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1.
Neural Regen Res ; 20(2): 402-415, 2025 Feb 01.
Article in English | MEDLINE | ID: mdl-38819044

ABSTRACT

With an increase in global aging, the number of people affected by cerebrovascular diseases is also increasing, and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate. However, few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients. Similarly in Alzheimer's disease and other neurological disorders, synaptic dysfunction is recognized as the main reason for cognitive decline. Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system. Recently, nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia. This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction, neuroinflammation, oxidative stress, and blood-brain barrier dysfunction that underlie the progress of vascular dementia. Additionally, we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

2.
J Pharm Biomed Anal ; 247: 116268, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38823222

ABSTRACT

Methotrexate (MTX) is commonly prescribed as the initial treatment for gestational trophoblastic neoplasia (GTN), but MTX monotherapy may not be effective for high-risk GTN and choriocarcinoma. The cellular uptake of MTX is essential for its pharmacological activity. Thus, our study aimed to investigate the cellular pharmacokinetics and transport mechanisms of MTX in choriocarcinoma cells. For the quantification of MTX concentrations in cellular matrix, a liquid chromatography-tandem mass spectrometry method was created and confirmed initially. MTX accumulation in BeWo, JEG-3, and JAR cells was minimal. Additionally, the mRNA levels of folate receptor α (FRα) and breast cancer resistance protein (BCRP) were relatively high in the three choriocarcinoma cell lines, whereas proton-coupled folate transporter (PCFT), reduced folate carrier (RFC), and organic anion transporter (OAT) 4 were low. Furthermore, the expression of other transporters was either very low or undetectable. Notably, the application of inhibitors and small interfering RNAs (siRNAs) targeting FRα, RFC, and PCFT led to a notable decrease in the accumulation of MTX in BeWo cells. Conversely, the co-administration of multidrug resistance protein 1 (MDR1) and BCRP inhibitors increased MTX accumulation. In addition, inhibitors of OATs and organic-anion transporting polypeptides (OATPs) reduced MTX accumulation, while peptide transporter inhibitors had no effect. Results from siRNA knockdown experiments and transporter overexpression cell models indicated that MTX was not a substrate of nucleoside transporters. In conclusion, the results indicate that FRα and multiple transporters such as PCFT, RFC, OAT4, and OATPs are likely involved in the uptake of MTX, whereas MDR1 and BCRP are implicated in the efflux of MTX from choriocarcinoma cells. These results have implications for predicting transporter-mediated drug interactions and offer potential directions for further research on enhancing MTX sensitivity.

3.
Food Res Int ; 188: 114508, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823847

ABSTRACT

Procyanidins, which are oligomerized flavan-3-ols with a polyphenolic structure, are bioactive substances that exhibit various biological effects. However, the relationship between the degree of polymerization (DP) of procyanidins and their bioactivities remains largely unknown. In this study, the preventive effects of procyanidins with different DP (EC, PB2 and PC1) on glucose improvement and liver lipid deposition were investigated using a high-fat diet/streptozotocin-induced diabetes mouse model. The results demonstrated that all the procyanidins with different DP effectively reduced fasting blood glucose and glucose/insulin tolerance, decreased the lipid profile (total cholesterol, triglyceride, and low-density lipoprotein cholesterol content) in serum and liver tissue as well as the liver oil red staining, indicating the improvement of glucose metabolism, insulin sensitivity and hepatic lipid deposition in diabetic mice. Furthermore, the procyanidins down-regulated expression of glucose regulated 78-kDa protein (GRP78) and C/EBP homologous protein (CHOP), indicating a regulation role of endoplasmic reticulum (ER) stress. The inhibition of ER stress by tauroursodeoxycholic acid (TUDCA) treatment abolished the effects of procyanidins with different DP in PA-induced HepG2 cells, confirming that procyanidins alleviate liver hyperlipidemia through the modulation of ER stress. Molecular docking results showed that EC and PB2 could better bind GRP78 and CHOP. Collectively, our study reveals that the structure of procyanidins, particularly DP, is not directly correlated with the improvement of blood glucose and lipid deposition, while highlighting the important role of ER stress in the bioactivities of procyanidins.


