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1.
Angew Chem Int Ed Engl ; : e202416286, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39305074

RESUMO

Organic linker-based luminescent metal-organic frameworks (LMOFs) have received extensive attention due to their promising applications in chemical sensing, energy transfer, solid-state-lighting and heterogeneous catalysis. Benefiting from the virtually unlimited emissive organic linkers and the intrinsic advantages of MOFs, significant progress has been made in constructing LMOFs with specific emission behaviors and outstanding performances. Among these reported organic linkers, 2,1,3-benzothiadiazole and its derivatives, as unique building units with tunable electron-withdrawing abilities, can be used to synthesize numerous emissive linkers with a donor-bridge-acceptor-bridge-donor type structure. These linkers were utilized to coordinate with different metal nodes, forming LMOFs with diverse underlying nets and optical properties. In this Minireview, 2,1,3-benzothiadiazole and its derivative-based organic linkers and their corresponding LMOFs are summarized with which an emission library is built between the linker structures and the emission behaviors of constructed LMOFs. In particular, the preparation of LMOFs with customized emission properties ranging from deep-blue to near-infrared and sizes from dozens to hundreds of nanometers is discussed in detail. The applications of these LMOFs, including chemical sensing, energy harvesting and transfer, and catalysis, are then highlighted. Key perspectives and challenges for the future development of LMOFs are also addressed.

2.
Cell Mol Biol Lett ; 29(1): 123, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39277732

RESUMO

BACKGROUND: Loss-of-function mutations of ZBTB24 cause immunodeficiency, centromeric instability, and facial anomalies syndrome 2 (ICF2). ICF2 is a rare autosomal recessive disorder with immunological defects in serum antibodies and circulating memory B cells, resulting in recurrent and sometimes fatal respiratory and gastrointestinal infections. The genotype-phenotype correlation in patients with ICF2 indicates an essential role of ZBTB24 in the terminal differentiation of B cells. METHODS: We used the clustered regularly interspaced short palindromic repeats (CRISPER)/Cas9 technology to generate B cell specific Zbtb24-deficient mice and verified the deletion specificity and efficiency by quantitative polymerase chain reaction (Q-PCR) and western blotting analyses in fluorescence-activated cell sorting (FACS)-sorted cells. The development, phenotype of B cells and in vivo responses to T cell dependent or independent antigens post immunization were analyzed by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Adoptive transfer experiment in combination with in vitro cultures of FACS-purified B cells and RNA-Seq analysis were utilized to specifically determine the impact of Zbtb24 on B cell biology as well as the underlying mechanisms. RESULTS: Zbtb24 is dispensable for B cell development and maintenance in naive mice. Surprisingly, B cell specific deletion of Zbtb24 does not evidently compromise germinal center reactions and the resulting primary and secondary antibody responses induced by T cell dependent antigens (TD-Ags), but significantly inhibits T cell independent antigen-elicited antibody productions in vivo. At the cellular level, Zbtb24-deficiency specifically impedes the plasma cell differentiation of B1 cells without impairing their survival, activation and proliferation in vitro. Mechanistically, Zbtb24-ablation attenuates heme biosynthesis partially through mTORC1 in B1 cells, and addition of exogenous hemin abrogates the differentiation defects of Zbtb24-null B1 cells. CONCLUSIONS: Zbtb24 seems to regulate antibody responses against TD-Ags B cell extrinsically, but it specifically promotes the plasma cell differentiation of B1 cells via heme synthesis in mice. Our study also suggests that defected B1 functions contribute to recurrent infections in patients with ICF2.


Assuntos
Diferenciação Celular , Doenças da Imunodeficiência Primária , Fatores de Transcrição , Animais , Camundongos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Face/anormalidades , Síndromes de Imunodeficiência/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Doenças da Imunodeficiência Primária/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Fatores de Transcrição/metabolismo
3.
J Asian Nat Prod Res ; : 1-18, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39287960

RESUMO

This study aimed to investigate the effects of wild Cordyceps sinensis on chronic obstructive pulmonary disease (COPD) rats through metabolomics approach, combined with biochemical parameters evaluations. Consequently, C. sinensis exhibited regulatory effects on the lung's metabolic profiles in COPD rats. Treatment with C. sinensis potentially modulated glycerophospholipid metabolism, glutathione metabolism, and tryptophan metabolism, thereby alleviating oxidative stress (by decreasing MDA and GSSG, while increasing SOD and GSH) and inflammatory response (by inhibiting TNF-α, IL-8, and MMP-9) in COPD rats while improving lung tissue damage.

