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Single-cell technology depicts integrated tumor profiles including both tumor cells and tumor microenvironments, which theoretically enables more robust diagnosis than traditional diagnostic standards based on only pathology. However, the inherent challenges of single-cell RNA sequencing (scRNA-seq) data, such as high dimensionality, low signal-to-noise ratio (SNR), sparse and non-Euclidean nature, pose significant obstacles for traditional diagnostic approaches. The diagnostic value of single-cell technology has been largely unexplored despite the potential advantages. Here, we present a graph neural network-based framework tailored for molecular diagnosis of primary liver tumors using scRNA-seq data. Our approach capitalizes on the biological plausibility inherent in the intercellular communication networks within tumor samples. By integrating pathway activation features within cell clusters and modeling unidirectional inter-cellular communication, we achieve robust discrimination between malignant tumors (including hepatocellular carcinoma, HCC, and intrahepatic cholangiocarcinoma, iCCA) and benign tumors (focal nodular hyperplasia, FNH) by scRNA data of all tissue cells and immunocytes only. The efficacy to distinguish iCCA from HCC was further validated on public datasets. Through extending the application of high-throughput scRNA-seq data into diagnosis approaches focusing on integrated tumor microenvironment profiles rather than a few tumor markers, this framework also sheds light on minimal-invasive diagnostic methods based on migrating/circulating immunocytes.

Assuntos

Neoplasias Hepáticas , Redes Neurais de Computação , Análise de Célula Única , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Análise de Célula Única/métodos , RNA/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Análise de Sequência de RNA

RESUMO

Measurable residual disease (MRD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an independent risk factor for relapse in patients with acute lymphoblastic leukemia (ALL). This study aimed to assess the efficacy, safety, and immune reconstitution of chimeric antigen receptor T-cell (CAR-T) therapy in patients with molecular relapse after allo-HSCT. Eleven patients with molecular relapse of B-cell-ALL who underwent CAR-T therapy after allo-HSCT were enrolled. The rate of MRD negativity after a month of CAR-T infusion was 81.8%. Patients who bridged to second-HSCT after CAR-T therapy (n = 3) showed a trend of higher 3-year leukemia-free survival and 3-year overall survival than those who did not (n = 8; 100% vs. 75.0%; 95% CI, 45.0-104.9%; p = 0.370). No treatment-related mortalities were observed. Among patients who did not bridge to second-HSCT and remained in complete remission until the last follow-up (n = 6), five of them had not recovered normal immunoglobulin concentrations with a median follow-up of 43 months. CAR-T therapy may be a safe and effective treatment strategy to improve survival after allo-HSCT; however, the problem of prolonged hypogammaglobulinemia in patients who do not bridge to second-HSCT is worth noting.

RESUMO

Ischemic heart disease refers to the imbalance between the supply and demand of myocardial blood; it has various causes and results in a class of clinical diseases characterized by myocardial ischemia (MI). In recent years, the incidence of cardiovascular disease has become higher and higher, and the number of patients with ischemic heart disease has also increased year by year. Traditional treatment methods include drug therapy and surgical treatment, both of which have limitations. The former maybe develop risks of drug resistance and has more significant side effects, while the latter may damage blood vessels and risk infection. At this stage, a new cell-free treatment method needs to be explored. Many research results have shown that exosomes from different cell sources can protect the ischemic myocardium via intercellular action methods, such as promoting angiogenesis, inhibiting myocardial fibrosis, apoptosis and pyroptosis, and providing a new basis for the treatment of MI. In this review, we briefly introduce the formation and consequences of myocardial ischemia and the biology of exosomes, and then focus on the role and mechanism of exosomes from different sources in MI. We also discuss the role and mechanism of exosomes pretreated with Chinese and Western medicines on myocardial ischemia. We also discuss the potential of exosomes as diagnostic markers and therapeutic drug for MI.

