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1.
Ann Hematol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958702

RESUMO

This study aims to analyze the risk factors for the development of multidrug-resistant (MDR) and carbapenem-resistant (CR) bacteria bloodstream infection (BSI) in a patient with acute leukemia (AL) and the mortality in gram-negative bacteria (GNB) BSI. This is a retrospective study conducted at West China Hospital of Sichuan University, which included patients diagnosed with AL and concomitant GNB BSI from 2016 to 2021. A total of 206 patients with GNB BSI in AL were included. The 30-day mortality rate for all patients was 26.2%, with rates of 25.8% for those with MDR GNB BSI and 59.1% for those with CR GNB BSI. Univariate and multivariate analyses revealed that exposure to quinolones (Odds ratio (OR) = 3.111, 95% confidence interval (95%CI): 1.623-5.964, p = 0.001) within the preceding 30 days was an independent risk factor for MDR GNB BSI, while placement of urinary catheter (OR = 6.311, 95%CI: 2.478-16.073, p < 0.001) and exposure to cephalosporins (OR = 2.340, 95%CI: 1.090-5.025, p = 0.029) and carbapenems (OR = 2.558, 95%CI: 1.190-5.497, p = 0.016) within the preceding 30 days were independently associated with CR GNB BSI. Additionally, CR GNB BSI (OR = 2.960, 95% CI: 1.016-8.624, p = 0.047), relapsed/refractory AL (OR = 3.035, 95% CI: 1.265-7.354, p = 0.013), septic shock (OR = 5.108, 95% CI: 1.794-14.547, p = 0.002), platelets < 30 × 109/L before BSI (OR = 7.785, 95% CI: 2.055-29.492, p = 0.003), and inappropriate empiric antibiotic therapy (OR = 3.140, 95% CI: 1.171-8.417, p = 0.023) were independent risk factors for 30-day mortality in AL patients with GNB BSI. Prior antibiotic exposure was a significant factor in the occurrence of MDR GNB BSI and CR GNB BSI. CR GNB BSI increased the risk of mortality in AL patients with GNB BSI.

2.
Ann Surg Oncol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958801

RESUMO

BACKGROUND: Upper limb lymphedema (ULL) is a common and deliberating complication for breast cancer survivors (BCSs). Breast cancer survivors with ULL reported a wide range of symptoms. However, little is known about symptom patterns and interrelationships among them. This study was designed to explore symptom clusters and construct symptom networks of ULL-related symptoms among BCSs and to identify the core symptoms. METHODS: This study is a secondary data analysis using datasets from three cross-sectional studies of BCSs in China. A total of 341 participants with maximum interlimb circumference ≥2 cm and complete responses in Part I of the Breast Cancer and Lymphedema Symptom Experience Index were included. Symptom clusters were identified through principal component analysis, and multiple linear regression analysis was employed to explore factors associated with severity of overall ULL-related symptoms. A contemporaneous network with 20 frequently reported symptoms were constructed after controlling for covariates. RESULTS: Three symptom clusters, including lymph stasis symptom cluster, nerve symptom cluster, and movement limitation symptom cluster, were identified. Postsurgery time, axillary lymph node dissection, and radiotherapy were associated with the severity of ULL-related symptoms. Tightness (rs = 1.379; rscov = 1.097), tingling (rs = 1.264; rscov = 0.925), and firmness (rs = 1.170; rscov = 0.923) were the most central symptoms in both networks with and without covariates. CONCLUSIONS: Breast cancer survivors with ULL experienced severe symptom burden. Tightness, tingling, and firmness were core symptoms of ULL among BCSs. Our findings demonstrated that the assessment and targeted intervention of specific core symptoms might help to relive effectively the burden of ULL-related symptom among BCSs.

