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1.
Genomics ; 116(5): 110896, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39025318

ABSTRACT

Pamphagidae is a family of Acridoidea that inhabits the desert steppes of Eurasia and Africa. This study employed flow cytometry to estimate the genome size of eight species in the Pamphagidae. The results indicate that the genome size of the eight species ranged from 13.88 pg to 14.66 pg, with an average of 14.26 pg. This is the largest average genome size recorded for the Orthoptera families, as well as for the entire Insecta. Furthermore, the study explored the role of repetitive sequences in the genome, including their evolutionary dynamics and activity, using low-coverage next-generation sequencing data. The genome is composed of 14 different types of repetitive sequences, which collectively make up between 59.9% and 68.17% of the total genome. The Pamphagidae family displays high levels of transposable element (TE) activity, with the number of TEs increasing and accumulating since the family's emergence. The study found that the types of repetitive sequences contributing to the TE outburst events are similar across species. Additionally, the study identified unique repetitive elements for each species. The differences in repetitive sequences among the eight Pamphagidae species correspond to their phylogenetic relationships. The study sheds new light on genome gigantism in the Pamphagidae and provides insight into the correlation between genome size and repetitive sequences within the family.

2.
Genomics ; 116(5): 110897, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39032617

ABSTRACT

Vaccinium L. is an important fruit tree with nutritional, medicinal, and ornamental values. However, the mitochondrial (mt) genome of Vaccinium L. remains largely unexplored. Vaccinium carlesii Dunn is an endemic wild resource in China, which is crucial for blueberry breeding. The V. carlesii mt genomes were sequenced using Illumina and Nanopore, which total length was 636,904 bp with 37 protein coding genes, 20 tRNA genes, and three rRNA genes. We found four pairs of long repeat fragments homologous recombination mediated the generation of substructures in the V. carlesii mt genome. We predicted 383 RNA editing sites, all converting cytosine (C) to uracil (U). According to the phylogenetic analysis, V. carlesii and V. macrocarpon of the Ericaceae exhibited the closest genetic relationship. This study provides a theoretical basis for understanding the evolution of higher plants, species classification and identification, and will also be useful for further utilization of Vaccinium germplasm resources.

3.
J Cell Biochem ; 125(8): e30613, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38860522

ABSTRACT

The importance of protein kinase B (AKT) in tumorigenesis and development is well established, but its potential regulation of metabolic reprogramming via phosphorylation of the hexokinase (HK) isozymes remains unclear. There are two HK family members (HK1/2) and three AKT family members (AKT1/2/3), with varied distribution of AKTs exhibiting distinct functions in different tissues and cell types. Although AKT is known to phosphorylate HK2 at threonine 473, AKT-mediated phosphorylation of HK1 has not been reported. We examined direct binding and phosphorylation of HK1/2 by AKT1 and identified the phosphorylation modification sites using coimmunoprecipitation, glutathione pull-down, western blotting, and in vitro kinase assays. Regulation of HK activity through phosphorylation by AKT1 was also examined. Uptake of 2-[1,2-3H]-deoxyglucose and production of lactate were investigated to determine whether AKT1 regulates glucose metabolism by phosphorylating HK1/2. Functional assays, immunohistochemistry, and tumor experiments in mice were performed to investigate whether AKT1-mediated regulation of tumor development is dependent on its kinase activity and/or the involvement of HK1/2. AKT interacted with and phosphorylated HK1 and HK2. Serine phosphorylation significantly increased AKT kinase activity, thereby enhancing glycolysis. Mechanistically, the phosphorylation of HK1 at serine 178 (S178) by AKT significantly decreased the Km and enhanced the Vmax by interfering with the formation of HK1 dimers. Mutations in the AKT phosphorylation sites of HK1 or HK2 significantly abrogated the stimulatory characteristics of AKT on glycolysis, tumorigenesis, and cell migration, invasion, proliferation, and metastasis. HK1-S178 phosphorylation levels were significantly correlated with the occurrence and metastasis of different types of clinical tumors. We conclude that AKT not only regulates tumor glucose metabolism by directly phosphorylating HK1 and HK2, but also plays important roles in tumor progression, proliferation, and migration.


