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1.
Artigo em Inglês | MEDLINE | ID: mdl-39193322

RESUMO

A 56-year-old male patient was diagnosed with a submucosal tumor in the fundus of the stomach. The conventional operation method is endoscopic submucosal dissection. We present a case of rapid tumor resection without employing traditional endoscopic submucosal dissection instruments such as a mucotomy knife and endoscopic injection needle, resulting in substantial cost savings for the patients.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39269400

RESUMO

BACKGROUND: The relationship between long-term outcomes and operator experience for left atrial appendage occlusion (LAAO) is still unknown. OBJECTIVES: This study sought to explore the association between operator LAAO experience and one-year clinical outcomes. METHODS: The RECORD study (Registry to Evaluate Chinese Real-World Clinical Outcomes in Patients With AF Using the WATCHMAN Left Atrial Appendage Closure Technology; NCT03917563) was a multicenter, prospective registry that included patients with the WATCHMAN LAAO device (Boston Scientific) in China from April 1, 2019, to October 31, 2020. The current analyses included patients with solely LAAO from the registry; those who had concomitant LAAO and ablation/other procedures were excluded. The primary outcome was a composite endpoint of death, stroke, systemic embolism, and Bleeding Academic Research Consortium (BARC)-defined type 3 or 5 bleeding at 1 year. RESULTS: A total of 1,547 LAAO patients and 111 operators were included. The mean ± SD CHA2DS2-VASc and HAS-BLED scores of patients were 4.0 ± 1.8 and 2.5 ± 1.1, respectively. The mean ± SD age of operators was 47.0 ± 7.2 years, 15 (13.5%) were female, and 52 (46.8%) were electrophysiologists. Utilizing maximally selected log-rank statistics, the thresholds to categorize an experienced operator were performing ≥32 LAAOs annually or ≥134 LAAOs in total. Performing ≥32 LAAOs annually is the better criterion than ≥134 LAAOs in total (absolute net reclassification index: 25.79%; P < 0.001). Compared with the ≥32 LAAO annually group, the <32 group was associated with a 1.8-fold (HRadjusted: 1.79; 95% CI: 1.16-2.78; P = 0.009) increase in the risk of the primary endpoint, and such risk in the <32 group can be reduced by ∼12% after performing each additional 5 cases (HRadjusted per 5 cases: 0.88; 95% CI: 0.78-0.99; P = 0.033). CONCLUSIONS: Performing ≥32 LAAOs annually could be a threshold to categorize an experienced operator. Before reaching this threshold, the risk of death, stroke, systemic embolism, and BARC-defined type 3 or 5 bleeding decreased by 12% after every 5 cases performed.

3.
Radiol Case Rep ; 19(11): 5071-5077, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39253046

RESUMO

Postoperative pancreatic fistula, a significant complication following pancreaticoduodenectomy, can lead to the development of pseudoaneurysms, which in turn can result in hemorrhagic and septic complications. Here, we present the case of a 67-year-old male patient diagnosed with pancreatic head carcinoma who underwent partial pancreatectomy. Ten days postsurgery, the patient experienced hemorrhagic shock due to intraperitoneal bleeding. Emergency exploratory laparotomy and implantation of a stent in the common hepatic artery successfully stopped the bleeding. However, the patient later developed gastrointestinal bleeding, and no apparent source was detected during endoscopic examination. Two complex transcatheter arterial embolization procedures were performed, successfully stopping the bleeding. It is crucial to consider pseudoaneurysm in cases of suspected biliary and pancreatic leakage. This case also underscores the importance of a thorough vascular assessment prior to placing a coated stent, to prevent postoperative obstruction of catheter access to the responsible vessel. Additionally, embolization via the external path of the stent proved feasible.

