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1.
Breast Cancer (Auckl) ; 18: 11782234241255856, 2024.
Article in English | MEDLINE | ID: mdl-38826850

ABSTRACT

Background: The application of sentinel lymph node biopsy (SLNB) has expanded from early breast cancer to locally advanced breast cancer with neoadjuvant chemotherapy (NAC). For patients with negative axillary lymph nodes, performing SLNB before or after NAC remains controversial. Objectives: To evaluate the diagnostic feasibility and reliability of SLNB after NAC in breast cancer patients with negative axillary nodes at initial diagnosis. Design: To calculate pooled identification rate (IR) and false negative rate (FNR) of SLNB after NAC on breast cancer patients with initially negative axillary nodes by enrolling relevant studies and perform subgroup analysis by the type of tracer and the number of biopsied sentinel lymph nodes in average. Data sources and methods: The PubMed, Embase, Cochrane, Web of Science, and Scopus databases from January 1, 2002, to March 1, 2022, were searched for studies. The QUADAS-2 tool and MINORS item were employed to evaluate the quality of the included studies. I2 and Q tests were used to evaluate the heterogeneity among the studies. Random-effects model and fixed-effects model were employed to calculate the pooled IR, FNR, and 95% confidence interval (CI). Publication bias was evaluated, and sensitivity analysis was performed. Subgroup analysis was performed according to the type of tracer (single/double) and the number of biopsied sentinel lymph nodes in average (⩽2/>2). Results: A total of 21 studies covering 1716 patients were enrolled in this study (IR = 93%, 95% CI = 90-96; FNR = 8%, 95% CI = 6-11). Conclusion: The SLNB after NAC can serve as a feasible and reliable approach in breast cancer patients with negative axillary lymph node. In our study, no significant impact of tracer was found on the IR and FNR of SLNB, and the number of biopsy nodes >2 leads to the decreased FNR of SLNB.

2.
ArXiv ; 2024 May 25.
Article in English | MEDLINE | ID: mdl-38903746

ABSTRACT

Gene set knowledge discovery is essential for advancing human functional genomics. Recent studies have shown promising performance by harnessing the power of Large Language Models (LLMs) on this task. Nonetheless, their results are subject to several limitations common in LLMs such as hallucinations. In response, we present GeneAgent, a first-of-its-kind language agent featuring self-verification capability. It autonomously interacts with various biological databases and leverages relevant domain knowledge to improve accuracy and reduce hallucination occurrences. Benchmarking on 1,106 gene sets from different sources, GeneAgent consistently outperforms standard GPT-4 by a significant margin. Moreover, a detailed manual review confirms the effectiveness of the self-verification module in minimizing hallucinations and generating more reliable analytical narratives. To demonstrate its practical utility, we apply GeneAgent to seven novel gene sets derived from mouse B2905 melanoma cell lines, with expert evaluations showing that GeneAgent offers novel insights into gene functions and subsequently expedites knowledge discovery.

3.
BMC Geriatr ; 24(1): 525, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886659

ABSTRACT

BACKGROUND: Healthy eating is one of the most important nonpharmacologic treatments for patients with atherosclerosis(AS). However, it is unclear how elderly AS patients in western China perceive their dietary status and which type of nutritional assistance they would be willing to receive. Therefore, the primary purpose of this study was to understand the level of knowledge about current dietary habits and healthy eating habits among elderly AS patients in western China, and the secondary purpose was to identify acceptable nutritional assistance measures or pathways for those patients to help them manage disease progression. METHODS: An implementation study approach was used to recruit elderly patients with AS-related diseases in western China for semistructured interviews. RESULTS: 14 participants were included in the study, and the following three themes were identified from the interviews:(1) the diet with regional characteristics; (2) low nutrition-related health literacy; (3) complex attitudes towards nutritional assistance. Most participants had misconceptions about healthy eating, and the sources of their knowledge might not be trustworthy. Participants expressed a preference for personalized nutritional assistance, especially that provided by medical-nursing combined institutions. CONCLUSION: Patients in western China need nutritional assistance for their regional dietary habits; therefore, healthy dietary patterns consistent with the regional culture are proposed to improve the prevailing lack of knowledge about healthy diets, improve the dietary structure of patients, and control the development of the disease.