Subject(s)
Carcinogenesis , Hexokinase , Proto-Oncogene Proteins c-akt , Hexokinase/metabolism , Hexokinase/genetics , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Humans , Animals , Phosphorylation , Mice , Carcinogenesis/metabolism , Carcinogenesis/genetics , Neoplasm Metastasis , Female , Cell Line, Tumor , Cell Proliferation , Cell Movement , Glucose/metabolism
4.
Anal Chem ; 96(5): 2253-2263, 2024 02 06.
Article in English | MEDLINE | ID: mdl-38277203

ABSTRACT

Current study in the heterogeneity and physiological behavior of tumor cells is limited by the fluorescence in situ hybridization technology in terms of probe assembly efficiency, background suppression capability, and target compatibility. In a typically well-designed assay, hybridization probes are constructed in a confined nanostructure to achieve a rapid assembly for efficient signal response, while the excessively high local concentration between different probes inevitably leads to nonspecific background leakage. Inspired by the fabric zipper, we propose a novel confinement reaction pattern in a zipper-confined DNA nanoframe (ZCDN), where two kinds of hairpin probes are independently anchored respective tracks. The metastable states of the dual tracks can well avoid signal leakage caused by the nonspecific probe configuration change. Biomarker-mediated proximity ligation reduces the local distance of dual tracks, kinetically triggering an efficient allosteric chain reaction between the hairpin probes. This method circumvents nonspecific background leakage while maintaining a high efficiency in responding to targets. ZCDN is employed to track different cancer biomarkers located in both the cytoplasm and cytomembrane, of which the expression level and oligomerization behavior can provide crucial information regarding intratumoral heterogeneity. ZCDN exhibits high target response efficiency and strong background suppression capabilities and is compatible with various types of biological targets, thus providing a desirable tool for advanced molecular diagnostics.


Subject(s)
Biosensing Techniques , Nanostructures , In Situ Hybridization, Fluorescence , DNA/chemistry , Diagnostic Imaging , Nanostructures/chemistry , DNA Probes/genetics , DNA Probes/chemistry , Biosensing Techniques/methods
5.
J Neuroinflammation ; 21(1): 138, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802927

ABSTRACT

Sepsis-associated encephalopathy (SAE) is a significant cause of mortality in patients with sepsis. Despite extensive research, its exact cause remains unclear. Our previous research indicated a relationship between non-hepatic hyperammonemia (NHH) and SAE. This study aimed to investigate the relationship between NHH and SAE and the potential mechanisms causing cognitive impairment. In the in vivo experimental results, there were no significant abnormalities in the livers of mice with moderate cecal ligation and perforation (CLP); however, ammonia levels were elevated in the hippocampal tissue and serum. The ELISA study suggest that fecal microbiota transplantation in CLP mice can reduce ammonia levels. Reduction in ammonia levels improved cognitive dysfunction and neurological impairment in CLP mice through behavioral, neuroimaging, and molecular biology studies. Further studies have shown that ammonia enters the brain to regulate the expression of aquaporins-4 (AQP4) in astrocytes, which may be the mechanism underlying brain dysfunction in CLP mice. The results of the in vitro experiments showed that ammonia up-regulated AQP4 expression in astrocytes, resulting in astrocyte damage. The results of this study suggest that ammonia up-regulates astrocyte AQP4 expression through the gut-brain axis, which may be a potential mechanism for the occurrence of SAE.


Subject(s)
Aquaporin 4 , Astrocytes , Brain-Gut Axis , Hyperammonemia , Sepsis-Associated Encephalopathy , Animals , Mice , Aquaporin 4/metabolism , Aquaporin 4/genetics , Aquaporin 4/biosynthesis , Astrocytes/metabolism , Hyperammonemia/metabolism , Sepsis-Associated Encephalopathy/metabolism , Male , Brain-Gut Axis/physiology , Mice, Inbred C57BL , Ammonia/metabolism , Ammonia/blood , Brain/metabolism , Fecal Microbiota Transplantation
6.
Small ; 20(27): e2311569, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38312092

ABSTRACT

Quasi-2D perovskites show great potential as photovoltaic devices with superior stability, but the power conversion efficiency (PCE) is limited by poor carrier transport. Here, it is simultaneously affected the hole transport layer (HTL) and the perovskite layer by incorporating pyridine-based materials into poly(3,4-ethylenedioxythiophene): polystyrene sulfonate (PEDOT:PSS) to address the key problem above in 2D perovskites. With this approach, the enhanced optoelectronic performance of the novel PEDOT:PSS is due to electron transfer between the additives and PEDOT or PSS, as well as a dissociation between PEDOT and PSS based on experimental and theoretical studies, which facilitates the charge extraction and transfer. Concurrently, in-situ X-ray scattering studies reveal that the introduction of pyridine-based molecules alters the transformation process of the perovskite intermediate phase, which leads to a preferred orientation and ordered distribution caused by the Pb─N chemical bridge, achieving efficient charge transport. As a result, the pyridine-treated devices achieve an increased short-circuit current density (Jsc) and PCE of over 17%.

