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1.
Front Cardiovasc Med ; 11: 1394889, 2024.
Article in English | MEDLINE | ID: mdl-38895538

ABSTRACT

Abdominal Aortic Aneurysm (AAA) is a disease characterized by localized dilation of the abdominal aorta, involving multiple factors in its occurrence and development, ultimately leading to vessel rupture and severe bleeding. AAA has a high mortality rate, and there is a lack of targeted therapeutic drugs. Epigenetic regulation plays a crucial role in AAA, and the treatment of AAA in the epigenetic field may involve a series of related genes and pathways. Abnormal expression of these genes may be a key factor in the occurrence of the disease and could potentially serve as promising therapeutic targets. Understanding the epigenetic regulation of AAA is of significant importance in revealing the mechanisms underlying the disease and identifying new therapeutic targets. This knowledge can contribute to offering AAA patients better clinical treatment options beyond surgery. This review systematically explores various aspects of epigenetic regulation in AAA, including DNA methylation, histone modification, non-coding RNA, and RNA modification. The analysis of the roles of these regulatory mechanisms, along with the identification of relevant genes and pathways associated with AAA, is discussed comprehensively. Additionally, a comprehensive discussion is provided on existing treatment strategies and prospects for epigenetics-based treatments, offering insights for future clinical interventions.

2.
Chemosphere ; 361: 142445, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38797212

ABSTRACT

The impact of thermally driven mountain-valley breezes (MVB) on the atmospheric environment remains poorly understood, especially in ozone (O3)-polluted regions with complex underlying topography. To address this knowledge gap, we focused on the western Sichuan Basin (SCB), situated immediately east of the Tibetan Plateau (TP), which is considered susceptible to MVB coupled with severe O3 pollution in southwest China. We revealed the MVB driving diurnal O3 variations and meteorological mechanisms using surface observations and ERA5 reanalysis data. Local MVB days accounted for up to 47% of cases in the summers of 2015-2022. Driven by the MVB, the near-surface O3 concentrations increased by 8.8%, with 12.7% and 50.0% deterioration in the O3 light and moderate exceedance rates, respectively, on the western SCB edge. The daytime upslope valley breeze with 20% higher wind speed drove the westward transport of rich O3 and precursors from the upwind-polluted inner SCB towards its western edge, and the O3 photochemical production, followed by intensifying solar radiation and air temperature, gave rise to 14.8% of surface O3 concentrations over the western SCB edge. The nighttime downward mountain breeze with a 20% increase in wind speed could transport the rich O3 in the mountainous area to the basin edge, causing O3 levels to increase by 2.8%. In summary, we quantitatively assessed the impacts of MVB on changes in O3 concentrations and air quality along with its meteorological mechanisms, facilitating a comprehensive understanding of meteorological drivers in the atmospheric environment.


Subject(s)
Air Pollutants , Environmental Monitoring , Ozone , China , Ozone/analysis , Air Pollutants/analysis , Air Pollution/statistics & numerical data , Seasons , Wind , Temperature , Atmosphere/chemistry
3.
PeerJ Comput Sci ; 10: e1948, 2024.
Article in English | MEDLINE | ID: mdl-38660210

ABSTRACT

Fusarium head blight (FHB) is a destructive disease that affects wheat production. Detecting FHB accurately and rapidly is crucial for improving wheat yield. Traditional models are difficult to apply to mobile devices due to large parameters, high computation, and resource requirements. Therefore, this article proposes a lightweight detection method based on an improved YOLOv8s to facilitate the rapid deployment of the model on mobile terminals and improve the detection efficiency of wheat FHB. The proposed method introduced a C-FasterNet module, which replaced the C2f module in the backbone network. It helps reduce the number of parameters and the computational volume of the model. Additionally, the Conv in the backbone network is replaced with GhostConv, further reducing parameters and computation without significantly affecting detection accuracy. Thirdly, the introduction of the Focal CIoU loss function reduces the impact of sample imbalance on the detection results and accelerates the model convergence. Lastly, the large target detection head was removed from the model for lightweight. The experimental results show that the size of the improved model (YOLOv8s-CGF) is only 11.7 M, which accounts for 52.0% of the original model (YOLOv8s). The number of parameters is only 5.7 × 106 M, equivalent to 51.4% of the original model. The computational volume is only 21.1 GFLOPs, representing 74.3% of the original model. Moreover, the mean average precision (mAP@0.5) of the model is 99.492%, which is 0.003% higher than the original model, and the mAP@0.5:0.95 is 0.269% higher than the original model. Compared to other YOLO models, the improved lightweight model not only achieved the highest detection precision but also significantly reduced the number of parameters and model size. This provides a valuable reference for FHB detection in wheat ears and deployment on mobile terminals in field environments.

