the univariate analysis were submitted to the multivariate analysis. By incorporating clinical information and enlargement on the CEUS pattern, independently significant indicators for Her-2-overexpression were used for further predictive modeling as follows: Model I, nomogram model based on clinical features (Clin); Model II, nomogram model combining enlargement (Clin + Enlargement); Model III, nomogram model based on typical clinical features combining enlargement (MC + BMI + diastolic pressure (DP) + outer upper quarter (OUQ) + Enlargement). Model II achieved an AUC value of 0.776 at nomogram cutoff score value of 190, which was higher than that of the other models in the training cohort without significant differences (all P>0.05). In the test cohort, the diagnostic efficiency of predictive model was poor (all AUCP>0.05), in either the training or the test cohort. In addition, Clin exhibited an AUC similar to that of model III (P=0.12). Moreover, model III exhibited a higher sensitivity (70.0%) than the other models with similar AUC and specificity, only in the test cohort.ConclusionThe main finding of the study was that the predictive model based on a CEUS-based nomogram and clinical features could not differentiate Her-2-overexpressing breast cancers from other breast cancers.

Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm mainly affecting young children. This study aimed to evaluate the outcomes of 449 pediatric patients enrolled in BCH-LCH 2014 study. 52.6% of patients were classified with single-system (SS) LCH, 28.1% with multisystem (MS) risk organ negative (RO-) LCH, and 19.4% with MS RO+ LCH. 396 patients (88.2%) were initially treated with first-line therapy based on the vindesine-prednisone combination. 139 patients who lacked a response to initial treatment were shifted to second-line therapy, 72 to intensive treatment Arm S1 (combination of cytarabine, cladribine, vindesine, and dexamethasone) and 67 to Arm S2 (without cladribine). The 5-year overall survival (OS), progression-free survival (PFS) and relapse rates were 98.2% (median: 97.6 months), 54.6% (median: 58.3 months), and 29.9%, respectively. MS RO+ patients had the worst prognosis among the three clinical subtypes. For the patients initially treated with first-line therapy, the 5-year OS, PFS, and relapse rates were 99.2%, 54.5%, and 29.3%, respectively. Patients in Arm S1 had a significantly better prognosis than patients in Arm S2 (5-year PFS: 69.2% vs. 46.5%, P = 0.042; relapse rate: 23.4% vs. 44.2%, P = 0.031). Multivariate analysis revealed that early treatment response, the involvement of RO, skin, and oral mucosa, as well as laboratory parameters, including CRP and γ-GT, were independent risk factors for PFS of LCH. Thus, the prognosis of LCH in children has been improved significantly with stratified chemotherapy, and progression and relapse remained the challenges, especially for RO+ patients. This article is protected by copyright. All rights reserved.

Mycotoxins are toxic contaminants in foods and feeds that are naturally occurring and largely unavoidable. Determining their contents in these products is essential to protect humans from harm. Immunoassays of mycotoxins have been well-established because they are fast, sensitive, simple, and cost-effective. However, a major limitation of immunoassays is the requirement of toxic mycotoxins as competing antigens, standards, or competing tracers. Mimotopes are peptides or proteins that can specifically bind to antibodies and compete with analytes for binding sites by mimicking antigenic epitopes. They can be employed as substitutes for competing antigens, standards, or competing tracers to avoid use of mycotoxins. This review summarizes the production and functionalization of the two main kinds of mimotopes, mimic peptides and anti-idiotypic antibodies (Ab2), and their applications in rapid analysis of mycotoxins.

Countries around the world are setting ambitious goals to achieve carbon neutrality by the mid-21st century. Most plans involve the integration of massive renewable energy resources into the electricity grid. In addition to the large wind and solar farms at the bulk power grid level, there is an increasing number of grid-edge distributed energy resources (DERs) in the queue of installation. Therefore, the role of electricity end users is shifting from passive consumers, who can only purchase electricity, to active prosumers, who can both produce and consume electricity.