Subject(s)
Blood Glucose , Diabetes Mellitus, Experimental , Diet, High-Fat , Endoplasmic Reticulum Chaperone BiP , Lipid Metabolism , Liver , Proanthocyanidins , Animals , Proanthocyanidins/pharmacology , Diet, High-Fat/adverse effects , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Male , Lipid Metabolism/drug effects , Mice , Blood Glucose/metabolism , Blood Glucose/drug effects , Liver/drug effects , Liver/metabolism , Hep G2 Cells , Humans , Polymerization , Endoplasmic Reticulum Stress/drug effects , Molecular Docking Simulation , Biflavonoids/pharmacology , Mice, Inbred C57BL , Streptozocin , Insulin Resistance , Catechin/pharmacology
4.
Discov Oncol ; 15(1): 194, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38806979

ABSTRACT

Accumulating evidence indicates that exosomal proteins are critical in diagnosing malignant tumors. To identify novel exosomal biomarkers for lung cancer diagnosis, we isolated plasma exosomes from 517 lung cancer patients and 168 healthy controls (NLs)-186 lung adenocarcinoma (LUAD) patients (screening (SN): 20, validation (VD): 166), 159 lung squamous carcinoma (LUSC) patients (SN: 20, VD: 139), 172 benign nodules (LUBN) patients (SN: 20, VD: 152) and 168 NLs (SN: 20, VD: 148)-and randomly assigned them to the SN or VD group. Proteomic analysis by LC-MS/MS and PRM were performed on all groups. The candidate humoral markers were evaluated and screened by a machine learning method. All selected biomarkers were identified in the VD groups. For LUAD, a 7-protein panel had AUCs of 97.9% and 87.6% in the training and test sets, respectively, and 89.5% for early LUAD. For LUSC, an 8-protein panel showed AUCs of 99.1% and 87.0% in the training and test sets and 92.3% for early LUSC. For LUAD + LUSC (LC), an 8-protein panel showed AUCs of 85.9% and 80.3% in the training and test sets and 87.1% for early LC diagnosis. The characteristics of the exosomal proteome make exosomes potential diagnostic tools.

5.
Phytomedicine ; 130: 155774, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38820659

ABSTRACT

BACKGROUND: Metabolic and alcohol-associated liver disease (MetALD) shows a high prevalence rate in liver patients, but there is currently no effective treatment for MetALD. As a typical edible traditional Chinese medicinal herb, the anti-inflammatory, antioxidant, and hepatoprotective properties of water extract of Chrysanthemum morifolium Ramat. (WECM) has been demonstrated. However, its therapeutic effect on MetALD and the associated mechanisms remain unclear. PURPOSE: To investigate the underlying mechanisms of WECM against MetALD. METHODS: We constructed a MetALD rat model following a high-fat & high-sucrose plus alcohol diet (HFHSAD). MetALD rats were treated with WECM at 2.1, 4.2, and 8.4 g/kg/d for six weeks. Efficacy was determined, and pathways associated with WECM against MetALD were predicted through serum and hepatic biochemical marker measurement, histopathological section analysis, 16S rDNA sequencing of the gut microbiota and untargeted serum metabolomics analyses. Changes in genes and proteins in the peroxisome proliferator-activated receptor alpha (PPARα) and gamma (PPARγ) signaling pathways were detected by RT‒PCR and Western blotting. RESULTS: WECM treatment significantly attenuated hepatic steatosis, hyperlipidemia and markers of liver injury in MetALD rats. Moreover, WECM improved vascular endothelial function, hypertension, and systematic oxidative stress. Mechanistically, WECM treatment altered the overall structure of the gut microbiota through maintaining Firmicutes/Bacteroidota ratio and reducing harmful bacterial abundances such as Clostridium, Faecalibaculum, and Herminiimonas. Notably, WECM promoted 15-deoxy-△12, 14-prostaglandin J2 (15d-PGJ2) release and further activated the PPARγ to reduce serum TNF-α, IL-1ß, and IL-6 levels. Additionally, WECM upregulated PPARα and downregulated the levels of CD36 and FABP4 to improve lipid metabolism. CONCLUSION: Our findings provide the first evidence that WECM treatment significantly improved hepatic steatosis, oxidative stress and inflammation in MetALD rats by regulating the gut microbiota and activating the 15d-PGJ2/PPARγ and PPARα signaling pathway.