4.
J Psychosom Res ; 187: 111913, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39260138

RESUMO

OBJECTIVE: This study aimed to explore the mediating roles of mindfulness and illness perception in the effects of a social media-based Mindfulness psyCho-behAvioRal intErvention (MCARE) on depressive and anxiety symptoms among patients with ACS. METHODS: This study conducted a secondary longitudinal mediation analysis using data from a randomized controlled trial of the MCARE grogram in patients with ACS. Participants were recruited at two tertiary hospitals in Jinan, China. The MCARE program consisted of six weekly sessions addressing mindfulness training and disease management to facilitate understanding and management of emotions and illness. The analytical sample included participants who completed measures of the primary outcomes, i.e., depression (PHQ-9) and anxiety (GAD-7) and potential mediators, i.e., mindfulness (CAMS-R) and illness perception (Brief-IPQ) at baseline (T0), immediate post-intervention (T1), and 12-week after the commencement of the intervention (T2). RESULTS: This study included 146 participants (mean age 58.9 years (SD = 8.9), 69.2 % male), including both intervention and control groups. The mediation analysis revealed a significant mediating effect of T1 mindfulness in the relationship between the group and T2 depression symptoms (indirect effect: -0.109, 95 % CI: -0.191, -0.041; P = 0.004), accounting for 26 % of the effect. For T2 anxiety symptoms, T1 illness perception exhibited a significant mediating effect (indirect effect: -0.055, 95 % CI: -0.110, -0.005; P = 0.035), accounting for 22 % of the effect. CONCLUSIONS: This study found that mindfulness and illness perception played a mediating role in the effects of the MCARE program on depressive and anxiety symptoms among patients with ACS.

5.
Nucleic Acids Res ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39265120

RESUMO

Perturb-Seq combines CRISPR (clustered regularly interspaced short palindromic repeats)-based genetic screens with single-cell RNA sequencing readouts for high-content phenotypic screens. Despite the rapid accumulation of Perturb-Seq datasets, there remains a lack of a user-friendly platform for their efficient reuse. Here, we developed PerturbDB (http://research.gzsys.org.cn/perturbdb), a platform to help users unveil gene functions using Perturb-Seq datasets. PerturbDB hosts 66 Perturb-Seq datasets, which encompass 4 518 521 single-cell transcriptomes derived from the knockdown of 10 194 genes across 19 different cell lines. All datasets were uniformly processed using the Mixscape algorithm. Genes were clustered by their perturbed transcriptomic phenotypes derived from Perturb-Seq data, resulting in 421 gene clusters, 157 of which were stable across different cellular contexts. Through integrating chemically perturbed transcriptomes with Perturb-Seq data, we identified 552 potential inhibitors targeting 1409 genes, including an mammalian target of rapamycin (mTOR) signaling inhibitor, retinol, which was experimentally verified. Moreover, we developed a 'Cancer' module to facilitate the understanding of the regulatory role of genes in cancer using Perturb-Seq data. An interactive web interface has also been developed, enabling users to visualize, analyze and download all the comprehensive datasets available in PerturbDB. PerturbDB will greatly drive gene functional studies and enhance our understanding of the regulatory roles of genes in diseases such as cancer.

6.
Nat Commun ; 15(1): 7778, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39237586

RESUMO

Luminescent materials that simultaneously embody bright singlet and triplet excitons hold great potential in optoelectronics, signage, and information encryption. However, achieving high-performance white-light emission is severely hampered by their inherent unbalanced contribution of fluorescence and phosphorescence. Herein, we address this challenge by pressure treatment engineering via the hydrogen bonding cooperativity effect to realize the mixture of n-π*/π-π* transitions, where the triplet state emission was boosted from 7% to 40% in isophthalic acid (IPA). A superior white-light emission based on hybrid fluorescence and phosphorescence was harvested in pressure-treated IPA, and the photoluminescence quantum yield was increased to 75% from the initial 19% (blue-light emission). In-situ high-pressure IR spectra, X-ray diffraction, and neutron diffraction reveal continuous strengthening of the hydrogen bonds with the increase of pressure. Furthermore, this enhanced hydrogen bond is retained down to the ambient conditions after pressure treatment, awarding the targeted IPA efficient intersystem crossing for balanced singlet/triplet excitons population and resulting in efficient white-light emission. This work not only proposes a route for brightening triplet states in organic small molecules, but also regulates the ratio of singlet and triplet excitons to construct high-performance white-light emission.

7.
Fitoterapia ; 179: 106216, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39303768

RESUMO

Genus Castanopsis are native to tropical and subtropical Asia, comprising about 120 species. Some species from Castanopsis have been used as folk medicines in Asia. Phytochemistry investigations of the different plant parts of Genus Castanopsis have disclosed the presences of natural products including phenolics, terpenoids, steroids, and essential oils. Phenolics exist in Castanopsis species widely, particularly, triterpene ellagitannins were found to be potential chemotaxonomic marks of this geuns. The crude extracts and chemical constituents from Castanopsis have extensive biological activities, such as anti-inflammatory, anti-oxidative, antimicrobial, etc. In conclusion, the phytochemistry and biological activities of genus Castanopsis make it a promising source of natural products for drug discovery and development. This review collected the literatures published prior to 2023 on the traditional medicinal uses, phytochemistry, and bioactivties of the genus Castanopsis by searching from several scientific databases, such as Elsevier, Sci-finder, PubMed, Web of Science, CNKI, and Baidu Scholar. The main purpose of this systematic review is to provide the available information for relevant scholars to understand the progress in phytochemistry and biological activies of the genus Castanopsis and help the further development of this genus.

