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Non-alcoholic fatty liver disease (NAFLD) is defined as a combination of a group of progressive diseases, presenting different structural features of the liver at different stages of the disease. According to epidemiological surveys, as living standards improve, the global prevalence of NAFLD increases. Acute kidney injury (AKI) is a class of clinical conditions characterized by a rapid decline in kidney function. NAFLD and AKI, as major public health diseases with high prevalence and mortality, respectively, worldwide, place a heavy burden on societal healthcare systems. Clinical observations of patients with NAFLD with AKI suggest a possible association between the two diseases. However, little is known about the pathogenic mechanisms linking NAFLD and AKI, and the combination of the diseases is poorly treated. Previous studies have revealed that liver-derived factors are transported to distal organs via circulation, such as the kidney, where they elicit specific effects. Of note, while NAFLD affects the expression of many hepatic factors, studies on the mechanisms whereby NAFLD mediates the generation of hepatic factors that lead to AKI are lacking. Considering the unique positioning of hepatic factors in coordinating systemic energy metabolism and maintaining energy homeostasis, we hypothesize that the effects of NAFLD are not only limited to the structural and functional changes in the liver but may also involve the entire body via the hepatic factors, e.g., playing an important role in the development of AKI. This raises the question of whether analogs of beneficial hepatic factors or inhibitors of detrimental hepatic factors could be used as a treatment for NAFLD-mediated and hepatic factor-driven AKI or other metabolic disorders. Accordingly, in this review, we describe the systemic effects of several types of hepatic factors, with a particular focus on the possible link between hepatic factors whose expression is altered under NAFLD and AKI. We also summarize the role of some key hepatic factors in metabolic control mechanisms and discuss their possible use as a preventive treatment for the progression of metabolic diseases.

Abstract Background Lumbar spinal stenosis is the most frequent reason for spinal surgery in elderly people. For patients with moderate or severe symptoms different conservative and surgical treatment modalities are recommended, but knowledge about the effectiveness, in particular of the conservative treatments, is scarce. There is some evidence that surgery improves outcome in about two thirds of the patients. The aims of this study are to derive and validate a prognostic prediction aid to estimate the probability of clinically relevant improvement after surgery and to gain more knowledge about the future course of patients treated by conservative treatment modalities. Methods/Design This is a prospective, multi-centre cohort study within four hospitals of Zurich, Switzerland. We will enroll patients with neurogenic claudication and lumbar spinal stenosis verified by Computer Tomography or Magnetic Resonance Imaging. Participating in the study will have no influence on treatment modality. Clinical data, including relevant prognostic data, will be collected at baseline and the Swiss Spinal Stenosis Questionnaire will be used to quantify severity of symptoms, physical function characteristics, and patient's satisfaction after treatment (primary outcome). Data on outcome will be collected 6 weeks, and 6, 12, 24 and 36 months after inclusion in the study. Applying multivariable statistical methods, a prediction rule to estimate the course after surgery will be derived. Discussion The ultimate goal of the study is to facilitate optimal, knowledge based and individualized treatment recommendations for patients with symptomatic lumbar spinal stenosis.

AIM: To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease (CTD-ILD) and healthy controls (HCs) by optical coherence tomography angiography (OCTA) and to investigate the changes in microvascular density in abnormal eyes. METHODS: For a retrospective case-control study, a total of 16 patients (32 eyes) diagnosed with CTD-ILD were selected as the ILD group. The 16 healthy volunteers with 32 eyes, matched in terms of age and sex with the patients, were recruited as control group. The macular retina's superficial retinal layer (SRL) and deep retinal layer (DRL) were examined and scanned using OCTA in each individual eye. The densities of retinal microvascular (MIR), macrovascular (MAR), and total microvascular (TMI) were calculated and compared. Changes in retinal vascular density in the macular region were analyzed using three different segmentation methods: central annuli segmentation method (C1-C6), hemispheric segmentation method [uperior right (SR), superior left (SL), inferior left (IL), and inferior right (IR)], and Early Treatment Diabetic Retinopathy Study (ETDRS) methods [superior (S), inferior (I), left (L), and right (R)]. The data were analyzed using Version 9.0 of GraphPad prism and Pearson analysis. RESULTS: The OCTA data demonstrated a statistically significant difference (P

