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Phosphorylation and dephosphorylation of viral movement proteins plays a crucial role in regulating virus movement. Our study focused on investigating the movement protein TGBp1 of Bamboo mosaic virus (BaMV), which is a single-stranded positive-sense RNA virus. Specifically, we examined four potential phosphorylation sites (S15, S18, T58, and S247) within the TGBp1 protein. To study the impact of phosphorylation, we introduced amino acid substitutions at the selected sites. Alanine substitutions were used to prevent phosphorylation, while aspartate substitutions were employed to mimic phosphorylation. Our findings suggest that mimicking phosphorylation at S15, S18 and T58 of TGBp1 might be linked to silencing suppressor activities. The phosphorylated form at these sites exhibits a loss of silencing suppressor activity, leading to reduced viral accumulation in the inoculated leaves. Furthermore, mimicking phosphorylation at residues S15 and S18 could diminish viral accumulation at the single-cell level, while doing so at residue T58 could influence virus movement. However, mimicking phosphorylation at residue S247 does not appear to be relevant to both functions of TGBp1. Overall, our study provides insights into the functional significance of specific phosphorylation sites in BaMV TGBp1, illuminating the regulatory mechanisms involved in virus movement and silencing suppression.
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Potexvirus , Fosforilação , Potexvirus/genética , Alanina , Substituição de AminoácidosRESUMO
The inherent ambiguity in reconstructed images from coherent diffraction imaging (CDI) poses an intrinsic challenge, as images derived from the same dataset under varying initial conditions often display inconsistencies. This study introduces a method that employs the Noise2Noise approach combined with neural networks to effectively mitigate these ambiguities. We applied this methodology to hundreds of ambiguous reconstructed images retrieved from a single diffraction pattern using a conventional retrieval algorithm. Our results demonstrate that ambiguous features in these reconstructions are effectively treated as inter-reconstruction noise and are significantly reduced. The post-Noise2Noise treated images closely approximate the average and singular value decomposition analysis of various reconstructions, providing consistent and reliable reconstructions.
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Extracellular vesicle (EV) research is rapidly advancing from fundamental science to translational applications in EV-based personalized therapeutics and diagnostics. Yet, fundamental questions persist regarding EV biology and mechanisms, particularly concerning the heterogeneous interactions between EVs and cells. While we have made strides in understanding virus delivery and intracellular vesicle transport, our comprehension of EV trafficking remains limited. EVs are believed to mediate intercellular communication through cargo transfer, but uncertainties persist regarding the occurrence and quantification of EV-cargo delivery within acceptor cells. This ambiguity is crucial to address, given the significant translational impact of EVs on therapeutics and diagnostics. This perspective article does not seek to provide exhaustive recommendations and guidance on EV-related studies, as these are well-articulated in position papers and statements by the International Society for Extracellular Vesicles (ISEV), including the 'Minimum Information for Studies of Extracellular Vesicles' (MISEV) 2014, MISEV2018, and the recent MISEV2023. Instead, recognizing the multilayered heterogeneity of EVs as both a challenge and an opportunity, this perspective emphasizes novel approaches to facilitate our understanding of diverse EV biology, address uncertainties, and leverage this knowledge to advance EV-based personalized diagnostics and therapeutics. Specifically, this perspective synthesizes current insights, identifies opportunities, and highlights exciting technological advancements in ultrasensitive single EV or "digital" profiling developed within the author's multidisciplinary group. These newly developed technologies address technical gaps in dissecting the molecular contents of EV subsets, contributing to the evolution of EVs as next-generation liquid biopsies for diagnostics and providing better quality control for EV-based therapeutics.
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Vesículas Extracelulares , Medicina de Precisão , Vesículas Extracelulares/metabolismo , Humanos , Medicina de Precisão/métodos , Comunicação Celular , AnimaisRESUMO
PURPOSE: This study aimed to identify the characteristics associated with the need for urinary intervention for a blunt renal injury with collection system involvement using a computed tomography (CT) protocol for trauma. MATERIALS AND METHODS: Abdominal CT images of patients with blunt renal injuries from 2016 to 2020 were reviewed. Patients with low-grade renal trauma, non-collecting system involvement, American Association for the Surgery of Trauma grade V shattered kidney, and emergent nephrectomy were excluded. The largest perinephric mass thickness was measured in the axial view using CT, and a cutoff value was obtained using a receiver-operating characteristic curve analysis. Risk factors for further urinary intervention were analyzed. RESULTS: Among the 70 patients included in this study, those with perinephric mass thicknesses < 25 mm (n = 36) had a significantly lower rate of urinary intervention than those with perinephric mass thicknesses ≥ 25 mm (0 vs. 5; p = 0.023). There was no significant difference in the follow-up durations of the groups (19 days vs. 38 days; p = 0.198). More than 90% of the perinephric mass in the < 25 mm group resolved within a median follow-up duration of 38 days, whereas nearly half of the ≥ 25 mm group had a residual perinephric mass during a median follow-up duration of 19 days. CONCLUSION: The initial CT protocol for trauma was useful for predicting the need for further urinary interventions for collecting system injuries. A perinephric mass thickness < 25 mm is predictive of a low likelihood of requiring urinary intervention.