4.
Gastroenterol Res Pract ; 2024: 8882667, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966598

RESUMO

Background and Aims: Acute liver injury (ALI) often follows biliary acute pancreatitis (BAP), but the exact cause and effective treatment are unknown. The aim of this study was to investigate the role of the gut microflora-bile acids-liver axis in BAP-ALI in mice and to assess the potential therapeutic effects of Yinchenhao decoction (YCHD), a traditional Chinese herbal medicine formula, on BAP-ALI. Methods: Male C57BL/6 mice were allocated into three groups: negative control (NC), BAP model, and YCHD treatment groups. The severity of BAP-ALI, intrahepatic bile acid levels, and the gut microbiota were assessed 24 h after BAP-ALI induction in mice. Results: Our findings demonstrated that treatment with YCHD significantly ameliorated the severity of BAP-ALI, as evidenced by the mitigation of hepatic histopathological changes and a reduction in liver serum enzyme levels. Moreover, YCHD alleviated intrahepatic cholestasis and modified the composition of bile acids, as indicated by a notable increase in conjugated bile acids. Additionally, 16S rDNA sequencing analysis of the gut microbiome revealed distinct alterations in the richness and composition of the microbiome in BAP-ALI mice compared to those in control mice. YCHD treatment effectively improved the intestinal flora disorders induced by BAP-ALI. Spearman's correlation analysis revealed a significant association between the distinct compositional characteristics of the intestinal microbiota and the intrahepatic bile acid concentration. Conclusions: These findings imply a potential link between gut microbiota dysbiosis and intrahepatic cholestasis in BAP-ALI mice and suggest that YCHD treatment may confer protection against BAP-ALI via the gut microflora-bile acids-liver axis.

5.
Carbohydr Polym ; 341: 122309, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38876712

RESUMO

Room temperature phosphorescence (RTP) materials with wood as framework are highly desirable due to their extended afterglow, high haze and good mechanical properties, which is highly desired in lighting materials. However, it remains challenging to obtain wood-based RTP materials that possess on-demand afterglow colors while maintaining high transparency across the entire visible spectrum. In this study, long-persistent phosphorescent transparent composite with tunable afterglow color is fabricated by infiltrating delignified wood with phosphors (including carbazole, naphthalene, and pyrene) doped polymethyl methacrylate (PMMA). Such RTP woods indicate remarkable transparency, over 70 %, and an extended afterglow duration of up to 8 s. Here, PMMA serves as rigid surrounding to suppress the non-radiative transition of phosphors to ensure phosphorescence, and to fulfill in the wood lumen to match the refractive index of cellulose for transparency. By formulating phosphors with different types and concentration ratios, transparent woods with diverse phosphorescence colors, and white emission, are successfully achieved. Furthermore, the RTP woods demonstrate dynamically tunable afterglow colors over time based on the varied phosphorescent lifetimes. Characterized by their high transparency and tunable colors, these natural wood-based RTP materials have great potentials for application in the fields of LED materials, optics, and building materials.

6.
J Trace Elem Med Biol ; 85: 127488, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38905877

RESUMO

BACKGROUND: Aluminum exerts neurotoxic effects through various mechanisms, mainly manifested as impaired learning and memory function. METHODS: Forty SD rats were divided into 0, 10, 20, and 40 mM maltol aluminum [Al(mal)3] groups. Cell experiments are divided into 0, 100, 200, and 400 µM Al(mal)3 dose group and control, Al(mal)3, Al(mal)3+inhibitor NC, Al(mal)3+miR-665 inhibitor intervention group. Water maze was used to detect the learning and memory function of rats, HE staining was used to observe the morphology and number of neurons in the CA1 area of the rat hippocampus, Flow cytometry was used to detect the apoptosis of PC12 cells, PCR and Western blotting were used to detect the expression of Caspase3, miR-665 and GNB3/PI3K/AKT proteins. The target binding relationship between miR-665 and GNB3 was verified by double luciferase reporter gene experiment. RESULTS: In vivo experimental results showed that with the increase of Al(mal)3 concentration, the escape latency of rats was prolonged, the target quadrant dwell time was shortened, and the number of crossing platform was reduced. Moreover, the arrangement of neurons was loose and the number decreased; the expression of Caspase3 and miR-665 increased, while the expression of GNB3/PI3K/AKT proteins decreased. In vitro experiments, with the increase of Al(mal)3 concentration, apoptosis rate of PC12 cells increased, the expression of Caspase3, miR-665 and GNB3/PI3K/AKT proteins were consistent with rat results. After inhibiting miR-665 in the intervention group experiment, apoptosis rate of PC12 cells in the aluminum exposure group decreased, the expression of Caspase3 and miR-665 decreased, and the expression of GNB3/PI3K/AKT proteins increased. CONCLUSION: MiR-665 plays an important role in aluminum induced neuronal apoptosis by targeting GNB3 and regulating the PI3K/AKT pathway.