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Gram-negative micro-flora dysbiosis occurs in multiple digestive tumors and is found to be the dominant micro-flora in esophageal squamous cell carcinoma (ESCC) micro-environment. The continuous stimulation of G- bacterium metabolites may cause tumorigenesis and reshape the micro-immune environment in ESCC. However, the mechanism of G- bacilli causing immune evasion in ESCC remains underexplored. We identified CC Chemokine receptor 1 (CCR1) as a tumor-indicating gene in ESCC. Interestingly, expression levels of CCR1 and PD-L1 were mutually up regulated after G- bacilli metabolites lipopolysaccharide (LPS) stimulation. Firstly, we found CCR1 high expression level to be associated with poor overall survival in ESCC. Importantly, we found that high level expression of CCR1 up-regulated PD-L1 expression by activating MAPK phosphorylation in ESCC and induced tumor malignant behavior. Finally, we found that T cells exhaustion and cytotoxicity suppression were associated with CCR1 expression in ESCC, which were decreased after CCR1 inhibiting. Our work identifies CCR1 as a potential immune check point regulator of PD-L1 and may cause T cell exhaustion and cytotoxicity suppression in ESCC micro-environment and highlights the potential value of CCR1 as therapeutic target of immunotherapy. Implications: The esophageal microbial environment and its metabolites significantly affect the outcome of immunotherapy for ESCC.

RESUMO

Upon the pressure of conventional land agriculture and marine environment facing the future of human beings, the emerging of alternative proteins represented by cultured meat is expected with a breakthrough of efficient, safe and sustainable production. However, the cell proliferation efficiency and final myofiber density in current animal-derived scaffolds are still limited. Here, we incorporated five plant-derived edible polymeric glucosyl nanoparticles (GNPs) into gelatin/alginate hydrogels to spontaneously form nanoaggregates where nanotopographies were observed inside. The nanoscale topological morphology significantly enhances the adhesion and proliferation efficiencies of piscine satellite cells (PSCs) in the tailored extracellular matrix of as-prepared scaffold. Physically, the presence of GNP-induced nanoaggregate increases the interaction between ITG-A1 (membrane protein of PSCs) and hydrogel microenvironment, which activates the focal adhesion-integrin-cytoskeleton mechanotransduction signaling to promote cell proliferation. With a controlled diameter of hydrogel filament, these inner topological GNP nanoaggregates can also improve the density, alignment and differentiation efficiency of PSCs. When cultured in vitro for 15 days, the cell density, size and orientation of muscle fibers in the GNP-stimulated cultured fish fillet are very similar to the total cell mass in native fish muscle tissue.

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Objective: We investigated the risk factors associated with severe or critical Coronavirus disease 2019 (COVID-19) infection due to the Omicron variant in patients with myasthenia gravis (MG) and determined the potential effect of COVID-19 on myasthenic exacerbation during the Omicron pandemic. Methods: This retrospective study included 287 patients with MG in Tianjin, China. Clinical data of the patients were collected using electronic questionnaires, databases, and clinical records. Results: The overall infection rate was 84.7%. Advanced age, comorbidities, generalized phenotype, and MG instability were drivers of COVID-19 severity, and post-COVID-19 myasthenic exacerbation. The concurrent use of a steroid-sparing agent did not affect COVID-19 susceptibility or severity. It did lower the risk of myasthenic exacerbation after COVID-19 infection. Patients with severe COVID-19 experienced myasthenic exacerbation earlier than patients with non-severe infection (p < 0.001). The severity of COVID-19 (Hazards Ratio = 3.04, 95% CI: 1.41-6.54, p = 0.004) and the clinical phenotype (Hazards Ratio = 3.29, 95% CI: 1.63-6.63, p < 0.001) emerged as independent risk factors for early MG exacerbation. Conclusion: Generally, patients with MG appear to be susceptible to the Omicron strains. Immunotherapy for MG did not increase COVID-19 susceptibility or severity. We do not advocate an immediate cessation of ongoing immunosuppressive treatments once a COVID-19 infection is diagnosed. Instead, a judicious evaluation of the risks and benefits, tailored to each individual, is recommended.