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Ferimentos não Penetrantes , Humanos , Ferimentos não Penetrantes/diagnóstico por imagem , Ferimentos não Penetrantes/terapia , Rim/diagnóstico por imagem , Nefrectomia , Procedimentos Cirúrgicos Urológicos , Fatores de RiscoRESUMO
BACKGROUND AND AIM: Primary liver cancer, particularly hepatocellular carcinoma (HCC), represents a substantial global health challenge. Although immune checkpoint inhibitors are effective in HCC treatment, several patients still experience disease progression. Interleukin-1 (IL-1) regulates immunity and inflammation. We investigate the role of IL-1 in HCC development and progression and determine the potential therapeutic impact of gemcitabine in treating HCC. METHODS: Hydrodynamics-based transfection, employing the sleeping beauty transposase system, delivered surrogate tumor antigens, NRAS (NRAS proto-oncogene, GTPase), ShP53, and SB100 to C57BL/6 mice. A basic HCC mouse model was established. Pathogen-free animals were tested for serum and hepatotoxicity. The HCC prognosis was monitored using alanine aminotransferase and aspartate aminotransferase levels. Liver histology immunohistochemistry and mouse splenocyte/intra-hepatic immune cell flow cytometry were conducted. IL-1ß levels in human and mouse serum were assessed. RESULTS: Interleukin-1ß levels were elevated in patients with HCC compared with those in non-HCC controls. Hepatic IL-1ß levels were higher in HCC mouse models than those in non-HCC mice, suggesting localized hepatic inflammation. IL-1 receptor type 1 (IL-1R1) knockout (IL-1R1-/-) mice exhibited less severe HCC progression than that in wild-type mice, despite the high intra-hepatic IL-1ß concentration. IL-1R1-/- mice exhibited increased hepatic levels of myeloid-derived suppressor cells and regulatory T cells, which may exacerbate HCC. Gemcitabine significantly reduced the HCC tumor burden, improved liver conditions, and increased survival rates in HCC mouse models. Gemcitabine reduced the hepatic levels of myeloid-derived suppressor cells and regulatory T cells, potentially alleviating immune suppression in the liver. CONCLUSIONS: Targeting IL-1 or combining gemcitabine with immunotherapy is a promising approach for treating advanced-stage HCC.
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OBJECTIVE: Patients with dizziness commonly present to Emergency Departments (ED) and 6% of these patients will be diagnosed with acute stroke. The TriAGe+ score comprises of eight clinical parameters and stratifies patients into four risk groups. The Japanese authors reported that the tool performed well, so our aim was to validate this diagnostic tool in our ED in Hong Kong. MATERIALS AND METHODS: A single-center retrospective observational study was conducted in the ED of our university hospital in Hong Kong. The primary outcome was the diagnosis of an acute cerebrovascular event. Receiver operator characteristic (ROC) analysis was performed to determine the best cut-off score. Secondary outcomes included univariable and multivariable analyses of stroke predictors. RESULTS: 455 patients aged 18 years or above with dizziness or vertigo at ED triage were recruited between 19 July and 30 September 2021. The overall prevalence of stroke was 11.9%. The median TriAGe+ score was 7 (IQR = 4-9). The AUC was 0.9. At a cut-off >5, sensitivity was 96.4% (95%CI: 87.3-99.5) and the negative likelihood ratio was 0.09 (95%CI: 0.02-0.3). At a cut-off >10, specificity was 99.8% (95%CI: 98.6-100.0), and the positive likelihood ratio was 237.6 (95%CI: 33.1-1704). On multivariable analyses, atrial fibrillation, blood pressure, gender, dizziness (not vertigo) and no history of dizziness, vertigo or labyrinth/vestibular disease were found to be positively associated with stroke outcomes significantly. CONCLUSION: The TriAGe+ score is an efficient stroke prediction score for patients presenting to the ED with dizziness.