4.
J Sci Food Agric ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39291490

RESUMO

BACKGROUND: Carnosine, a natural bioactive dipeptide derived from meat muscle, possesses strong antioxidant properties. Dexamethasone, widely employed for treating various inflammatory diseases, raises concerns regarding its detrimental effects on bone health. This study aimed to investigate the protective effects of carnosine against dexamethasone-induced oxidative stress and bone impairment, along with its underlying mechanisms, utilizing chick embryos and a zebrafish model in vivo, as well as MC3T3-E1 cells in vitro. RESULTS: Our findings revealed that carnosine effectively mitigated bone injury in dexamethasone-exposed chick embryos, accompanied by reduced oxidative stress. Further investigation demonstrated that carnosine alleviated impaired osteoblastic differentiation in MC3T3-E1 cells and zebrafish by suppressing the excessive production of reactive oxygen species (ROS) and enhancing the activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPX). Moreover, mechanistic studies elucidated that carnosine promoted the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), thereby facilitating the transcription of its downstream antioxidant response elements, including heme oxyense-1 (HO-1), glutamate cysteine ligase modifier (GCLM), and glutamate cysteine ligase catalytic (GCLC) to counteract dexamethasone-induced oxidative stress. CONCLUSION: Overall, this study underscores the potential therapeutic efficacy of carnosine in mitigating oxidative stress and bone damage induced by dexamethasone exposure, shedding light on its underlying mechanism of action by activating the NRF2 signaling pathway. © 2024 Society of Chemical Industry.

5.
ACS Pharmacol Transl Sci ; 7(9): 2869-2877, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39296274

RESUMO

Synthetic DNAzyme-based structures enable dynamic cell regulation. However, engineering an effective and targeted DNAzyme-based structure to perform customizable multistep regulation remains largely unexplored. Herein, we designed a membrane-anchored DNAzyme-based molecular machine to implement dynamic inter- and intracellular cascade regulation, which realizes efficient T-cell/cancer cell interactions and subsequent receptor mediated cancer cell uptake. Using CD8+ T-cells and HeLa cancer cells as a proof of concept, we demonstrate that the designed DNAzyme-based molecular machine enables customized cascade regulation including (1) specific recognition between T-cells and cancer cells, (2) specific response and fluorescence sensing upon extracellular stimuli, and (3) cascade regulation including intercellular distance shortening, cell-cell communication, and intracellular delivery of anticancer drugs. Together, this work provides a promising pathway for customized cascade cell regulation based on a DNAzyme-based molecular machine, which enables enhanced cancer therapy by combining T-cell immunotherapy and chemotherapy.

6.
Micromachines (Basel) ; 15(9)2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39337799

RESUMO

Metal micro-droplet ejection technology has attracted attention for its potential applications in the rapid prototyping of micro-metal parts and microelectronic packaging. The current micro-droplet ejection device developed based on this technology faces challenges such as the requirement of a micro-oxygen ejection environment, a complex feeding structure, and high costs. Therefore, a drop-on-demand droplet generator for metallic pellets with impact feed ejection is designed in this paper. This device has a simple and compact structure, does not require a high-cost heat source, and can perform drop-on-demand ejection of metallic pellets in an atmospheric environment. A micro-channel feeding method based on piezoelectric ceramic actuator drives is proposed. A rigid dynamics metallic pellet flight trajectory model is established to analyze the relationships between the driving voltage and the flight trajectory of the pellets. With the help of Fluent to simulate and analyze the melting and ejection processes of the pellets inside the nozzle, the changes in the variable parameters of the flow field in the process of the melting and flight of a single molten drop are studied. The droplet generator produces stable droplets with a 500 µs pulse width and 1100 mm/s initial velocity of the projectile. The simulation results show that a single projectile has to go through three stages including feeding, melting, and ejecting, which take 39.5 ms, 7.85 ms, and 17.65 ms. The total simulation time is 65.0 ms. It is expected that the injection frequency of the metal projectile droplet-generating device will reach 15 Hz.