Assuntos

COVID-19 , Miastenia Gravis , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/complicações , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Adulto , Fatores de Risco , Idoso , Índice de Gravidade de Doença , Comorbidade

RESUMO

INTRODUCTION: Asthma is a common chronic respiratory disease characterized by chronic airway inflammation and abnormal airway remodeling. The RhoA/ROCK pathway and myocardin-related transcription factor A (MRTF-A) demonstrate significant associations with the proliferation of airway smooth muscle cells (ASCMs), which tightly correlates with the process of airway remodeling. MYOCD, which is homologous to MRTF-A but specifically expressed in smooth muscle cells, potentially regulates RhoA/ROCK activated cell proliferation and subsequent airway remodeling. METHODS: The RhoA/ROCK overexpression and silencing cell lines were constructed in vitro, as well as MYOCD overexpression/silencing. The cytoskeleton alterations induced by RhoA/ROCK pathway were identified by the measuring of globular actin and filamentous actin. RESULTS: The comparison between controls for overexpression/silencing and ROCK overexpression/silencing revealed that MYOCD presented consistent change trends with cytoskeleton and RhoA/ROCK pathway. The ROCK1 facilitates the proliferation and migration of ASCMs. The MYOCD enhanced the proliferation and migration of HASMCs. CONCLUSION: Our study indicates that Rho/ROCK/MYOCD is a key pathway involved in the migration and proliferation of airway smooth muscle cells. Inhibition of Rho/ROCK may be an effective approach to breaking the vicious cycle of asthmatic ASCMs proliferation, providing a novel strategy in treating asthma airway remodeling.

RESUMO

APETALA2/ethylene-responsive (AP2/ERF) plays crucial roles in resisting diverse stresses and in regulating plant growth and development. However, little is known regarding the structure and function of the AP2/ERF genes in pearl millet (Pennisetum glaucum). The AP2/ERF gene family may be involved in the development and maintenance of P. glaucum resilience to abiotic stresses, central to its role as a vital forage and cereal crop. In this study, PgAP2/ERF family members were identified and comprehensive bioinformatics analyses were performed, including determination of phylogenetic relationships, gene structures, conserved motifs, chromosomal localization, gene duplication, expression pattern, protein interaction network, and functional characterization of PgRAV_01 (Related to ABI3/VP1). In total, 78 PgAP2/ERF members were identified in the P. glaucum genome and classified into five subfamilies: AP2, ERF, DREB, RAV, and soloist. Members within the same clade of the PgAP2/ERF family showed similar gene structures and motif compositions. Six duplication events were identified in the PgAP2/ERF family; calculation of Ka/Ks values showed that purification selection dominated the evolution of PgAP2/ERFs. Subsequently, a potential interaction network of PgAP2/ERFs was generated to predict the interaction relationships. Additionally, abiotic stress expression analysis showed that most PgAP2/ERFs were induced in response to drought and heat stresses. Furthermore, overexpression of PgRAV_01 negatively regulated drought tolerance in Nicotiana benthamiana by reducing its antioxidant capacity and osmotic adjustment. Taken together, these results provide valuable insights into the characteristics and functions of PgAP2/ERF genes, with implications for abiotic stress tolerance, and will ultimately contribute to the genetic improvement of cereal crop breeding.

RESUMO

ß-Ionone, sustainably derived from Petunia hybrida as a natural bioresource, was identified as a lead compound for integrated aphid management. A series of ß-ionone derivatives containing ester groups were designed and synthesized for the purpose of discovering renewable botanical-based products. The odorant-binding protein (OBP) binding test indicated that ß-ionone and its derivatives displayed binding affinities with Acyrthosiphon pisum OBP9 (ApisOBP9) and Harmonia axyridis OBP15 (HaxyOBP15). Bioactivity assays revealed that most ß-ionone derivatives exhibited a higher repellent activity than that of ß-ionone. ß-Ionone and derivatives 4g and 4l displayed attractiveness to H. axyridis. Specifically, 4g was a highly promising derivative, possessing good repellent activity against A. pisum and attractiveness to H. axyridis. Molecular dynamics simulations revealed that integrating the hydrophobic ester group into the ß-ionone framework strengthened the van der Waals interactions of 4g with ApisOBP9/HaxyOBP15, improving the binding affinity with OBPs and producing higher push-pull activity than ß-ionone; 4g also had low toxicity toward nontarget organisms. Thus, 4g is a potential ecofriendly, botanical-based option for aphid management.