Patchouli alcohol (PA) has been widely used for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) in traditional Chinese medicine, and the related mechanism remains to be fully understood. Our previous study has indicated that PA significantly reduced visceral sensitivity and defecation area in IBS-D rats. In this study, we prepared an IBS-D rat model and observed the dynamic intestinal motility and colonic longitudinal muscle and myenteric plexus (LMMP) neurons, as well as their subtypes at D14, D21, and D28. After PA administration, we observed the effects on the changes in intestinal motility, colonic LMMP neurons, and LMMP Myosin Va in IBS-D rats and their co-localization with inhibitory neurotransmitter-related proteins. The results indicated that PA treatment could alleviate IBS-D symptoms, regulate the abnormal expression of LMMP neurons, increase Myosin Va expression, up-regulate co-localization levels of Myosin Va with neuronal nitric oxide synthase (nNOS), and promote co-localization levels of Myosin Va with vasoactive intestinal polypeptide (VIP). In conclusion, this study demonstrated the neuropathic alterations in the colon of chronic restraint stress-induced IBS-D rat model. PA reversed the neuropathological alteration by affecting the transport process of nNOS and VIP vesicles via Myosin Va and the function of LMMP inhibitory neurons, and these effects were related to the mechanism of enteric nervous system (ENS) remodeling.

Aims COVID-19 has long-term impacts on public mental health, while few research studies incorporate multidimensional methods to thoroughly characterise the psychological profile of general population and little detailed guidance exists for mental health management during the pandemic. This research aims to capture long-term psychological profile of general population following COVID-19 by integrating trajectory modelling approaches, latent trajectory pattern identification and network analyses. Methods Longitudinal data were collected from a nationwide sample of 18 804 adults in 12 months after COVID-19 outbreak in China. Patient Health Questionnaire-9, Generalised Anxiety Disorder-7 and Insomnia Severity Index were used to measure depression, anxiety and insomnia, respectively. The unconditional and conditional latent growth curve models were fitted to investigate trajectories and long-term predictors for psychological symptoms. We employed latent growth mixture model to identify the major psychological symptom trajectory patterns, and ran sparse Gaussian graphical models with graphical lasso to explore the evolution of psychopathological network. Results At 12 months after COVID-19 outbreak, psychological symptoms generally alleviated, and five psychological symptom trajectories with different demographics were identified: normal stable (63.4%), mild stable (15.3%), mild-increase to decrease (11.7%), mild-decrease to increase (4.0%) and moderate/severe stable (5.5%). The finding indicated that there were still about 5% individuals showing consistently severe distress and approximately 16% following fluctuating psychological trajectories, who should be continuously monitored. For individuals with persistently severe trajectories and those with fluctuating trajectories, central or bridge symptoms in the network were mainly ‘motor abnormality’ and ‘sad mood’, respectively. Compared with initial peak and late COVID-19 phase, aftermath of initial peak might be a psychologically vulnerable period with highest network connectivity. The central and bridge symptoms for aftermath of initial peak (‘appetite change’ and ‘trouble of relaxing’) were totally different from those at other pandemic phases (‘sad mood’). Conclusions This research identified the overall growing trend, long-term predictors, trajectory classes and evolutionary pattern of psychopathological network of psychological symptoms in 12 months after COVID-19 outbreak. It provides a multidimensional long-term psychological profile of the general population after COVID-19 outbreak, and accentuates the essentiality of continuous psychological monitoring, as well as population- and time-specific psychological management after COVID-19. We believe our findings can offer reference for long-term psychological management after pandemics.