Subject(s)
Atherosclerosis , Qualitative Research , Humans , Male , Female , Aged , China/epidemiology , Atherosclerosis/psychology , Atherosclerosis/therapy , Atherosclerosis/epidemiology , Aged, 80 and over , Middle Aged , Diet/methods , Feeding Behavior/psychology , Feeding Behavior/physiology , Cognition/physiology , Diet, Healthy/methods , Diet, Healthy/psychology , Coronary Artery Disease/psychology , Coronary Artery Disease/epidemiology , Health Knowledge, Attitudes, Practice
4.
Int J Cardiol ; 411: 132268, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38880418

ABSTRACT

BACKGROUND: Acute myocardial infarction (AMI) is a serious condition with high mortality rates. Early risk stratification is of significant importance to assess the prognosis. Insulin-like growth factor-binding protein 5 (IGFBP5) levels in AMI patients and its potential as a prognosis biomarker were unclear. OBJECTIVE: To investigate serum IGFBP5 levels in AMI and its prognostic value for short-term major adverse cardiovascular events (MACE). METHODS: We collected serum IGFBP5 levels from 200 patients with new-onset AMI and 71 coronary heart disease (CAD) patients without AMI. Linear regression was used to analyze the relationship between IGFBP5 and baseline variables. AMI patients were followed up, and the risk of major adverse cardiovascular events (MACE) was assessed using Kaplan-Meier curve, multivariate Cox models and restricted cubic spline (RCS) analysis. RESULTS: During a median follow-up of 217 days, 40 patients developed MACE. Serum IGFBP5 was associated with serum cardiac troponin T (cTnT) and C-reactive protein (CRP) (P = 0.013 and P = 0.013). In multivariable survival analyses, higher IGFBP5 was associated with an increased risk of MACE [HR = 1.183, 95%CI (1.104, 1.268), P < 0.001)]. There was a positive and linear association between IGFBP5 levels and the occurrence of MACE (P for nonlinearity = 0.283). The positive association between IGFBP5 and MACE risk consist across subgroups characterized by demographics and comorbidities. CONCLUSION: Serum IGFBP5 was highly expressed in patients with AMI and positively associated with the short-term risk of MACE. Circulating IGFBP5 may be a diagnostic and prognostic indicator for AMI, and further studies with larger sample and longer follow-up are warranted.

5.
Inorg Chem ; 63(25): 11745-11756, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38865684

ABSTRACT

Piezo-photocatalytic efficiency is severely constrained by the wide band gap and bad piezoelectric properties. Herein, La(Mn0.5Ni0.5)O3 was successfully introduced into NaNbO3 lattices (referred to as 0LMN, 0.05LMN, 0.10LMN, and 0.15LMN) through a water-based sol-gel method. The piezo-photocatalytic degradation ratio for Rhodamine B (RhB) is enhanced from 59.7% (0LMN) to 89.7% (0.10LMN) within 100 min, and the kinetic rate constant (k) is increased from 0.009 to 0.022 min-1. The enhanced performance is attributed to (i) the narrowed band gap (from 3.40 to 2.84 eV), which is conducive to the generation of photogenerated electrons and holes, and (ii) the enhanced piezoelectric properties, which can strengthen the piezoelectric polarization, thereby accelerating the separation of the photogenerated electrons and holes. And we also found that the synergetic effect of photocatalysis and piezocatalysis was superior to that of photocatalysis and piezocatalysis alone. This study could provide new perspectives for the reasonable construction of an efficient catalyst in the piezo-photocatalytic field.