7.
J Food Sci ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39323284

RESUMO

Pingyin rose is an edible flower rich in anthocyanins. In this study, antioxidant capacity and color were used as the main evaluation indexes to investigate the effects of common physical and chemical factors on the stability of rose anthocyanin extracts (RAEs). In addition, the physicochemical properties of the whey protein isolate (WPI)-RAEs complex after spray drying were studied. Vitamin C, temperature, and some metal ions can cause different degrees of discoloration of RAEs solution. More importantly, heat treatment, as well as most metal ions and sugars, had no significant effect on the antioxidant capacity of RAEs solution (p > 0.05). Moreover, compared to spray-dried pure WPI, the WPI-RAEs powder was delicate and uniform, and had higher particle size, bulk density, moisture activity, and better gel properties. The release rate of all WPI-RAEs sol/gel to RAEs reached about 89% in the intestinal digestion stage, but the WPI-RAEs interaction reduced the digestibility of protein in the intestinal digestion stage. We hope that this study can provide a theoretical basis for the development and utilization of WPI-RAEs as food ingredients.

8.
Small ; : e2405887, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39248647

RESUMO

Covalent organic frameworks (COFs) have emerged as one of the most studied photocatalysts owing to their adjustable structure and bandgaps. However, there is limited research on regulating the light-harvesting capabilities of acceptor building blocks in donor-acceptor (D-A) isomer COFs with different bond orientations. This investigation is crucial for elucidating the structure-property-performance relationship of COF photocatalysts. Herein, a series of D-A isostructural COFs are synthesized with different imine bond orientations using benzothiadiazole and its derivatives-based organic building units. Extended light absorption is achieved in COFs with acceptor groups that have strong electron-withdrawing capacities, although this resulted a decreased hydrogen generation efficiency. Photocatalytic experiments indicated that dialdehyde benzothiadiazole-based COFs, HIAM-0015, exhibit the highest hydrogen generation rate (17.99 mmol g-1 h-1), which is 15 times higher than its isomer. The excellent photocatalytic performance of HIAM-0015 can be attributed to its fast charge separation and migration. This work provides insights into the rational design and synthesis of D-A COFs to achieve efficient photocatalytic activity.

9.
Diagn Pathol ; 19(1): 122, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39244586

RESUMO

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are rare but severe complications that occur after solid organ or allogeneic hematopoietic stem cell transplantations (allo-HSCT), with rapid progression and high mortality. Primary central nervous system (CNS)-PTLD are rarely recognized histo-pathologically. In addition, the diagnostic value of the Epstein-Barr virus (EBV) DNA copies in CNS-PTLD remains poorly understood. OBJECTIVES: We herein report a case of monomorphic EBV-associated CNS-PTLD (diffuse large B-cell lymphoma, DLBCL) after allo-HSCT and perform a meta-analysis to assess the efficacy of PTLD treatment strategies in recent years. METHODS: We present the case report covering clinical manifestations, diagnosis, treatment, and outcomes of a patient with primary CNS-PTLD. Additionally, we include a systematic review and meta-analysis of the clinical characteristics of 431 patients with PTLD after allo-HSCT. We evaluate the main treatment options and outcomes of PTLD management, including rituximab, chemotherapies, and autologous or human leukocyte antigen (HLA)-matched EBV-specific cytotoxic T lymphocyte infusion (EBV-CTLs)/donor lymphocyte infusion (DLI). RESULTS: The meta-analysis revealed an overall response rate of 69.0% for rituximab alone (95% CI: 0.47-0.84), 45.0% for rituximab plus chemotherapies (95% CI: 0.15-0.80), and 91.0% for rituximab plus EBV-CTLs/DLI (95% CI: 0.83-0.96). The complete response (CR) rate after treatments for PTLD was 67.0% (95% CI: 0.56-0.77). Moreover, the 6-month and 1-year overall survival (OS) rate was 64.0% (95% CI: 0.31-0.87) and 49.0% (95% CI: 0.31-0.68), respectively. CONCLUSIONS: This case highlighted the urgent need for effective, low-toxic treatment regimens for CNS-PTLD. Our meta-analysis suggested that rituximab combined with EBV-CTLs/DLI could be a favorable strategy for the management of PTLD after allo-HSCT.