Anion exchange membrane (AEM) stability has been a long-standing challenge that limited the widespread development and adoption of AEM fuel cells (AEMFCs). The past five years have been a period of exceptional progress in the development of several alkaline-stable AEMs with remarkable both ex situ and in situ AEMFC stability. Certain cycloaliphatic quaternary ammonium (cQA) (mainly five- and six-membered) based AEMs appear to be among those having the most promising overall performance. In this review, we categorize cQAs as cage-like (such as quaternized 1,4-diazabicyclo[2.2.2]octane, (QDABCO) and quinuclidinium), non-cage-like (such as pyrrolidinium and piperidinium) and N-spirocyclic (such as 6-azonia-spiro[5.5]undecane (ASU)). The degradation mechanisms of categorized cQAs are first elucidated. Through an understanding of how the cations are attacked by strongly nucleophilic OH–, improved structural design of incorporating alkaline-stable cations into AEMs is facilitated. Before a detailed description and comparison of the alkaline stability of cQAs and their respective AEMs, current protocols for the assessment of alkaline stability are discussed in detail. Furthermore, the initial AEMFC performance and fuel cell performance stability based on cQA AEMs are also examined. The main focus and highlight of this review are recent advances (2015–2020) of cQA-based AEMs, which exhibit both excellent cation and membrane alkaline stability. We aim to shed light on the development of alkaline-stable cQA-type AEMs, which are trending in the AEM community, and to provide insights into possible solutions for designing long-lived AEM materials.

Fucosylation alteration is involved in several steps of human cancer pathogenesis. Dysregulated long non-coding RNA (lncRNA) often leads to malignancy in colorectal cancer (CRC). Differential levels of LEF1-AS1, LEF1 and FUT8 are analyzed by qRT-PCR and western blot. Chip, RIP, EMSA and luciferase reporter assay confirm the direct interaction among LEF1-AS1, MLL1, H3K4me3, LEF1 and FUT8. Functionally, CRC cell proliferation, migration and invasion are analyzed by CCK8 assay, colony formation assay, transwell assay and flow cytometry. The xenografts nude mice models, lung metastasis and liver metastasis are established to determine the effect of LEF1-AS1/LEF1/FUT8 axis on CRC progression in vivo. Here, we identify that LEF1-AS1 and LEF1 are higher in CRC tissues than that in adjacent tissues, as well as upregulated in CRC cell lines than that in normal colorectal cells. Altered levels of LEF1-AS1 modulate LEF1 expression, while altered LEF1 could not regulate LEF1-AS1. LEF1-AS1 recruits MLL1 to the promoter region of LEF1, induces H3K4me3 methylation modification and mediates LEF1 transcription. Furthermore, α1-6 fucosyltransferase FUT8 is overexpressed in CRC tissues and positively correlated to LEF1. FUT8 is a direct target of transcription factor LEF1, which regulates FUT8 level. Altered FUT8 also regulates the core fucosylation of CRC cells, and LEF1-AS1 mediates FUT8 level through activation of Wnt/β-catenin/LEF1 pathway, thereby resulting in β-catenin nuclear translocation. In addition, LEF1-AS1 mediates the proliferation, migration and invasion of CRC cells in vitro. LEF1-AS1 silence hinders the tumorigenesis, liver and lung metastasis of SW620 cells in vivo, while overexpressed FUT8 abolishes the suppressive impact of LEF1-AS1 repression on the biological behavior of SW620 cells. Our studies uncovered a novel mechanism for constitutive LEF1-AS1/LEF1/FUT8 axis in CRC progression by regulating α1, 6-fucosylation via Wnt/β-catenin pathway, and consequently, as a potential therapeutic target in CRC.

Aloperine (ALO), a quinolizidine alkaloid extracted from Sophora alopecuroides L., modulates hypertension, ventricular remodeling, and myocardial ischemia. However, few studies have evaluated the effects of ALO on other cardiovascular parameters. Accordingly, in this study, we used a rat model of aconitine-induced ventricular arrhythmia to assess the effects of ALO. Notably, ALO pretreatment delayed the onset of ventricular premature and ventricular tachycardia and reduced the incidence of fatal ventricular fibrillation. Moreover, whole-cell patch-clamp assays in rats’ ventricular myocyte showed that ALO (3, 10, and 30 μM) significantly reduced the peak sodium current density of voltage-gated Na+ channel currents (INa) in a concentration-dependent manner. The gating kinetics characteristics showed that the steady-state activation and recovery curve were shifted in positive direction along the voltage axis, respectively, and the steady-state inactivation curve was shifted in negative direction along the voltage axis, i.e., which was similar to the inhibitory effects of amiodarone. These results indicated that ALO had anti-arrhythmic effects, partly attributed to INa inhibition. ALO may act as a class I sodium channel anti-arrhythmia agent.