6.
Cell Death Dis ; 15(6): 437, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902257

ABSTRACT

TNF receptor superfamily member 11a (TNFRSF11a, RANK) and its ligand TNF superfamily member 11 (TNFRSF11, RANKL) are overexpressed in many malignancies. However, the clinical importance of RANKL/RANK in colorectal cancer (CRC) is mainly unknown. We examined CRC samples and found that RANKL/RANK was elevated in CRC tissues compared with nearby normal tissues. A higher RANKL/RANK expression was associated with a worse survival rate. Furthermore, RANKL was mostly produced by regulatory T cells (Tregs), which were able to promote CRC advancement. Overexpression of RANK or addition of RANKL significantly increased the stemness and migration of CRC cells. Furthermore, RANKL/RANK signaling stimulated C-C motif chemokine ligand 20 (CCL20) production by CRC cells, leading to Treg recruitment and boosting tumor stemness and malignant progression. This recruitment process was accomplished by CCL20-CCR6 interaction, demonstrating a connection between CRC cells and immune cells. These findings suggest an important role of RANKL/RANK in CRC progression, offering a potential target for CRC prevention and therapy.


Subject(s)
Chemokine CCL20 , Colorectal Neoplasms , Neoplastic Stem Cells , RANK Ligand , Receptor Activator of Nuclear Factor-kappa B , Receptors, CCR6 , Signal Transduction , T-Lymphocytes, Regulatory , Humans , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/genetics , Chemokine CCL20/metabolism , Chemokine CCL20/genetics , RANK Ligand/metabolism , Receptors, CCR6/metabolism , Receptors, CCR6/genetics , Receptor Activator of Nuclear Factor-kappa B/metabolism , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Animals , Male , Mice , Female , Neoplasm Metastasis , Cell Line, Tumor , Middle Aged , Mice, Nude , Cell Movement
7.
ArXiv ; 2024 Feb 17.
Article in English | MEDLINE | ID: mdl-38903745

ABSTRACT

In radiology, Artificial Intelligence (AI) has significantly advanced report generation, but automatic evaluation of these AI-produced reports remains challenging. Current metrics, such as Conventional Natural Language Generation (NLG) and Clinical Efficacy (CE), often fall short in capturing the semantic intricacies of clinical contexts or overemphasize clinical details, undermining report clarity. To overcome these issues, our proposed method synergizes the expertise of professional radiologists with Large Language Models (LLMs), like GPT-3.5 and GPT-4. Utilizing In-Context Instruction Learning (ICIL) and Chain of Thought (CoT) reasoning, our approach aligns LLM evaluations with radiologist standards, enabling detailed comparisons between human and AI-generated reports. This is further enhanced by a Regression model that aggregates sentence evaluation scores. Experimental results show that our "Detailed GPT-4 (5-shot)" model achieves a 0.48 score, outperforming the METEOR metric by 0.19, while our "Regressed GPT-4" model shows even greater alignment with expert evaluations, exceeding the best existing metric by a 0.35 margin. Moreover, the robustness of our explanations has been validated through a thorough iterative strategy. We plan to publicly release annotations from radiology experts, setting a new standard for accuracy in future assessments. This underscores the potential of our approach in enhancing the quality assessment of AI-driven medical reports.