Abstract Background Treatment efficacy may differ among patients with nasopharyngeal carcinoma (NPC) at similar tumor–node–metastasis stages. Moreover, end-of-treatment tumor regression is a reliable indicator of treatment sensitivity. This study aimed to investigate whether quantitative dual-energy computed tomography (DECT) parameters could predict sensitivity to neck–lymph node radiotherapy in patients with NPC. Methods Overall, 388 lymph nodes were collected from 98 patients with NPC who underwent pretreatment DECT. The patients were divided into complete response (CR) and partial response (PR) groups. Clinical characteristics and quantitative DECT parameters were compared between the groups, and the optimal predictive ability of each parameter was determined using receiver operating characteristic (ROC) analysis. A nomogram prediction model was constructed and validated using univariate and binary logistic regression. Results DECT parameters were higher in the CR group than in the PR group. The iodine concentration (IC), normalized IC, Mix-0.6, spectral Hounsfield unit curve slope, effective atomic number, and virtual monoenergetic images were significantly different between the groups. The area under the ROC curve of the DECT parameters was 0.73–0.77. Based on the binary logistic regression, a column chart was constructed using 10 predictive factors, including age, sex, N stage, maximum lymph node diameter, arterial phase NIC, venous phase NIC, λHU and spectral Hounsfield units at 70 keV. The area under the ROC curve value of the constructed model was 0.813, with a sensitivity and specificity of 85.6% and 81.3%, respectively. Conclusion Quantitative DECT parameters could effectively predict the sensitivity of NPC to radiotherapy. Therefore, DECT parameters and NPC clinical features can be combined to construct a nomogram with high predictive power and used as a clinical analytical tool.

Abstract The clinical significance of the combination of neutrophil–lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) is unclear. This study investigated the predictive value of pretreatment NLR (pre-NLR) combined with pretreatment PLR (pre-PLR) for the survival and prognosis of nasopharyngeal carcinoma (NPC). A total of 765 patients with non-metastatic NPC from two hospitals were retrospectively analyzed. The pre-NLR-PLR groups were as follows: HRG, high pre-NLR and high pre-PLR. MRG, high pre-NLR and low pre-PLR or low pre-NLR and high pre-PLR. LRG, neither high pre-NLR nor high pre-PLR. Receiver operating characteristic (ROC) curves were used to identify the cutoff-value and discriminant performance of the model. We compared survival rates and factors affecting the prognosis among different groups. The 5-year overall survival (OS), local regional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) of NPC patients in HRG were significantly poorer than those in MRG and LRG. The pre-NLR-PLR score was positively correlated with T stage, clinical stage, ECOG, and pathological classification. Multivariate cox regression analysis showed that pre-NLR-PLR scoring system, ECOG, pre-ALB, pre-CRP and pre-LMR were independent risk factors affecting 5-year OS, LRRFS and DMFS. The ROC curve showed that area under the curve (AUC) values of pre-NLR-PLR of 5-year OS, LRRFS and DMFS were higher than those of pre-NLR and pre-PLR. pre-NLR-PLR is an independent risk factor for the prognosis of NPC. The pre-NLR-PLR scoring system can be used as an individualized clinical assessment tool to predict the prognosis of patients with non-metastatic NPC more accurately and easily.

