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Immune inflammation is one of the main factors in the pathogenesis of depression. It is an effective and active way to find more safe and effective anti-inflammatory depressant drugs from plant drugs. The purpose of this study is to explore the potential of marine plant Sargassum pallidum (Turn).C.Ag. (Haihaozi, HHZ) in the prevention and treatment of depression and to explain the related mechanism. Phytochemical analysis showed that alkaloids, terpenes, and organic acids are the main constituents. In vitro and in vivo activity studies showed the anti-neuroinflammatory and antidepressant effect of Sargassum pallidum, furthermore, confirmed that 7-Hydroxycoumarin, Scoparone, and Kaurenoic Acid are important plant metabolites in Sargasum pallidum for anti-neuroinflammation. Mechanism exploration showed that inhibition of ERK1/2/p38 inflammatory signaling pathway contributing to the antidepressant effect of Sargassum pallidum in reducing intestinal inflammatory levels. This study confirmed the value of Sargassum pallidum and its rich plant metabolites in anti-inflammatory depression, providing a new choice for the follow-up research and development of antidepressant drugs.
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Streptococcus suis (S. suis) is a Gram-positive bacterium and the main culprit behind zoonotic outbreaks, posing a serious threat to public health. The prevalent strains in China are mainly of sequence types (ST) 1 and 7, with few cases of human infections caused by other sequence type being reported. This study presents the first isolation of a ST25 strain from the blood of a septicemic patient. A 57-year-old febrile patient was admitted to a hospital in Hainan of China, diagnosed as septicemia and hepatic dysfunction. A strain of S. suis was isolated from blood culture and confirmed to be serotype 2 and ST25 through 16S rRNA sequencing and whole-genome sequencing, and its genome was further analyzed for gene functions and presence of drug resistance genes. The full-length genome of strain HN28 spans 2,280,124 bp and encodes a total of 2291 proteins. Genes annotated in COG, GO, KEGG, CAZy, and PHl databases accounted for 75.38 %, 69.14 %, 55.35 %, 4.58 %, and 11.87 % of the total predicted proteins, respectively. Virulence factor analysis revealed the presence of seven putative virulence genes in strain HN28. Analysis using the CARD database identified 51 resistance genes in HN28, alongside abundant exocytosis systems. These findings underscore the occurrence of S. suis infections in humans caused by less common ST, emphasizing the need for enhanced epidemiological investigations and monitoring of S. suis infections in the human population.
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Extracellular vesicles (EVs) have emerged as promising biomaterials for the treatment of different disease. However, only handful types of EVs with clinical transformation potential have been reported to date, and their preparation on a large scale under biosafety-controlled conditions is limited. In this study, we characterize a novel type of EV with promising clinical application potential: dehydration-induced extracellular vesicles (DIMVs). DIMV is a type of micron-diameter cell vesicle that contains more bioactive molecules, such as proteins and RNA, but not DNA, than previously reported cell vesicles. The preparation of DIMV is extraordinarily straightforward, which possesses a high level of biosafety, and the protein utilization ratio is roughly 600 times greater than that of naturally secreted EVs. Additional experiments demonstrate the viability of pre- or post-isolation DIMV modification, including gene editing, nucleic acid encapsulation or surface anchoring, size adjustment. Finally, on animal models, we directly show the biosafety and immunogenicity of DIMV, and investigate its potential application as tumour vaccine or drug carrier in cancer treatment.