7.
Opt Express ; 32(12): 21506-21516, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38859503

ABSTRACT

Vector vortex beams (VVBs) have attracted extensive attention due to their unique properties and their wide applications in fields such as optical manipulation and optical imaging. However, the wavefronts of the vector vortex beams are highly scrambled when they encounter highly scattering media (HSM), such as thick biological tissues, which greatly prevents the applications of VVBs behind HSM. To address this issue, we propose a scheme to construct VVBs of freewill position on the surface of hybrid-order Poincaré sphere (HyOPS) through HSM. With the measurement of two orthogonal scalar transmission matrices, the conjugated wavefronts for constructing orbital angular momentum beams with arbitrary topological charge in right and left circularly polarized states through HSM can be calculated, respectively. When an input wavefront superimposed by the two conjugated wavefronts with an appropriate ratio and phase delay, impinges on the HSM, the desired VVB can be created through HSM. To demonstrate the viability of our scheme, a series of VVBs on different locations of various HyOPSs have been reconstructed through a ZnO scattering layer experimentally. Furthermore, to characterize the polarization distribution of the generated beams, the polarization maps of these beams are derived by measuring the four Stokes parameters, which agree well with the theoretical distributions. This work will promote the applications of VVBs in highly scattering environments.

8.
Inorg Chem ; 63(4): 2060-2071, 2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38232754

ABSTRACT

The synthesis of two versatile fluorescent metal-organic frameworks (MOFs), [Eu(4-NCP)(1,4-bdc)]n·0.5H2O (1) and [Eu(4-NCP)(4,4'-bpdc)]n·0.75H2O (2) (HNCP = 2-(4-carboxyphenyl)imidazo(4,5-f)-(1,10)phenanthroline, 1,4-H2bdc = benzene-1,4-dicarboxylic acid, 4,4'-H2bpdc = 4,4'-biphenyldicarboxylic acid), was carried out using a hydrothermal method. These MOFs were characterized through various advanced technologies to determine their structural information. The results indicate that both MOFs exhibited 3D network structures with specific topologies. Furthermore, these MOFs demonstrated exceptional thermal stabilities and adsorption capabilities. Additionally, complex 2 was utilized for studying the fluorescence sensing properties of various micronutrients including metal ions, nitro aromatic compounds, and biological small molecules. Notably, complex 2 showed promising potential as a multifunctional sensor for selectively detecting Fe3+, nitrobenzene, and ascorbic acid in aqueous solutions through fluorescence quenching with low limits of detection (LODs ∼ 10-7 M) and high quenching constants (Ksv ∼ 103 M-1). Moreover, the detection mechanism of complex 2 was further investigated by using experimental methods and DFT calculations.

9.
J Chem Inf Model ; 64(9): 3874-3883, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38652138

ABSTRACT

The lipid raft subdomains in cancer cell membranes play a key role in signal transduction, biomolecule recruitment, and drug transmembrane transport. Augmented membrane rigidity due to the formation of a lipid raft is unfavorable for the entry of drugs, a limiting factor in clinical oncology. The short-chain ceramide (CER) has been reported to promote drug entry into membranes and disrupt lipid raft formation, but the underlying mechanism is not well understood. We recently explored the carrier-membrane fusion dynamics of PEG-DPPE micelles in delivering doxorubicin (DOX). Based on the phase-segregated membrane model composed of DPPC/DIPC/CHOL/GM1/PIP2, we aim to explore the dynamic mechanism of the PEG-DPPE micelle-encapsulating DOXs in association with the raft-included cell membrane modulated by C8 acyl tail CERs. The results show that the lipid raft remains integrated and DOX-resistant subjected to free DOXs and the micelle-encapsulating ones. Addition of CERs disorganizes the lipid raft by pushing CHOL aside from DPPC. It subsequently allows for a good permeability for PEG-DPPE micelle-encapsulated DOXs, which penetrate deeper as CER concentration increases. GM1 is significant in guiding drugs' redistributing between bilayer phases, and the anionic PIP2 further helps DOXs attain the inner bilayer surface. These results elaborate on the perturbing effect of CERs on lipid raft stability, which provides a new comprehensive approach for further design of drug delivery systems.


