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1.
Plant Physiol ; 195(2): 1414-1431, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38401160

RESUMO

Understanding somatic cell totipotency remains a challenge facing scientific inquiry today. Plants display remarkable cell totipotency expression, illustrated by single-cell differentiation during somatic embryogenesis (SE) for plant regeneration. Determining cell identity and exploring gene regulation in such complex heterogeneous somatic cell differentiation have been major challenges. Here, we performed high-throughput single-cell sequencing assays to define the precise cellular landscape and revealed the modulation mode of marker genes during embryogenic differentiation in cotton (Gossypium hirsutum L.) as the crop for biotechnology application. We demonstrated that nonembryogenic calli (NEC) and primary embryogenic calli (PEC) tissues were composed of heterogeneous cells that could be partitioned into four broad populations with six distinct cell clusters. Enriched cell clusters and cell states were identified in NEC and PEC samples, respectively. Moreover, a broad repertoire of new cluster-specific genes and associated expression modules were identified. The energy metabolism, signal transduction, environmental adaptation, membrane transport pathways, and a series of transcription factors were preferentially enriched in cell embryogenic totipotency expression. Notably, the SE-ASSOCIATED LIPID TRANSFER PROTEIN (SELTP) gene dose-dependently marked cell types with distinct embryogenic states and exhibited a parabolic curve pattern along the somatic cell embryogenic differentiation trajectory, suggesting that SELTP could serve as a favorable quantitative cellular marker for detecting embryogenic expression at the single-cell level. In addition, RNA velocity and Scissor analysis confirmed the pseudo-temporal model and validated the accuracy of the scRNA-seq data, respectively. This work provides valuable marker-genes resources and defines precise cellular taxonomy and trajectory atlases for somatic cell embryogenic differentiation in plant regeneration.


Assuntos
Diferenciação Celular , Regulação da Expressão Gênica de Plantas , Gossypium , Regeneração , Análise de Célula Única , Transcriptoma , Diferenciação Celular/genética , Transcriptoma/genética , Análise de Célula Única/métodos , Gossypium/genética , Gossypium/citologia , Gossypium/fisiologia , Gossypium/crescimento & desenvolvimento , Regeneração/genética , Técnicas de Embriogênese Somática de Plantas/métodos
2.
New Phytol ; 242(3): 1172-1188, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38501463

RESUMO

Somatic cell totipotency in plant regeneration represents the forefront of the compelling scientific puzzles and one of the most challenging problems in biology. How somatic embryogenic competence is achieved in regeneration remains elusive. Here, we discover uncharacterized organelle-based embryogenic differentiation processes of intracellular acquisition and intercellular transformation, and demonstrate the underlying regulatory system of somatic embryogenesis-associated lipid transfer protein (SELTP) and its interactor calmodulin1 (CAM1) in cotton as the pioneer crop for biotechnology application. The synergistic CAM1 and SELTP exhibit consistent dynamical amyloplast-plasmodesmata (PD) localization patterns but show opposite functional effects. CAM1 inhibits the effect of SELTP to regulate embryogenic differentiation for plant regeneration. It is noteworthy that callus grafting assay reflects intercellular trafficking of CAM1 through PD for embryogenic transformation. This work originally provides insight into the mechanisms responsible for embryogenic competence acquisition and transformation mediated by the Ca2+/CAM1-SELTP regulatory pathway, suggesting a principle for plant regeneration and cell/genetic engineering.


Assuntos
Proteínas de Transporte , Plantas , Organelas
3.
Plant J ; 103(2): 858-868, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32239588

RESUMO

As the gene pool is exposed to both strain on land resources and a lack of diversity in elite allotetraploid cotton, the acquisition and identification of novel alleles has taken on epic importance in facilitating cotton genetic improvement and functional genomics research. Ethyl methanesulfonate (EMS) is an excellent mutagen that induces genome-wide efficient mutations to activate the mutagenic potential of plants with many advantages. The present study established, determined and verified the experimental procedure suitable for EMS-based mutant library construction as the general reference guide in allotetraploid upland cotton. This optimized method and procedure are efficient, and abundant EMS mutant libraries (approximately 12 000) in allotetraploid cotton were successfully obtained. More than 20 mutant phenotypes were observed and screened, including phenotypes of the leaf, flower, fruit, fiber and plant architecture. Through the plants mutant library, high-throughput and high-resolution melting technology-based variation evaluation detected the EMS-induced site mutation. Additionally, based on overall genome-wide mutation analyses by re-sequencing and mutant library assessment, the examination results demonstrated the ideal quality of the cotton EMS-treated mutant library constructed in this study with appropriate high mutation density and saturated genome. What is more, the collection is composed of a broad repertoire of mutants, which is the valuable resource for basic genetic research and functional genomics underlying complex allotetraploid traits, as well as cotton breeding.