7.
Disasters ; : e12628, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38872615

RESUMO

This study combined network analysis with message-level content analysis to investigate patterns of information flow and to examine messages widely distributed on social media during Hurricane Irma of 2017. The results show that while organisational users and media professionals dominated the top 100 information sources, individual citizens played a critical role in information dissemination. Public agencies should increase their retweeting activities and share the information posted by other trustworthy sources; doing so will contribute to the timely exchange of vital information during a disaster. This study also identified the active involvement of nonprofit organisations as information brokers during the post-event stage, indicating the potential for emergency management organisations to integrate their communication efforts into those of nonprofit entities. These findings will inform emergency management practices regarding implementation of communication plans and policies, facilitate the embracement of new partner organisations, and help with establishing and sustaining effective communication ties with a wide range of stakeholders.

8.
Eur J Pharmacol ; 977: 176756, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38897021

RESUMO

Repeated exposure to propofol during early brain development is associated with anxiety disorders in adulthood, yet the mechanisms underlying propofol-induced susceptibility to anxiety disorders remain elusive. The lateral septum (LS), primarily composed of γ-aminobutyric acidergic (GABAergic) neurons, serves as a key brain region in the regulation of anxiety. However, it remains unclear whether LS GABAergic neurons are implicated in propofol-induced anxiety. Therefore, we conducted c-Fos immunostaining of whole-brain slices from mice exposed to propofol during early life. Our findings indicate that propofol exposure activates GABAergic neurons in the LS. Selective activation of LS GABAergic neurons resulted in increased anxiety-like behavior, while selective inhibition of these neurons reduced such behaviors. These results suggest that the LS is a critical brain region involved in propofol-induced anxiety. Furthermore, we investigated the molecular mechanism of propofol-induced anxiety in the LS. Microglia activation underlies the development of anxiety. Immunofluorescence staining and Western blot analysis of LS revealed activated microglia and significantly elevated levels of phospho-NF-κB p65 protein. Additionally, a decrease in the number of neuronal spines was observed. Our study highlights the crucial role of the LS in the development of anxiety-like behavior in adulthood following childhood propofol exposure, accompanied by the activation of inflammatory pathways.


Assuntos
Ansiedade , Comportamento Animal , Neurônios GABAérgicos , Microglia , Propofol , Propofol/farmacologia , Animais , Ansiedade/induzido quimicamente , Camundongos , Masculino , Neurônios GABAérgicos/efeitos dos fármacos , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/patologia , Comportamento Animal/efeitos dos fármacos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Camundongos Endogâmicos C57BL , Fator de Transcrição RelA/metabolismo , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/patologia , Espinhas Dendríticas/metabolismo
9.
Nat Commun ; 15(1): 4703, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830868