8.
Adv Sci (Weinh) ; : e2309642, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816950

ABSTRACT

Cholesterol 25-hydroxylase (CH25H), an enzyme involved in cholesterol metabolism, regulates inflammatory responses and lipid metabolism. However, its role in kidney disease is not known.  The author found that CH25H transcript is expressed mostly in glomerular and peritubular endothelial cells and that its expression increased in human and mouse diabetic kidneys.  Global deletion of Ch25h in Leprdb/db mice aggravated diabetic kidney disease (DKD), which is associated with increased endothelial cell apoptosis. Treatment of 25-hydroxycholesterol (25-HC), the product of CH25H, alleviated kidney injury in Leprdb/db mice. Mechanistically, 25-HC binds to GTP-binding protein ADP-ribosylation factor 4 (ARF4), an essential protein required for maintaining protein transport in the Golgi apparatus. Interestingly, ARF4's GTPase-activating protein ASAP1 is also predominantly expressed in endothelial cells and its expression increased in DKD. Suppression of ARF4 activity by deleting ARF4 or overexpressing ASAP1 results in endothelial cell death. These results indicate that 25-HC binds ARF4 to inhibit its interaction with ASAP1, and thereby resulting in enhanced ARF4 activity to confer renoprotection. Therefore, treatment of 25-HC improves kidney injury in DKD in part by restoring ARF4 activity to maintain endothelial cell survival. This study provides a novel mechanism and a potential new therapy for DKD.

9.
Environ Res ; 252(Pt 4): 119077, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38714222

ABSTRACT

Household products, in response to regulations, increasingly incorporate phthalate (PAE) alternatives instead of traditional PAEs. However, limited information exists regarding the fate and exposure risk of these PAE alternatives and their monoesters in indoor environments. The contamination levels of PAE alternatives and their monoesters in indoor dust might vary across regions due to climate, population density, industrial activities, and interior decoration practices. By analyzing indoor dust samples from six geographical regions across China, this study aims to shed light on concentrations, profiles, and human exposure to 12 PAE alternatives and 9 their monoesters. Bis(2-ethylhexyl) benzene-1,4-dicarboxylate (DEHTP), tributyl 2-acetyloxypropane-1,2,3-tricarboxylate (ATBC), and tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate (TOTM) were the main PAE alternatives in dust across all regions. The total concentrations of 12 PAE alternatives ranged from 0.125 to 4160 µg/g in indoor dust. High molecular weight PAE alternatives had significantly correlated concentrations (p < 0.05) based on Spearman analysis, suggesting their co-use in heat-resistant plastic products. A collective of nine monoesters were identified in most samples, with total concentrations ranging from 0.048 to 29.6 µg/g. The median concentrations of PAE alternatives were highest in North China (66.8 µg/g), while those of monoesters were highest in Southwest China (6.93 µg/g). A significant correlation (p < 0.05) between the concentrations of DEHTP and its monoester suggested that degradation could be a potential source of monoesters. Although hazard quotients (HQs) have been calculated to suggest that the current exposure is unlikely to pose a significant health risk, the lack of toxicity threshold data and the existence of additional exposure pathways necessitate a further confirmation.


Subject(s)
Air Pollution, Indoor , Dust , Phthalic Acids , Dust/analysis , China , Phthalic Acids/analysis , Humans , Air Pollution, Indoor/analysis , Environmental Exposure/analysis , Air Pollutants/analysis , Esters/analysis , Environmental Monitoring
10.
Environ Sci Technol ; 58(19): 8117-8134, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38701366

ABSTRACT

Due to its widespread applications in various fields, antibiotics are continuously released into the environment and ultimately enter the human body through diverse routes. Meanwhile, the unreasonable use of antibiotics can also lead to a series of adverse outcomes. Pregnant women and developing fetuses are more susceptible to the influence of external chemicals than adults. The evaluation of antibiotic exposure levels through questionnaire surveys or prescriptions in medical records and biomonitoring-based data shows that antibiotics are frequently prescribed and used by pregnant women around the world. Antibiotics may be transmitted from mothers to their offspring through different pathways, which then adversely affect the health of offspring. However, there has been no comprehensive review on antibiotic exposure and mother-to-child transmission in pregnant women so far. Herein, we summarized the exposure levels of antibiotics in pregnant women and fetuses, the exposure routes of antibiotics to pregnant women, and related influencing factors. In addition, we scrutinized the potential mechanisms and factors influencing the transfer of antibiotics from mother to fetus through placental transmission, and explored the adverse effects of maternal antibiotic exposure on fetal growth and development, neonatal gut microbiota, and subsequent childhood health. Given the widespread use of antibiotics and the health threats posed by their exposure, it is necessary to comprehensively track antibiotics in pregnant women and fetuses in the future, and more in-depth biological studies are needed to reveal and verify the mechanisms of mother-to-child transmission, which is crucial for accurately quantifying and evaluating fetal health status.