Assuntos
Metanossulfonato de Etila/metabolismo , Genoma de Planta/genética , Gossypium/genética , Mutagênicos/metabolismo , Mutação/genética , Tetraploidia , Metanossulfonato de Etila/farmacologia , Fertilidade/genética , Biblioteca Gênica , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Células Germinativas Vegetais , Germinação/genética , Gossypium/anatomia & histologia , Mutagênicos/farmacologia , Polimorfismo de Nucleotídeo Único/genética , Característica Quantitativa Herdável
4.
Br J Haematol ; 193(4): 761-768, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33559893

RESUMO

We performed a multicentre, non-randomised trial (NCT03533790) to investigate the efficacy of ruxolitinib combined with the doxorubicin-etoposide-methylprednisolone (Ru-DEP) regimen as a salvage therapy for refractory/relapsed haemophagocytic lymphohistiocytosis (HLH). All patients failing to achieve a complete or partial response 2 weeks after initial HLH-94/HLH-04 regimen or relapsed after remission were enrolled in the study between June 2018 and June 2019. The efficacy was evaluated 2 weeks after initiating Ru-DEP salvage therapy. Fifty-four eligible patients with refractory/relapsed (R/R) HLH were enrolled. One case could not be evaluated for efficacy. Excluding 12 patients who had previously received the DEP regimen, the overall response rate was 32 of 41 (78·0%) patients, with eight of 41 (19·5%) achieving complete response and 24 of 41 (58·5%) attaining a partial response. Of the R/R HLH patients who had previously received the DEP regimen, 7 of 12 (58·3%) achieved a partial response. Ferritin and soluble CD25 concentrations were significantly lower (P < 0·05), while the platelet count increased significantly (P = 0·034), and triglycerides decreased significantly (P = 0·002) compared with those before treatment. The Ru-DEP regimen may be a safe and effective salvage therapy, remaining effective in refractory/relapsed HLH following DEP treatment, especially in macrophage activation syndrome. In addition, the regimen can be considered for patients with contraindications to glucocorticoid, especially those with gastrointestinal bleeding.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Terapia de Salvação , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Lactente , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/mortalidade , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Nitrilas , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirimidinas
5.
Int J Mol Sci ; 21(2)2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31936561

RESUMO

The somatic embryogenesis (SE) process of plants is regulated by exogenous hormones. During the SE, different genes sensitively respond to hormone signals through complex regulatory networks to exhibit plant totipotency. When cultured in indole-3-butyric acid (IBA) concentration gradient medium supplemented with 0 mg dm-3, 0.025 mg dm-3, and 0.05 mg dm-3 IBA, the callus differentiation rate first increased then decreased in cotton. To characterize the molecular basis of IBA-induced regulating SE, transcriptome analysis was conducted on embryogenic redifferentiation. Upon the examination of the IBA's embryogenic inductive effect, it was revealed that pathways related to plant hormone signal transduction and alcohol degradation were significantly enriched in the embryogenic responsive stage (5 days). The photosynthesis, alcohol metabolism and cell cycle pathways were specifically regulated in the pre-embryonic initial period (20 days). Upon the effect of the IBA dose, in the embryogenic responsive stage (5 days), the metabolism of xenobiotics by the cytochrome P450 pathway and secondary metabolism pathways of steroid, flavonoid, and anthocyanin biosynthesis were significantly enriched. The phenylpropanoid, brassinosteroid, and anthocyanin biosynthesis pathways were specifically associated in the pre-embryonic initial period (20 days). At different developmental stages of embryogenic induction, photosynthesis, flavonoid biosynthesis, phenylpropanoid biosynthesis, mitogen-activated protein kinase (MAPK) signaling, xenobiotics metabolism by cytochrome P450, and brassinosteroid biosynthesis pathways were enriched at low a IBA concentration. Meanwhile, at high IBA concentration, the carbon metabolism, alcohol degradation, circadian rhythm and biosynthesis of amino acids pathways were significantly enriched. The results reveal that complex regulating pathways participate in the process of IBA-induced redifferentiation in cotton somatic embryogenesis. In addition, collections of potential essential signaling and regulatory genes responsible for dose IBA-induced efficient embryogenic redifferentiation were identified. Quantitative real-time PCR (qRT-PCR) was performed on the candidate genes with different expression patterns, and the results are basically consistent with the RNA-seq data. The results suggest that the complicated and concerted IBA-induced mechanisms involving multiple cellular pathways are responsible for dose-dependent plant growth regulator-induced SE. This report represents a systematic study and provides new insight into molecular signaling and regulatory basis underlying the process of dose IBA-induced embryogenic redifferentiation during SE.