6.
Sci Total Environ ; : 173632, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38821268

ABSTRACT

Soil organic carbon (SOC) dynamics are strongly controlled by plant roots. Yet, how variation of root traits under precipitation change influences SOC stability remains unclear. As part of a 5-year field experiment manipulating precipitation including 90 % (0.1P), 50 % (0.5P), 30 % (0.7P) decrease, and 50 % increase (1.5P), this study was designed to assess the effects of changing precipitation on root traits and production dynamics by minirhizotron and examine how such influences regulate SOC stability in an alpine meadow on the Qinghai-Tibetan Plateau. We found that root length density (RLD), specific root length (SRL), root branching intensity (RBI), and root residue carbon input (RC input) exhibited no significant response, whereas root turnover (RT), root carbon (C), nitrogen (N) concentrations and C/N ratio were altered by precipitation change with nonlinear trends. Absorptive root RT positively correlated to manipulated precipitation within the interannual precipitation range in topsoil, but it showed no significant change under extreme drought treatment. Alpine meadows can maintain the SOC content and density under varied precipitation. However, it showed significant variation in aggregate stability and organic carbon (OC) distribution in aggregates in topsoil, which were mainly due to the strong direct effects of soil moisture and partly related to RLD and RC input of transport roots. Although subsurface soil aggregate stability and OC associated with aggregates were not modified, our results indicated a risk of SOC stability variation in subsurface soil if absorptive root RT and SRL changed. These findings provide vital information to predict responses of SOC dynamics of alpine meadow to future climate change.

7.
Int J Ophthalmol ; 17(3): 558-563, 2024.
Article in English | MEDLINE | ID: mdl-38721507

ABSTRACT

AIM: To evaluate the effectiveness and safety of scleral buckling for the treatment of rhegmatogenous retinal detachment (RRD) using a novel foldable capsular buckle (FCB). METHODS: This was a series of case observation studies. Eighteen patients (18 eyes) who visited our ophthalmology department between August 2020 and August 2022 and were treated for RRD with scleral buckling using FCB were included. The procedure was similar to conventional scleral buckling, while a balloon-like FCB was placed onto the retinal break with balanced salt solution filling for a broad, external indentation instead of the silicone buckle. The retinal reattachment rate, best corrected visual acuity (BCVA), intraocular pressure (IOP), refractive dioptre and astigmatism degree, and complications were evaluated and recorded. RESULTS: There were 7 males and 11 females aged 19-58y. The average time course of RRD was 12d, ranging from 7-20d. The retinal break was located in the superior quadrants in 8 eyes and in the inferior quadrants in 10 eyes, with macula-off detachments in 12 eyes. The patients were followed-up for at least 6mo. The final retinal reattachment rate was 100%. The BCVA was significantly improved compared with the baseline (P<0.05). There was no significant change in refractive dioptre or astigmatism degree at each follow-up (all P>0.05). Three patients had transiently high IOPs within one week after surgery. Mild diplopia occurred in 5 patients after surgery and then disappeared after the balloon fluid was removed. CONCLUSION: The success rate of FCB scleral buckling for RRD is satisfactory. This procedure can be expected to be applied in new, uncomplicated cases of RRD.

8.
Food Chem X ; 22: 101410, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38707780

ABSTRACT

Cruciferous vegetables (CVs) are globally consumed with some health benefits believed to arise from indole-3-carbinol (I3C), a labile phytochemical liberated from indole glucosinolates, but few reports describe the effect of cooking on I3C reactions. Here, we present heat-promoted direct conversions of I3C in broccoli florets into indole derivatives, which are unique in the N-indolylmethylation and -hydroxymethylation of indole nuclei by 3-methyleneindole and formaldehyde formed in situ from the I3C dehydration and the dimerization of I3C to 3,3'-diindolylmethane (DIM), respectively. Such N-substituted indoles were found in a range of 0.4-4.6 µg per gram of steamed broccoli florets, with a novel compound N-(indol-3-ylmethyl)-3,3'-diindolylmethane (DIM-1) bio-evaluated to inhibit A375 cells with an IC50 value of 1.87 µM. In aggregation, the investigation discloses the promoting effect of heating on the I3C transformation in CVs and identifies DIM-1 as an anti-cancer drug candidate, and thus updates the knowledge of I3C and bioactive derivatives thereof.