Subject(s)
Anti-Bacterial Agents , Maternal Exposure , Humans , Female , Pregnancy , Maternal-Fetal Exchange , Fetus/drug effects
11.
J Hazard Mater ; 470: 134187, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38574659

ABSTRACT

The increasing use of phthalate acid esters (PAEs) in various applications has inevitably led to their widespread presence in the aquatic environment. This presents a considerable threat to plants. However, the interactions between PAEs and plants in the aquatic environment have not yet been comprehensively reviewed. In this review, the properties, occurrence, uptake, transformation, and toxic effects of PAEs on plants in the aquatic environment are summarized. PAEs have been prevalently detected in the aquatic environment, including surface water, groundwater, seawater, and sediment, with concentrations ranging from the ng/L or ng/kg to the mg/L or mg/kg range. PAEs in the aquatic environment can be uptake, translocated, and metabolized by plants. Exposure to PAEs induces multiple adverse effects in aquatic plants, including growth perturbation, structural damage, disruption of photosynthesis, oxidative damage, and potential genotoxicity. High-throughput omics techniques further reveal the underlying toxicity molecular mechanisms of how PAEs disrupt plants on the transcription, protein, and metabolism levels. Finally, this review proposes that future studies should evaluate the interactions between plants and PAEs with a focus on long-term exposure to environmental PAE concentrations, the effects of PAE alternatives, and human health risks via the intake of plant-based foods.


Subject(s)
Esters , Phthalic Acids , Plants , Water Pollutants, Chemical , Phthalic Acids/toxicity , Phthalic Acids/metabolism , Esters/toxicity , Plants/drug effects , Plants/metabolism , Water Pollutants, Chemical/toxicity
12.
Nat Aging ; 4(4): 527-545, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38594460

ABSTRACT

Limited understanding exists regarding how aging impacts the cellular and molecular aspects of the human ovary. This study combines single-cell RNA sequencing and spatial transcriptomics to systematically characterize human ovarian aging. Spatiotemporal molecular signatures of the eight types of ovarian cells during aging are observed. An analysis of age-associated changes in gene expression reveals that DNA damage response may be a key biological pathway in oocyte aging. Three granulosa cells subtypes and five theca and stromal cells subtypes, as well as their spatiotemporal transcriptomics changes during aging, are identified. FOXP1 emerges as a regulator of ovarian aging, declining with age and inhibiting CDKN1A transcription. Silencing FOXP1 results in premature ovarian insufficiency in mice. These findings offer a comprehensive understanding of spatiotemporal variability in human ovarian aging, aiding the prioritization of potential diagnostic biomarkers and therapeutic strategies.


Subject(s)
Forkhead Transcription Factors , Ovary , Animals , Female , Humans , Mice , Forkhead Transcription Factors/genetics , Gene Expression Profiling , Granulosa Cells/metabolism , Oocytes/metabolism , Ovary/metabolism , Repressor Proteins/metabolism , Transcription Factors/metabolism , Primary Ovarian Insufficiency/genetics , Primary Ovarian Insufficiency/metabolism , Cyclin-Dependent Kinase Inhibitor p21/genetics , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Aging/genetics
13.
Heliyon ; 10(5): e26731, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38486772