Assuntos
Diferenciação Celular/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Gossypium/embriologia , Gossypium/genética , Indóis/farmacologia , Processamento Alternativo/genética , Diferenciação Celular/efeitos dos fármacos , Cromossomos de Plantas/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Gossypium/efeitos dos fármacos , Cinetina/farmacologia , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Anotação de Sequência Molecular , Reprodutibilidade dos Testes , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
6.
Int J Mol Sci ; 20(7)2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30987365

RESUMO

The somatic embryogenesis (SE) process of plants, as one of the typical responses to abiotic stresses with hormone, occurs through the dynamic expression of different proteins that constitute a complex regulatory network in biological activities and promotes plant totipotency. Plant SE includes two critical stages: primary embryogenic calli redifferentiation and somatic embryos development initiation, which leads to totipotency. The isobaric labels tandem mass tags (TMT) large-scale and quantitative proteomics technique was used to identify the dynamic protein expression changes in nonembryogenic calli (NEC), primary embryogenic calli (PEC) and globular embryos (GEs) of cotton. A total of 9369 proteins (6730 quantified) were identified; 805, 295 and 1242 differentially accumulated proteins (DAPs) were identified in PEC versus NEC, GEs versus PEC and GEs versus NEC, respectively. Eight hundred and five differentially abundant proteins were identified, 309 of which were upregulated and 496 down regulated in PEC compared with NEC. Of the 295 DAPs identified between GEs and PEC, 174 and 121 proteins were up- and down regulated, respectively. Of 1242 differentially abundant proteins, 584 and 658 proteins were up- and down regulated, respectively, in GEs versus NEC. We have also complemented the authenticity and accuracy of the proteomic analysis. Systematic analysis indicated that peroxidase, photosynthesis, environment stresses response processes, nitrogen metabolism, phytohormone response/signal transduction, transcription/posttranscription and modification were involved in somatic embryogenesis. The results generated in this study demonstrate a proteomic molecular basis and provide a valuable foundation for further investigation of the roles of DAPs in the process of SE transdifferentiation during cotton totipotency.


Assuntos
Transdiferenciação Celular/fisiologia , Gossypium/metabolismo , Proteínas de Plantas/metabolismo , Proteoma/metabolismo , Transdiferenciação Celular/genética , Desenvolvimento Embrionário/genética , Desenvolvimento Embrionário/fisiologia , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Gossypium/embriologia , Gossypium/genética , Proteínas de Plantas/genética , Proteômica
7.
Int J Mol Sci ; 20(9)2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31027387

RESUMO

Plant regeneration via somatic embryogenesis (SE) is a key step during genetic engineering. In the current study, integrated widely targeted metabolomics and RNA sequencing were performed to investigate the dynamic metabolic and transcriptional profiling of cotton SE. Our data revealed that a total of 581 metabolites were present in nonembryogenic staged calli (NEC), primary embryogenic calli (PEC), and initiation staged globular embryos (GE). Of the differentially accumulated metabolites (DAMs), nucleotides, and lipids were specifically accumulated during embryogenic differentiation, whereas flavones and hydroxycinnamoyl derivatives were accumulated during somatic embryo development. Additionally, metabolites related to purine metabolism were significantly enriched in PEC vs. NEC, whereas in GE vs. PEC, DAMs were remarkably associated with flavonoid biosynthesis. An association analysis of the metabolome and transcriptome data indicated that purine metabolism and flavonoid biosynthesis were co-mapped based on the Kyoto encyclopedia of genes and genomes (KEGG) database. Moreover, purine metabolism-related genes associated with signal recognition, transcription, stress, and lipid binding were significantly upregulated. Moreover, several classic somatic embryogenesis (SE) genes were highly correlated with their corresponding metabolites that were involved in purine metabolism and flavonoid biosynthesis. The current study identified a series of potential metabolites and corresponding genes responsible for SE transdifferentiation, which provides a valuable foundation for a deeper understanding of the regulatory mechanisms underlying cell totipotency at the molecular and biochemical levels.