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Tontura , Acidente Vascular Cerebral , Humanos , Tontura/diagnóstico , Tontura/epidemiologia , Serviço Hospitalar de Emergência , Hong Kong/epidemiologia , Hospitais Universitários , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Triagem , Vertigem/diagnóstico , Vertigem/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Low back pain (LBP) is a leading cause of disability worldwide and has posed numerous health and socioeconomic challenges. This study compared whether nonsteroidal anti-inflammatory drugs (NSAIDs) in combination with tramadol, tizanidine or placebo would be the best treatment regime to improve the Roland Morris Disability Questionnaire (RMDQ) scores at 1 week. METHODS: This was a multi-center, double-blind, randomized, and placebo-controlled trial including adult patients with acute LBP and sciatica in three emergency departments in Hong Kong. Patients were randomized to the receive tramadol 50 mg, tizanidine 2 mg, or placebo every 6 hours for 2 weeks in a 1:1:1 ratio. The RMDQ and other secondary outcomes were measured at baseline, Day 2, 7, 14, 21, and 28. Data were analyzed on an intention to treat basis. Crude and adjusted mean differences in the changes of RMDQ and NRS scores from baseline to Day 7 between tizanidine/tramadol and placebo were determined with 95% confidence intervals. RESULTS: Two hundred and ninety-one patients were analyzed with the mean age of 47.4 years and 57.7% were male. The primary outcome of mean difference in RMDQs on Day 7 (compared with baseline) was non-significant for tizanidine compared with placebo (adjusted mean difference - 0.56, 95% CI -2.48 to 1.37) and tramadol compared with placebo (adjusted mean difference - 0.85, 95% CI -2.80 to 1.10). Only 23.7% were fully compliant to the treatment allocated. Complier Average Causal Effect analysis also showed no difference in the primary outcome for the tizanidine and tramadol versus placebo. CONCLUSION: Among patients with acute LBP and sciatica presenting to the ED, adding tramadol or tizanidine to diclofenac did not improve functional recovery.
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Movement sonification has emerged as a promising approach for rehabilitation and motion control. Despite significant advancements in sensor technologies, challenges remain in developing cost-effective, user-friendly, and reliable systems for gait detection and sonification. This study introduces a novel wearable personalised sonification and biofeedback device to enhance movement awareness for individuals with irregular gait and posture. Through the integration of inertial measurement units (IMUs), MATLAB, and sophisticated audio feedback mechanisms, the device offers real-time, intuitive cues to facilitate gait correction and improve functional mobility. Utilising a single wearable sensor attached to the L4 vertebrae, the system captures kinematic parameters to generate auditory feedback through discrete and continuous tones corresponding to heel strike events and sagittal plane rotations. A preliminary test that involved 20 participants under various audio feedback conditions was conducted to assess the system's accuracy, reliability, and user synchronisation. The results indicate a promising improvement in movement awareness facilitated by auditory cues. This suggests a potential for enhancing gait and balance, particularly beneficial for individuals with compromised gait or those undergoing a rehabilitation process. This paper details the development process, experimental setup, and initial findings, discussing the integration challenges and future research directions. It also presents a novel approach to providing real-time feedback to participants about their balance, potentially enabling them to make immediate adjustments to their posture and movement. Future research should evaluate this method in varied real-world settings and populations, including the elderly and individuals with Parkinson's disease.
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Biorretroalimentação Psicológica , Marcha , Movimento , Dispositivos Eletrônicos Vestíveis , Humanos , Movimento/fisiologia , Biorretroalimentação Psicológica/instrumentação , Marcha/fisiologia , Masculino , Feminino , Adulto , Fenômenos Biomecânicos , Equilíbrio Postural/fisiologia , Postura/fisiologia , Adulto JovemRESUMO
The sympathetic nervous system(SNS)plays a pivotal role in maintaining organ homeostasis and the pathogenesis of various ailments.Studies have unveiled a profound interconnection between sympathetic nerves and the development of liver cirrhosis,cirrhotic cardiomyopathy,and hepatorenal syndrome.Therefore,researchers have proposed SNS as a candidate therapeutic target for liver-related disorders.This article reviewed the research progress of sympathetic nerves in liver cirrhosis,cirrhotic cardiomyopathy,and hepatorenal syndrome,aiming to enrich the knowledge about the roles of sympathetic nerves in cirrhosis and its complications and provide new ideas for the treatment of liver cirrhosis and its complications.