Assuntos
Infecções por Vírus Epstein-Barr , Transplante de Células-Tronco Hematopoéticas , Transtornos Linfoproliferativos , Humanos , Infecções por Vírus Epstein-Barr/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 4/genética , Linfoma Difuso de Grandes Células B/virologia , Linfoma Difuso de Grandes Células B/terapia , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/terapia , Rituximab/uso terapêutico , Transplante Homólogo/efeitos adversos
10.
J Ginseng Res ; 48(5): 464-473, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39263312

RESUMO

Background: The effects of individual panaxadiol saponin and panaxatriol saponin on rodent models of Parkinson's disease (PD) have been recognized. However, it is not clear whether purified total ginsenosides as an entirety has effect against PD in rat model. This study compared the protective effects of a purified panaxadiol saponin fraction (PDSF), a purified panaxatriol saponin fraction (PTSF), and their mixtures against the rotenone (ROT)-induced PD in rats. Methods: Potential effects of PDSF, PTSF, and their mixtures against motor dysfunction and impairments of nigrostriatal dopaminergic neurons (DN), blood-brain barrier (BBB), cerebrovascular endothelial cells (CEC), and glial cells were measured in the models of ROT-induced PD rats and cell damage. Pro-inflammatory NF-kB p65 (p65) activation was localized in DN and other cells in the striatum. Results: PDSF and PTSF had a dose-dependent effect against motor dysfunction with a larger effective dose range for PDSF. PDSF protected CEC, glial cells, and DN in models of PD rats and cell damage, while PTSF had no such protections. Chronic ROT exposure potently activated p65 in CEC with enhanced pro-inflammatory and decreased anti-inflammatory factors and impaired BBB in the striatum, PDSF almost completely blocked the ROT-induced p65 activation and maintained both anti- and pro-inflammatory factors at normal levels and BBB integrity, but PTSF aggravated the p65 activation with impaired BBB. Furthermore, PTSF nullified all the effects of PDSF when they were co-administrated. Conclusion: PDSF had significant protective effect against the ROT-induced PD in rats by protecting CEC, glial cells, and DN, likely through inhibiting NF-κB p65 in CEC from triggering neuroinflammation, and also directly protecting glial cells and neurons against ROT-induced toxicity. PDSF has great potential for preventing and treating PD.

11.
RNA Biol ; 21(1): 1-7, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39219231

RESUMO

Argonaute proteins (Agos) represent a highly conserved family of proteins prevalent in all domains of life and have been implicated in various biological processes. Based on the domain architecture, Agos can be divided into long Agos and short Agos. While long Agos have been extensively studied over the past two decades, short Agos, found exclusively in prokaryotes, have recently gained attention for their roles in prokaryotic immune defence against mobile genetic elements, such as plasmids and phages. Notable functional and structural studies provide invaluable insights into the underlying molecular mechanisms of representative short Ago systems. Despite the diverse domain arrangements, short Agos generally form heterodimeric complexes with their associated effector proteins, activating the effector's enzymatic activities upon target detection. The activation of effector proteins in the short Ago systems leads to bacterial cell death, a mechanism of sacrificing individuals to protect the community.