Assuntos
Flavonoides/metabolismo , Gossypium/metabolismo , Purinas/metabolismo , Transdiferenciação Celular , Regulação da Expressão Gênica de Plantas/genética , Gossypium/genética , Metaboloma/genética , Metaboloma/fisiologia , Transcriptoma/genética
8.
Pediatr Blood Cancer ; 65(7): e27026, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29512932

RESUMO

BACKGROUND: The objective of this study was to evaluate the feasibility of a modified conditioning regimen for the treatment of patients with ß-thalassaemia major (TM), using unrelated donor peripheral blood stem cell transplantation (UD-PBSCT). METHODS: A modified conditioning regimen based on intravenous busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin was performed in 50 consecutive childhood patients with ß-TM and a median age of 4.6 years (range, 2-12 years). According to Pesaro's classification, three classes of risk are identified using the criteria of degree of hepatomegaly, portal fibrosis, and quality of the chelation treatment. Patients with three adverse criteria constituted class III, none of the adverse criteria constituted class I, and one or two of the adverse criteria formed class II. Ten patients were class I, 36 class II, and four class III. All patients were transplanted with UDs containing 37 of 10/10 human leukocyte antigen (HLA)-matched pairs, 11 of 9/10 matched pairs, and two of 8/10 matched pairs. The median follow-up was 36 months (range, 9-96 months). RESULTS: All patients successfully achieved engraftment, two of whom developed persistent thrombocytopaenia. The incidence of acute graft-versus-host disease (aGVHD) grade III-IV and chronic graft-versus-host disease (cGVHD) were 12% and 8%, respectively. However, 8.3% of HLA-matched and 15.4% of HLA-mismatched patients developed aGVHD. The incidence of severe bacterial infections and fungal pneumonia was 12% and 20%, respectively. The 3-year overall survival, disease-free survival, graft rejection, and transplant-related mortality were 94%, 92%, 2%, and 6%, respectively. CONCLUSION: This modified conditioning protocol effectively improved outcomes of UD-PBSCT for patients with ß-TM.


Assuntos
Rejeição de Enxerto/mortalidade , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Condicionamento Pré-Transplante , Talassemia beta/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Resultado do Tratamento , Doadores não Relacionados , Talassemia beta/complicações
9.
Pediatr Exerc Sci ; 30(2): 266-272, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28872417

RESUMO

PURPOSE: To determine if weight status modifies the relationship between motor skill (MS) performance and physical activity (PA) in preschoolers. METHODS: Preschoolers (N = 227, age 3-5 y) were recruited from 22 preschools. Preschoolers' MS (locomotor, object control, and total MS) were assessed with the Children's Activity and Movement in Preschool Study MS protocol. PA was measured by accelerometry. Mixed linear models were used to examine the relationship of MS performance and body mass index (BMI) z score to PA. Models were adjusted for age, race, sex, and parent education, with preschool as a random effect. RESULTS: There was a significant correlation between MS performance and PA (r = .14-.17, P < .05). A significant interaction was observed between BMI z score and object control, and between BMI z score and total MS score on PA (P = .03). Preschoolers with higher BMI z scores and high object control scores engaged in significantly (P = .03) more PA than preschoolers with lower BMI z scores and high object control scores (PA = 15.04 min/h and 13.54 min/h, respectively). Similarly, preschoolers with higher BMI z scores and high total MS scores spent significantly (P = .01) more time in PA compared with those with lower BMI z scores and high total MS scores (PA = 15.65 min/h and 13.91 min/h, respectively). CONCLUSION: Preschool children's MS performance is positively correlated with PA, and BMI z score modified the relationship between MS performance and PA.