8.
New Phytol ; 2024 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-39307530

RESUMO

Genome editing is a revolution in biotechnology for crop improvement with the final product lacking transgenes. However, most derived traits have been generated through edits that create gene knockouts. Our study pioneers a novel approach, utilizing gene editing to enhance gene expression by eliminating transcriptional repressor binding motifs. Building upon our prior research demonstrating the protein-boosting effects of the transcription factor NF-YC4, we identified conserved motifs targeted by RAV and WRKY repressors in the NF-YC4 promoters from rice (Oryza sativa) and soybean (Glycine max). Leveraging CRISPR/Cas9 technology, we deleted these motifs, resulting in reduced repressor binding and increased NF-YC4 expression. This strategy led to increased protein content and reduced carbohydrate levels in the edited rice and soybean plants, with rice exhibiting up to a 68% increase in leaf protein and a 17% increase in seed protein, and soybean showing up to a 25% increase in leaf protein and an 11% increase in seed protein. Our findings provide a blueprint for enhancing gene expression through precise genomic deletions in noncoding sequences, promising improved agricultural productivity and nutritional quality.

9.
J Neuroimmunol ; 396: 578460, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39317078

RESUMO

BACKGROUND: Autoimmune nodopathy (AN) is a very rare new disease entity, especially when combined with membranous nephropathy (MN). METHODS: Antibodies against nodal-paranodal cell adhesion molecules in the serum were detected using cell-based assays. Antibody subtypes against contactin-1 (CNTN1) were confirmed. Cases of anti-CNTN1 antibody-positive AN with and without MN were retrieved through a literature search to compare clinical and electrophysiological characteristics. RESULTS: A 65-year-old male patient with MN developed limb numbness and weakness, along with walking instability. Serum CNTN1 antibodies were positive, primarily those of the IgG4 subtype. Electromyography showed prominent demyelination patterns in both the proximal and distal segments of the nerves compared to the middle nerve trunk. Magnetic resonance imaging revealed enlargement of the bilateral brachial and lumbosacral plexuses and local hyperintensity of the right C5-C6 nerve roots. Thirty-five cases with anti-CNTN1 antibody-positive AN with MN and 51 cases with anti-CNTN1 antibody-positive AN without MN were compared. Furthermore, the proportion of patients with MN combined with AN presenting with acute or subacute onset was higher than that observed in the MN without AN group. Nevertheless, no substantial differences were noted between the two groups concerning the clinical and electrophysiological characteristics, which were mainly elderly men, manifested as sensory ataxia, IgG4 antibody subtype, electrophysiological demyelination, and a certain effect on immunotherapy. CONCLUSION: In cases of electrophysiological manifestation of demyelinating peripheral neuropathy, especially in distal and poximal segments of nerves, AN should be considered, and further screening for renal function should be performed. Concomitant MN does not aggravate or alleviate peripheral nerve symptoms.

10.
Heart Lung ; 68: 359-366, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39260267

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide, particularly affecting low- and middle-income countries. Food environments may be linked with the risk of CVD; however, current study findings regarding their relationship are inconsistent. A systematic review of their associations is needed to guide interventions to improve cardiovascular health. OBJECTIVE: This systematic review aimed to comprehensively assess the relationship between food environments and CVD outcomes, including incidence, hospitalization, mortality, and recurrence rates. METHOD: According to PRISMA guidelines, a systematic search was conducted until 28th March 2024, using eight databases, including PubMed, Embase, Ovid, CINAHL, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Data. The review quality was assessed according to the Agency for Healthcare Research and Quality (AHRQ) and Newcastle-Ottawa Scale (NOS). The included studies were categorized based on their exposure factors into unhealthy, healthy, and comprehensive food environments, encompassing facilities that offer healthy and unhealthy foods. The findings were narratively synthesized according to this classification. RESULT: A total of 23 studies, encompassing 13 cross-sectional studies and 10 cohort-longitudinal studies, were included in this review. Among the 20 studies on unhealthy food environments, 13 found a positive association with CVD outcomes. Of the seven studies on healthy food environments, 3 found a negative association with CVD outcomes. Additionally, 4 out of 8 studies on comprehensive food environments found a significant but inconsistent association with CVD outcomes. CONCLUSION: This study suggested that unhealthy food environments are probably associated with CVD outcomes. At the same time, there is currently no conclusive evidence to indicate a relationship between healthy food environments or comprehensive food environments and CVD outcomes.