Subject(s)
Extracellular Vesicles , Extracellular Vesicles/metabolism , Animals , Humans , Mice , Dehydration/metabolism , Cancer VaccinesABSTRACT
Two bacterial strains (XCT-34T and XCT-53) isolated from sediment samples of an artificial freshwater reservoir were analyzed using a polyphasic approach. The two isolates are aerobic, Gram-stain-negative, oxidase-negative, catalase-positive, motile with polar flagella, rod-shaped, and approximately 1.4-3.4 × 0.4-0.9 µm in size. Phylogenetic analyses based on 16S rRNA gene and whole-genome sequences showed that the two strains formed a distinct branch within the evolutionary radiation of the genus Pannonibacter, closest to Pannonibacter carbonis Q4.6T (KCTC 52466). Furthermore, lower than threshold average nucleotide identity values (ANI, 85.7-86.4%) and digital DNA-DNA hybridization values (dDDH, 22.3-30.5%) of the two strains compared to the nearest type strains also confirmed that they represented a novel species. Genomic analyses, including annotation of the KEGG pathways, prediction of the secondary metabolism biosynthetic gene clusters and PHI phenotypes, supported functional inference and differentiation of the strains from the closely related taxa. Results of chemotaxonomic and physiological studies revealed that their distinct phenotypic characteristics distinguished them from existing Pannonibacter species. Thus, the two strains are considered to represent a novel species of Pannonibacter, for which the name of Pannonibacter tanglangensis sp. nov. is proposed, with XCT-34T (= KCTC 82332T = GDMCC 1.1947T) as the respective type strain.
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BACKGROUND: The change of serum hepatitis B surface antigen (HBsAg) during treatment are associated with HBsAg loss. However, little is known about the trajectory patterns of HBsAg in early treatment and their relationship with subsequent HBsAg loss. This study aimed to identify trajectories of HBsAg in children with HBeAg-positive chronic hepatitis B (CHB) and investigate the association between trajectory patterns and HBsAg loss. METHODS: A retrospective study was conducted on 166 treatment-naive children with HBeAg-positive CHB. Latent class trajectory analysis was used to identify trajectory groups of serum HBsAg. Cox proportional hazard model was used to assess the association between HBsAg trajectory groups and HBsAg loss. RESULTS: The median follow-up time was 20.70 (12.54, 34.17) months, and HBsAg loss occurred in 70(42.17%) of all study participants. Using latent class trajectory analysis, HBeAg-positive CHB patients were classified into three trajectory groups: trajectory 1 (sustained stability, 24.70%), trajectory 2 (slow decline, 38.55%), and trajectory 3 (rapid decline, 36.75%), respectively. The median decline levels of HBsAg at the 3-month and 6-month follow-ups were the highest in trajectory 3 (1.08 and 3.28 log10 IU/ml), followed by trajectory 2 (0.27 and 1.26 log10 IU/ml), and no change in trajectory 1. The risk of achieving HBsAg loss was higher in both trajectory 2 (HR, 3.65 [95% CI, 1.70-7.83]) and trajectory 3 (HR, 7.27 [95% CI, 3.01-17.61]), respectively. CONCLUSION: Serum HBsAg levels during early treatment can be classified into distinct trajectory groups, which may serve as an additional predictive indicator for HBsAg loss in HBeAg-positive CHB children.
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Serological pattern of simultaneous positivity for hepatitis B surface antigen (HBsAg) and antibody against HBsAg (anti-HBs) is considered a specific and atypical phenomenon among patients with chronic hepatitis B virus (HBV) infection, especially in pediatric patients. Unfortunately, there is limited understanding of the clinical and virological characteristics among children having chronic HBV infection and the coexistence of HBsAg and anti-HBs. Hence, our objective was to determine the prevalence of coexistent HBsAg and anti-HBs and to explore the associated clinical and virological features in this patient population. The researchers conducted a retrospective cohort study on the 413 pediatric patients with chronic HBV infection from December 2011 to June 2022. The patients were stratified into two groups based on their anti-HBs status. Demographic, serum biochemical and virological parameters of two group were compared. Of the total 413 enrolled subjects, 94 (22.8%) were tested positive for both HBsAg and anti-HBs. Patients with anti-HBs were younger and demonstrated significantly higher ratio of albumin to globulin (A/G), elevated serum levels of alanine transaminase (ALT), lower ratio of aspartate transaminase (AST)/ALT (AST/ALT) and reduced serum levels of globulin, HBsAg and HBV DNA, Additionally, these patients were more likely to show coexistent HBeAg and anti-HBe when compared to patients without anti-HBs. The results of multivariate logistical analysis revealed that AST/ALT, serum levels of globulin and HBsAg were negatively associated with coexistence of HBsAg and anti-HBs. Our data demonstrated a considerable prevalence of coexisting HBsAg and anti-HBs in pediatric patients. Children with this specific serological pattern were commonly of a younger age, seemly predisposing them to early liver impairment and lower HBV replication activity.