4.
Anal Chim Acta ; 1304: 342540, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38637050

ABSTRACT

BACKGROUND: Mastitis, a pervasive and detrimental disease in dairy farming, poses a significant challenge to the global dairy industry. Monitoring the milk somatic cell count (SCC) is vital for assessing the incidence of mastitis and the quality of raw cow's milk. However, existing SCC detection methods typically require large-scale instruments and specialized operators, limiting their application in resource-constrained settings such as dairy farms and small-scale labs. To address these limitations, this study introduces a novel, smartphone-based, on-site SCC testing method that leverages smartphone capabilities for milk somatic cell identification and enumeration, offering a portable and user-friendly testing platform. RESULTS: The central findings of our study demonstrate the effectiveness of the proposed method for counting milk somatic cells. Its on-site applicability, facilitated by the microfluidic chip, optical system, and smartphone integration, heralds a paradigm shift in point-of-care testing (POCT) for dairy farms and smaller laboratories. This approach bypasses complex processing and presents a user-friendly solution for real-time SCC monitoring in resource-limited settings. This device boasts several unique features: small size, low cost (<$1,000 total manufacturing cost and <$1 per test), and high accuracy. Remarkably, it delivers test results within just 2 min. Actual-sample testing confirmed its consistency with results from the commercial Bentley FTS/FCM cytometer, affirming the reliability of the proposed method. Overall, these results underscore the potential for transformative change in dairy farm management and laboratory testing practices. SIGNIFICANCE: In summary, this study concludes that the proposed smartphone-based method significantly contributes to the accessibility and ease of SCC testing in resource-limited environments. By fostering the use of POCT technology in food safety control, particularly in the dairy industry, this innovative approach has the potential to revolutionize the monitoring and management of mastitis, ultimately benefiting the global dairy sector.


Subject(s)
Mastitis , Milk , Humans , Animals , Female , Cattle , Point-of-Care Systems , Reproducibility of Results , Smartphone , Cell Count/methods , Dairying/methods , Mastitis/veterinary
5.
Biosens Bioelectron ; 257: 116325, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38669843

ABSTRACT

In dairy industry, expensive yak's milk, camel's milk, and other specialty dairy products are often adulterated with low-cost cow's milk, goat's milk and so on. Currently, the detection of specialty dairy products typically requires laboratory settings and relies on skilled operators. Therefore, there is an urgent need to develop a multi-detection technology and on-site rapid detection technique to enhance the efficiency and accuracy of the detection of specialty dairy products. In this study, we introduced a fully integrated and portable microfluidic detection platform called Sector Self-Driving Microfluidics (SDM), designed to simultaneously detect eight common species-specific components in milk. SDM integrated nucleic acid extraction, purification, loop-mediated isothermal amplification (LAMP), and lateral flow strip (LFS) detection functions into a closed microfluidic system, enabling contamination-free visual detection. The SDM platform used a constant-temperature heating plate, powered by a mobile battery, eliminated the need for additional power support. The SDM platform achieved nucleic acid enrichment and transfer through magnetic force and liquid flow driven by capillary forces, operating without external pumps. The standalone SDM platform could detect dairy components with as low as 1% content within 1 h. Validation with 35 commercially available samples demonstrated 100% specificity and accuracy compared to the gold standard real-time PCR. The SDM platform provided the dairy industry with an efficient, convenient, and accurate detection tool, enabling rapid on-site testing at production facilities or sales points. This facilitated real-time monitoring of quality issues during the production process, quickly identifying potential risks and preventing substandard products from entering the market.