RESUMO

Nuclear factor erythroid 2-related factor 2 (NRF2) hyperactivation has been established as an oncogenic driver in a variety of human cancers, including non-small cell lung cancer (NSCLC). However, despite massive efforts, no specific therapy is currently available to target NRF2 hyperactivation. Here, we identify peptidylprolyl isomerase A (PPIA) is required for NRF2 protein stability. Ablation of PPIA promotes NRF2 protein degradation and blocks NRF2-driven growth in NSCLC cells. Mechanistically, PPIA physically binds to NRF2 and blocks the access of ubiquitin/Kelch Like ECH Associated Protein 1 (KEAP1) to NRF2, thus preventing ubiquitin-mediated degradation. Our X-ray co-crystal structure reveals that PPIA directly interacts with a NRF2 interdomain linker via a trans-proline 174-harboring hydrophobic sequence. We further demonstrate that an FDA-approved drug, cyclosporin A (CsA), impairs the interaction of NRF2 with PPIA, inducing NRF2 ubiquitination and degradation. Interestingly, CsA interrupts glutamine metabolism mediated by the NRF2/KLF5/SLC1A5 pathway, consequently suppressing the growth of NRF2-hyperactivated NSCLC cells. CsA and a glutaminase inhibitor combination therapy significantly retard tumor progression in NSCLC patient-derived xenograft (PDX) models with NRF2 hyperactivation. Our study demonstrates that targeting NRF2 protein stability is an actionable therapeutic approach to treat NRF2-hyperactivated NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Proteína 1 Associada a ECH Semelhante a Kelch , Neoplasias Pulmonares , Fator 2 Relacionado a NF-E2 , Peptidilprolil Isomerase , Estabilidade Proteica , Ubiquitinação , Animais , Feminino , Humanos , Camundongos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Progressão da Doença , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Camundongos Nus , Fator 2 Relacionado a NF-E2/metabolismo , Proteólise , Peptidilprolil Isomerase/metabolismo
10.
Environ Res ; 258: 119480, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909948

RESUMO

In this study, g-C3N4/PANI was prepared by in situ oxidative polymerization. Graphite-phase carbon nitride (g-C3N4) with surface defects was deposited onto the surface of conductive polyaniline (PANI) to form a p-n heterojunction. This construction aimed to create an efficient heterogeneous catalyst, increasing the surface defect level and active sites of the composite, and augmenting its capability to capture and transfer extracellular electrons under anaerobic conditions. This addresses the challenge of low efficiency in direct interspecies electron transfer between bacteria and archaea during anaerobic digestion for methane production. The results showed that the prepared g-C3N4/PANI increased the CH4 yield and CH4 production rate by 82% and 96%, respectively. Notably, the conductivity and XPS test results showed that the ratio of g-C3N4 to PANI was 0.15, and the composite exhibited favorable conductivity, with a uniform distribution of pyrrolic nitrogen, pyridinic nitrogen, and graphitic nitrogen, each accounting for approximately 30%. Furthermore, g-C3N4/PANI effectively enhanced the metabolic efficiency of intermediate products such as acetate and butyrate. Analysis of the microbial community structure revealed that g-C3N4/PANI led to a significant increase in the abundance of hydrogenotrophic methanogen Methanolinea (from 48% to 64%) and enriched Clostridium (a rise of 1%) with direct interspecies electron transfer capability. Microbial community function analysis demonstrated that the addition of g-C3N4/PANI boosted the activities of key enzymes involved in anaerobic digestion, including phosphate transacetylase (PTA), phospho-butyryl transferase (PTB), and NAD-independent lactate dehydrogenase (NNLD), by 47%, 135%, and 153%, respectively. This acceleration in enzymatic activity promoted the metabolism of acetyl-CoA, butyryl-CoA, and pyruvate. Additionally, the function of ABC transporters was enhanced, thereby improving the efficiency of material and energy exchange among microorganisms.