Subject(s)
Hepatitis B Antibodies , Hepatitis B Surface Antigens , Hepatitis B, Chronic , Humans , Male , Hepatitis B Surface Antigens/blood , Female , Child , Retrospective Studies , Hepatitis B, Chronic/virology , Hepatitis B, Chronic/epidemiology , Hepatitis B Antibodies/blood , Child, Preschool , Hepatitis B virus/immunology , Alanine Transaminase/blood , Adolescent , DNA, Viral/blood , China/epidemiology , Prevalence , Aspartate Aminotransferases/bloodABSTRACT
The demand for lithium-ion batteries has been rapidly increasing with the development of new energy vehicles. The cascaded utilization of lithium iron phosphate (LFP) batteries in communication base stations can help avoid the severe safety and environmental risks associated with battery retirement. This study conducts a comparative assessment of the environmental impact of new and cascaded LFP batteries applied in communication base stations using a life cycle assessment method. It analyzes the influence of battery costs and power structure on carbon emissions reduction. Results indicate: When consuming the same amount of electricity in a cascaded battery system (CBS), LFP batteries with a retirement state of health (SOH) range between 76.5 % and 90.0 % can reduce 30.3 % of the global warming potential (GWP) compared to new batteries. From the perspective of battery costs, when the price ratio of new to old batteries is greater than 31.0 %, the GWP of batteries retired at 70.0 % SOH is higher than that of new batteries. As the proportion of renewable energy sources in the power structure increases, the GWP of new batteries in 2035 is 15.0 % lower than in 2020. For batteries retired at 80.0 % SOH, their GWP decreases by 12.3 % compared to 2020. This study offers a new approach to determining the retirement point for LFP batteries from an environmental perspective, promoting carbon emission reduction throughout the entire battery life cycle and the sustainable development of the transportation sector.
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With the rapid demand for lithium-ion batteries due to the widespread application of electric vehicles, a significant amount of battery electrode pieces requiring urgent treatment are generated during battery production and disposal. The strong bonding caused by the presence of binders makes it challenging to achieve thorough separation between the cathode active materials and Al foil, posing difficulties in efficient battery material recycling. To address this issue, a plasma-ultrasonically combined physical separation method is proposed in this study. This method utilizes plasma-generated excited-state radicals assisted by ultrasonic waves to separate active materials and current collectors. The results indicate that the binders are effectively decomposed under plasma treatment at 13.56 MHz, 100 W, and 10 min in an oxygen atmosphere, resulting in a separation efficiency of 96.8 wt % for the cathode materials. Characterization results demonstrate that the morphology, crystal structure, and chemical composition of the recycled cathode active materials remain unchanged, facilitating subsequent direct restoration and hydrometallurgical recycling. Simultaneously, the Al foil is also completely recycled for subsequent reuse. Compared with traditional methods of separating cathode active materials and aluminum foil, the method proposed in this study has significant economic and environmental potential. It can promote the recycling of battery materials and the development of sustainable transportation.