Subject(s)
Ceramides , Membrane Microdomains , Micelles , Molecular Dynamics Simulation , Polyethylene Glycols , Humans , Ceramides/chemistry , Doxorubicin/chemistry , Doxorubicin/pharmacology , Doxorubicin/metabolism , Membrane Microdomains/metabolism , Membrane Microdomains/chemistry , Phosphatidylethanolamines/chemistry , Polyethylene Glycols/chemistry
10.
Eur J Nutr ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38814365

ABSTRACT

IMPORTANCE: Epidemiological evidences regarding the association between whole grain intake and the risk of new-onset hypertension are still controversial. OBJECTIVE: We aimed to investigate the relationship between whole grain intake and new-onset hypertension and examine possible effect modifiers in the general population. METHODS: A total of 10,973 participants without hypertension from the China Health and Nutrition Survey were enrolled, with follow-up beginning in 1997 and ending in 2015. Whole grain intake was assessed by 3 consecutive 24-h dietary recalls combined with a household food inventory. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression model after adjusting for potential risk factors. RESULTS: During a median follow-up of 7.0 years, 3,733 participants developed new-onset hypertension. The adjusted HRs (95% CIs) were as follows: for quartile 2 (HR: 0.52; 95% CI: 0.47-0.57), quartile 3 (HR: 0.46; 95% CI: 0.42-0.51), and quartile 4 (HR: 0.35; 95% CI: 0.31-0.38), compared with quartile 1. Different types of whole grain types, including wheat (adjusted HR, 0.35; 95% CI, 0.32-0.39), maize (adjusted HR, 0.50; 95% CI, 0.42-0.59), and millet (adjusted HR, 0.38; 95% CI, 0.30-0.48), showed significant associations with a reduced risk of hypertension. The association between whole grain intake and new-onset hypertension was stronger in individuals with older age (P for interaction < 0.001) and higher BMI (P for interaction < 0.001). CONCLUSION: Higher consumption of whole grains was significantly associated with a lower risk of new-onset hypertension. This study provides further evidence supporting the importance of increasing whole grain intake for hypertension prevention among Chinese adults.

11.
Biomed Eng Online ; 23(1): 14, 2024 Feb 03.
Article in English | MEDLINE | ID: mdl-38310297

ABSTRACT

PURPOSE: Convolution operator-based neural networks have shown great success in medical image segmentation over the past decade. The U-shaped network with a codec structure is one of the most widely used models. Transformer, a technology used in natural language processing, can capture long-distance dependencies and has been applied in Vision Transformer to achieve state-of-the-art performance on image classification tasks. Recently, researchers have extended transformer to medical image segmentation tasks, resulting in good models. METHODS: This review comprises publications selected through a Web of Science search. We focused on papers published since 2018 that applied the transformer architecture to medical image segmentation. We conducted a systematic analysis of these studies and summarized the results. RESULTS: To better comprehend the benefits of convolutional neural networks and transformers, the construction of the codec and transformer modules is first explained. Second, the medical image segmentation model based on transformer is summarized. The typically used assessment markers for medical image segmentation tasks are then listed. Finally, a large number of medical segmentation datasets are described. CONCLUSION: Even if there is a pure transformer model without any convolution operator, the sample size of medical picture segmentation still restricts the growth of the transformer, even though it can be relieved by a pretraining model. More often than not, researchers are still designing models using transformer and convolution operators.


Subject(s)
Natural Language Processing , Neural Networks, Computer , Technology , Image Processing, Computer-Assisted
12.
Pharmacoepidemiol Drug Saf ; 33(8): e5880, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39135518