Assuntos
Proteínas Argonautas , Proteínas Argonautas/metabolismo , Proteínas Argonautas/genética , Proteínas Argonautas/química , Bactérias/metabolismo , Bactérias/genética , Relação Estrutura-Atividade , Conformação Proteica , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Humanos , Modelos Moleculares
12.
Int Immunopharmacol ; 142(Pt A): 113064, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39243560

RESUMO

Sophora flavescens Ait. (SFA), an extensively utilized herb for the treatment of fevers, inflammatory disorders, ulcers and skin diseases related to bur, contains oxymatrine (OMT) as its principal active constituent. OMT exerts regulatory effects over inflammation, oxidative stress and apoptosis. Neutrophils, critical regulators of the inflammation response, have not been thoroughly elucidated regarding the protective properties and underlying mechanisms of OMT-mediated anti-inflammation. This study was aim to explore the protective effect of OMT on neutrophils under inflammatory conditions and delve into its potential mechanism. Leveraging the advantages of zebrafish, an animal model with a real-time dynamic observation system, we established an in vivo caudal fin wound model and a copper sulfate induced-inflammation model in zebrafish line Tg (mpx:GFP). The result revealed that OMT significantly attenuated neutrophil migration, upregulated the mRNA expression levels of JNK, casp3, mapk14a, mapkapk2a and map2k1 damaged by zebrafish caudal fin wound model, and downregulated mRNA expression levels of JNK, casp3, mapk14a, mapkapk2a and map2k1 in the copper sulfate injury model. In vitro experiments demonstrated that OMT modulated the chemotaxis response of primary neutrophils from mice, enhanced phagocytosis, reduced oxidative stress and alleviated inflammation level. We hypothesize that the OMT may exert its anti-inflammatory effects by regulating primary neutrophils through the MAPK signaling pathway.

13.
Asian J Androl ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39285693

RESUMO

Spermatogenesis is a fundamental process that requires a tightly controlled epigenetic event in spermatogonial stem cells (SSCs). The mechanisms underlying the transition from SSCs to sperm are largely unknown. Most studies utilize gene knockout mice to explain the mechanisms. However, the production of genetically engineered mice is costly and time-consuming. In this study, we presented a convenient research strategy using an RNA interference (RNAi) and testicular transplantation approach. Histone H3 lysine 9 (H3K9) methylation was dynamically regulated during spermatogenesis. As Jumonji domain-containing protein 1A (JMJD1A) and Jumonji domain-containing protein 2C (JMJD2C) demethylases catalyze histone H3 lysine 9 dimethylation (H3K9me2), we firstly analyzed the expression profile of the two demethylases and then investigated their function. Using the convenient research strategy, we showed that normal spermatogenesis is disrupted due to the downregulated expression of both demethylases. These results suggest that this strategy might be a simple and alternative approach for analyzing spermatogenesis relative to the gene knockout mice strategy.

14.
Angew Chem Int Ed Engl ; : e202414026, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39291884

RESUMO

Organic linker-based luminescent metal-organic frameworks (LMOFs) have received extensive studies due to the unlimited species of emissive organic linkers and tunable structure of MOFs. However, the multiple-step organic synthesis is always a great challenge for the development of LMOFs. As an alternative strategy, in situ "one-pot" strategy, in which the generation of emissive organic linkers and sequential construction of LMOFs happen in one reaction condition, can avoid time-consuming pre-synthesis of organic linkers. In the present work, we demonstrate the successful utilization of in situ "one-pot" strategy to construct a series of LMOFs via the single-site modification between the reaction of aldehydes and o-phenylenediamine-based tetratopic carboxylic acid. The resultant MOFs possess csq topology with emission covering blue to near-infrared. The nanosized LMOFs exhibit excellent sensitivity and selectivity for tryptophan detection. In addition, two component-based LMOFs can also be prepared via the in situ "one-pot" strategy and used to study energy transfer. This work not only reports the construction of LMOFs with full-color emissions, which can be utilized for various applications, but also indicates that in situ "one-pot" strategy indeed is a useful and powerful method to complement the traditional MOFs construction method for preparing porous materials with tunable functionalities and properties.