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The exponential growth in data volume has necessitated the adoption of alternative storage solutions, and DNA storage stands out as the most promising solution. However, the exorbitant costs associated with synthesis and sequencing impeded its development. Pre-compressing the data is recognized as one of the most effective approaches for reducing storage costs. However, different compression methods yield varying compression ratios for the same file, and compressing a large number of files with a single method may not achieve the maximum compression ratio. This study proposes a multi-file dynamic compression method based on machine learning classification algorithms that selects the appropriate compression method for each file to minimize the amount of data stored into DNA as much as possible. Firstly, four different compression methods are applied to the collected files. Subsequently, the optimal compression method is selected as a label, as well as the file type and size are used as features, which are put into seven machine learning classification algorithms for training. The results demonstrate that k-nearest neighbor outperforms other machine learning algorithms on the validation set and test set most of the time, achieving an accuracy rate of over 85% and showing less volatility. Additionally, the compression rate of 30.85% can be achieved according to k-nearest neighbor model, more than 4.5% compared to the traditional single compression method, resulting in significant cost savings for DNA storage in the range of $0.48 to 3 billion/TB. In comparison to the traditional compression method, the multi-file dynamic compression method demonstrates a more significant compression effect when compressing multiple files. Therefore, it can considerably decrease the cost of DNA storage and facilitate the widespread implementation of DNA storage technology.
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This paper presents a new technique for estimating the two-dimensional direction of departure (2D-DOD) and direction of arrival (2D-DOA) in bistatic uniform planar array Multiple-Input Multiple-Output (MIMO) radar systems. The method is based on the reduced-dimension (RD) MUSIC algorithm, aiming to achieve improved precision and computational efficiency. Primarily, this pioneering approach efficiently transforms the four-dimensional (4D) estimation problem into two-dimensional (2D) searches, thus reducing the computational complexity typically associated with conventional MUSIC algorithms. Then, exploits the spatial diversity of array response vectors to construct a 4D spatial spectrum function, which is crucial in resolving the complex angular parameters of multiple simultaneous targets. Finally, the objective is to simplify the spatial spectrum to a 2D search within a 4D measurement space to achieve an optimal balance between efficiency and accuracy. Simulation results validate the effectiveness of our proposed algorithm compared to several existing approaches, demonstrating its robustness in accurately estimating 2D-DOD and 2D-DOA across various scenarios. The proposed technique shows significant computational savings and high-resolution estimations and maintains high precision, setting a new benchmark for future explorations in the field.
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This study aimed to assess the predictive capacity of emerging serological markers, serum HBV RNA and HBcrAg, for HBeAg seroconversion in children with HBeAg-positive chronic hepatitis B (CHB). Treatment-naïve HBeAg-positive CHB children who admitted to the Liver Disease Center of Hunan Children's Hospital between April 2021 and September 2022 and received treatment with the combined entecavir and interferon-alpha treatment were recruited. Serum HBV RNA and HBcrAg were measured at baseline and Weeks 12, 24, and 48 of treatment. Our study showed that serum HBV RNA (HR = 0.71, 95% CI: 0.56-0.91, p = 0.006), HBcrAg (HR = 0.60, 95% CI: 0.43-0.84, p = 0.003), and HBsAg (HR = 0.49, 95%CI: 0.36-0.69, p < 0.001) at Week 12 were independent predictors of HBeAg seroconversion. ROC curve analysis presented that serum HBV RNA decline value (ΔHBV RNA) at Week 36 and HBcrAg decline value (ΔHBcrAg) at Week 12 (AUC = 0.871, p = 0.003 and AUC = 0.810, p = 0.003, respectively) could effectively predict HBeAg seroconversion. Furthermore, the optimal critical values were determined and the children with ΔHBV RNA > 3.759 log10 copies/mL at Week 36 or ΔHBcrAg >0.350 log10 U/mL at Week 12 more likely to achieve HBeAg seroconversion. The serum HBV RNA and HBcrAg provide new insights into the treatment of CHB in children. Early assessment of serum HBV RNA and HBcrAg during treatment can assist clinical decision-making and optimize individualized therapeutic approaches.