Abstract Background Lipids found in plant seeds are essential for controlling seed dormancy, dispersal, and defenses against biotic and abiotic stress. Additionally, these lipids provide nutrition and energy and are therefore important to the human diet as edible oils. Acer truncatum, which belongs to the Aceaceae family, is widely cultivated around the world for its ornamental value. Further because its seed oil is rich in unsaturated fatty acids (UFAs)- i.e. α-linolenic acid (ALA) and nervonic acid (NA)- and because it has been validated as a new food resource in China, the importance of A. truncatum has greatly risen. However, it remains unknown how UFAs are biosynthesized during the growth season, to what extent environmental factors impact their content, and what areas are potentially optimal for their production. Results In this study, transcriptome and metabolome of A. truncatum seeds at three representative developmental stages was used to find the accumulation patterns of all major FAs. Cumulatively, 966 metabolites and 87,343 unigenes were detected; the differential expressed unigenes and metabolites were compared between stages as follows: stage 1 vs. 2, stage 1 vs. 3, and stage 2 vs. 3 seeds, respectively. Moreover, 13 fatty acid desaturases (FADs) and 20 β-ketoacyl-CoA synthases (KCSs) were identified, among which the expression level of FAD3 (Cluster-7222.41455) and KCS20 (Cluster-7222.40643) were consistent with the metabolic results of ALA and NA, respectively. Upon analysis of the geographical origin-affected diversity from 17 various locations, we found significant variation in phenotypes and UFA content. Notably, in this study we found that 7 bioclimatic variables showed considerable influence on FAs contents in A. truncatum seeds oil, suggesting their significance as critical environmental parameters. Ultimately, we developed a model for potentially ecological suitable regions in China. Conclusion This study provides a comprehensive understanding of the relationship between metabolome and transcriptome in A. truncatum at various developmental stages of seeds and a new strategy to enhance seed FA content, especially ALA and NA. This is particularly significant in meeting the increasing demands for high-quality edible oil for human consumption. The study offers a scientific basis for A. truncatum’s novel utilization as a woody vegetable oil rather than an ornamental plant, potentially expanding its cultivation worldwide.

During outdoor work in April 2022, a 48-year-old man was stabbed by a tree branch and underwent intraocular foreign body extraction and repair of the scleral wound with sutures and amniotic membrane graft at a local hospital. Steroid therapy with prednisone was prescribed after a diagnosis of uveitis. Vitrectomy was performed in June 2023; a fungal culture was positive, and ITS sequencing identified the organism as Paradictyoarthrinium diffractum. Empiric antifungal therapy did not have an effect, and, because of deterioration of the condition, the left eye was enucleated in October 2023. P. diffractum is a mangrove host-specific saprophytic fungus that has not been reported in humans.

BackgroundChildhood and adolescent cancer represent a significant health burden in the United States. Current and precise epidemiological data are crucial to develop effective cancer control plans and ultimately reduce the burden of childhood and adolescent cancer.MethodsWe analyzed data obtained from cancer registries in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Age-standardized incidence and death rates, assessed using joinpoint analysis, were quantified as annual percentage changes (APC) and average percentage changes (AAPC).ResultsThe overall cancer incidence rate in 2008–2018 was 187.9 per 1,000,000 persons. Cancer incidence rates demonstrated a sustained upward trend, with an APC of 0.8 from 1975 to 2018. Incidence rates during 2008–2018 remained stable among non-Hispanic Black children but increased among other racial and ethnic groups. Leukemias, central nervous system tumors, and lymphomas were the most common cancer groups for patients aged 0–19 years. Cancer death rates decreased among children [AAPC, −1.3 (95% CI, −1.5 to −1.1)] during 2009–2019, while were stable among adolescents during that period.ConclusionsIn this study, we analyzed cancer incidence and mortality rates and trends in children aged 0–19 years in the United States. Our findings revealed an overall increase in cancer incidence rates among children and adolescents, accompanied by a decline in cancer mortality rates over time. These rates and trends varied by age, sex, and particularly race and ethnicity, highlighting the significance of comprehending and addressing disparities and ultimately reducing the disease burden of childhood and adolescent cancer.