ABSTRACT

BACKGROUND: Polypharmacy (PP) is common in elderly population and associated with some adverse clinical outcomes and increases healthcare burdens. We performed this systemic review and meta-analysis to estimate worldwide prevalence of PP and explore associated factors in the elderly. METHODS: The PubMed, Web of Science, Cochrane Library, and Ovid EMBASE databases were searched for studies published until May 30, 2022. We included observational studies representative of general patients aged ≥60 in which PP was defined as multiple drugs ≥5. Studies were excluded if only a particular group of the elderly population (e.g., with diabetes) were included. The primary outcome was the prevalence of PP. Random-effect models were employed to estimate the overall or variable-specific pooled estimates of PP. Secondary outcomes were hyperpolypharmacy (HPP, defined as multiple drugs ≥10) and PP prevalence based on different study years, genders, locations, populations, and so forth. RESULTS: We included 122 original observational studies with an overall population of 57 328 043 individuals in the meta-analysis. The overall prevalence of PP and HPP in the elderly population worldwide was 39.1% (95% confidence interval [CI], 35.5%-42.7%) and 13.3% (95% CI, 10.4%-16.5%), respectively. The prevalence of PP in Europe, Oceania, North America, Asia, and South America was 45.8% (95% CI, 41.5%-50.2%), 45.5% (95% CI, 26.7%-64.3%), 40.8% (95% CI, 29.8%-51.6%), 29.0% (95% CI, 20.0%-38.0%), and 28.4% (95% CI, 24.0%-32.8%), respectively (p < 0.01). Multivariate meta-regressions showed geographical regions of Europe or North America, age ≥70, and residence from nursing homes were independently associated with higher PP prevalence. CONCLUSIONS: Nearly 40% of the elderly population is exposed to PP. The prevalence of PP is significantly higher in elderly individuals aged 70 or older, in developed regions and in nursing homes. It is important to focus on avoiding inappropriate PP in this population to address the growing burden of PP.


Subject(s)
Polypharmacy , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Age Factors , Global Health/statistics & numerical data , Observational Studies as Topic , Polypharmacy/statistics & numerical data , Prevalence
13.
Acta Pharmacol Sin ; 45(9): 1951-1963, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38760543

ABSTRACT

Bevacizumab is a recombinant humanized monoclonal immunoglobulin (Ig) G1 antibody of VEGF, and inhibits angiogenesis and tumor growth in hepatocellular carcinoma (HCC). Ferroptosis, a new form of regulated cell death function independently of the apoptotic machinery, has been accepted as an attractive target for pharmacological intervention; the ferroptosis pathway can enhance cell immune activity of anti-PD1 immunotherapy in HCC. In this study we investigated whether and how bevacizumab regulated ferroptosis and immune activity in liver cancer. Firstly, we performed RNA-sequencing in bevacizumab-treated human liver cancer cell line HepG2 cells, and found that bevacizumab significantly altered the expression of a number of genes including VEGF, PI3K, HAT1, SLC7A11 and IL-9 in liver cancer, bevacizumab upregulated 37 ferroptosis-related drivers, and downregulated 17 ferroptosis-related suppressors in particular. We demonstrated that bevacizumab triggered ferroptosis in liver cancer cells by driving VEGF/PI3K/HAT1/SLC7A11 axis. Clinical data confirmed that the expression levels of VEGF were positively associated with those of PI3K, HAT1 and SLC7A11 in HCC tissues. Meanwhile, we found that bevacizumab enhanced immune cell activity in tumor immune-microenvironment. We identified that HAT1 up-regulated miR-143 targeting IL-9 mRNA 3'UTR in liver cancer cells; bevacizumab treatment resulted in the increase of IL-9 levels and its secretion via VEGF/PI3K/HAT1/miR-143/IL-9 axis, which led to the inhibition of tumor growth in vivo through increasing the release of IL-2 and Granzyme B from activated CD8+ T cells. We conclude that in addition to inhibiting angiogenesis, bevacizumab induces ferroptosis and enhances CD8+ T cell immune activity in liver cancer. This study provides new insight into the mechanisms by which bevacizumab synergistically modulates ferroptosis and CD8+ T cell immune activity in liver cancer.


Subject(s)
Bevacizumab , CD8-Positive T-Lymphocytes , Ferroptosis , Liver Neoplasms , Ferroptosis/drug effects , Humans , Bevacizumab/pharmacology , Bevacizumab/therapeutic use , Liver Neoplasms/drug therapy , Liver Neoplasms/immunology , Liver Neoplasms/pathology , Animals , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Mice , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/immunology , Hep G2 Cells , Tumor Microenvironment/drug effects , Vascular Endothelial Growth Factor A/metabolism , Antineoplastic Agents, Immunological/pharmacology , Antineoplastic Agents, Immunological/therapeutic use , Amino Acid Transport System y+/metabolism , Amino Acid Transport System y+/genetics , Male
14.
Acta Pharmacol Sin ; 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39090392