Subject(s)
Antiviral Agents , Hepatitis B e Antigens , Hepatitis B virus , Hepatitis B, Chronic , RNA, Viral , Seroconversion , Humans , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/virology , Hepatitis B, Chronic/blood , Male , Female , Child , Hepatitis B e Antigens/blood , Antiviral Agents/therapeutic use , RNA, Viral/blood , Hepatitis B virus/genetics , Hepatitis B virus/immunology , Adolescent , Interferon-alpha/therapeutic use , Child, Preschool , Biomarkers/blood , Guanine/therapeutic use , Guanine/analogs & derivatives , Hepatitis B Core Antigens/blood , Hepatitis B Core Antigens/immunology , ROC CurveABSTRACT
Zinc (Zn) is a crucial trace element essential for human growth and development, particularly for reproductive health. Previous research has shown a decrease in serum zinc concentration with age and individuals with conditions such as polycystic ovary syndrome (PCOS) and diabetes mellitus. However, the specific effects of zinc deficiency on the female reproductive system, especially ovarian function, are not fully understood. In our study, we observed a significant reduction in the total number of follicles and mature follicles in the zinc deficiency group. This reduction correlated with decreased level of anti-Mullerian hormone (AMH) and abnormal gene expression affecting hormone secretion regulation. Furthermore, we found that zinc deficiency disrupted mitochondrial dynamics, leading to oxidative stress in the ovaries, which further inhibited autophagy and increased ovarian apoptosis. These changes ultimately resulted in the failure of germinal vesicle breakdown (GVBD) and reduced oocyte quality. Meanwhile, administration of zinc glycine effectively alleviated the oocyte meiotic arrest caused by dietary zinc deficiency. In conclusion, our findings demonstrated that dietary zinc deficiency can affect hormone secretion and follicle maturation by impairing mitochondrial function and autophagy.
Subject(s)
Mitochondria , Ovarian Follicle , Zinc , Female , Zinc/deficiency , Zinc/metabolism , Ovarian Follicle/metabolism , Ovarian Follicle/growth & development , Ovarian Follicle/drug effects , Mitochondria/metabolism , Animals , Autophagy , Oocytes/metabolism , Oocytes/drug effects , Oocytes/growth & development , Anti-Mullerian Hormone/metabolism , Oxidative Stress , Mice , Apoptosis , HumansABSTRACT
This research addressed the drawbacks of the conventional hybrid structure and processing technique by presenting a novel distributed fiber optic sensor based on a hybrid Michelson and Mach-Zehnder interferometer. The sensor can achieve blind spot free positioning and has a wide response frequency, additionally its structure is not complex. It can obtain two phase signals from each of the two interferometers by using a demodulation method that uses a 3 × 3 optical coupler. To determine the position of the disturbance, we computed cross-correlations on the two signals following basic mathematical techniques. Markov Transition Field was used to transform the phase signals-which had been filtered by a band pass filter-into two-dimensional images. Tagged photos built a dataset, which is then fed into a neural network to identify patterns. Experiments have shown that the frequency response capacity of the structure was verified, and it was able to achieve location within 0-30â km with location errors of ±85 m. In a six-category pattern recognition, the testing set accuracy was 98.74%.
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Magnesium is one of the essential nutrients for plant growth, and plays a pivotal role in plant development and metabolism. Soil magnesium deficiency is evident in citrus production, which ultimately leads to failure of normal plant growth and development, as well as decreased productivity. Citrus is mainly propagated by grafting, so it is necessary to fully understand the different regulatory mechanisms of rootstock and scion response to magnesium deficiency. Here, we characterized the differences in morphological alterations, physiological metabolism and differential gene expression between trifoliate orange rootstocks and lemon scions under normal and magnesium-deficient conditions, revealing the different responses of rootstocks and scions to magnesium deficiency. The transcriptomic data showed that differentially expressed genes were enriched in 14 and 4 metabolic pathways in leaves and roots, respectively, after magnesium deficiency treatment. And the magnesium transport-related genes MHX and MRS2 may respond to magnesium deficiency stress. In addition, magnesium deficiency may affect plant growth by affecting POD, SOD, and CAT enzyme activity, as well as altering the levels of hormones such as IAA, ABA, GA3, JA, and SA, and the expression of related responsive genes. In conclusion, our research suggests that the leaves of lemon grafted onto trifoliate orange were more significantly affected than the roots under magnesium-deficient conditions, further indicating that the metabolic imbalance of scion lemon leaves was more severe.