Exosomal microRNAs (miRNAs) are miRNAs that are mediated by exosomes to achieve cell-to-cell communication, and they are widespread in organisms. In recent years, the key role of the multiple biological functions of exosomal miRNAs in the occurrence and development of cardiovascular diseases has been confirmed by a large number of studies, which has become a hot spot in clinical and basic research. Sudden cardiac death caused by cardiovascular disease is one of the important contents in forensic medical identification. This article introduces the research progress of cardiovascular disease prediction, treatment and prognosis on exosomal miRNA. The prospects of the application in forensic medical identification are discussed.外泌体微小RNA（microRNA，miRNA）是由外泌体介导以实现细胞间通讯的miRNA，在生物体内广泛存在。近年来，外泌体miRNA的多重生物学功能在心血管疾病发生、发展过程中的关键作用已被大量研究证实，成为临床及基础研究的热点。由心血管疾病导致的心脏性猝死是法医学鉴定工作中的重要内容之一，本文就外泌体miRNA在心血管疾病的预测、治疗及预后等方面的研究进展进行综述，并对其在法医学鉴定中的应用前景进行讨论。.

IntroductionAdult genetic leukoencephalopathies are rare neurological disorders that present unique diagnostic challenges due to their clinical and radiological overlap with more common white matter diseases, notably multiple sclerosis (MS). In this context, a strong collaborative multidisciplinary network is beneficial for shortening the diagnostic odyssey of these patients and preventing misdiagnosis. The White Matter Rounds (WM Rounds) are multidisciplinary international online meetings attended by more than 30 physicians and scientists from 15 participating sites that gather every month to discuss patients with atypical white matter disorders. We aim to present the experience of the WM Rounds Network and demonstrate the value of collaborative multidisciplinary international case discussion meetings in differentiating and preventing misdiagnoses between genetic white matter diseases and atypical MS.MethodsWe retrospectively reviewed the demographic, clinical and radiological data of all the subjects presented at the WM Rounds since their creation in 2013.ResultsSeventy-four patients (mean age 44.3) have been referred and discussed at the WM Rounds since 2013. Twenty-five (33.8%) of these patients were referred by an MS specialist for having an atypical presentation of MS, while in most of the remaining cases, the referring physician was a geneticist (23; 31.1%). Based on the WM Rounds recommendations, a definite diagnosis was made in 36/69 (52.2%) patients for which information was available for retrospective review. Of these diagnosed patients, 20 (55.6%) had a genetic disease, 8 (22.2%) had MS, 3 (8.3%) had both MS and a genetic disorder and 5 (13.9%) had other non-genetic conditions. Interestingly, among the patients initially referred by an MS specialist, 7/25 were definitively diagnosed with MS, 5/25 had a genetic condition (e.g., X-linked adrenoleukodystrophy and hereditary small vessel diseases like Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) and COL4A1-related disorder), and one had both MS and a genetic demyelinating neuropathy. Thanks to the WM Rounds collaborative efforts, the subjects who currently remain without a definite diagnosis, despite extensive investigations performed in the clinical setting, have been recruited in research studies aimed at identifying novel forms of genetic MS mimickers.ConclusionsThe experience of the WM Rounds Network demonstrates the benefit of collective discussions on complex cases to increase the diagnostic rate and decrease misdiagnosis in patients with rare or atypical white matter diseases. Networks of this nature allow physicians and scientists to compare and share information on challenging cases from across the world, provide a basis for future multicenter research studies, and serve as model for other rare diseases.