9.
Infect Drug Resist ; 17: 1669-1673, 2024.
Article in English | MEDLINE | ID: mdl-38707986

ABSTRACT

Lemierre syndrome (LS) is a rare and life-threatening condition predominantly caused by Fusobacterium necrophorum. Currently, there are no standardized clinical guidelines for LS management. Here, we describe the case of a 40-year-old male with fever, productive cough, and dyspnea but no sore throat. Diagnostic radiological examinations revealed multiple pulmonary cavitary nodules and an internal jugular vein occlusion. Metagenomic Next-Generation Sequencing (mNGS) of the alveolar lavage fluid identified Fusobacterium necrophorum, thereby confirming the diagnosis of LS. Intriguingly, the patient exhibited a delayed clinical response despite receiving the appropriate antibiotic. After integrating tigecycline into the treatment to address potential co-infecting bacteria, we observed a marked improvement in his clinical symptoms. Subsequent follow-up over 12 weeks post-discharge revealed complete alleviation of symptoms, and a chest CT scan showed marked regression of the lung lesions.

10.
Nucleic Acids Res ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38709873

ABSTRACT

Small ubiquitin-like modifiers (SUMOs) are tiny but important protein regulators involved in orchestrating a broad spectrum of biological processes, either by covalently modifying protein substrates or by noncovalently interacting with other proteins. Here, we report an updated server, GPS-SUMO 2.0, for the prediction of SUMOylation sites and SUMO-interacting motifs (SIMs). For predictor training, we adopted three machine learning algorithms, penalized logistic regression (PLR), a deep neural network (DNN), and a transformer, and used 52 404 nonredundant SUMOylation sites in 8262 proteins and 163 SIMs in 102 proteins. To further increase the accuracy of predicting SUMOylation sites, a pretraining model was first constructed using 145 545 protein lysine modification sites, followed by transfer learning to fine-tune the model. GPS-SUMO 2.0 exhibited greater accuracy in predicting SUMOylation sites than did other existing tools. For users, one or multiple protein sequences or identifiers can be input, and the prediction results are shown in a tabular list. In addition to the basic statistics, we integrated knowledge from 35 public resources to annotate SUMOylation sites or SIMs. The GPS-SUMO 2.0 server is freely available at https://sumo.biocuckoo.cn/. We believe that GPS-SUMO 2.0 can serve as a useful tool for further analysis of SUMOylation and SUMO interactions.

11.
Small ; : e2402277, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773868

ABSTRACT

It is still challenging to stabilize α-FAPbI3 perovskite for high performance optoelectrical devices. Herein, a novel strategy is proposed utilizing the synergetic electrostatic and steric effect to stabilize the α-FAPbI3 phase and suppress the ion migration. Dimethylamine (DMA+) cations are chosen as the dopant to fabricate FA0.96DMA0.04PbI3 single crystals (SCs). DFT calculations reveal that DMA+ cations can improve the stability of α-FAPbI3 phase in both thermodynamics (lower Gibbs free energy) and kinetics (higher defect formation and migration energy). The resulting SCs exhibit an environmental stability over 100 days and an extraordinary low dark current drift of 3.7 × 10-7 nA cm-1 s-1 V-1, comparable to 2D perovskite SCs. The X-ray detectors have also achieved the-state-of-the-art performance in X-ray detection and imaging. This work demonstrates the significance of electrostatic and steric effects in improving the phase and operational stability of perovskites.