Subject(s)
Citrus , Gene Expression Regulation, Plant , Magnesium , Seedlings , Citrus/metabolism , Citrus/genetics , Seedlings/metabolism , Seedlings/genetics , Seedlings/growth & development , Magnesium/metabolism , Plant Roots/metabolism , Plant Roots/growth & development , Plant Roots/genetics , Magnesium Deficiency/metabolism , Plant Leaves/metabolism , Stress, Physiological , Plant Growth Regulators/metabolism , Plant Proteins/metabolism , Plant Proteins/geneticsABSTRACT
Introduction: T cell receptor (TCR) repertoires provide valuable insights into complex human diseases, including cancers. Recent advancements in immune sequencing technology have significantly improved our understanding of TCR repertoire. Some computational methods have been devised to identify cancer-associated TCRs and enable cancer detection using TCR sequencing data. However, the existing methods are often limited by their inadequate consideration of the correlations among TCRs within a repertoire, hindering the identification of crucial TCRs. Additionally, the sparsity of cancer-associated TCR distribution presents a challenge in accurate prediction. Methods: To address these issues, we presented DeepLION2, an innovative deep multi-instance contrastive learning framework specifically designed to enhance cancer-associated TCR prediction. DeepLION2 leveraged content-based sparse self-attention, focusing on the top k related TCRs for each TCR, to effectively model inter-TCR correlations. Furthermore, it adopted a contrastive learning strategy for bootstrapping parameter updates of the attention matrix, preventing the model from fixating on non-cancer-associated TCRs. Results: Extensive experimentation on diverse patient cohorts, encompassing over ten cancer types, demonstrated that DeepLION2 significantly outperformed current state-of-the-art methods in terms of accuracy, sensitivity, specificity, Matthews correlation coefficient, and area under the curve (AUC). Notably, DeepLION2 achieved impressive AUC values of 0.933, 0.880, and 0.763 on thyroid, lung, and gastrointestinal cancer cohorts, respectively. Furthermore, it effectively identified cancer-associated TCRs along with their key motifs, highlighting the amino acids that play a crucial role in TCR-peptide binding. Conclusion: These compelling results underscore DeepLION2's potential for enhancing cancer detection and facilitating personalized cancer immunotherapy. DeepLION2 is publicly available on GitHub, at https://github.com/Bioinformatics7181/DeepLION2, for academic use only.
Subject(s)
Neoplasms , Receptors, Antigen, T-Cell , Humans , Peptides , Immunotherapy , Neoplasms/geneticsABSTRACT
P2-type layered manganese-based oxides have attracted considerable interest as economical, cathode materials with high energy density for sodium-ion batteries (SIBs). Despite their potential, these materials still face challenges related to sluggish kinetics and structural instability. In this study, a composite cathode material, Na0.67Ni0.23Mn0.67V0.1O2@Na3V2O2(PO4)2F was developed by surface-coating P2-type Na0.67Ni0.23Mn0.67V0.1O2 with a thin layer of Na3V2O2(PO4)2F to enhance both the electrochemical sodium storage and material air stability. The optimized Na0.67Ni0.23Mn0.67V0.1O2@5wt %Na3V2O2(PO4)2F exhibited a high discharge capacity of 176â mA h g-1 within the 1.5-4.1â V range at a low current density of 17â mA g-1. At an increased current density of 850â mA g-1 within the same voltage window, it still delivered a substantial initial discharge capacity of 112â mAh g-1. These findings validate the significant enhancement of ion diffusion capabilities and rate performance in the P2-type Na0.67Ni0.33Mn0.67O2 material conferred by the composite cathode.