ABSTRACT

Deficiency in regulatory T cells (Tregs) is an important mechanism underlying the pathogenesis of pediatric aplastic anemia, but its specific mechanism is unclear. In our study, we aimed to investigate whether IL-2/STAT5 can regulate the proliferation of Tregs in aplastic anemia (AA) by regulating their expression of B lymphocyte-induced mature protein-1 (BLIMP-1) or interferon regulatory factor 4 (IRF4). Through clinical research and animal experiments, we found that poor activation of the IL-2/STAT5 signaling pathway may leads to low expression of BLIMP-1 in Tregs of children with AA, which leads to defects in the differentiation and proliferation of Tregs in AA. In AA model mice, treatment with IL-2c reversed the decrease in Treg proportions and reduction in Blimp-1 expression in Tregs by increasing the phosphorylation of Stat5 in Tregs. In AA, deficiency of IRF4 expression in Tregs is closely related to the deficiency of Tregs, but is not regulated by the IL-2/STAT5 pathway.

14.
J Hazard Mater ; 469: 134054, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38503214

ABSTRACT

Pollution of micro/nano-plastics (MPs/NPs) is ubiquitously prevalent in the environment, leading to an unavoidable exposure of the human body. Despite the protection of the blood-brain barrier, MPs/NPs can be transferred and accumulated in the brain, which subsequently exert negative effects on the brain. Nevertheless, the potential neurodevelopmental and/or neurodegenerative risks of MPs/NPs remain largely unexplored. In this review, we provide a systematic overview of recent studies related to the neurotoxicity of MPs/NPs. It covers the environmental hazards and human exposure pathways, translocation and distribution into the brain, the neurotoxic effects, and the possible mechanisms of environmental MPs/NPs. MPs/NPs are widely found in different environment matrices, including air, water, soil, and human food. Ambient MPs/NPs can enter the human body by ingestion, inhalation and dermal contact, then be transferred into the brain via the blood circulation and nerve pathways. When MPs/NPs are present in the brain, they can initiate a series of molecular or cellular reactions that may harm the blood-brain barrier, cause oxidative stress, trigger inflammatory responses, affect acetylcholinesterase activity, lead to mitochondrial dysfunction, and impair autophagy. This can result in abnormal protein folding, loss of neurons, disruptions in neurotransmitters, and unusual behaviours, ultimately contributing to the initiation and progression of neurodegenerative changes and neurodevelopmental abnormalities. Key challenges and further research directions are also proposed in this review as more studies are needed to focus on the potential neurotoxicity of MPs/NPs under realistic conditions.


Subject(s)
Neurotoxicity Syndromes , Water Pollutants, Chemical , Humans , Microplastics , Acetylcholinesterase , Neurotoxicity Syndromes/etiology , Brain , Blood-Brain Barrier , Plastics
15.
ACS Appl Mater Interfaces ; 16(9): 11849-11859, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38411114

ABSTRACT

To prepare anion exchange membranes with high water electrolysis and single fuel cell performance, an inorganic-organic composite (IOC) strategy with click cross-linked membranes coated with different contents of hydrophilic polar nanozirconia is proposed to fabricate composite membranes (CM) PBP-SH-Zrx. The performance test results showed that the CM PBP-SH-Zr4 not only has good through-plane ionic conductivity (167.7 mS cm-1, 80 °C), but also exhibits satisfactory dimensional stability (SR 16.5%, WU 206.4%, 80 °C), especially demonstrating excellent alkaline stability with only 16% degradation (2 M NaOH for 2200 h). In water electrolysis, the "microgap" between the membrane and catalyst layer (solid-solid interface) is alleviated, and the membrane electrode assembly (MEA) interfacial compatibility (liquid-solid-solid interface) is enhanced. The CM PBP-SH-Zr4 showed the lowest charge transfer resistance (Rct, 0.037 Ω cm2) and a high current density of 2.5 A cm-2 at 2.2 V, while the voltage drop was 0.361 mV h-1 after 360 h of endurance (six start-stop cycles) at 60 °C and 500 mA cm-2, proving a good water electrolysis durability. Moreover, an acceptable peak power density of 0.464 W cm-2 at 80 °C is achieved in a H2/O2 fuel cell with a PBP-SH-Zr4-AEM. Therefore, the IOC strategy can enhance the membrane's comprehensive performance and interface compatibility of MEA and may promote the development of anion exchange membranes (AEMs) for water electrolysis and fuel cells.