12.
J Am Chem Soc ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39283721

RESUMO

The selective hydrogenation of carbon dioxide (CO2) to value-added chemicals, e.g., methanol, using green hydrogen retrieved from renewable resources is a promising approach for CO2 emission reduction and carbon resource utilization. However, this process suffers from the competing side reaction of reverse water-gas shift (RWGS) and methanol decomposition, which often leads to a strong conversion-selectivity trade-off and thus a poor methanol yield. Here, we report that InOx coating of PdCu bimetallic nanoparticles (NPs) to construct intimate InOx/Cu and InOx/PdIn dual interfaces enables the break of conversion-selectivity trade-off by achieving ∼80% methanol selectivity at ∼20% CO2 conversion close to the thermodynamic limit, far superior to that of conventional metal catalysts with a single active metal/oxide interface. Comprehensive microscopic and spectroscopic characterization revealed that the InOx/PdIn interface favors the activation of CO2 to formate, while the adjacent InOx/Cu interface readily converts formate intermediates to methoxy species in tandem, which thus cooperatively boosts methanol production. These findings of dual-interface synergies via oxide coating of bimetallic NPs open a new avenue to the design of active and selective catalysts for advanced catalysis.

13.
Sensors (Basel) ; 24(17)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39275602

RESUMO

ZnO film ultrasonic transducers for temperature and stress measurements with dual-mode wave excitation (longitudinal and shear) were deposited using the reactive RF magnetron sputtering technique on Si and stainless steel substrates and construction steel bolts. It was found that the position in the substrate plane had a significant effect on the structure and ultrasonic performance of the transducers. The transducers deposited at the center of the deposition zone demonstrated a straight columnar structure with a c-axis parallel to the substrate normal and the generation of longitudinal waves. The transducers deposited at the edge of the deposition zone demonstrated inclined columnar structures and the generation of dominant shear or longitudinal shear waves. Transducers deposited on the bolts with dual-wave excitation were used to study the effects of high temperatures in the range from 25 to 525 °C and tensile stress in the range from 0 to 268 MPa on ultrasonic response. Dependencies between changes in the relative time of flight and temperature or axial stress were obtained. The dependencies can be described by second-order functions of temperature and stress. An analysis of the contributions of thermal expansion, strain, and the speed of sound to changes in the time of flight was performed. At high temperatures, a decrease in the signal amplitude was observed due to the decreasing resistivity of the transducer. The ZnO ultrasonic transducers can be used up to temperatures of ~500 °C.

14.
bioRxiv ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39345455

RESUMO

Insulators are cis -regulatory elements that separate transcriptional units, whereas silencers are elements that repress transcription regardless of their position. In plants, these elements remain largely uncharacterized. Here, we use the massively parallel reporter assay Plant STARR-seq with short fragments of eight large insulators to identify more than 100 fragments that block enhancer activity. The short fragments can be combined to generate more powerful insulators that abolish the capacity of the strong viral 35S enhancer to activate the 35S minimal promoter. Unexpectedly, when tested upstream of weak enhancers, these fragments act as silencers and repress transcription. Thus, these elements are capable of both insulating or repressing transcription dependent upon regulatory context. We validate our findings in stable transgenic Arabidopsis , maize, and rice plants. The short elements identified here should be useful building blocks for plant biotechnology efforts.

15.
J Dent Sci ; 19(4): 2035-2044, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39347052

RESUMO

Background/purpose: Mesenchymal stem cells exhibit therapeutic efficacy for brain injury. This study examined the effect of mesenchymal stem cells derived from human exfoliated deciduous teeth (SHED) on alleviating symptoms of Parkinson's disease (PD). Materials and methods: SHED were isolated to examine the biosafety and bioavailability of stem cells derived from human exfoliated deciduous teeth-derived conditioned medium (SHED-CM) for the alleviation of PD symptoms in a 6-hydroxydopamine (6-OHDA)-induced PD zebrafish model. Results: SHED-CM administration did not induce neurological, skin or muscle toxicity in control zebrafish at any dose, and estrogen equivalent testing showed no chronic toxicants. Induction of PD with 6-OHDA suppressed zebra SHED-CM was administered to zebrafish treated with 6-OHDA to induce PD symptoms. Similar to nomifensine, a drug with proven anti-PD potential, SHED-CM repaired the motor deficiencies in the zebrafish PD model. Conclusion: Our results indicate the biosafety of SHED-CM and its therapeutic potential in treating PD in a zebrafish model.