Subject(s)
Biosensing Techniques , Milk , Nucleic Acid Amplification Techniques , Animals , Nucleic Acid Amplification Techniques/instrumentation , Nucleic Acid Amplification Techniques/methods , Biosensing Techniques/instrumentation , Biosensing Techniques/methods , Milk/chemistry , Cattle , Food Contamination/analysis , Lab-On-A-Chip Devices , Equipment Design , Microfluidic Analytical Techniques/instrumentation , Dairy Products/analysis , Molecular Diagnostic Techniques
6.
Environ Pollut ; 349: 123932, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38583796

ABSTRACT

By analyzing environmental and meteorological monitoring data over recent years of 2015-2022, the Twain-Hu Basin (THB) in central China was identified as a regional O3 pollution center over China with the highest increasing trend at 1.10 %⸱yr-1 in interannual variations of O3 concentrations with deteriorating O3 pollution over recent years. We explored the spatiotemporal variations in O3 pollution in the THB with ozone suppression (OS) under high air temperature over metropolitan, small urban, and mountainous areas. The bipolarized interannual trends in interannual O3 variations in urban and mountainous areas over central China were characterized with the increasing and decreasing 90th percentiles of the daily maximum 8-h (MDA8-90) O3 concentrations respectively in polluted urban areas and clean mountainous areas over recent eight years. The changes of the near-surface O3 concentrations with air temperature exhibited the inflection points of OS from increasing to decreasing O3 at air temperature of 30.5 °C in mountainous areas, 32.5 °C in small urban areas, and 34.5 °C in metropolitan areas, and the intensity of OS was estimated in the ranking with mountainous areas (-2.30 µg⸱m-3⸱°C-1) > small urban areas (-1.96 µg⸱m-3⸱°C-1) > metropolitan areas (-1.54 µg⸱m-3⸱°C-1), indicating that the OS was more significant over the lower-O3 mountainous areas. This study has implications for understanding O3 pollution variations with the meteorological drivers.


Subject(s)
Air Pollutants , Air Pollution , Environmental Monitoring , Ozone , Ozone/analysis , China , Environmental Monitoring/methods , Air Pollutants/analysis , Air Pollution/statistics & numerical data , Hot Temperature , Temperature , Cities
7.
Front Immunol ; 15: 1339971, 2024.
Article in English | MEDLINE | ID: mdl-38426096

ABSTRACT

Aplastic anemia (AA) and hypoplastic myelodysplastic syndrome are paradigms of autoimmune hematopoietic failure (AHF). Myelodysplastic syndrome and acute myeloid leukemia are unequivocal myeloid neoplasms (MNs). Currently, AA is also known to be a clonal hematological disease. Genetic aberrations typically observed in MNs are detected in approximately one-third of AA patients. In AA patients harboring MN-related genetic aberrations, a poor response to immunosuppressive therapy (IST) and an increased risk of transformation to MNs occurring either naturally or after IST are predicted. Approximately 10%-15% of patients with severe AA transform the disease phenotype to MNs following IST, and in some patients, leukemic transformation emerges during or shortly after IST. Phenotypic transformations between AHF and MNs can occur reciprocally. A fraction of advanced MN patients experience an aplastic crisis during which leukemic blasts are repressed. The switch that shapes the disease phenotype is a change in the strength of extramedullary inflammation. Both AHF and MNs have an immune-active bone marrow (BM) environment (BME). In AHF patients, an inflamed BME can be evoked by infiltrated immune cells targeting neoplastic molecules, which contributes to the BM-specific autoimmune impairment. Autoimmune responses in AHF may represent an antileukemic mechanism, and inflammatory stressors strengthen antileukemic immunity, at least in a significant proportion of patients who have MN-related genetic aberrations. During active inflammatory episodes, normal and leukemic hematopoieses are suppressed, which leads to the occurrence of aplastic cytopenia and leukemic cell regression. The successful treatment of underlying infections mitigates inflammatory stress-related antileukemic activities and promotes the penetration of leukemic hematopoiesis. The effect of IST is similar to that of treating underlying infections. Investigating inflammatory stress-powered antileukemic immunity is highly important in theoretical studies and clinical practice, especially given the wide application of immune-activating agents and immune checkpoint inhibitors in the treatment of hematological neoplasms.


Subject(s)
Anemia, Aplastic , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Myeloproliferative Disorders , Humans , Anemia, Aplastic/therapy , Bone Marrow , Myelodysplastic Syndromes/genetics , Leukemia, Myeloid, Acute/genetics
8.
Sci Total Environ ; 923: 171527, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38453079