12.
J Blood Med ; 15: 217-225, 2024.
Article in English | MEDLINE | ID: mdl-38737581

ABSTRACT

Introduction: COVID-19 infection has brought new challenges to the treatment of adult patients with immune thrombocytopenia (ITP). In adult ITP patients, there have been no relevant reports exploring the incidence, clinical characteristics, and risk factors of platelet elevation after COVID-19 infection. Materials and Methods: A total of 66 patients with previously diagnosed ITP from December 2022 to February 2023 in a single-center were collected and analyzed for this real-world clinical retrospective observational study. Results: In the platelet count increased group (n = 19), 13 patients (68.4%) were using thrombopoietin receptor agonists (TPO-RA) treatment at the time of COVID-19 infection; the median platelet count was 52 (2-207) ×109/L at the last visit before infection and 108 (19-453) ×109/L at the first visit after infection. In the platelet count stable group (n = 19) and platelet count decreased group (n = 28), 9 (47.4%) and 8 (28.6%) patients were using TPO-RA at the time of infection, respectively. ITP patients treated with TPO-RA had a significantly higher risk of increased platelet count than those not treated with TPO-RA at the time of infection (platelet count increased group vs platelet count decreased group: OR: 5.745, p = 0.009; platelet count increased group vs the non-increased group: OR: 3.616, p = 0.031). In the platelet count increased group, the median platelet count at 6 months post-infection was 67 (14-235) × 109/L, which was significantly higher than the platelet level at the last visit before infection (p = 0.040). Conclusion: This study showed that some adult ITP patients had an increase in platelet count after COVID-19 infection, and this phenomenon was strongly associated with the use of TPO-RA at the time of infection. Although no thrombotic events were observed in this study, it reminds clinicians that they should be alert to the possibility of thrombotic events in the long-term management of adult ITP patients during the COVID-19 pandemic.

13.
J Adolesc ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769773

ABSTRACT

BACKGROUND: Young men who have sex with men (YMSM) may experience high levels of sexual minority stigma (SMS) and depressive symptoms (DS) over the world and in China. However, there is a lack of studies investigating the longitudinal effects of SMS on DS of YMSM, especially focusing on YMSM and separating the between-person and within-person effects. This study aimed to fill the said gaps. METHODS: Study data were derived from a prospective cohort of 349 YMSM from central China (Wuhan, Changsha, Nanchang), the baseline survey was started in 2017 with one follow-up visit every year. SMS and DS were measured three times using valid and reliable instruments. The cross-lagged panel model (CLPM) and the random intercept CLPM (RI-CLPM) were used to examine the between-person and within-person concurrent and lagged effects, respectively. RESULTS: Findings of CLPM revealed bidirectional associations between SMS and DS over time. RI-CLPM suggested that at the between-person level, SMS was significantly associated with DS, echoing the results of CLPM. However, this reciprocal relationship has not been found at the within-person level. CONCLUSION: The associations between SMS and DS among YMSM at the population level is more significant than that at the individual level. We suggest that interventions should be against the adverse effects of cultural marginalization and systemic change the social concepts to reduce the amount of SMS in society.

14.
Nano Lett ; 24(19): 5729-5736, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38708832

ABSTRACT

Quantum-dot light-emitting diodes (QLEDs), a kind of promising optoelectronic device, demonstrate potential superiority in next-generation display technology. Thermal cross-linked hole transport materials (HTMs) have been employed in solution-processed QLEDs due to their excellent thermal stability and solvent resistance, whereas the unbalanced charge injection and high cross-linking temperature of cross-linked HTMs can inhibit the efficiency of QLEDs and limit their application. Herein, a low-temperature cross-linked HTM of 4,4'-bis(3-(((4-vinylbenzyl)oxy)methyl)-9H-carbazol-9-yl)-1,1'-biphenyl (DV-CBP) with a flexible styrene side chain is introduced, which reduces the cross-linking temperature to 150 °C and enhances the hole mobility up to 1.01 × 10-3 cm2 V-1 s-1. More importantly, the maximum external quantum efficiency of 21.35% is successfully obtained on the basis of the DV-CBP as a cross-linked hole transport layer (HTL) for blue QLEDs. The low-temperature cross-linked high-mobility HTL using flexible side chains could be an excellent alternative for future HTL development.