15.
Cell ; 187(19): 5253-5266.e16, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39173632

RESUMO

Horizontal gene transfer is a key driver of bacterial evolution, but it also presents severe risks to bacteria by introducing invasive mobile genetic elements. To counter these threats, bacteria have developed various defense systems, including prokaryotic Argonautes (pAgos) and the DNA defense module DdmDE system. Through biochemical analysis, structural determination, and in vivo plasmid clearance assays, we elucidate the assembly and activation mechanisms of DdmDE, which eliminates small, multicopy plasmids. We demonstrate that DdmE, a pAgo-like protein, acts as a catalytically inactive, DNA-guided, DNA-targeting defense module. In the presence of guide DNA, DdmE targets plasmids and recruits a dimeric DdmD, which contains nuclease and helicase domains. Upon binding to DNA substrates, DdmD transitions from an autoinhibited dimer to an active monomer, which then translocates along and cleaves the plasmids. Together, our findings reveal the intricate mechanisms underlying DdmDE-mediated plasmid clearance, offering fundamental insights into bacterial defense systems against plasmid invasions.


Assuntos
Proteínas de Bactérias , Transferência Genética Horizontal , Plasmídeos , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , DNA/metabolismo , DNA Helicases/metabolismo , DNA Bacteriano/metabolismo , DNA Bacteriano/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Modelos Moleculares , Plasmídeos/metabolismo , Plasmídeos/genética
16.
Small ; : e2405540, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39205545

RESUMO

The establishment of reticular chemistry has significantly facilitated the development of porous materials, especially for metal-organic frameworks (MOFs). On the other hand, as an alternative approach, in situ "one-pot" strategy has been explored as a promising approach to constructing MOFs, in which the synthesis of organic linkers and the sequential construction of MOFs are integrated into one solvothermal condition. This strategy can efficiently avoid the limitations faced in the traditional construction method, such as time-consuming organic synthesis and multiple separation and purification. Herein, inspired by the reaction of aldehydes and o-phenylenediamine and deep structural analysis of UiO-68, a series of tetra-, hexa-, and octa-topic carboxylic acids are synthesized using 2',3'-diamino-[1,1':4',1'"-terphenyl]-4,4'"-dicarboxylic acid and di-, tri-, and tetra-topic aldehydes as precursor. Then nine multicarboxylate-based zirconium MOFs (Zr-MOFs) are successfully constructed via the combination of reticular chemistry and in situ "one-pot" strategy. The resultant Zr-MOFs can be regarded as the partial face decoration of UiO-68. More importantly, the emission properties of resultant Zr-MOFs can be well controlled using aldehydes with tunable electronic structures. This work provides a new path to rational design and construction of porous materials with specific structures guided by reticular chemistry and conducted using in situ "one-pot" strategy.

17.
World J Clin Oncol ; 15(8): 1061-1077, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39193162

RESUMO

BACKGROUND: Chemoresistance is the primary contributor to distant metastasis in the context of neoadjuvant chemoradiotherapy (nCRT) for rectal cancer. However, the underlying mechanisms remain elusive. AIM: To detect the differential expression profiles of plasma exosomal microRNAs (miRNAs) in poor and good responders and explore the potential mechanisms of chemoresistance. METHODS: In this study, the profiles of plasma exosomal miRNAs were compared in two dimensions according to treatment responses (poor/good responders) and treatment courses (pre/post-nCRT) using RNA sequencing. RESULTS: Exosome hsa-miR-483-5p was up-regulated in good responders post-nCRT. Bioinformatics analysis revealed that the target genes of hsa-miR-483-5p were mainly enriched in tumor-specific pathways, such as the MAPK signaling pathway, EGFR tyrosine kinase inhibitor resistance, Toll-like receptor signaling pathway, VEGF signaling pathway, and mTOR signaling pathway. Further analysis indicated that MAPK3, RAX2, and RNF165 were associated with inferior recurrence-free survival in patients with rectal cancer, and the profiles of MAPK3, TSPYL5, and ZNF417 were correlated with tumor stage. In addition, the expression profiles of MAPK3, RNF165, and ZNF417 were negatively correlated with inhibitory concentration 50 values. Accordingly, an hsa-miR-483-5p/MAPK3/RNF 165/ZNF417 network was constructed. CONCLUSION: This study provides insights into the mechanism of chemoresistance in terms of exosomal miRNAs. However, further research is required within the framework of our established miRNA-mRNA network.