RESUMO

Bitterness, as one of the most important physiological sensations in animals, is primarily recognized through the mediation of bitter taste receptors. In recent years, it has been found that these receptors are not only expressed in taste bud cells on the tongue but also in the respiratory, cardiovascular, digestive, reproductive, and nervous systems. They are involved in regulating various fundamental physiological processes and are now considered important targets for the treatment of various diseases. This paper reviewed the structure, classification, distribution, and signaling pathways of bitter taste receptors, their relationship with different diseases, and the role of bitter taste receptors agonists, aiming to provide a basis for scientific research on bitter taste receptors.

Assuntos

Receptores Acoplados a Proteínas G , Paladar , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Animais , Papilas Gustativas/metabolismo , Transdução de Sinais

RESUMO

BACKGROUND: Oxidative stress is closely associated with hypertensive outcomes. The oxidative balance score (OBS) measures oxidative stress exposure from dietary and lifestyle elements. The objective of this study was to investigate the association between OBS and mortality in hypertensive patients. METHODS: This study included 7823 hypertensive patients from the National Health and Nutrition Examination Survey (NHANES) 1999-2014. Several models, including Cox regression, restricted cubic splines (RCS), Kaplan‒Meier survival analysis, subgroup, and sensitivity analyses, were exploited to investigate the relationship between OBS and the risk of mortality. RESULTS: Controlling for all potential confounders, a significantly inverse association was observed between elevated OBS and all-cause [hazard ratio (HR) = 0.90, 95% CI: 0.85-0.95] and cardiovascular mortality (HR = 0.85, 95% CI: 0.75-0.95). With adjustment for covariates, significant associations between lifestyle OBS and mortality risks diminished, whereas associations between dietary OBS and these mortality risks remained robust (all-cause mortality: HR = 0.91, 95% CI: 0.86-0.96; cardiovascular mortality: HR = 0.85, 95% CI: 0.76-0.96). RCS demonstrated a linear relationship between OBS and all-cause and cardiovascular mortality risk (P nonlinear = 0.088 and P nonlinear = 0.447, respectively). Kaplan‒Meier curves demonstrated that the mortality rate was lower with a high OBS (P < 0.001). The consistency of the association was demonstrated in subgroup and sensitivity analyses. RCS after stratification showed that among current drinkers, those with higher OBS had a lower risk of mortality compared with former or never drinkers. CONCLUSIONS: In hypertensive individuals, there was a negative association between OBS and all-cause and cardiovascular mortality. Encouraging hypertensive individuals, especially those currently drinking, to maintain high levels of OBS may be beneficial in improving their prognosis.

RESUMO

Patients with relapsed/refractory acute myeloid leukaemia (R/R AML), especially those who failed in novel target agents are related to dismal survival. We developed a multi-institutional, single-arm, prospective phase II trial, to investigate intensified conditioning with 'Mega-Dose' decitabine (MegaDAC) following allogeneic haematopoietic cell transplantation (allo-HCT) for R/R AML. From 2019 to 2023, 70 heavily treated R/R AML patients in active disease were consecutively enrolled. Significantly, every patient (n = 18) harbouring specific mutations exhibited no response to their best available target agents (BATs). Moreover, 74.3% of the enrolled patients did not reach remission following venetoclax-based regimens. All patients underwent intravenous decitabine (400 mg/m2) along with busulfan and cyclophosphamide. Median follow-up was 26 months (8-65) after HCT. All engrafted patients achieved MRD negativity post-HCT, with a median 3.3-log reduction in recurrent genetic abnormalities. The regimen was well tolerated, without irreversible grades III-IV toxicity peri-engraftment. The estimated 2-year CIR was 29.6% (18.4%-41.7%) and the est-2-year NRM was 15.5% (7.8%-25.5%). The est-2-year LFS, OS, and GRFS were 55.0% (43.5%-69.4%), 58.6% (47.0%-73.0%), and 42.9% (31.9%-57.6%), respectively. Multivariate analysis showed that pre-HCT drug exposures had no significant impact on primary outcomes. MegaDAC is highlighted as an effective and safe option for R/R AML in the new era of targeted therapies.