16.
Front Nutr ; 11: 1451112, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39318383

RESUMO

Introduction: There is growing evidence indicating a complex interaction between blood metabolites and atopic dermatitis (AD). The objective of this study was to investigate and quantify the potential influence of plasma metabolites on AD through Mendelian randomization (MR) analysis. Methods: Our procedures followed these steps: instrument variable selection, primary analysis, replication analysis, Meta-analysis of results, reverse MR analysis, and multivariate MR (MVMR) analysis. In our study, the exposure factors were derived from the Canadian Longitudinal Study on Aging (CLSA), encompassing 8,299 individuals of European descent and identifying 1,091 plasma metabolites and 309 metabolite ratios. In primary analysis, AD data, was sourced from the GWAS catalog (Accession ID: GCST90244787), comprising 60,653 cases and 804,329 controls. For replication, AD data from the Finnish R10 database included 15,208 cases and 367,046 controls. We primarily utilized the inverse variance weighting method to assess the causal relationship between blood metabolites and AD. Results: Our study identified significant causal relationships between nine genetically predicted blood metabolites and AD. Specifically, 1-palmitoyl-2-stearoyl-GPC (16:0/18:0) (OR = 0.92, 95% CI 0.89-0.94), 1-methylnicotinamide (OR = 0.93, 95% CI 0.89-0.98), linoleoyl-arachidonoyl-glycerol (18:2/20:4) [1] (OR = 0.94, 95% CI 0.92-0.96), and 1-arachidonoyl-GPC (20:4n6) (OR = 0.94, 95% CI 0.92-0.96) were associated with a reduced risk of AD. Conversely, phosphate / linoleoyl-arachidonoyl-glycerol (18:2/20:4) [2] (OR = 1.07, 95% CI 1.04-1.10), docosatrienoate (22:3n3) (OR = 1.07, 95% CI 1.04-1.10), retinol (Vitamin A) / linoleoyl-arachidonoyl-glycerol (18:2/20:4) [2] (OR = 1.08, 95% CI 1.05-1.11), retinol (Vitamin A) / linoleoyl-arachidonoylglycerol (18:2/20:4) [1] (OR = 1.08, 95% CI 1.05-1.12), and phosphate / linoleoyl-arachidonoyl-glycerol (18:2/20:4) [1] (OR = 1.09, 95% CI 1.07-1.12 were associated with an increased risk of AD. No evidence of reverse causality was found in the previously significant results. MVMR analysis further confirmed that 1-palmitoyl-2-stearoyl-GPC (16:0/18:0) and 1-methylnicotinamide are independent and dominant contributors to the development of AD. Conclusion: Our study revealed a causal relationship between genetically predicted blood metabolites and AD. This discovery offers specific targets for drug development in the treatment of AD patients and provides valuable insights for investigating the underlying mechanisms of AD in future research.

17.
Inorg Chem ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39321341

RESUMO

The exploration of short-wave ultraviolet (SUV; λ < 280 nm) transparent phosphates with substantial birefringence is crucial for the advancement of SUV laser industry. Despite their SUV transparency and potential for constructing materials with large birefringence, open-framework (OF) phosphates have rarely been explored for their birefringent properties. Herein, through a systematic exploration in this field, a new ethylenediamine-based OF zincophosphate, Na(C2H10N2)2[Zn3(PO4)2(H0.5PO4)]2 (NEZPO), has been developed. NEZPO exhibits remarkable SUV transparency and significant birefringence (Δn = 0.060 at 546 nm), highlighting the potential for the development of benign SUV crystals within the OF phosphates family.