ABSTRACT

The Tibetan Plateau (TP) is essential in modulating climate change in downstream Eastern China (EC). As a meteorology-sensitive pollutant, changes in ozone (O3) in connection with the TP have received limited attention. In this study, using climate analysis of the China High Air Pollutants O3 product and ERA5 reanalysis data of meteorology for 1980-2020, the effect of springtime TP thermal forcing on the warm season (April-September) O3 pollution over EC was investigated. The strong TP thermal effect significantly modulates the interannual variations in O3 pollution with a dipole pattern over EC, inducing more O3 pollution in northern EC regions and alleviating O3 pollution in the southern regions. In northern (southern) EC, strong TP thermal forcing triggers a significant anomalous high (low) pressure center accompanied by anticyclonic (cyclonic) anomalies, resulting in decreased (increased) total cloud cover, increased (reduced) surface downward solar radiation and air temperature, which are conducive to the anomalous increase (decrease) in surface O3 concentrations. Moreover, the key sources of springtime thermal forcing over the TP influence the major O3 pollution regions over southern and northern EC with an inverse pattern, depending on their locations and orientations to the large topography of the TP. This research reveals an important driving factor for the dipole interannual variation in O3 pollution over EC, providing a new prospect for the effect of the TP on atmospheric environmental change.

9.
Angew Chem Int Ed Engl ; 63(22): e202403492, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38482742

ABSTRACT

The development of self-replicating systems is of great importance in research on the origin of life. As the most iconic molecules, nucleic acids have provided prominent examples of the fabrication of self-replicating artificial nanostructures. However, it is still challenging to construct sophisticated synthetic systems that can create large-scale or three-dimensionally ordered nanomaterials using self-replicating nanostructures. By integrating a template system containing DNA-functionalized colloidal seeds with a simplified DNA strand-displacement circuit programmed subsystem to produce DNA-functionalized colloidal copies, we developed a facile enthalpy-mediated strategy to control the replication and catalytic assembly of DNA-functionalized colloids in a time-dependent manner. The replication efficiency and crystal quality of the resulting superlattice structures can be effectively increased by regulating the molar ratio of the template to the copy colloids. By constructing binary systems from two types of gold nanoparticles (or proteins), superlattice structures with different crystal symmetries can be obtained through the replication and catalytic assembly processes. This programmable enthalpy-mediated approach was easily leveraged to achieve the phase transformation and catalytic amplification of colloidal crystals starting from different initial template crystals. This work offers a potential way to construct self-replicating artificial systems that exhibit complicated phase behaviors and can produce large-scale superlattice nanomaterials.


Subject(s)
Colloids , DNA , Colloids/chemistry , DNA/chemistry , Gold/chemistry , Crystallization , Metal Nanoparticles/chemistry , Thermodynamics , Nanostructures/chemistry
10.
Biosens Bioelectron ; 252: 116140, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38394702

ABSTRACT

With the globalization and complexity of the food supply chain, the market is becoming increasingly competitive and food fraudulent activities are intensifying. The current state of food detection faced two primary challenges. Firstly, existing testing methods were predominantly laboratory-based, requiring complex procedures and precision instruments. Secondly, there was a lack of accurate and efficient quantitative detection methods. Taking cow's milk as an example, this study introduced a novel method for nucleic acid quantification in dairy products, based on lateral flow strips (LFS). The core idea of this method is to design single-stranded DNA (ssDNA) probes to hybridize with mitochondrial genes, which are abundant, stable, and species-specific in dairy products, as detection targets. Drawing inspiration from the principles of nucleic acid amplification, this research innovatively established a new DNA hybridization method, named LAMP-Like Hybridization (HybLAMP-Like). Leveraging the denaturation and DNA polymerization functions of the bst enzyme, efficient binding of the probe and template strand was achieved. This method eliminated the need for nucleic acid amplification, simplifying the procedure and mitigating aerosol contamination, thereby ensuring the accuracy of the detection results. The method exhibited exceptional sensitivity, capable of detecting extremely low to 12.5 ng in visual inspection and 3.125 ng when using a reader. In terms of practicality, it could achieve visual detection of cow's milk content as low as 1% in adulterated dairy products. When combined with a portable LFS reader, it also enabled precise quantitative analysis of milk adulteration.


Subject(s)
Biosensing Techniques , Milk , Animals , Biosensing Techniques/methods , DNA/genetics , DNA/chemistry , Nucleic Acid Amplification Techniques/methods , DNA, Single-Stranded , Genomics
11.
Food Chem ; 445: 138755, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38387318

ABSTRACT

Monitoring and evaluating food quality, especially meat quality, has received a growing interest to ensure human health and decrease waste of raw materials. Standard analytical approaches used for meat spoilage assessment suffer from time consumption, being labor-intensive, operation complexity, and destructiveness. To overcome shortfalls of these traditional methods and monitor spoilage microorganisms or related metabolites of meat products across the supply chain, emerging analysis devices/systems with higher sensitivity, better portability, on-line/in-line, non-destructive and cost-effective property are urgently needed. Herein, we first overview the basic concepts, causes, and critical monitoring indicators associated with meat spoilage. Then, the conventional detection methods for meat spoilage are outlined objectively in their strengths and weaknesses. In addition, we place the focus on the recent research advances of emerging non-destructive devices and systems for assessing meat spoilage. These novel strategies demonstrate their powerful potential in the real-time evaluation of meat spoilage.