Assuntos
Índice de Massa Corporal , Exercício Físico , Destreza Motora , Acelerometria , Pré-Escolar , Feminino , Humanos , Masculino
10.
Mol Genet Genomics ; 292(1): 37-52, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27679507

RESUMO

Light is a major environmental factor that affects metabolic pathways and stimulates the production of secondary metabolites in potato. However, adaptive changes in potato metabolic pathways and physiological functions triggered by light are partly explained by gene expression changes. Regulation of secondary metabolic pathways in potato has been extensively studied at transcriptional level, but little is known about the mechanisms of post-transcriptional regulation by miRNAs. To identify light-responsive miRNAs/mRNAs and construct putative metabolism pathways regulated by the miRNA-mRNA pairs, an integrated omics (sRNAome and transcriptome) analysis was performed to potato under light stimulus. A total of 31 and 48 miRNAs were identified to be differentially expressed in the leaves and tubers, respectively. Among the DEGs, 1353 genes in the leaves and 1841 genes in the tubers were upregulated, while 1595 genes in the leaves and 897 genes in the tubers were downregulated by light. Mapman enrichment analyses showed that genes related to MVA pathway, alkaloids-like, phenylpropanoids, flavonoids, and carotenoids metabolism were significantly upregulated, while genes associated with major CHO metabolism were repressed in the leaves and tubers. Integrated miRNA and mRNA profiles revealed that light-responsive miRNAs are important regulators in alkaloids metabolism, UMP salvage, lipid biosynthesis, and cellulose catabolism. Moreover, several miRNAs may participate in glycoalkaloids metabolism via JA signaling pathway, UDP-glucose biosynthesis and hydroxylation reaction. This study provides a global view of miRNA and mRNA expression profiles in potato response to light, our results suggest that miRNAs might play important roles in secondary metabolic pathways, especially in glycoalkaloid biosynthesis. The findings will enlighten us on the genetic regulation of secondary metabolite pathways and pave the way for future application of genetically engineered potato.


Assuntos
Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Transcriptoma , Regulação da Expressão Gênica de Plantas , Luz , Redes e Vias Metabólicas , MicroRNAs/genética , Folhas de Planta/genética , Tubérculos/genética , RNA Mensageiro/genética , RNA de Plantas/genética , Metabolismo Secundário
13.
Front Immunol ; 15: 1355314, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455059

RESUMO

Background: The aim of this study was to identify inflammatory biomarkers in traumatic proliferative vitreoretinopathy (TPVR) patients and further validate the expression curve of particular biomarkers in the rabbit TPVR model. Methods: The Olink Inflammation Panel was used to compare the differentially expressed proteins (DEPs) in the vitreous of TPVR patients 7-14 days after open globe injury (OGI) (N = 19) and macular hole patients (N = 22), followed by correlation analysis between DEPs and clinical signs, protein-protein interaction (PPI) analysis, area under the receiver operating characteristic curve (AUC) analysis, and function enrichment analysis. A TPVR rabbit model was established and expression levels of candidate interleukin family members (IL-6, IL-7, and IL-33) were measured by enzyme-linked immunosorbent assay (ELISA) at 0, 1, 3, 7, 10, 14, and 28 days after OGI. Results: Forty-eight DEPs were detected between the two groups. Correlation analysis showed that CXCL5, EN-RAGE, IL-7, ADA, CD5, CCL25, CASP8, TWEAK, and IL-33 were significantly correlated with clinical signs including ocular wound characteristics, PVR scoring, PVR recurrence, and final visual acuity (R = 0.467-0.699, p < 0.05), and all with optimal AUC values (0.7344-1). Correlations between DEP analysis and PPI analysis further verified that IL-6, IL-7, IL-8, IL-33, HGF, and CXCL5 were highly interactive (combined score: 0.669-0.983). These DEPs were enriched in novel pathways such as cancer signaling pathway (N = 14, p < 0.000). Vitreous levels of IL-6, IL-7, and IL-33 in the rabbit TPVR model displayed consistency with the trend in Olink data, all exhibiting marked differential expression 1 day following the OGI. Conclusion: IL-7, IL-33, EN-RAGE, TWEAK, CXCL5, and CD5 may be potential biomarkers for TPVR pathogenesis and prognosis, and early post-injury may be an ideal time for TPVR intervention targeting interleukin family biomarkers.