15.
FASEB J ; 38(10): e23668, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38742811

ABSTRACT

Podocyte injury plays a critical role in the progression of diabetic kidney disease (DKD), but the underlying cellular and molecular mechanisms remain poorly understanding. MicroRNAs (miRNAs) can disrupt gene expression by inducing translation inhibition and mRNA degradation, and recent evidence has shown that miRNAs may play a key role in many kidney diseases. In this study, we identified miR-4645-3p by global transcriptome expression profiling as one of the major downregulated miRNAs in high glucose-cultured podocytes. Moreover, whether DKD patients or STZ-induced diabetic mice, expression of miR-4645-3p was also significantly decreased in kidney. In the podocytes cultured by normal glucose, inhibition of miR-4645-3p expression promoted mitochondrial damage and podocyte apoptosis. In the podocytes cultured by high glucose (30 mM glucose), overexpression of miR-4645-3p significantly attenuated mitochondrial dysfunction and podocyte apoptosis induced by high glucose. Furthermore, we found that miR-4645-3p exerted protective roles by targeting Cdk5 inhibition. In vitro, miR-4645-3p obviously antagonized podocyte injury by inhibiting overexpression of Cdk5. In vivo of diabetic mice, podocyte injury, proteinuria, and impaired renal function were all effectively ameliorated by treatment with exogenous miR-4645-3p. Collectively, these findings demonstrate that miR-4645-3p can attenuate podocyte injury and mitochondrial dysfunction in DKD by targeting Cdk5. Sustaining the expression of miR-4645-3p in podocytes may be a novel strategy to treat DKD.


Subject(s)
Cyclin-Dependent Kinase 5 , Diabetes Mellitus, Experimental , Diabetic Nephropathies , Mice, Inbred C57BL , MicroRNAs , Mitochondria , Podocytes , Podocytes/metabolism , Podocytes/pathology , Animals , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Diabetic Nephropathies/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Mice , Mitochondria/metabolism , Male , Humans , Diabetes Mellitus, Experimental/metabolism , Cyclin-Dependent Kinase 5/metabolism , Cyclin-Dependent Kinase 5/genetics , Apoptosis , Glucose
16.
Domest Anim Endocrinol ; 88: 106851, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38733944

ABSTRACT

Colostrum and milk offer a complete diet and vital immune protection for newborn mammals with developing immune systems. High immunoglobulin levels in colostrum serve as the primary antibody source for newborn piglets and calves. Subsequent milk feeding support continued local antibody protection against enteric pathogens, as well as maturation of the developing immune system and provide nutrients for newborn growth. Mammals have evolved hormonal strategies that modulate the levels of immunoglobulins in colostrum and milk to facilitate effective lactational immunity. In addition, hormones regulate the gut-mammary gland-secretory immunoglobulin A (sIgA) axis in pregnant mammals, controlling the levels of sIgA in milk, which serves as the primary source of IgA for piglets and helps them resist pathogens such as PEDV and TGEV. In the present study, we review the existing studies on the interactions between hormones and the gut-mammary-sIgA axis/lactogenic immunity in mammals and explore the potential mechanisms of hormonal regulation that have not been studied in detail, to draw attention to the role of hormones in influencing the immune response of pregnant and lactating mammals and their offspring, and highlight the effect of hormones in regulating sIgA-mediated anti-infection processes in colostrum and milk. Discussion of the relationship between hormones and lactogenic immunity may lead to a better way of improving lactogenic immunity by determining a better injection time and developing new vaccines.

17.
Poult Sci ; 103(7): 103775, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38713985

ABSTRACT

Goose circovirus (GoCV), a potential immunosuppressive virus possessing a circular single-stranded DNA genome, is widely distributed in both domesticated and wild geese. This virus infection causes significant economic losses in the waterfowl industry. The codon usage patterns of viruses reflect the evolutionary history and genetic architecture, allowing them to adapt quickly to changes in the external environment, particularly to their hosts. In this study, we retrieved the coding sequences (Rep and Cap) and the genome of GoCV from GenBank, conducting comprehensive research to explore the codon usage patterns in 144 GoCV strains. The overall codon usage of the GoCV strains was relatively similar and exhibited a slight bias. The effective number of codons (ENC) indicated a low overall extent of codon usage bias (CUB) in GoCV. Combined with the base composition and relative synonymous codon usage (RSCU) analysis, the results revealed a bias toward A- and G-ending codons in the overall codon usage. Analysis of the ENC-GC3s plot and neutrality plot suggested that natural selection plays an important role in shaping the codon usage pattern of GoCV, with mutation pressure having a minor influence. Furthermore, the correlations between ENC and relative indices, as well as correspondence analysis (COA), showed that hydrophobicity and geographical distribution also contribute to codon usage variation in GoCV, suggesting the possible involvement of natural selection. In conclusion, GoCV exhibits comparatively slight CUB, with natural selection being the major factor shaping the codon usage pattern of GoCV. Our research contributes to a deeper understanding of GoCV evolution and its host adaptation, providing valuable insights for future basic studies and vaccine design related to GoCV.