Subject(s)
Food Quality , Meat , Humans , Meat/analysis
12.
Sci Total Environ ; 917: 170319, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38278241

ABSTRACT

Regional transport of air pollutants is a crucial factor influencing atmospheric environment, and aerosol radiative forcing (ARF) feedback to atmospheric boundary layer (ABL) structure and ambient air pollution is yet to be comprehensively understood over the receptor region of regional transport. By simulating meteorology and air pollutants during a heavy PM2.5 pollution event with WRF-Chem model, we quantitatively investigated the ARF and ABL interaction for PM2.5 pollution over the Twain-Hu Basin (THB), a key receptor region of regional transport over central China. Driven by northerly winds, PM2.5 was transported from upstream north China to downstream THB accompanied by high PM2.5 levels in the free troposphere. The ARF exacerbated local PM2.5 accumulation by up to 20 µg m-3 and inhibited the impact of regional transport on PM2.5 levels in the ABL with reducing near-surface PM2.5 concentrations of 5 µg m-3 over the THB. The ARF-intensified air temperature inversion at the top of ABL was unfavorable for the transported air pollutants crossing the ABL top to the near-surface layer, thus weakening the impact of regional PM2.5 transport on air quality in the receptor region. Meanwhile, the ARF of transported PM2.5 induced updrafts in the free troposphere, promoting vertical mixing of air pollutants with positive feedback on increasing secondary PM2.5 concentrations in the free troposphere. The ARF induced more and less secondary PM2.5 formations respectively in the free troposphere and the near-surface layer during the regional transport period of air pollution. These results enhance our comprehension of aerosol-meteorology feedback in regional changes of atmospheric environment with inverse effects of ARF on PM2.5 pollution of local accumulation and regional transport.

13.
Nano Lett ; 23(24): 11540-11547, 2023 Dec 27.
Article in English | MEDLINE | ID: mdl-38085915

ABSTRACT

Sophisticated dynamic molecular systems with diverse functions have been fabricated by using the fundamental tool of toehold-mediated strand displacement (TMSD) in the field of dynamic DNA nanotechnology. However, simple approaches to reset these TMSD-based dynamic systems are lacking due to the difficulty in creating kinetically favored pathways to implement the backward resetting reactions. Here, we develop a facile proton-driven strategy to achieve complete resetting of a modular DNA circuit by integrating a pH-responsive intermolecular CG-C+ triplex DNA and an i-motif DNA into the conventional DNA substrate. The pH-programmed strategy allows modular DNA components to specifically associate/dissociate to promote the forward/backward TMSD reactions, thereby enabling the modular DNA circuit to be repeatedly operated at a constant temperature without generating any DNA waste products. Leveraging this tractable approach, we further constructed two resettable DNA logic gates used for logical computation and two resettable catalytic DNA systems with good performance in signal transduction and amplification.


Subject(s)
DNA, Catalytic , DNA , DNA/chemistry , Nanotechnology , Hydrogen-Ion Concentration
14.
World J Clin Cases ; 11(28): 6908-6919, 2023 Oct 06.
Article in English | MEDLINE | ID: mdl-37901004