Assuntos
Vitreorretinopatia Proliferativa , Humanos , Coelhos , Animais , Vitreorretinopatia Proliferativa/diagnóstico , Vitreorretinopatia Proliferativa/etiologia , Vitreorretinopatia Proliferativa/metabolismo , Corpo Vítreo/metabolismo , Interleucina-33/metabolismo , Interleucina-6/metabolismo , Interleucina-7/metabolismo , Proteômica , Prognóstico , Biomarcadores/metabolismo
14.
Cell Death Dis ; 15(5): 344, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762508

RESUMO

Lupus nephritis (LN) occurs in 50% of cases of systemic lupus erythematosus (SLE) and is one of the most serious complications that can occur during lupus progression. Mesangial cells (MCs) are intrinsic cells in the kidney that can regulate capillary blood flow, phagocytose apoptotic cells, and secrete vasoactive substances and growth factors. Previous studies have shown that various types of inflammatory cells can activate MCs for hyperproliferation, leading to disruption of the filtration barrier and impairment of renal function in LN. Here, we characterized the heterogeneity of kidney cells of LN mice by single-nucleus RNA sequencing (snRNA-seq) and revealed the interaction between macrophages and MCs through the CXC motif chemokine ligand 12 (CXCL12)/dipeptidyl peptidase 4 (DPP4) axis. In culture, macrophages modulated the proliferation and migration of MCs through this ligand-receptor interaction. In LN mice, treatment with linagliptin, a DPP4 inhibitor, effectively inhibited MC proliferation and reduced urinary protein levels. Together, our findings indicated that targeting the CXCL12/DPP4 axis with linagliptin treatment may serve as a novel strategy for the treatment of LN via the CXCL12/DPP4 axis.


Assuntos
Proliferação de Células , Quimiocina CXCL12 , Dipeptidil Peptidase 4 , Nefrite Lúpica , Macrófagos , Células Mesangiais , Nefrite Lúpica/patologia , Nefrite Lúpica/metabolismo , Animais , Dipeptidil Peptidase 4/metabolismo , Quimiocina CXCL12/metabolismo , Células Mesangiais/metabolismo , Células Mesangiais/patologia , Células Mesangiais/efeitos dos fármacos , Camundongos , Macrófagos/metabolismo , Proliferação de Células/efeitos dos fármacos , Humanos , Feminino , Movimento Celular/efeitos dos fármacos , Comunicação Celular/efeitos dos fármacos , Linagliptina/farmacologia , Transdução de Sinais , Inibidores da Dipeptidil Peptidase IV/farmacologia , Camundongos Endogâmicos C57BL
15.
Biomater Sci ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916436

RESUMO

Symblepharon is an adverse ocular disease resulting in ocular discomfort and impaired vision, severely dragging down a patient's quality of life. Due to the specificity of the ocular surface, the retention time of drugs on it is short, leading to limited therapeutic effects for ocular diseases. Therefore, it is imperative to design a novel drug delivery system, which can not only prolong the retention time of a drug but also play an anti-fibrosis role in symblepharon. Herein, an antifouling supramolecular polymer ophthalmic ointment consisting of poly(N-acryloyl alaninamide) (PNAAA), vitamin C (VitC) and levofloxacin (Levo) was developed (termed PNAVL ophthalmic ointment), which acted as a mucoadhesive and long-acting ocular delivery system. This antifouling PNAVL ophthalmic ointment improved the retention time of VitC and Levo, and simultaneously provided anti-inflammation and anti-fibrosis effects for mitigating symblepharon after ocular alkali burn injury.

16.
Cancer Res Treat ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38810968

RESUMO

Purpose: The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored. Materials and Methods: On the basis of the non-Hodgkin's lymphoma Berlin-Frankfurt-Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL). Results: A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% [95% Confidence Interval (CI), 69.0%-83.9%] and 92.3% (95% CI,86.1%-95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5%-95.5%, and 67.9% (95% CI, 55.4%-77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6%-19.0%), 65.7% (95% CI, 47.6%-78.9%), 55.7% (95% CI, 26.2%-77.5%), and 70.7% (95% CI, 48.6%-84.6%), respectively. At the end of follow-up, one of the 5 patients who received maintenance therapy with VBL relapsed, and seven patients receiving ALK inhibitor maintenance therapy did not experience relapse. Conclusion: This study has confirmed the poor prognostic of MDD (+) ,high risk site and SC/LH ,but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).