Objective To study the effect of the problem-based learning (PBL) method in ultrasonography (US) resident standardization training during the COVID-19 pandemic. Methods Fifty residents were divided into two groups to participate in a 30-day US training program. The residents in the observation group underwent PBL combined with the lecture-based learning (LBL) method, while the residents in the control group experienced the LBL method alone, with 25 residents in each group. A basic theoretical test, practical examination, and questionnaire were used to evaluate the teaching effect of the PBL + LBL method and the LBL method alone. Results The basic theoretical pretest score of the observation group was not significantly different from that of the control group. However, the posttest theoretical score and practical score were significantly higher in the observation group than in the control group (P P Conclusion The combination of PBL with the LBL method has obvious advantages over the LBL method alone in regard to the training of US residents during the COVID-19 pandemic.

Covalent organic framework nanosheets (COF-NSs) are emerging building blocks for functional materials, and their scalable fabrication is highly desirable. Current synthetic methods suffer from low volume yields resulting from confined on-surface/at-interface growth space and complex multiple-phase synthesis systems. Herein, we report the synthesis of charged COF-NSs in open space using a single-phase organic solution system, achieving magnitudes higher volume yields of up to 18.7 mg mL

Suicide is a serious public health issue worldwide. In China, suicide is the fifth leading cause of death and the second leading cause of death among 15- to 34-year-olds. Research has shown that th...

This paper proposes a data-driven algorithm of locating the source of forced oscillations and suggests the physical interpretation of the method. By leveraging the sparsity of the forced oscillation sources along with the low-rank nature of synchrophasor data, the problem of source localization under resonance conditions is cast as computing the sparse and low-rank components using Robust Principal Component Analysis (RPCA), which can be efficiently solved by the exact Augmented Lagrange Multiplier method. Based on this problem formulation, an efficient and practically implementable algorithm is proposed to pinpoint the forced oscillation source during real-time operation. Furthermore, we provide theoretical insights into the efficacy of the proposed approach by use of physical model-based analysis, in specific by establishing the fact that the rank of the resonance component matrix is at most 2. The effectiveness of the proposed method is validated in the IEEE 68-bus power system and the WECC 179-bus benchmark system., This manuscript has been submitted to IEEE Transactions on Power Systems

The advent of SELEX (systematic evolution of ligands by exponential enrichment) technology has shown the ability to evolve artificial ligands with affinity and specificity able to meet growing clinical demand for probes that can, for example, distinguish between the target leukemia cells and other cancer cells within the matrix of heterogeneity, which characterizes cancer cells. Though antibodies are the conventional and ideal choice as a molecular recognition tool for many applications, aptamers complement the use of antibodies due to many unique advantages, such as small size, low cost, and facile chemical modification. This Minireview will focus on the novel applications of aptamers and SELEX, as well as opportunities to develop molecular tools able to meet future clinical needs in biomedicine.

Lipid–oligonucleotide conjugates (LONs) are powerful molecular-engineering materials for various applications ranging from biosensors to biomedicine. Their unique amphiphilic structures enable the self-assembly and the conveyance of information with high fidelity. In particular, LONs present remarkable potential in measuring cellular mechanical forces and monitoring cell behaviors. LONs are also essential sensing tools for intracellular imaging and have been employed in developing cell-surface-anchored DNA nanostructures for biomimetic-engineering studies. When incorporating therapeutic oligonucleotides or small-molecule drugs, LONs hold promise for targeted therapy. Moreover, LONs mediate the controllable assembly and fusion of vesicles based on DNA-strand displacements, contributing to nanoreactor construction and macromolecule delivery. In this review, we will summarize the general synthesis strategies of LONs, provide some characterization analysis and emphasize recent advances in bioanalytical and biomedical applications. We will also consider the relevant challenges and suggest future directions for building better functional LONs in nanotechnology and materials-science applications.