16.
Haematologica ; 2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38385251

ABSTRACT

Mutations in the master hematopoietic transcription factor GATA1 are often associated with functional defects in erythropoiesis and megakaryopoiesis. In this study, we identified a novel GATA1 germline mutation (c.1162delGG, p.Leu387Leufs*62) in a patient with congenital anemia and occasional thrombocytopenia. The C-terminal GATA1, a rarely studied mutational region, undergoes frameshifting translation as a consequence of this double-base deletion mutation. To investigate the specific function and pathogenic mechanism of this mutant, in vitro mutant models of stable re-expression cells were generated. The mutation was subsequently validated to cause diminished transcriptional activity of GATA1 and defective differentiation of erythroid and megakaryocytes. Using proximity labeling and mass spectrometry, we identified selective alterations in the proximal protein networks of the mutant, revealing decreased binding to a set of normal GATA1-interaction proteins, including the essential co-factor FOG1. Notably, our findings further demonstrated enhanced recruitment of the protein arginine methyltransferase PRMT6, which mediates histone modification at H3R2me2a and represses transcription activity. We also found an enhanced binding of this mutant GATA1/PRMT6 complex to the transcriptional regulatory elements of GATA1's target genes. Moreover, treatment of the PRMT6 inhibitor MS023 could partially rescue the inhibited transcriptional and impaired erythroid differentiation caused by the GATA1 mutation. Taken together, our results provide molecular insights into erythropoiesis in which mutation leads to partial loss of GATA1 function and the broader role of PRMT6 and its inhibitor MS023 in congenital anemia, highlighting PRMT6 binding as a negative factor of GATA1 transcriptional activity in aberrant hematopoiesis.

17.
J Colloid Interface Sci ; 663: 345-357, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38412720

ABSTRACT

Hydrodeoxygenation of furfural over non-noble metal catalyst is an effective route to synthesis 2-methylfuran, but the reaction is often hampered by the low activity and selectivity of the catalyst. Herein, a bimetallic catalyst with CuCo alloy encapsulated in a hollow nitrogen-doped carbon cages (CuCo/NC) are fabricated by using ZIF-67 as a sacrificial template, which exhibited superior catalytic performance and a full conversion of furfural with a 95.7 % selectivity towards 2-methylfuran was achieved at an under relatively mild reaction conditions (150 ℃, 1.5 MPa H2 and 4.0 h). The characterizations and density functional theory calculations clearly evidenced that the introduced Cu species acts as a switch to regulate the activity and selectivity of the catalyst via two aspects. On the one hand, the Cu species perturb the Co electronic structure leading to adsorption configuration of furfural change from flat to vertical on the catalyst surface, which successfully hindered the hydrogenation of furan ring, resulting high selectivity towards 2-methylfuran. On the other hand, the formed CuCo (111) sites promotes the dissociation of hydrogen, cleavage of the CO bond and reduces the diffusion barrier of hydrogen so as to advance the formation of 2-methylfuran. This work may provide a feasible strategy for the design of nanoalloy catalyst for the hydrodeoxygenation of biomass platforms to value-added chemicals.