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Cardiomiopatias , Síndrome Hepatorrenal , Humanos , Cirrose Hepática , Sistema Nervoso Simpático , HomeostaseRESUMO
Background: Cardiovascular diseases are the leading cause of death among patients on hemodialysis, with approximately 40% of the cardiovascular deaths linked to acute coronary syndrome. We aimed to investigate the incidence and risk factors of acute coronary syndrome in patients undergoing hemodialysis. Methods: Patients undergoing hemodialysis were prospectively enrolled from January 2018. Data regarding hospitalization due to acute coronary syndrome were collected at 3-month intervals through December 31, 2021. Cox regression model was used to estimate the association between baseline factors and incident acute coronary syndrome during follow-up. Results: Patients' mean age was 66 years, 48% were men, and 16% had a history of coronary artery disease at enrolment. Over a median follow-up of 1,187 days, 85 patients were hospitalized due to acute coronary syndrome. Left main or triple vessel disease was identified in 67 patients. Risk factors associated with incident acute coronary syndrome included aging, male sex, smoking, low diastolic blood pressure, and baseline comorbidities, in addition to dialysis factors including low urea clearance, central venous catheter use, and history of dialysis access dysfunction. After multivariate analysis, age, diabetes, hyperlipidemia, smoking, and frequent interventions for vascular access remained significant risk factors. Conclusions: A high acute coronary syndrome incidence was observed in our cohort, with traditional risk factors playing a consistent role with that in the general population. A history of frequent dialysis access dysfunction was also associated with incident acute coronary syndrome.
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Biomarcadores , Humanos , Biomarcadores/análise , História do Século XXI , História do Século XXRESUMO
The recently proposed Ehrenfest M-urn model with interactions on a ring is considered as a paradigm model which can exhibit a variety of distinct nonequilibrium steady states. Unlike the previous three-urn model on a ring which consists of a uniform steady state and a nonuniform nonequilibrium steady state, it is found that for even M≥4, an additional nonequilibrium steady state can coexist with the original ones. Detailed analysis reveals that this additional nonequilibrium steady state emerged via a pitchfork bifurcation which cannot occur if M is odd. Properties of this nonequilibrium steady state, such as stability, and steady-state flux are derived analytically for the four-urn case. The full phase diagram with the phase boundaries is also derived explicitly. The associated thermodynamic stability is also analyzed, confirming its stability. These theoretical results are also explicitly verified by direct Monte Carlo simulations for the three-urn and four-urn ring models.
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Sparganosis has been a neglected parasitic zoonosis for a long time. The accurate identification of Spirometra tapeworms in clinical practice is poorly understood. A case of breast sparganosis was reported in Henan Province of central China. One plerocercoid approximately 3.5 cm in length was collected from the patient. The clinical isolate was identified as Spirometra mansoni based on the barcoding sequences of mitochondrial cytochrome c oxidase subunit 1 (cox1). Finally, the epidemiology of sparganosis in central China was reviewed. Comprehensive public health education should be carried out, and the risky habit of eating live tadpoles must be discouraged in Henan Province.
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Esparganose , Spirometra , Animais , Spirometra/genética , Spirometra/isolamento & purificação , Spirometra/classificação , Esparganose/parasitologia , Esparganose/diagnóstico , Humanos , China , Complexo IV da Cadeia de Transporte de Elétrons/genética , Feminino , FilogeniaRESUMO
The spectral and spatial characteristics of Acousto-Optic Tunable Filters (AOTFs), such as a tuning curve, spectral resolution, angular aperture, and diffraction efficiency, are determined by the device's acousto-optic crystal configuration and piezoelectric transducer. For high-throughput spectral imaging applications, it is essential to enlarge the spectral bandwidth and angular aperture during the design phase of AOTFs. Thus, phase mismatch due to incident angle or wavelength was studied analytically using phase diagrams in this paper. Additionally, a performance parameter analysis model was established based on the use of mercurous bromide crystals for large angular aperture AOTF device design, and the impact of crystal and transducer design parameters on the spectral bandwidth and angular aperture was evaluated. This also experimentally validates the diffraction capability of AOTFs made from mercurous bromide crystal, which possess a broad spectral transmission ability ranging from visible to long-wave infrared.