ABSTRACT

BACKGROUND: Accumulating evidence demonstrates that autoimmune hematopoietic failure and myeloid neoplasms have an intrinsic relationship with regard to clonal hematopoiesis and disease evolution. In approximately 10%-15% of patients with severe aplastic anemia (SAA), the disease phenotype is transformed into myeloid neoplasms following antithymocyte globulin plus cyclosporine-based immunosuppressive therapy. In some of these patients, myeloid neoplasms appear during or shortly after immunosuppressive therapy. Leukemic transformation in SAA patients during anti-tuberculosis treatment has not been reported. CASE SUMMARY: A middle-aged Chinese female had a 6-year history of non-SAA and a 2-year history of paroxysmal nocturnal hemoglobinuria (PNH). With aggravation of systemic inflammatory symptoms, severe pancytopenia developed, and her hemoglobinuria disappeared. Laboratory findings in cytological, immunological and cytogenetic analyses of bone marrow samples met the diagnostic criteria for "SAA." Definitive diagnosis of disseminated tuberculosis was made in the search for infectious niches. Remarkable improvement in hematological parameters was achieved within 1 mo of anti-tuberculosis treatment, and complete hematological remission was achieved within 4 mo of treatment. Frustratingly, the hematological response lasted for only 3 mo, and pancytopenia reemerged. At this time, cytological findings (increased bone marrow cellularity and an increased percentage of myeloblasts that accounted for 16.0% of all nucleated hematopoietic cells), immunological findings (increased percentage of cluster of differentiation 34+ cells that accounted for 12.28% of all nucleated hematopoietic cells) and molecular biological findings (identification of somatic mutations in nucleophosmin-1 and casitas B-lineage lymphoma genes) revealed that "SAA" had transformed into acute myeloid leukemia with mutated nucleophosmin-1. The transformation process suggested that the leukemic clones were preexistent but were suppressed in the PNH and SAA stages, as development of symptomatic myeloid neoplasm through acquisition and accumulation of novel oncogenic mutations is unlikely in an interval of only 7 mo. Aggravation of inflammatory stressors due to disseminated tuberculosis likely contributed to the repression of normal and leukemic hematopoiesis, and the relief of inflammatory stressors due to anti-tuberculosis treatment contributed to penetration of neoplastic hematopoiesis. The concealed leukemic clones in the SAA and PNH stages raise the possibility of an inflammatory stress-fueled antileukemic mechanism. CONCLUSION: Aggravated inflammatory stressors can repress normal and leukemic hematopoiesis, and relieved inflammatory stressors can facilitate penetration of neoplastic hematopoiesis.

15.
World J Clin Cases ; 11(19): 4713-4722, 2023 Jul 06.
Article in English | MEDLINE | ID: mdl-37469724

ABSTRACT

BACKGROUND: Myelodysplastic syndrome (MDS) is caused by malignant proliferation and ineffective hematopoiesis. Oncogenic somatic mutations and increased apoptosis, necroptosis and pyroptosis lead to the accumulation of earlier hematopoietic progenitors and impaired productivity of mature blood cells. An increased percentage of myeloblasts and the presence of unfavorable somatic mutations are signs of leukemic hematopoiesis and indicators of entrance into an advanced stage. Bone marrow cellularity and myeloblasts usually increase with disease progression. However, aplastic crisis occasionally occurs in advanced MDS. CASE SUMMARY: A 72-year-old male patient was definitively diagnosed with MDS with excess blasts-1 (MDS-EB-1) based on an increase in the percentages of myeloblasts and cluster of differentiation (CD)34+ hematopoietic progenitors and the identification of myeloid neoplasm-associated somatic mutations in bone marrow samples. The patient was treated with hypomethylation therapy and was able to maintain a steady disease state for 2 years. In the treatment process, the advanced MDS patient experienced an episode of progressive pancytopenia and bone marrow aplasia. During the aplastic crisis, the bone marrow was infiltrated with sparsely distributed atypical lymphocytes. Surprisingly, the leukemic cells disappeared. Immunological analysis revealed that the atypical lymphocytes expressed a high frequency of CD3, CD5, CD8, CD16, CD56 and CD57, suggesting the activation of autoimmune cytotoxic T-lymphocytes and natural killer (NK)/NKT cells that suppressed both normal and leukemic hematopoiesis. Elevated serum levels of inflammatory cytokines, including interleukin (IL)-6, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), confirmed the deranged type I immune responses. This morphological and immunological signature led to the diagnosis of severe aplastic anemia secondary to large granule lymphocyte leukemia. Disseminated tuberculosis was suspected upon radiological examinations in the search for an inflammatory niche. Antituberculosis treatment led to reversion of the aplastic crisis, disappearance of the atypical lymphocytes, increased marrow cellularity and 2 mo of hematological remission, providing strong evidence that disseminated tuberculosis was responsible for the development of the aplastic crisis, the regression of leukemic cells and the activation of CD56+ atypical lymphocytes. Reinstitution of hypomethylation therapy in the following 19 mo allowed the patient to maintain a steady disease state. However, the patient transformed the disease phenotype into acute myeloid leukemia and eventually died of disease progression and an overwhelming infectious episode. CONCLUSION: Disseminated tuberculosis can induce CD56+ lymphocyte infiltration in the bone marrow and in turn suppress both normal and leukemic hematopoiesis, resulting in the development of aplastic crisis and leukemic cell regression.