RESUMO

The Nab-paclitaxel combined with gemcitabine (AG) regimen is the main chemotherapy regimen for pancreatic cancer, but drug resistance often occurs. Currently, the ability to promote sensitization in drug-resistant cases is an important clinical issue, and the strategy of repurposing conventional drugs is a promising strategy. This study aimed to identify a classic drug that targets chemotherapy resistance's core signaling pathways and combine it with the AG regimen to enhance chemosensitivity. We also aimed to find reliable predictive biomarkers of drug combination sensitivity. Using RNA sequencing, we found that abnormal PI3K/Akt pathway activation plays a central role in mediating resistance to the AG regimen. Subsequently, through internal and external verification of randomly selected AG-resistant patient-derived organoid (PDO) and PDO xenograft models, we discovered for the first time that the classic anti-inflammatory drug sulindac K-80003, an inhibitor of the PI3K/Akt pathway that we focused on, promoted sensitization in half (14/28) of AG-resistant pancreatic ductal adenocarcinoma cases. Through RNA-sequencing, multiplex immunofluorescent staining, and immunohistochemistry experiments, we identified cFAM124A as a novel biomarker through which sulindac K-80003 promotes AG sensitization. Its role as a sensitization marker is explained via the following mechanism: cFAM124A enhances both the mRNA expression of cathepsin L and the activity of the cathepsin L enzyme. This dual effect stimulates the cleavage of RXRα, leading to large amounts of truncated RXRα, which serves as a direct target of K-80003. Consequently, this process results in the pathological activation of the PI3K/Akt pathway. In summary, our study provides a new treatment strategy and novel biological target for patients with drug-resistant pancreatic cancer.

Assuntos

Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina , Resistencia a Medicamentos Antineoplásicos , Gencitabina , Paclitaxel , Neoplasias Pancreáticas , Sulindaco , Ensaios Antitumorais Modelo de Xenoenxerto , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Humanos , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Animais , Camundongos , Albuminas/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Sulindaco/farmacologia , Sulindaco/análogos & derivados , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Feminino , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Masculino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos

RESUMO

Prognostic significance of soluble immune checkpoint molecule TIM-3 and its ligands in the plasma has been illustrated in various solid tumors, but such study in newly diagnosed acute myeloid leukemia (AML) remains absent. Soluble TIM-3, Gal-9 and CEACAM1 levels in the bone marrow plasma samples collected from 90 adult AML patients at diagnosis and 12 healthy donors were measured by enzyme-linked immunosorbent assays (ELISA), and 16 AML patients were simultaneously tested cell membrane TIM-3 expression by multi-color flow cytometry. AML patients had significantly elevated soluble TIM-3 levels and similar soluble Gal-9 and CEACAM1 levels compared with healthy donors (p = 0.0003, 0.26 and 0.96). In the whole cohort, high soluble TIM-3 level was the sole independent adverse prognostic factor for relapse-free survival (RFS) (p = 0.0060), and it together with adverse ELN genetic risk were independent poor prognostic factors for event-free survival (EFS) (p = 0.0030 and 0.0040); High soluble CEACAM1 level were significantly related to lower RFS (p = 0.028). In addition, high soluble Gal-9 level had significant association with lower RFS in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the first complete remission (p = 0.037). Furthermore, soluble TIM-3 level tended to have positive correlation with the percentage of non-blast myeloid TIM-3+ cells in nucleated cells in AML (r = 0.48, p = 0.073). Therefore, the high soluble TIM-3 level in the diagnostic BM plasma predicted poor outcome in adult AML patients, and high sGal-9 level was associated with relapse after allo-HSCT.

RESUMO

We aimed to identify dynamic changes of lysine (K)-specific methyltransferase 2A partial tandem duplications (KMT2A-PTD) before and after haploidentical donor hematopoietic stem cell transplantation (HID HSCT) and explore the prognostic value of pre-transplantation levels of KMT2A-PTD in acute myeloid leukemia (AML) receiving HID HSCT. Consecutive 64 AML patients with KMT2A-PTD positivity at diagnosis receiving HID HSCT were included in this study. Patients with KMT2A-PTD ≥1% before HSCT had a slower decrease of KMT2A-PTD after HID HSCT. Patients with KMT2A-PTD ≥1% before HID HSCT had a higher cumulative incidence of relapse (36.4%, 95% confidence interval [CI]: 6.3%-66.5%) at 2 years after HSCT than those with KMT2A-PTD <1% (7.5%, 95% CI: 0.3%-14.7%, P = .010). In multivariable analysis, KMT2A-PTD ≥1% before HID HSCT was the only independent risk factor for relapse (hazard ratio [HR]: 4.90; 95% CI: 1.22-19.59; P = .025). Thus, pre-transplantation levels of KMT2A-PTD could predict relapse in AML patients following HID HSCT.