ABSTRACT

Aristolochic acids (AAs) have been identified as a significant risk factor for hepatocellular carcinoma (HCC). Ferroptosis is a type of regulated cell death involved in the tumor development. In this study, we investigated the molecular mechanisms by which AAs enhanced the growth of HCC. By conducting bioinformatics and RNA-Seq analyses, we found that AAs were closely correlated with ferroptosis. The physical interaction between p53 and AAs in HepG2 cells was validated by bioinformatics analysis and SPR assays with the binding pocket sites containing Pro92, Arg174, Asp207, Phe212, and His214 of p53. Based on the binding pocket that interacts with AAs, we designed a mutant and performed RNA-Seq profiling. Interestingly, we found that the binding pocket was responsible for ferroptosis, GADD45A, NRF2, and SLC7A11. Functionally, the interaction disturbed the binding of p53 to the promoter of GADD45A or NRF2, attenuating the role of p53 in enhancing GADD45A and suppressing NRF2; the mutant did not exhibit the same effects. Consequently, this event down-regulated GADD45A and up-regulated NRF2, ultimately inhibiting ferroptosis, suggesting that AAs hijacked p53 to down-regulate GADD45A and up-regulate NRF2 in HepG2 cells. Thus, AAs treatment resulted in the inhibition of ferroptosis via the p53/GADD45A/NRF2/SLC7A11 axis, which led to the enhancement of tumor growth. In conclusion, AAs-hijacked p53 restrains ferroptosis through the GADD45A/NRF2/SLC7A11 axis to enhance tumor growth. Our findings provide an underlying mechanism by which AAs enhance HCC and new insights into p53 in liver cancer. Therapeutically, the oncogene NRF2 is a promising target for liver cancer.

15.
Acta Pharmacol Sin ; 45(8): 1686-1700, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38589688

ABSTRACT

Lymphocyte activation gene 3 (LAG3), an immune checkpoint molecule expressed on activated T cells, functions as a negative regulator of immune responses. Persistent antigen exposure in the tumor microenvironment results in sustained LAG3 expression on T cells, contributing to T cell dysfunction. Fibrinogen-like protein 1 (FGL1) has been identified as a major ligand of LAG3, and FGL1/LAG3 interaction forms a novel immune checkpoint pathway that results in tumor immune evasion. In addition, ubiquitin-specific peptidase 7 (USP7) plays a crucial role in cancer development. In this study we investigated the role of USP7 in modulation of FGL1-mediated liver cancer immune evasion. We showed that knockdown of USP7 or treatment with USP7 inhibitor P5091 suppressed liver cancer growth by promoting CD8+ T cell activity in Hepa1-6 xenograft mice and in HepG2 or Huh7 cells co-cultured with T cells, whereas USP7 overexpression produced the opposite effect. We found that USP7 upregulated FGL1 in HepG2 and Huh7 cells by deubiquitination of transcriptional factor PR domain zinc finger protein 1 (PRDM1), which transcriptionally activated FGL1, and attenuated the CD8+ T cell activity, leading to the liver cancer growth. Interestingly, USP7 could be transcriptionally stimulated by PRDM1 as well in a positive feedback loop. P5091, an inhibitor of USP7, was able to downregulate FGL1 expression, thus enhancing CD8+ T cell activity. In an immunocompetent liver cancer mouse model, the dual blockade of USP7 and LAG3 resulted in a superior antitumor activity compared with anti-LAG3 therapy alone. We conclude that USP7 diminishes CD8+ T cell activity by a USP7/PRDM1 positive feedback loop on FGL1 production in liver cancer; USP7 might be a promising target for liver cancer immunotherapy.


Subject(s)
CD8-Positive T-Lymphocytes , Liver Neoplasms , Ubiquitin-Specific Peptidase 7 , Up-Regulation , Ubiquitin-Specific Peptidase 7/metabolism , Ubiquitin-Specific Peptidase 7/antagonists & inhibitors , Ubiquitin-Specific Peptidase 7/genetics , Animals , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Humans , Liver Neoplasms/immunology , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Mice , Positive Regulatory Domain I-Binding Factor 1/metabolism , Positive Regulatory Domain I-Binding Factor 1/genetics , Cell Line, Tumor , Mice, Inbred C57BL , Fibrinogen , Thiophenes
16.
Skin Res Technol ; 30(6): e13604, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38858846