Fe-based amorphous coating was produced using high-velocity arc-spraying (HVAS), and then laser remelting (LR) technology was used to treat the as-sprayed coatings (ASC) to prepare the laser remelted coatings (LRC). The morphology, phase composition, microhardness, porosity, and corrosion property of the Fe-based amorphous coatings before and after LR were investigated. The outcomes demonstrated that the internal defects of the ASC were eliminated and the porosity was significantly reduced after LR, which was significant in dramatically enhancing corrosion resistance. After the LR procedure, the ASC's free corrosion potential (Ecorr) in 3.5 wt% NaCl solution increased, and the corrosion current density (Icorr) almost reduced by a factor of ten. Therefore, LR helped to strengthen the corrosion characteristics of Fe-based amorphous coating and improve its microstructure.

Abstract Myocardial infarction is defined as a sudden decrease or interruption in blood flow to the coronary arteries, causing ischemic necrosis of the corresponding cardiomyocytes. It is unclear whether systemic macrovascular alterations are associated with retinal microvascular changes. This study utilized optical coherence tomography angiography (OCTA) to compare variations in conjunctival vascular density and fundus retinal vessel density between patients with myocardial infarction (MI) and healthy controls. This study recruited 16 patients (32 eyes) with MI and 16 healthy controls (32 eyes). The superficial retinal layer (SRL), deep retinal layer (DRL) and conjunctival capillary plexus in each eye were evaluated by OCTA. Parameters measured included the density of the temporal conjunctival capillary, retinal microvascular (MIR) and macrovascular (MAR) alterations and total MIR (TMI). The microvascular density of each retinal region was evaluated by the hemisphere segmentation (SR, SL, IL, and IR), annular partition (C1, C2, C3, C4, C5 and C6), and modified early treatment of diabetic retinopathy study (R, S, L, and I) methods. In the macular area, the superficial and deep retinal microvascular densities displayed notable variations. In the superficial layers, the superficial TMI, superficial MIR, and superficial MAR, as well as densities in the SL, IL, S, L, C1, C2, C5 and C6 regions, were significantly lower in MI patients (p

ABSTRACT: A novel strain of duck picornavirus was isolated from duck tissue in Taian, Shandong Province, in 2017 in our laboratory. The virus was amplified in specific-pathogen-free (SPF) chicken embryos, purified and then analyzed by whole genome sequencing, which revealed a new duck-derived small RNA virus that was designated as Duck/FC22/China/2017 (FC22, GenBank accession no. MN102111) based on its genome structure and phylogenetic relationship. An in-depth study revealed that the virus grew well on the Leghorn male hepatoma (LMH) cell line. After propagation of the virus, SPF ducks were inoculated for pathogenicity tests, and their mental state, growth and development were observed after inoculation; the ducks were dissected to observe the organs and histopathological changes. A TaqMan fluorescence quantitative PCR method was utilized to detect the proliferation and shedding patterns of the virus within the ducks, while the SYBR Green I fluorescence quantitative PCR method was used to assess cytokine expression levels in the organs. The results showed that following inoculation with the FC22 strain, the mental status of the SPF ducks remained unchanged. Mild oedema was observed in some tissue organs during dissection; however, no pathological changes, such as congestion or degeneration, were noted. Histopathological analysis revealed cellular necrosis in organs, including the heart, liver, and bursa of Fabricius, as well as a reduced volume and deep staining of certain neurons in the cerebrum. Following infection, the virus titres in various organs and in cloacal swabs of the SPF ducks peaked on the first day before gradually decreasing daily. By the 10th d, the virus titres in all organs had decreased to less than 101 copies/μL. Additionally, notable alterations were observed in the expression levels of the cytokines IFNα, IL6, IL10, and TNFα. This indicates that the FC22 strain does not cause significant disease in ducks. This report presents the initial study on a recently discovered picornavirus, offering a thorough and methodical examination of its pathogenic characteristics and provides a reference for the clinical evaluation and scientific strategies for the prevention and treatment of this particular picornavirus.