Epidermal adult stem cells (EpiASCs) have the potential for unlimited proliferation and differentiation, however, the ability of these stem cells to activate corneal genetic programs in response to corneal stroma stimulation needs to be further validated. Herein, a feasible strategy was developed to reconstruct the damaged corneal surface in a goat model with total limbal stem cell deficiency (LSCD) by transplanting EpiASCs, which had been explanted and cultured from the skin of an adult ram goat and were then purified by selecting single cell-derived clones and cultivating them on a denuded human amniotic membrane (HAM). These artificial tissues were then successfully transplanted into ewe goats with total LSCD. Binding of EpiASCs to the base membrane of an EpiASCs-HAM-Sheet (EHS) indicated their proliferating status. After transplantation, the EpiASCs could survive in the host tissue and they reconstructed the damaged ocular surface of total LSCD. The crystal reconstructed corneal epithelium expressed CK3 and Pax-6 similar to normal corneal epithelium and expressed the Sry gene after transplantation. These results demonstrated that EpiASCs could be induced to differentiate into corneal epithelial cell types in a corneal microenvironment and had the ability to activate corneal genetic programs. This work offer a foundation for promoting tissue-engineered cornea into clinical application.

PURPOSE To investigate whether subconjunctival bevacizumab help prevent corneal graft neovascularization and prolong the graft survival of patients with chemical burns. METHODS We performed a prospective nonrandomized comparative case series study. Twenty-six eyes received subconjunctival bevacizumab (10 mg/0.4 mL) once and topical immunosuppressive agents after sclerocorneal lamellar keratoplasty as the treatment, and 13 eyes received a topical immunosuppressant alone and served as the control group. The main outcomes were a cumulative probability of graft survival, development of corneal neovascularization, and complications. RESULTS The postoperative follow-up time was 14.3 months (range, 2-62 mo). The cumulative graft survival time was significantly longer in the treatment group than that in the control group (42.9 ± 5.9 vs. 4.8 ± 0.7 mo; log rank < 0.001). In the treatment group, 19 of the 26 grafts (73.1%) survived as transparent with a mean follow-up of 18.7 ± 3.0 months. At the end of the follow-up, 4 grafts remained free of neovascularization, 2 developed edema without neovascularization, and 15 remained transparent with a stable ocular surface and some neovascular vessels in the peripheral transplant interface. The other 5 grafts became opaque and neovascularized. In the control group, all grafts became opaque and neovascularized within the follow-up period (5.5 ± 0.7 mo). During the follow-up, a corneal epithelial defect developed in 9 eyes in the treatment group and 7 in the control group. CONCLUSIONS Early application of subconjunctival bevacizumab after sclerocorneal lamellar keratoplasty can significantly prevent corneal neovascularization and promote graft survival for severe late-stage ocular chemical burns.

Background Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm. A few LCH patients had Macrophage activation syndrome-hemophagocytic lymphohistiocytosis (MAS-HLH), a life-threatening, hyper-inflammatory syndrome. We retrospectively described the clinical-biological characteristics of a series of 28 pediatric LCH patients with MAS-HLH in a single center. We further analyzed the difference in treatment outcomes between second-line chemotherapy (cytarabine and cladribine) and targeted therapy (dabrafenib) for BRAF-V600E-positive patients. Results LCH patients with MAS-HLH were aged P = 0.034). Conclusions LCH patients with MAS-HLH harbored specific clinical-biology characteristics compared to the multisystem LCH without MAS-HLH. The BRAF inhibitor dabrafenib provides a promising treatment option for LCH with MAS-HLH.