ABSTRACT

BACKGROUND: Many consumers use cosmetic eye products to counteract age-related changes in appearance. Measurements of eyelid shape in Asian women have been reported in the frontal view or 45-degree profile only. The aim of this study was to describe morphological characteristics of the upper eyelid in Japanese and Chinese females from the frontal and profile aspects and examine morphological changes with age. MATERIALS AND METHODS: Standardized digital photographs of 772 Japanese and 346 Chinese women (15-79 years of age) were acquired in frontal and 90-degree profile aspects. Eleven upper eyelid parameters (e.g., width, length, depth, aperture, and curvature) were measured using image analysis to determine age-related changes and compare by ethnicity. RESULTS: Eyelid width, area between eyebrow and eyelid, and eyelid curvature were comparable for both ethnicities under age 40, but the aging effect was more pronounced in Chinese subjects. Eyelid height, depth, and upper eyelid aperture angle were also comparable for both ethnicities under age 40, but the aging effect was more evident in Japanese subjects. Upper eyelid incline angle, eye orientation, and upper eyelid protrusion angle changed comparably with age for both ethnicities. No prominent age-related changes were evident for eyelid length or area between eyebrow and eye with the eye closed. CONCLUSION: Upper eyelid morphology changes with age in Japanese and Chinese females, starting around 40 years of age. Ethnic differences are limited in younger age groups but become more prominent with age. The findings suggest that aging affects some upper eyelid features earlier than others.


Subject(s)
Aging , Asian People , Eyelids , Adolescent , Adult , Aged , Female , Humans , Middle Aged , Young Adult , Aging/ethnology , Aging/pathology , Aging/physiology , China , East Asian People , Eyelids/anatomy & histology , Eyelids/diagnostic imaging , Japan , Photography , Skin Aging/ethnology , Skin Aging/pathology , Skin Aging/physiology
17.
BMC Public Health ; 24(1): 195, 2024 01 16.
Article in English | MEDLINE | ID: mdl-38229065

ABSTRACT

BACKGROUND: Exposure to ethylene oxide (EO) induces inflammation and oxidative stress, which are the main mechanisms of periodontitis. However, the effect of EO on periodontal health is not unclear. In this study, we aimed to explore the relationship between EO exposure and the risk of periodontitis in general US adults. METHODS: Data used in our study from the National Health and Nutritional Examination Survey (NHANES) 2013-2014. The EO biomarker, hemoglobin adduct of EO (HbEO), was measured in blood samples utilizing high-performance liquid chromatography-tandem mass spectrometry. Periodontitis category was defined by the CDC/AAP according to clinical periodontal parameters. Natural cubic spline, weight multivariable logistic regression analyses and subgroup analysis were used to explore the association between EO exposure and the risk of periodontitis. RESULTS: A total of 1497 participants over the age of 30 were included in our study. A non-linear positive association with periodontitis was identified for HbEO levels. Participants in the highest tertile of HbEO levels were more likely to have poorer periodontal health compared to the lowest tertile (ORtertile3vs1 = 2.80, 95% CI: 1.85-4.24). Similar results were also found in different subgroups. CONCLUSIONS: HbEO levels are positively associated with poor periodontal health in US adults. Additional longitudinal studies are necessary to further enhance our comprehension of the impact of exposure to EO on periodontal status.


Subject(s)
Ethylene Oxide , Periodontitis , Adult , Humans , Cross-Sectional Studies , Nutrition Surveys , Periodontitis/epidemiology , Longitudinal Studies
18.
Echocardiography ; 41(3): e15779, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38477165

ABSTRACT

BACKGROUND: Radiofrequency catheter ablation (RFCA) is an effective method for controlling the heart rate of paroxysmal atrial fibrillation (PAF). However, recurrence is trouble under the RFCA. To gain a deeper understanding of the risk factors for recurrence in patients, we created a nomogram model to provide clinicians with treatment recommendations. METHODS: A total of two hundred thirty-three patients with PAF treated with RFCA at Guizhou Medical University Hospital between January 2021 and December 2022 were consecutively included in this study, and after 1 year of follow-up coverage, 166 patients met the nadir inclusion criteria. Patients with AF were divided into an AF recurrence group and a non-recurrence group. The nomogram was constructed using univariate and multivariate logistic regression analyses. By calculating the area under the curve, we analyzed the predictive ability of the risk scores (AUC). In addition, the performance of the nomogram in terms of calibration, discrimination, and clinical utility was evaluated. RESULTS: At the 12-month follow-up, 48 patients (28.92%) experienced a recurrence of AF after RFCA, while 118 patients (71.08%) maintained a sinus rhythm. In addition to age, sex, and TRV, LAD, and TTPG were independent predictors of recurrence of RFCA. The c-index of the nomogram predicted AF recurrence with an accuracy of .723, showing good decision curves and a calibrated nomogram, as determined by internal validation using a bootstrap sample size of 1000. CONCLUSION: We created a nomogram based on multifactorial logistic regression analysis to estimate the probability of recurrence in patients with atrial fibrillation 1 year after catheter ablation. This plot can be utilized by clinicians to predict the likelihood of recurrence.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Radiofrequency Ablation , Humans , Treatment Outcome , Nomograms , Predictive Value of Tests , Risk Factors , Catheter Ablation/methods , Catheters , Recurrence
19.
BMC Musculoskelet Disord ; 25(1): 435, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38831425