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Rotaviruses (RV) are a major cause of severe gastroenteritis, particularly in neonatal piglets. Despite the availability of effective vaccines, the development of antiviral therapies for RV remains an ongoing challenge. Retinoic acid (RA), a metabolite of vitamin A, has been shown to have anti-oxidative and antiviral properties. However, the mechanism by which RA exerts its intestinal-protective and antiviral effects on RV infection is not fully understood. The study investigates the effects of RA supplementation in Duroc × Landrace × Yorkshire (DLY) piglets challenged with RV. Thirty-six DLY piglets were assigned into six treatments, including a control group, RA treatment group with two concentration gradients (5 and 15 mg/d), RV treatment group, and RV treatment group with the addition of different concentration gradients of RA (5 and 15 mg/d). Our study revealed that RV infection led to extensive intestinal architecture damage, which was mitigated by RA treatment at lower concentrations by increasing the villus height and villus height/crypt depth ratio (P < 0.05), enhancing intestinal stem cell signaling and promoting intestinal barrier functions. In addition, 15 mg/d RA supplementation significantly increased NRF2 and HO-1 protein expression (P < 0.05) and GSH content (P < 0.05), indicating that RA supplementation can enhance anti-oxidative signaling and redox homeostasis after RV challenge. Additionally, the research demonstrated that RA exerts a dual impact on the regulation of autophagy, both stimulating the initiation of autophagy and hindering the flow of autophagic flux. Through the modulation of autophagic flux, RA influence the progression of RV infection. These findings provide new insights into the regulation of redox hemostasis and autophagy by RA and its potential therapeutic application in RV infection.
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AIMS: Cardiac dysfunction is commonly observed in patients with subarachnoid haemorrhage (SAH). However, the specific timeline of cardiac remodelling and the underlying mechanisms responsible for this effect following SAH remain unknown. This study aims to explore the impact of SAH on cardiac dysfunction and its potential mechanisms over time. METHODS AND RESULTS: In Protocol 1, we investigated cardiac function and potential mechanisms in a Sprague-Dawley rat model of SAH at six time points (baseline and Days 1, 3, 7, 14, and 28) while exploring the underlying mechanisms. Our assessments included the haemodynamic profile, echocardiography, and the concentrations of plasma biomarkers at various time points post-SAH. We determined neuropeptide Y (NPY) 1-5 receptor protein expression levels through western blotting. In Protocol 2, we administered an NPY1 receptor antagonist to evaluate the effects of cardiac dysfunction induced by SAH on Day 3. In Protocol 1, SAH gradually provoked cardiac systolic dysfunction during the acute phase, reaching its peak on Day 3 without concurrent alterations in wall thickness. However, no significant changes were observed from Days 14 to 28 compared with Day 0. The changes in cardiac dysfunction were consistent with myocardial injury, inflammatory biomarkers, and NPY levels. SAH resulted in a heightened heart rate and systolic blood pressure, correlating with elevated epinephrine and norepinephrine levels. In Protocol 2, the administration of the NPY1 receptor antagonist effectively ameliorated cardiac dysfunction. CONCLUSIONS: SAH induces transient cardiac dysfunction in the acute phase, and the underlying mechanisms for this response involve the NPY-NPY1 receptor pathway, otherwise known as catecholamines.