17.
Water Sci Technol ; 68(5): 1055-62, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24037156

RESUMO

Wenchuan Earthquake triggered a large number of geological hazards, dramatically stimulating soil erosion. This study was carried out in Pengzhou County, Sichuan Province. By comparison of sediment, runoff and nutrient losses in earthquake-damaged forests (EF) and unaffected forests (UF), the actual status of soil erosion after the Wenchuan Earthquake was investigated by runoff plots. Results showed that water and soil losses were dramatically increased after earthquake. During the study period (from August to November 2010), UF runoffs were 19.26, 36.76, 10.68 and 7.51 L m(-2), while total runoffs in EF sites were 30.41, 25.79, 5.03 and 2.67 L m(-2) respectively, which were 15, 15, 18 and 19 times more than those in UF. Total sediment losses in EF sites were 28.94, 25.16, 4.11 and 1.98 t km(-2) respectively while in UF they were 707.69, 610.05, 113.43 and 58.95 t km(-2) respectively during the same study period, i.e. 23, 23, 32 and 29 times more than those in UF. Path analysis showed that both vegetation and rainfall exerted an indirect influence on sediment loss by significantly influencing runoff, which correlated with sediment loss very significantly. Although no obvious differences of the nutrients' concentration in runoff water (soluble organic carbon (SOC), total nitrogen (TN), total phosphorus (TP) and total potassium (TK)) between EF and UF sites were observed, total losses of the four nutrients were significantly higher in EF than in UF sites (for example, in EF sites, SOC, TN, TP and TK losses were 970.52, 114.46, 2.26 and 307.00 g m(-2) respectively, while in UF they were 38.13, 4.22, 0.10 and 13.28 g m(-2)) due to significantly higher runoff in EF sites. In conclusion, soil erosion was significantly more serious due to the loss of forested lands resulting from the Wenchuan Earthquake, delaying the restoring process of forest cover and weakening the ecological linkage between upstream and downstream.


Assuntos
Terremotos , Solo , Água , China , Monitoramento Ambiental , Sedimentos Geológicos/análise , Movimentos da Água
18.
Mar Environ Res ; 183: 105832, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36423460

RESUMO

Harmful algal blooms (HABs) are a frequent occurrence in China's offshore waters due to climate change and human activity, particularly in the Yangtze River Estuary and adjacent waters. Here, we studied HABs and their relationship with climatic and environmental factors in these waters from 1979 to 2016 using historical observations and reanalysis data. We then projected HABs frequency under various climate scenarios using the "environmental impact factor-frequency of HABs" mathematical model built using the BP neural network method and CIMP5 model data (RCP 2.6, RCP 4.5, and RCP 8.5). The results suggest a significant positive correlation between HABs frequency and seawater nutrient concentration, winter sea surface temperature, and low-wind days, and HABs frequency is anticipated to increase significantly by the 2040s compared with that of the historical era. Furthermore, future phytoplankton conditions are predicted to favor HAB species.


Assuntos
Proliferação Nociva de Algas , Rios , Humanos , Estuários , Fitoplâncton , Água do Mar
19.
Environ Sci Pollut Res Int ; 30(4): 10079-10098, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36064853

RESUMO

In order to deal with severe problems such as environmental pollution and climate change, the Chinese government has proposed the goal of carbon neutrality in 2030 and carbon peak in 2060. Strategic emerging industries have become key areas of high-quality growth of green economy. In order to solve the practical problems of insufficient funds and financing constraints, this paper empirically measures the financing efficiency of strategic emerging industries. Based on the Super Slack-Based Measure model, this paper selects the data analysis of listed companies in Beijing, Tianjin and Hebei from 2011 to 2020. At the same time, this paper systematically combs the index system that affects financing efficiency based on grounded theory. Based on the binary relation and structural level of adjacent matrix and reachable matrix, the explanatory analysis is carried out. On this basis, a systematic GMM model is established to explore the significance of different factors influencing financing efficiency. The research shows that the strategic emerging industry is still in the initial stage, the financing efficiency is not high and the financing output is insufficient. The factors affecting financing efficiency can be divided into 6 dimensions, 20 indicators in total and 5 multipole hierarchical levels. Credit financing, equity financing, financing constraints, technological innovation and government support are the important factors affecting financing efficiency.


Assuntos
Poluição do Ar , Carbono , Indústrias , Pequim , China , Mudança Climática , Desenvolvimento Econômico , Eficiência , Poluição do Ar/prevenção & controle
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