18.
Anal Chim Acta ; 1287: 342049, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38182364

ABSTRACT

BACKGROUND: Typically, in vitro studies on the exposure of complex gaseous substances are performed in multi-well plate experiments by trapping and redissolving them, which could introduce potential bias into the results due to the use of inadequate trapping methods. Therefore, a more effective method is to expose complex gaseous substances in gaseous form online, such as using microfluidic chips in experiments. To address these challenges, we introduce a methodology that integrates a self-designed bionic-lung chip with transcriptome analysis to assess the impact of cigarette smoke (CS) exposure on changes in BEAS-2B cells cultured on-chip. RESULTS: After the microfluidic chip underwent online gas exposure, total RNA was extracted via in situ cell lysis, and RNA-Seq transcriptome analysis was conducted. And the RNA-Seq findings revealed the significant involvement of the MAPK signaling pathway associated with the inflammatory response in the cellular effects induced by CS exposure. Moreover, the validation of inflammatory response-related biomarkers through in situ fluorescence corroborated the outcomes of the transcriptome analysis. Besides, the experiment involving the inhibition of inflammation by DEX on the microfluidic chip provided additional confirmation of the previous experimental findings. SIGNIFICANT: In this study, we present an analytical strategy that combines microfluidic-based CS in situ exposure method with RNA-Seq technology. This strategy offers an experimental scheme for in situ exposure to complex gases, transcriptome analysis, and in situ fluorescence detection. Through the integration of the comprehensiveness of transcriptome analysis with the chip's direct and intuitive in situ fluorescence detection with the stability and reliability of RT-PCR and Western blot experiments, we have successfully addressed the challenges associated with in vitro risk assessment for online exposure to complex gaseous substances.


Subject(s)
Cigarette Smoking , Humans , Microfluidics , Reproducibility of Results , Gene Expression Profiling , Gases , Inflammation
19.
ACS Appl Mater Interfaces ; 16(6): 7660-7669, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38295432

ABSTRACT

In order to improve the mechanical and water electrolysis performance of anion exchange membranes (AEMs), we adjusted the ratio between p-terphenyl and m-terphenyl to balance the backbone conformation, which gives it a better suitability for a better combination with cations. The results showed that poly(m-terphenyl-co-p-terphenyl)-based AEMs have excellent mechanical properties. Among them, the m-p-TP-40-BOP-ASU membrane has the highest tensile strength and elongation at break (75.72 MPa and 16.07%). The ionic conductivity reaches 137.14 mS cm-1 at 80 °C owing to the fact that efficient ion-conducting channels are formed by well-balanced molecular structures. The current density of the m-p-TP-40-BOP-ASU membrane reached 1.96 A cm-2 (1 M KOH aq, 2.0 V and 60 °C). After testing for 112 h under a current density of 500 mA cm-2, the voltage increased by 102 mV compared to the initial electrolysis voltage. All results have shown that m-p-TP-x-BOP-ASU has excellent electrolysis performance and electrochemical durability and has a promising application prospect in AEM water electrolyzers.

20.
Int J Rheum Dis ; 27(1): e14762, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37270684

ABSTRACT

Takayasu arteritis (TAK) is the main type of large vessel arteritis in young adults, which mainly affects the aorta and its main branches, leading to clinical manifestations such as syncope, intermittent limb claudication, hypertension, and abdominal pain. Among them, venous involvement is rarely reported. Here we show a case of TAK presenting as phlebitis. This was a 27-year-old woman, who initially admitted to our hospital with myalgia of the upper and lower extremities and night sweats. She was diagnosed as TAK according to the 1990 American College of Rheumatology TAK criteria. Surprisingly, vascular ultrasonography revealed wall thickening as indicated by macaroni sign of the multiple veins. TAK phlebitis appeared at the active phase, while disappearing rapidly at remission. Phlebitis might have a close relationship with disease activity. By retrospective study in our department, the estimated incidence rate of phlebitis might be 9.1% in TAK. With the literature review, it revealed that phlebitis might be an ignored manifestation in active TAK. However, due to the smaller sample size, it should be noted that a direct cause-effect relationship cannot be established.


Subject(s)
Hypertension , Phlebitis , Takayasu Arteritis , Female , Young Adult , Humans , Adult , Takayasu Arteritis/diagnosis , Takayasu Arteritis/diagnostic imaging , Retrospective Studies , Aorta , Phlebitis/diagnostic imaging , Phlebitis/etiology
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