16.
Cell Rep ; 42(8): 112867, 2023 08 29.
Article in English | MEDLINE | ID: mdl-37494184

ABSTRACT

The POGZ gene has been found frequently mutated in neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and intellectual disability (ID). We have recently shown that POGZ maintains mouse embryonic stem cells (ESCs). However, the exact mechanisms remain unclear. Here, we show that POGZ plays an important role in the maintenance of ESCs by silencing Dux and endogenous retroviruses (ERVs). POGZ maintains a silent chromatin state at Dux and ERVs by associating with and recruiting TRIM28 and SETDB1, and its loss leads to decreased levels of H3K9me3/H4K20me3, resulting in up-regulation of 2C transcripts and ESC transition to a 2C-like state. POGZ suppresses different classes of ERVs through direct (IAPEy, the intracisternal A-type particle elements) and indirect regulation (MERVL). Activation of POGZ-bound ERVs is associated with up-regulation of nearby neural disease genes such as Serpina3m. Our findings provide important insights into understanding the disease mechanism caused by POGZ dysfunction.


Subject(s)
Autism Spectrum Disorder , Endogenous Retroviruses , Animals , Mice , Autism Spectrum Disorder/genetics , Chromatin , Embryonic Stem Cells , Endogenous Retroviruses/genetics , Genes, cdc , Mouse Embryonic Stem Cells
17.
World J Clin Cases ; 11(17): 4105-4116, 2023 Jun 16.
Article in English | MEDLINE | ID: mdl-37388797

ABSTRACT

BACKGROUND: Myelodysplastic syndrome (MDS) is a hematological neoplasm, and an increase in myeloblasts is representative of leukemic hematopoiesis in advanced MDS. Low-risk MDS usually exhibits deranged autoimmunity resembling that of aplastic anemia (AA), whereas advanced MDS is characterized by a phenotype of immune exhaustion. MDS can be normo/hyperplastic or hypoplastic. Generally, bone marrow cellularity and myeloblasts increase with disease progression. Transformation from advanced MDS to AA-like syndrome with leukemic cell regression has not previously been reported. CASE SUMMARY: A middle-aged Chinese woman had a 4-year history of leukocytopenia. Six months prior to admission, the patient developed gradually worsening fatigue and performance status. The leukocytopenia further progressed. She was diagnosed with MDS with excess blasts-2 based on increased bone marrow cellularity and an increased percentage of myeloblasts on marrow and blood smears, an increased percentage of cluster of differentiation (CD)34+CD33+ progenitors in immunotyping analysis, a normal karyotype in cytogenetic analysis, and the identification of somatic mutations in CBL, KMT2D and NF1 in molecular analysis. Initially, neutropenia was the predominant hematological abnormality, with mild anemia and thrombocytosis, and the degree of fatigue was far more severe than the degree of anemia. In the following months, the patient experienced several febrile episodes. Intravenous antibiotic treatments were able to control the febrile episodes, but the elevated inflammatory indices persisted. The hematological parameters dramatically fluctuated with the waxing and waning of the inflammatory episodes. With recurrent flares of the inflammatory condition, agranulocytosis and severe anemia developed, with mild thrombocytopenia. During the patient's hospitalization, computed tomography (CT) scans revealed the presence of extensive inflammatory lesions involving the lungs, mediastinum, pleura, gastrointestinal tract, peritoneum and urinary tract, with imaging features suggestive of the reactivation of disseminated tuberculosis. Reevaluation of the bone marrow smears revealed that the cellularity became hypoplastic, and the leukemic cells regressed, suggesting that both normal and leukemic hematopoiesis had been heavily suppressed. Immunological analysis of the bone marrow samples revealed a decreased percentage of CD34+ cells and an immunological signature resembling that of severe AA (SAA), confirming the regression of the leukemic cells by autoimmune-mediated attacks. The patient demonstrated resistance to multiple drugs, including antituberculotics, recombinant human granulocyte colony-stimulating factor, broad-spectrum antibiotics, voriconazole, ganciclovir, immune suppressants, eltrombopag and intravenous immunoglobulin, which further worsened the hematological injury and patient's performance status. The patient eventually died of overwhelming infection and multidrug resistance. CONCLUSION: Advanced MDS can transform to aplastic cytopenia with leukemic cell regression and an immunological signature of SAA during inflammatory flare-ups.