Acute kidney injury (AKI) is known as a sudden episode of kidney injury, which happens suddenly within a few hours or a few days. Quercetin (3,3',4',5,7-pentahydroxyflavone) is a flavonoid found in plants. Quercetin is known to have several biological activities, such as anti-oxidant, anti-inflammatory, and anti-carcinogenic effects. However, low water solubility and bioavailability are the limitations of quercetin for its clinical applications. Moreover, ischemia/reperfusion (I/R) injury is a common cause of AKI. There are no satisfactory strategies for I/R-induced AKI. Developing suitable preventive or therapeutic intervention for AKI is an important and urgent issue. We investigated the benefit effect of synthesized polyethylene glycol (PEG) conjugated polyethyleneimine (PEI) nanoparticles for targeted delivery of quercetin on AKI in a mouse model. An I/R-induced AKI mouse model was used to evaluate the therapeutic effect of quercetin polymeric nanoparticles by intravenous injection. Biochemical changes for renal function in blood samples were analyzed. Histological and immunohistochemical changes were also analyzed. The biochemical changes of blood urea nitrogen (BUN), creatinine, and cystatin C were significantly increased in I/R-induced AKI mice, which could be significantly reversed by quercetin polymeric nanoparticles. Quercetin polymeric nanoparticles could also significantly decrease the histological lesions, positive staining for 3-nitrotyrosine and cyclooxygenase-2, and lipid peroxidation in the kidneys of I/R-induced AKI mice. These results demonstrate for the first time that quercetin polymeric nanoparticles possess therapeutic potential for the treatment of I/R-induced AKI in vivo.

Digital mental health services (DMHSs) have great potential for mitigating the mental health burden related to COVID-19, but public accessibility (ease of acquiring services when needed) to DMHSs during the pandemic is largely unknown. Accessibility to DMHSs was tracked longitudinally among a nationwide sample of 18,804 adults in China from before to one year after COVID-19 outbreak. Unconditional and conditional latent growth curve models and latent growth mixture models were fitted to explore the overall growth trend, influencing factors, and latent trajectory classes of accessibility to DMHSs throughout COVID-19. Generalized estimating equation models and generalized linear mixed models were employed to explore the association between accessibility to DMHSs and long-term mental health symptoms. We found that people generally reported increased difficulty in accessing DMHSs from before to one year after COVID-19 outbreak. Males, youngsters, individuals with low socioeconomic status, and individuals greatly affected by COVID-19 reported greater difficulty in accessing DMHSs. Four DMHS accessibility trajectory classes were identified: “lowest–great increase” (6.3%), “moderate low–slight increase” (44.4%), “moderate high–slight decrease” (18.1%) and “highest–great decrease” (31.2%). Trajectory classes reporting greater difficulty in accessing DMHSs were at higher risk for long-term mental symptoms. In conclusion, an overall increase in difficulty in accessing DMHSs is observed throughout COVID-19, and heterogeneity exists in DMHS accessibility trajectories. Our results suggest that easy access to DMHSs should be consistently facilitated. Moreover, access gaps should be reduced across demographic groups, and target populations for service allocation should alter as the pandemic evolves.

Glycosylation exhibits crucial effect on hepatocellular carcinoma (HCC) progression. Long non-coding RNAs (lncRNAs) are involved in multilevel regulation of gene transcription during tumor development. The purpose of this study is to clarify the potential mechanism that HOTAIR modulates hepatocellular carcinoma progression by activating FUT8/core-fucosylated Hsp90/MUC1/STAT3 feedback loop via JAK1/STAT3 cascade.qRT-PCR was used to show the differential expression of genes. Functional experiments were used to measure the malignancy of HCC cells. ChIP and co-IP assays showed the directly interaction of the key molecules. Xenografts was conducted to show the in vivo effects.Upregulation of FUT8 showed closely correlation with HCC progression. Core-fucosylation of Hsp90 stabilized MUC1 binding to the downstream p-STAT3, which involved in the activation of JAK1/STAT3 cascade. STAT3 was identified as the regulator of FUT8 and MUC1 transcription, while FUT8 and MUC1 impacted STAT3 level both in nuclear and cytoplasm. HOTAIR recruited P300 to efficiently bind with STAT3. The transcript complex co-modulated the transcrption of FUT8 and MUC1. Moreover, highly HOTAIR expression also exhibited closely correlation with HCC progression.FUT8 triggered core-fucosylated-Hsp90/MUC1/P300-HOTAIR-STAT3 cascade via JAK1/STAT3 pathway, which exhibited as positive feedback loop during HCC progression.