Assuntos

Luxações Articulares , Fraturas do Rádio , Fraturas da Ulna , Humanos , Luxações Articulares/cirurgia , Fraturas do Rádio/cirurgia , Fraturas do Rádio/diagnóstico por imagem , Masculino , Criança , Fraturas da Ulna/cirurgia , Fraturas da Ulna/diagnóstico por imagem , Articulação do Cotovelo/cirurgia , Articulação do Cotovelo/diagnóstico por imagem , Lesões no Cotovelo , Feminino

RESUMO

Aggregation-induced emission luminogens (AIEgens) that respond to mechanical force are increasingly used as force probes, memory devices, and advanced security systems. Most of the known mechanisms to modulate mechanoresponsive AIEgens have been based on changes in aggregation states, involving only physical alterations. Instances that employ covalent bond cleavage are still rare. We have developed a novel mechanochemical uncaging strategy to unveil AIEgens with diverse emission characteristics using engineered norborn-2-en-7-one (NEO) mechanophores. These NEO mechanophores were covalently integrated into polymer molecules and activated in both the solution and solid states. This activation resulted in highly tunable fluorescence upon immobilization through solidification or aggregation, producing blue, green, yellow, and orange-red emissions. By designing the caged and uncaged forms as donor-acceptor pairs for Förster resonance energy transfer (FRET), we achieved multicolor mechanofluorescence, effectively broadening the color spectrum to include white emission. Additionally, we computationally explored the electronic structures of activated NEOs, providing insights into the observed regiochemical effects of the substituents. This understanding, together with the novel luminogenic characteristics of the caged and activated species, provides a highly tunable reporter that traces progress with continuous color evolution. This advancement paves the way for future applications of mechanoresponsive materials in areas like damage detection and bioimaging.

RESUMO

The apoptosis resistance of myofibroblasts is a hallmark in the irreversible progression of pulmonary fibrosis (PF). While the underlying molecular mechanism remains elusive. In this study, we unveiled a previously unrecognized mechanism underlying myofibroblast apoptosis resistance during PF. Our investigation revealed heightened expression of mesenchyme homeobox 1 (MEOX1) in the lungs of idiopathic pulmonary fibrosis (IPF) patients and bleomycin-induced PF mice. Silencing MEOX1 significantly attenuated PF progression in mice. In vitro, we found a notable increase in MEOX1 expression in transforming growth factor-ß1 (TGF-ß1)-induced myofibroblasts. Silencing MEOX1 enhanced apoptosis of myofibroblasts. Mechanistically, we identified G-protein signaling pathway regulatory factor 4 (RGS4) as a critical downstream target of MEOX1, as predicted by bioinformatics analysis. MEOX1 enhanced apoptosis resistance by upregulating RGS4 expression in myofibroblasts. In conclusion, our study highlights MEOX1 as a promising therapeutic target for protecting against PF by modulating myofibroblast apoptosis resistance.

RESUMO

Over past two years, a total of 39,918 hematopoietic stem cell transplantation (HSCT) cases were reported, with 18,194 and 21,714 transplants performed in 2022 and 2023, respectively. Autologous HSCT accounted for 6562 cases (31%) in 2022, while allogeneic HSCT comprised 12,632 cases (69%). In 2023, the number of allogeneic HSCTs exceeded 15,000, maintaining a 69% share. Participation in the 2022 and 2023 surveys included 193 and 212 transplantation teams, respectively, from 27 provinces, municipalities, or autonomous regions. The leading indication of HSCT was acute leukemia, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and mixed phenotype acute leukemia, with a total of 17,421 cases. AML was the most common disease (10,339, 38%) for allogeneic HSCT, which was followed by ALL (5925 cases, 21%). Peripheral blood emerged as the primary source of stem cell grafts, utilized in 54% of matched sibling donor transplants and 77% of haploidentical donor transplants. The BuCy-based conditioning regimen was the most prevalent, used in 53% of allogeneic HSCT cases in the past two years. This survey offers a comprehensive overview of the current HSCT landscape and serves as a valuable resource for clinical practice.