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Medical device-associated infection remains a critical problem in the healthcare setting. Different clinical- or device-related methods have been attempted to reduce the infection rate. Among these approaches, creating a surface with bactericidal cationic functionality has been proposed. To do so, a sophisticated multi-step chemical procedure would be needed. Instead, a simple immersion approach was utilized in this investigation to render the titanium and polypropylene surface with the quaternary ammonium functionality by using a mussel-inspired novel lab-synthesized biomimetic catechol-terminated polymer, PQA-C8. The chemical oxidants, CuSO4/H2O2, as well as dopamine, were added into the novel PQA-C8 polymer immersion solution for one-step surface modification. Additionally, a two-step immersion scheme, in which the polypropylene substrate was first immersed in the dopamine solution and then in the PQA-C8 solution, was also attempted. Surface analysis results indicated the surface characteristics of the modified substrates were affected by the immersion solution formulation as well as the procedure utilized. The antibacterial assay has shown the titanium substrates modified by the one-step dopamine + PQA-C8 mixtures with the oxidants added and the polypropylene modified by the two-step scheme exhibited bacterial reduction percentages greater than 90% against both Gram-positive S. aureus and Gram-negative E. coli and these antibacterial substrates were non-cytotoxic.
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The angular and spectral properties crucial for the functionality of acousto-optic (AO) devices are determined by phase-matching geometries in AO interactions. In applications such as spectral imagers based on acousto-optic tunable filters (AOTFs), systematic throughput is constrained by the angle separating diffracted and transmitted light. This research introduces an analytical model that elucidates the angular-spectral properties of diffracted beams in mercurous halide crystals. These crystals possess a wide transmissive spectral range, from visible light to long-wave infrared light. The study computes and confirms correlations between the separation angle and parameters including incident angle, polarization, acoustic angle, and crystal birefringence. Experimental validation conducted on mercurous halide and tellurium dioxide crystals demonstrates that higher birefringence in crystals significantly amplifies the separation angle, augmenting the device's performance. The study contributes to the development of devices with large separation angles during the design phase, enhancing systematic throughput in spectral imaging applications.
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Diagnostic imaging is essential in modern trauma care for initial evaluation and identifying injuries requiring intervention. Deep learning (DL) has become mainstream in medical image analysis and has shown promising efficacy for classification, segmentation, and lesion detection. This narrative review provides the fundamental concepts for developing DL algorithms in trauma imaging and presents an overview of current progress in each modality. DL has been applied to detect free fluid on Focused Assessment with Sonography for Trauma (FAST), traumatic findings on chest and pelvic X-rays, and computed tomography (CT) scans, identify intracranial hemorrhage on head CT, detect vertebral fractures, and identify injuries to organs like the spleen, liver, and lungs on abdominal and chest CT. Future directions involve expanding dataset size and diversity through federated learning, enhancing model explainability and transparency to build clinician trust, and integrating multimodal data to provide more meaningful insights into traumatic injuries. Though some commercial artificial intelligence products are Food and Drug Administration-approved for clinical use in the trauma field, adoption remains limited, highlighting the need for multi-disciplinary teams to engineer practical, real-world solutions. Overall, DL shows immense potential to improve the efficiency and accuracy of trauma imaging, but thoughtful development and validation are critical to ensure these technologies positively impact patient care.
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BACKGROUND: Monitoring Intraabdominal Pressure (IAP) is essential in critical care, as elevated IAP can lead to severe complications, including Abdominal Compartment Syndrome (ACS). Advances in technology, such as digital capsules, have opened new avenues for measuring IAP non-invasively. This study assesses the feasibility and effectiveness of using a capsular device for IAP measurement in an animal model. METHOD: In our controlled experiment, we anesthetized pigs and simulated elevated IAP conditions by infusing CO2 into the peritoneal cavity. We compared IAP measurements obtained from three different methods: an intravesical catheter (IAPivp), a capsular device (IAPdot), and a direct peritoneal catheter (IAPdir). The data from these methods were analyzed to evaluate agreement and accuracy. RESULTS: The capsular sensor (IAPdot) provided continuous and accurate detection of IAP over 144 h, with a total of 53,065,487 measurement triplets recorded. The correlation coefficient (R²) between IAPdot and IAPdir was excellent at 0.9241, demonstrating high agreement. Similarly, IAPivp and IAPdir showed strong correlation with an R² of 0.9168. CONCLUSION: The use of capsular sensors for continuous and accurate assessment of IAP marks a significant advancement in the field of critical care monitoring. The high correlation between measurements from different locations and methods underscores the potential of capsular devices to transform clinical practices by providing reliable, non-invasive IAP monitoring.