Mouse orthotopic xenograft tumor models are commonly employed in studies investigating the mechanisms underlying the development and progression of tumors and their preclinical treatment. However, the unavailability of mature and visualized orthotopic xenograft models of nasopharyngeal carcinoma limits the development of treatment strategies for this cancer. The aim of this study was to provide a simple and reliable method for building an orthotopic xenograft model of nasopharyngeal carcinoma. Human nasopharyngeal carcinoma (C666–1-luc) cells, stably expressing the firefly luciferase gene, were injected subcutaneously into the right axilla of BALB/C nude mice. Four weeks later, the resulting subcutaneous tumors were cut into small blocks and grafted into the nasopharynx of immunodeficient BALB/C nude mice to induce tumor formation. Tumor growth was monitored by bioluminescence imaging and small animal magnetic resonance imaging (MRI). The expression of histological and immunological antigens associated with orthotopic xenograft nasopharyngeal carcinoma was analyzed by tissue section analysis and immunohistochemistry (IHC). A visualized orthotopic xenograft nasopharyngeal carcinoma model was successfully developed in this study. Luminescence signal detection, micro-MRI, and hematoxylin and eosin staining revealed the successful growth of tumors in the nasopharynx of the nude mice. Moreover, IHC analysis detected cytokeratin (CK), CK5/6, P40, and P63 expression in the orthotopic tumors, consistent with the reported expression of these antigens in human nasopharyngeal tumors. This study established a reproducible, visual, and less lethal orthotopic xenograft model of nasopharyngeal carcinoma, providing a platform for preclinical research.

China has been continuously improving its monitoring methods and strategies to address key infectious diseases (KIDs). After the severe acute respiratory syndrome epidemic in 2003, China established a comprehensive reporting system for infectious diseases (IDs) and public health emergencies. The relatively lagging warning thresholds, limited warning information, and outdated warning technology are insufficient to meet the needs of comprehensive monitoring for modern KIDs. Strengthening early monitoring and warning capabilities to enhance the public health system has become a top priority, with increasing demand for early warning thresholds, information, and techniques, thanks to constant innovation and development in molecular biology, bioinformatics, artificial intelligence, and other identification and analysis technologies. A panel of 31 experts has recommended a fourth-generation comprehensive surveillance system targeting KIDs (41 notifiable diseases and emerging IDs). The aim of this surveillance system is to systematically monitor the epidemiology and causal pathogens of KIDs in hosts such as humans, animals, and vectors, along with associated environmental pathogens. By integrating factors influencing epidemic spread and risk assessment, the surveillance system can serve to detect, predict, and provide early warnings for the occurrence, development, variation, and spread of known or novel KIDs. Moreover, we recommend comprehensive ID monitoring based on the fourth-generation surveillance system, along with a data-integrated monitoring and early warning platform and a consortium pathogen detection technology system. This series of considerations is based on systematic and comprehensive monitoring across multiple sectors, dimensions, factors, and pathogens that is supported by data integration and connectivity. This expert consensus will provides an opportunity for collaboration in various fields and relies on interdisciplinary application to enhance comprehensive monitoring, prediction, and early warning capabilities for the next generation of ID surveillance. This expert consensus will serve as a reference for ID prevention and control as well as other related activities.

The Probabilistic Reward Task (PRT) is widely used to investigate the impact of Major Depressive Disorder (MDD) on reinforcement learning (RL), and recent studies have used it to provide insight into decision-making mechanisms affected by MDD. The current project used PRT data from unmedicated, treatment-seeking adults with MDD to extend these efforts by: (1) providing a more detailed analysis of standard PRT metrics—response bias and discriminability—to better understand how the task is performed; (2) analyzing the data with two computational models and providing psychometric analyses of both; and (3) determining whether response bias, discriminability, or model parameters predicted responses to treatment with placebo or the atypical antidepressant bupropion. Analysis of standard metrics replicated recent work by demonstrating a dependency between response bias and response time (RT), and by showing that reward totals in the PRT are governed by discriminability. Behavior was well-captured by the Hierarchical Drift Diffusion Model (HDDM), which models decision-making processes; the HDDM showed excellent internal consistency and acceptable retest reliability. A separate “belief” model reproduced the evolution of response bias over time better than the HDDM, but its psychometric properties were weaker. Finally, the predictive utility of the PRT was limited by small samples; nevertheless, depressed adults who responded to bupropion showed larger pre-treatment starting point biases in the HDDM than non-responders, indicating greater sensitivity to the PRT’s asymmetric reinforcement contingencies. Together, these findings enhance our understanding of reward and decision-making mechanisms that are implicated in MDD and probed by the PRT.