Subject(s)
Disease Models, Animal , Rats, Sprague-Dawley , Receptors, Neuropeptide Y , Subarachnoid Hemorrhage , Animals , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/physiopathology , Rats , Male , Receptors, Neuropeptide Y/antagonists & inhibitors , Receptors, Neuropeptide Y/metabolism , Time Factors , Echocardiography , Biomarkers/blood , Neuropeptide Y/metabolism , Ventricular Remodeling/physiologyABSTRACT
BACKGROUND: The coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) represents an uncommon serological pattern observed in patients with hepatitis B virus (HBV) infection, and its underlying mechanism and clinical significance have not been well established. The aim of this study was to investigate the association between this serological profile and clinical treatment outcomes in children with chronic hepatitis B (CHB). METHODS: This retrospective cohort study included 372 treatment-naïve CHB children from the Hunan Children's Hospital. The participants were categorized into HBsAb-positive group and HBsAb-negative group. The associations between HBsAb positive status to clinical outcomes were assessed using Cox proportional hazard regression. Receiver operating characteristic curve was conducted to evaluate the prediction ability in HBsAg loss. RESULTS: The coexistence of HBsAg and HBsAb accounted for 23.39% (87/372) of the participants. The crude incidence rates of HBsAg loss, hepatitis B e antigen (HBeAg) clearance, and HBV-DNA undetectability were higher in the HBsAb-positive group compared with the HBsAb-negative group (37.46 vs. 17.37, 49.51 vs. 28.66, 92.11 vs. 66.54 per 100 person-years, respectively, all P < 0.05). The Cox regression analysis revealed a significant association between this serological profile and an increased likelihood of HBsAg loss (HR = 1.78, P = 0.001), and HBeAg clearance (HR = 1.78, P = 0.001). In addition, a combination of HBsAb ≥ 0.84 log10 IU/L and age ≤ 5 years can help identify patients likely to achieve HBsAg loss after antiviral therapy, with an AUC of 0.71. CONCLUSIONS: Children who are positive for both HBsAg and HBsAb demonstrate a higher probability of favorable outcomes after antiviral treatment. Thus, children with HBsAb-positive CHB should be actively treated to achieve functional cure.
Subject(s)
Hepatitis B Surface Antigens , Hepatitis B, Chronic , Child , Humans , Child, Preschool , Hepatitis B Surface Antigens/therapeutic use , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/epidemiology , Hepatitis B e Antigens/therapeutic use , Retrospective Studies , Hepatitis B virus , Treatment Outcome , Hepatitis B Antibodies/therapeutic use , Antiviral Agents/therapeutic useABSTRACT
PURPOSE: Initial treatment for Recurrent/Metastatic Nasopharyngeal Carcinoma (R/M NPC) often involves Gemcitabine plus cisplatin with or without PD-1 inhibitors. However, PD-1 inhibitors' effectiveness varies, prompting for better treatments. This study explores effect and safety of combining PD-1 inhibitors with chemoradiotherapy for oligometastatic NPC patients. METHODS: Oligometastatic NPC patients underwent radical treatment with PD-1 inhibitors and chemotherapy, followed by concurrent PD-1 inhibitors and chemoradiotherapy, and then maintenance PD-1 inhibitors. Objective response rate (ORR) and disease control rate (DCR) were calculated by irRECIST-1.1, and CTCAE-4.0 was used to evaluate the toxicity. RESULTS: The study enrolled 47 patients with a median age of 46. The median follow-up lasted 16.5 months, with metastatic lesions receiving a median radiation dose of 45 Gy. The median courses of PD-1 inhibitors and chemotherapy were 9.5 and 5 respectively. The metastasis sites included lung (40.8 %), liver (21.1 %), mediastinal lymph node (7.9 %), abdominal lymph nodes (3.9 %), bone (21.1 %), adrenal gland (3.9 %), and brain (1.3 %). ORR and DCR were 85.1 % and 100 % at 3 months after radiotherapy. The median survival was not reached yet, and 1 and 2-year OS rates were 93.1 % and 78.4 %. The median PFS was 18 months, with 1 and 2-year PFS rates of 70.2 % and 47.7 % respectively. PD-L1 expression showed a positive correlation for PFS. Twenty-five patients experienced grade 3 or 4 adverse events (AE) that were possibly related to chemotherapy. No grade 5 AE was observed. CONCLUSIONS: The synergy of concurrent PD-1 inhibitors and chemoradiotherapy shows promising efficacy and an acceptable toxicity for oligometastasis NPC patients.