18.
Virulence ; 15(1): 2350892, 2024 12.
Article in English | MEDLINE | ID: mdl-38745370

ABSTRACT

The evasive tactics of Treponema pallidum pose a major challenge in combating and eradicating syphilis. Natural killer (NK) cells mediate important effector functions in the control of pathogenic infection, preferentially eliminating targets with low or no expression of major histocompatibility complex (MHC) class I. To clarify T. pallidum's mechanisms in evading NK-mediated immunosurveillance, experiments were performed to explore the cross-talk relations among T. pallidum, NK cells, and platelets. T. pallidum adhered to, activated, and promoted particle secretion of platelets. After preincubation with T. pallidum, platelets expressed and secreted high levels of MHC class I, subsequently transferring them to the surface of T. pallidum, potentially inducing an immune phenotype characterized by the "pseudo-expression" of MHC class I on the surface of T. pallidum (hereafter referred to a "pseudo-expression" of MHC class I). The polA mRNA assay showed that platelet-preincubated T. pallidum group exhibited a significantly higher copy number of polA transcript than the T. pallidum group. The survival rate of T. pallidum mirrored that of polA mRNA, indicating that preincubation of T. pallidum with platelets attenuated NK cell lethality. Platelets pseudo-expressed the MHC class I ligand on the T. pallidum surface, facilitating binding to killer cell immunoglobulin-like receptors with two immunoglobulin domains and long cytoplasmic tail 3 (KIR2DL3) on NK cells and initiating dephosphorylation of Vav1 and phosphorylation of Crk, ultimately attenuating NK cell lethality. Our findings elucidate the mechanism by which platelets transfer MHC class I to the T. pallidum surface to evade NK cell immune clearance.


Subject(s)
Blood Platelets , Histocompatibility Antigens Class I , Killer Cells, Natural , Syphilis , Treponema pallidum , Killer Cells, Natural/immunology , Treponema pallidum/immunology , Treponema pallidum/genetics , Humans , Blood Platelets/immunology , Blood Platelets/microbiology , Histocompatibility Antigens Class I/immunology , Syphilis/immunology , Syphilis/microbiology , Immune Evasion
19.
Opt Lett ; 49(9): 2401-2404, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38691729

ABSTRACT

Transition-metal dichalcogenides (TMDCs), as emerging optoelectronic materials, necessitate the establishment of an experimentally viable system to study their interaction with light. In this study, we propose and analyze a WS2/PMMA/Ag planar Fabry-Perot (F-P) cavity, enabling the direct experimental measurement of WS2 absorbance. By optimizing the structure, the absorbance of A exciton of WS2 up to 0.546 can be experimentally achieved, which matches well with the theoretical calculations. Through temperature and thermal expansion strain induced by temperature, the absorbance of the A exciton can be tuned in situ. Furthermore, temperature-dependent photocurrent measurements confirmed the consistent absorbance of the A exciton under varying temperatures. This WS2/PMMA/Ag planar structure provides a straightforward and practical platform for investigating light interaction in TMDCs, laying a solid foundation for future developments of TMDC-based optoelectronic devices.

20.
Nat Prod Bioprospect ; 14(1): 26, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38691189

ABSTRACT

Seven undescribed compounds, including three flavones (1-3), one phenylpropanoid (19), three monoaromatic hydrocarbons (27-29), were isolated from the twigs of Mosla chinensis Maxim together with twenty-eight known compounds. The structures were characterized by HRESIMS, 1D and 2D NMR, and ECD spectroscopic techniques. Compound 20 displayed the most significant activity against A/WSN/33/2009 (H1N1) virus (IC50 = 20.47 µM) compared to the positive control oseltamivir (IC50 = 6.85 µM). Further research on the anti-influenza mechanism showed that compound 20 could bind to H1N1 virus surface antigen HA1 and inhibit the early attachment stage of the virus. Furthermore, compounds 9, 22, 23, and 25 displayed moderate inhibitory effects on the NO expression in LPS inducing Raw 264.7 cells with IC50 values of 22.78, 20.47, 27.66, and 30.14 µM, respectively.

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