Recently, herpesvirus of turkeys (HVT), which was initially employed as a vaccine against Marek’s disease (MD), has been shown to be a highly effective viral vector for producing recombinant vaccines that can simultaneously express the protective antigens of multiple poultry diseases. Prior to the development of commercial HVT-vectored dual-insert vaccines, the majority of HVT-vectored vaccines in use only contained a single foreign gene and were often generated using time-consuming and inefficient traditional recombination methods. The development of multivalent HVT-vectored vaccines that induce simultaneous protection against several avian diseases is of great value. In particular, efficacy interference between individual recombinant HVT vaccines can be avoided. Herein, we demonstrated the use of CRISPR/Cas9 gene editing technology for the insertion of an IBDV (G2d) VP2 expression cassette into the UL45/46 region of the recombinant rHVT-HA viral genome to generate the dual insert rHVT-VP2-HA recombinant vaccine. The efficacy of this recombinant virus was also evaluated in specific pathogen-free (SPF) chickens. PCR and sequencing results showed that the recombinant virus rHVT-VP2-HA was successfully constructed. Vaccination with rHVT-VP2-HA produced high levels of specific antibodies against IBDV (G2d) and H9N2/Y280. rHVT-VP2-HA can provide 100% protection against challenges with IBDV (G2d) and H9N2/Y280. These results demonstrate that rHVT-VP2-HA is a safe and highly efficacious vaccine for the simultaneous control of IBDV (G2d) and H9N2/Y280.

BackgroundHead and neck squamous cell carcinoma (HNSCC), an extremely aggressive tumor, is often associated with poor outcomes. The standard anatomy-based tumor–node–metastasis staging system does not satisfy the requirements for screening treatment-sensitive patients. Thus, an ideal biomarker leading to precise screening and treatment of HNSCC is urgently needed.MethodsTen machine learning algorithms—Lasso, Ridge, stepwise Cox, CoxBoost, elastic network (Enet), partial least squares regression for Cox (plsRcox), random survival forest (RSF), generalized boosted regression modelling (GBM), supervised principal components (SuperPC), and survival support vector machine (survival-SVM)—as well as 85 algorithm combinations were applied to construct and identify a consensus immune-derived gene signature (CIDGS).ResultsBased on the expression profiles of three cohorts comprising 719 patients with HNSCC, we identified 236 consensus prognostic genes, which were then filtered into a CIDGS, using the 10 machine learning algorithms and 85 algorithm combinations. The results of a study involving a training cohort, two testing cohorts, and a meta-cohort consistently demonstrated that CIDGS was capable of accurately predicting prognoses for HNSCC. Incorporation of several core clinical features and 51 previously reported signatures, enhanced the predictive capacity of the CIDGS to a level which was markedly superior to that of other signatures. Notably, patients with low CIDGS displayed fewer genomic alterations and higher immune cell infiltrate levels, as well as increased sensitivity to immunotherapy and other therapeutic agents, in addition to receiving better prognoses. The survival times of HNSCC patients with high CIDGS, in particular, were shorter. Moreover, CIDGS enabled accurate stratification of the response to immunotherapy and prognoses for bladder cancer. Niclosamide and ruxolitinib showed potential as therapeutic agents in HNSCC patients with high CIDGS.ConclusionCIDGS may be used for stratifying risks as well as for predicting the outcome of patients with HNSCC in a clinical setting.