18.
Pharmaceuticals (Basel) ; 17(9)2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39338282

RESUMO

Volatile oil stabilization strategies based on encapsulation with a large number of excipients limit further applications. The primary objective of this study is to improve the stability of volatile oils using Pickering emulsion (PE) stabilized by Chinese medicinal powder based on the principle of "integrating drug and excipient". Modified amber was acquired through surface modification, and a stable oil-in-water PE loaded with Acorus tatarinowii volatile oil (ATVO) was constructed from modified amber. The stability, including the peroxide value (PV), malondialdehyde (MDA) content, and the content and composition of volatile components in modified amber-PE (MAPE) under intense light exposure, was analyzed deeply. In addition, the in vitro release and pharmacokinetics of MAPE and ATVO were investigated. The results demonstrate that the PV and MDA content in MAPE were significantly lower than in free ATVO, and the content and composition of volatile components in MAPE were closer to those in untreated ATVO. The release kinetics of ß-asarone and α-asarone in MAPE demonstrated rapid and higher release, and pharmacokinetic studies show that MAPE has better bioavailability. This research provides a distinctive Chinese medicine solution to address the vaporization of volatile oil in solid formulations.

19.
Microorganisms ; 12(9)2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39338589

RESUMO

Fungal communities are critical players in the biogeochemical soil processes of forest ecosystems. However, the factors driving their diversity and community assembly are still unclear. In the present study, five typical vegetation types of soil fungal communities in Liziping Nature Reserve, China, were investigated using fungal ITS sequences. The results show that the topsoil fungal community is mainly dominated by the phyla Ascomycota, Basidiomycota, and Mortierellomycota. Although there was no significant difference in α diversity (Shannon, Simpson, and Pielou evenness indices) among different forest types, there was a significant difference in ß diversity (community composition). This study found that soil pH, soil organic carbon, total nitrogen (TN), total phosphorus (TP), and the total nitrogen/total phosphorus (N/P) ratio are the main environmental factors that affect soil fungal communities. Each forest type has a specific co-occurrence network, indicating that these community structures have significant specificities and complexities. Deciduous evergreen broad-leaved forests as well as deciduous broad-leaved and evergreen broad-leaved mixed forests showed high modularity and average path lengths, indicating their highly modular nature without distinct small-scale characteristics. Furthermore, our findings indicate that the structures of topsoil fungal communities are mainly shaped by stochastic processes, with the diffusion limitation mechanism playing a particularly significant role.

20.
Nat Commun ; 15(1): 8388, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333125

RESUMO

Methionine adenosyltransferase 2 A (MAT2A) and MAT2B are essential for hepatic stellate cells (HSCs) activation. Forkhead box M1 (FOXM1) transgenic mice develop liver inflammation and fibrosis. Here we examine if they crosstalk in male mice. We found FOXM1/MAT2A/2B are upregulated after bile duct ligation (BDL) and carbon tetrachloride (CCl4) treatment in hepatocytes, HSCs and Kupffer cells (KCs). FDI-6, a FOXM1 inhibitor, attenuates the development and reverses the progression of CCl4-induced fibrosis while lowering the expression of FOXM1/MAT2A/2B, which exert reciprocal positive regulation on each other transcriptionally. Knocking down any of them lowers HSCs and KCs activation. Deletion of FOXM1 in hepatocytes, HSCs, and KCs protects from BDL-mediated inflammation and fibrosis comparably. Interestingly, HSCs from Foxm1Hep-/-, hepatocytes from Foxm1HSC-/-, and HSCs and hepatocytes from Foxm1KC-/- have lower FOXM1/MAT2A/2B after BDL. This may be partly due to transfer of extracellular vesicles between different cell types. Altogether, FOXM1/MAT2A/MAT2B axis drives liver inflammation and fibrosis.


Assuntos
Tetracloreto de Carbono , Proteína Forkhead Box M1 , Células Estreladas do Fígado , Hepatócitos , Células de Kupffer , Cirrose Hepática , Metionina Adenosiltransferase , Animais , Metionina Adenosiltransferase/metabolismo , Metionina Adenosiltransferase/genética , Proteína Forkhead Box M1/metabolismo , Proteína Forkhead Box M1/genética , Masculino , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Cirrose Hepática/genética , Camundongos , Hepatócitos/metabolismo , Hepatócitos/patologia , Células de Kupffer/metabolismo , Tetracloreto de Carbono/toxicidade , Células Estreladas do Fígado/metabolismo , Camundongos Endogâmicos C57BL , Fígado/patologia , Fígado/metabolismo , Camundongos Knockout , Camundongos Transgênicos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/genética , Humanos , Ductos Biliares/patologia , Ductos Biliares/metabolismo , Ductos Biliares/cirurgia
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