ABSTRACT

BACKGROUND: Prior studies have suggested a potential relationship between osteoporosis and sarcopenia, both of which can present symptoms of compromised mobility. Additionally, fractures among the elderly are often considered a common outcome of both conditions. There is a strong correlation between fractures in the elderly population, decreased muscle mass, weakened muscle strength, heightened risk of falls, and diminished bone density. This study aimed to pinpoint crucial diagnostic candidate genes for osteoporosis patients with concomitant sarcopenia. METHODS: Two osteoporosis datasets and one sarcopenia dataset were obtained from the Gene Expression Omnibus (GEO). Differential expression genes (DEGs) and module genes were identified using Limma and Weighted Gene Co-expression Network Analysis (WGCNA), followed by functional enrichment analysis, construction of protein-protein interaction (PPI) networks, and application of a machine learning algorithm (least absolute shrinkage and selection operator (LASSO) regression) to determine candidate hub genes for diagnosing osteoporosis combined with sarcopenia. Receiver operating characteristic (ROC) curves and column line plots were generated. RESULTS: The merged osteoporosis dataset comprised 2067 DEGs, with 424 module genes filtered in sarcopenia. The intersection of DEGs between osteoporosis and sarcopenia module genes consisted of 60 genes, primarily enriched in viral infection. Through construction of the PPI network, 30 node genes were filtered, and after machine learning, 7 candidate hub genes were selected for column line plot construction and diagnostic value assessment. Both the column line plots and all 7 candidate hub genes exhibited high diagnostic value (area under the curve ranging from 1.00 to 0.93). CONCLUSION: We identified 7 candidate hub genes (PDP1, ALS2CL, VLDLR, PLEKHA6, PPP1CB, MOSPD2, METTL9) and constructed column line plots for osteoporosis combined with sarcopenia. This study provides reference for potential peripheral blood diagnostic candidate genes for sarcopenia in osteoporosis patients.


Subject(s)
Computational Biology , Machine Learning , Osteoporosis , Sarcopenia , Humans , Sarcopenia/genetics , Sarcopenia/diagnosis , Osteoporosis/genetics , Osteoporosis/diagnosis , Gene Expression Profiling , Protein Interaction Maps/genetics , Gene Regulatory Networks , Aged , Transcriptome , Databases, Genetic , Female
20.
Article in English | MEDLINE | ID: mdl-38401111

ABSTRACT

Objective: To explore the influence of early psychological intervention on AIDS patients receiving hospital-led case management. Methods: Between December 2022 and May 2023, 100 cases of AIDS patients were gathered at the Fifth Hospital of Shijiazhuang. They were randomly assigned to either a psychological intervention group or a conventional intervention group. Each group consists of 50 individuals affected by AIDS. The conventional intervention group received care through traditional care models. In contrast, the psychological intervention group received immediate psychological support upon being screened positive for HIV antibodies, in addition to the conventional intervention group. The intervention period for both groups lasted 3 months, during which medication adherence, adverse emotional conditions, self-management skills, and quality of life were compared. Results: During the intervention period, the psychological intervention group exhibited higher medication adherence than the conventional intervention group. Post-intervention, the levels of anxiety as assessed by the SAS and the degree of depression as evaluated by the SDS of the conventional intervention group were higher than those of the psychological intervention group. Additionally, the psychological intervention group demonstrated higher scores in 7 dimensions the total score on the self-management ability scale, and a higher score in the WHOQOL-HIV-BREF compared to the conventional intervention group. Conclusion: In the context of hospital-led case management for AIDS, early psychological intervention in patients has been shown to enhance medication adherence, reduce negative emotions, improve self-management skills, and enhance overall quality of life.

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