18.
Mitochondrial DNA B Resour ; 9(8): 1122-1126, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39170881

RESUMO

Semiaquilegia danxiashanensis is currently known only from the type locality, Danxia Mountain, characterized by its spectacular red sandstone cliffscape. In this study, we assembled the complete chloroplast genome sequence of S. danxiashanensis and inferred its phylogenetic relationships. Total length of the chloroplast genome was 160,548 bp, with an overall GC content of 39%. The chloroplast genome had typical quadripartite structure and contained one LSC region (89,882 bp) and one SSC region (17,386 bp), which were separated by two IRs regions (26,640 bp, respectively). It comprised 133 genes, including 84 protein coding genes, 41 tRNA genes and eight rRNA genes. The maximum likelihood phylogenetic analysis indicated that S. danxiashanensis was sister to S. adoxoides; meanwhile, Semiaquilegia was closely related to both Urophysa and Aquilegia in Ranunculaceae. This study sheds light on the evolutionary history of Semiaquilegia and provides preliminary data for future comparative analysis of chloroplast genomes.

19.
Drug Resist Updat ; 77: 101142, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39214042

RESUMO

The spread of antibiotic resistance genes (ARGs), particularly those carried on plasmids, poses a major risk to global health. However, the extent and frequency of ARGs transfer in microbial communities among human, animal, and environmental sectors is not well understood due to a lack of effective tracking tools. We have developed a novel fluorescent tracing tool, CRISPR-AMRtracker, to study ARG transfer. It combines CRISPR/Cas9 fluorescence tagging, fluorescence-activated cell sorting, 16S rRNA gene sequencing, and microbial community analysis. CRISPR-AMRtracker integrates a fluorescent tag immediately downstream of ARGs, enabling the tracking of ARG transfer without compromising the host cell's antibiotic susceptibility, fitness, conjugation, and transposition. Notably, our experiments demonstrate that sfGFP-tagged plasmid-borne mcr-1 can transfer across diverse bacterial species within fecal samples. This innovative approach holds the potential to illuminate the dynamics of ARG dissemination and provide valuable insights to shape effective strategies in mitigating the escalating threat of antibiotic resistance.

20.
Front Pharmacol ; 15: 1442022, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39139644

RESUMO

Background: Ovarian cancer (OC) is a gynecological malignancy with a high mortality rate worldwide. The unfavorable prognosis of OC is mainly attributed to the recurrent propensity. Recently, mortality from OC has exhibited a downward trend. These favorable patterns are likely to be driven by advancements in novel therapeutic regimens. However, there is a lack of visualize analysis of the application of these new drugs on women with recurrent OC (ROC). Therefore, we aimed to provide a bibliometric analysis of the evolving paradigms in the ROC treatment. Methods: Documents on ROC treatment were systematically collected from the MEDLINE database and Web of Science Core Collection (WOSCC). The retrieved documents were exported in the plain text file format, and files were named and saved to the paths specified by the Java application. Microsoft Excel (version 2010), Citespace (6.2.R4) and VOSviewer (1.6.19) were used for data analysis, and included the following: 1) annual publication trend; 2) contributions of countries, institutions and authors; 3) co-citation of journals and references; and 4) co-occurrence of keywords. Results: A total of 914 documents published in the MEDLINE and 9,980 ones in WOSCC were retrieved. There has been an upward trend in the productivity of publications on ROC treatment on by years. The United States was the leading contributor in this field, and the University of Texas System stood out as the most productive institution. Giovanni Scambia and Maurie Markman were the research leaders in the field of ROC treatment. The journal Gynecologic Oncology had the highest citation frequency. The reference entitled with "Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer" got highest centrality of 0.14 in the co-citation network. Keyword analysis revealed that the focus of current ROC treatment was on platinum-based anticancer drugs, paclitaxel, angiogenesis inhibitors (AIs), immune checkpoint inhibitors (ICIs) and poly (ADP-ribose) polymerase inhibitors (PARPis). Conclusion: Scholars from a multitude of countries have been instrumental in the advancement of ROC treatment. The research hotspots and trend in the field of predominantly originated from leading international journals and specialized periodicals focused on gynecologic oncology. Maintenance therapy using AIs or (and) PARPis has emerged as a significant complement to platinum-based chemotherapy for patients with ROC.

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