18.
Int J Biol Macromol ; 244: 125399, 2023 Jul 31.
Article in English | MEDLINE | ID: mdl-37331535

ABSTRACT

Lipophilic adsorbents for oil-water separation are usually synthesized using the template method, in which hydrophobic materials are coated on a ready-made sponge. Herein, a novel solvent-template technique is used to directly synthesize a hydrophobic sponge, by crosslinking polydimethylsiloxane (PDMS) with ethyl cellulose (EC) which plays a vital role in the formation of 3D porous structure. The as-prepared sponge has advantages of strong hydrophobility, high elasticity, as well as excellent adsorption performance. In addition, the sponge can be readily decorated by nano-coatings. After the sponge was simply dipped in nanosilica, the water contact angle increases from 139.2° to 144.5°, and the maximum adsorption capacity for chiroform rises from 25.6 g/g to 35.4 g/g. The adsorption equilibrium can be reached within 3 min, and, the sponge can be regenerated by squeezing, without any change in hydrophobility or evident decline in capacity. The simulation tests of emulsion separation and oil-spill cleanup demonstrate that the sponge has great potential in oil-water separation.


Subject(s)
Dimethylpolysiloxanes , Water , Solvents , Adsorption
19.
Nanotechnology ; 34(37)2023 Jun 28.
Article in English | MEDLINE | ID: mdl-37257445

ABSTRACT

High orientation consistency and adjustable convex width of the low-spatial-frequency laser-induced periodic surface structures (LSFLs), crucial to the functional surface characteristics, have remained elusive. This paper proposes a new method to fabricate LSFLs with high orientation consistency on the rough surface of titanium by combining laser polishing and laser induction with LSFLs with a tunable convex width via laser melting as the post-treatment. Picosecond pulses trained with a 50-ns interval are applied to regulate the thermal incubation effect and achieve laser polishing and laser nanoscale melting. The melting time of titanium for laser polishing and laser nanoscale melting is determined to be on a microsecond time scale and around 100 ns, respectively. Experimental studies show that the surface texture of titanium lowers the orientation consistency of LSFLs and that its divergence angle is 30°. Picosecond pulses with a sub-pulse number of three are applied to achieve surface polishing and the formation of the rudiment of the LSFLs, followed by the picosecond laser induction. As a result, the divergence angle of LSFLs decreases from 30° to 12°. On this basis, aiming at the problem of the narrow adjustability of the convexity ratio of LSFLs, a nanoscale melting processing method based on picosecond pulse trains with a sub-pulse number of four is proposed, and LSFLs with the tunable convexity ratios from 0.3 to 0.87 are obtained.

20.
Aging Dis ; 14(3): 892-903, 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-37191419

ABSTRACT

We previously demonstrated that inhibition of miR-200c was protective against stroke in young adult male mice by augmenting sirtuin-1 (Sirt1). In the present study we assessed the role of miR-200c on injury, Sirt1, and bioenergetic and neuroinflammatory markers in aged male and female mice after experimental stroke. Mice were subjected to 1hr of transient middle cerebral artery occlusion (MCAO) and assessed for post-injury expression of miR-200c, Sirt1 protein and mRNA, N6-methyladenosine (m6A) methylated Sirt1 mRNA, ATP, cytochrome C oxidase activity, tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), infarct volume and motor function. MCAO induced a decrease in Sirt1 expression at 1d post-injury only in males. No differences in SIRT1 mRNA were observed between the sexes. Females had greater baseline miR-200c expression and a greater increase in miR-200c in response to stroke, while pre-MCAO levels of m6A SIRT1 was greater in females. Males had lower post-MCAO ATP levels and cytochrome C oxidase activity, and higher TNFα and IL-6. Post-injury intravenous treatment with anti-miR-200c reduced miR-200c expression in both sexes. In males, anti-miR-200c increased Sirt1 protein expression, reduced infarct volume, and improved neurological score. Conversely in females anti-miR-200c had no effect on Sirt1 levels and provided no protection against injury from MCAO. These results provide the first evidence of sexual dimorphism in the role of a microRNA in aged mice after experimental stroke and suggest sex-differences in epigenetic modulation of the transcriptome and downstream effects on miR biological activity may play a role in sexually dimorphic outcomes after stroke in aged brains.

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