11.
Oecologia ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829403

RESUMO

Knowledge of the effect of harsh weather on the phenotypic traits of organisms is essential for understanding the environmental influence on phenotype evolution and holds implications for predicting how species respond to current climate change. For many birds, harsh weather in winter often imposes a strong selective effect on their survival, and only the individuals with certain phenotypes may survive. However, whether the selective effect on phenotype varies with winter weather conditions has been poorly investigated. Here, we explored the selective effect of winter weather on black-throated tit's (Aegithalos concinnus) morphological traits under winters with and without severe snowstorms. We found that for males, the sizes of their bills, heads and wings significantly affected their overwinter survival, but the effects varied with winter conditions. In relatively benign winters, males with smaller bill depths, smaller bill surface areas, and greater head lengths survived better; whereas, in winters with severe snowstorms, a reverse pattern was found. This phenomenon was likely driven by selection pressures from heat retention and foraging requirements, with their relative importance depending on winter conditions. Additionally, wing length was positively correlated with male survival and the relationship was stronger in harsher winters, which was probably due to longer wings' higher flight efficiency in adverse weather. By contrast, we found no correlation between morphological traits and survival in females. These results suggest a sex-specific and condition-dependent selective effect of environment on bird phenotypes, implying complicated interactions between different selection pressures and phenotype evolution.

12.
Neurochem Res ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864944

RESUMO

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease with a challenging treatment landscape, due to its complex pathogenesis and limited availability of clinical drugs. Ferroptosis, an iron-dependent form of programmed cell death (PCD), stands distinct from apoptosis, necrosis, autophagy, and other cell death mechanisms. Recent studies have increasingly highlighted the role of iron deposition, reactive oxygen species (ROS) accumulation, oxidative stress, as well as systemic Xc- and glutamate accumulation in the antioxidant system in the pathogenesis of amyotrophic lateral sclerosis. Therefore, targeting ferroptosis emerges as a promising strategy for amyotrophic lateral sclerosis treatment. This review introduces the regulatory mechanism of ferroptosis, the relationship between amyotrophic lateral sclerosis and ferroptosis, and the drugs used in the clinic, then discusses the current status of amyotrophic lateral sclerosis treatment, hoping to provide new directions and targets for its treatment.

13.
Drug Des Devel Ther ; 18: 2485-2529, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919962

RESUMO

Ferroptosis, a unique form of programmed cell death, is initiated by an excess of iron accumulation and lipid peroxidation-induced damage. There is a growing body of evidence indicating that ferroptosis plays a critical role in the advancement of tumors. The increased metabolic activity and higher iron levels in tumor cells make them particularly vulnerable to ferroptosis. As a result, the targeted induction of ferroptosis is becoming an increasingly promising approach for cancer treatment. This review offers an overview of the regulatory mechanisms of ferroptosis, delves into the mechanism of action of traditional small molecule ferroptosis inducers and their effects on various tumors. In addition, the latest progress in inducing ferroptosis using new means such as proteolysis-targeting chimeras (PROTACs), photodynamic therapy (PDT), sonodynamic therapy (SDT) and nanomaterials is summarized. Finally, this review discusses the challenges and opportunities in the development of ferroptosis-inducing agents, focusing on discovering new targets, improving selectivity, and reducing toxic and side effects.


Assuntos
Antineoplásicos , Ferroptose , Neoplasias , Ferroptose/efeitos dos fármacos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Fotoquimioterapia , Animais , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/química
14.
Front Neurosci ; 18: 1367649, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933817

RESUMO

Background: The rehabilitation of central post-stroke pain (CPSP) is a complex clinical challenge, and repetitive transcranial magnetic stimulation (rTMS) has been widely applied in the research of neurofunctional recovery following stroke. However, there is currently no reliable evidence-based medicine supporting the efficacy of rTMS in central post-stroke pain. This review aims to evaluate the effects of rTMS on central post-stroke pain. Methods: Following the PRISMA guidelines, we conducted searches on PubMed, Cochrane Library, Embase, Web of Science, CNKI, and Wan Fang Data Knowledge Service Platform. We searched for randomized controlled trials (RCTs) investigating the use of rTMS in treating central post-stroke pain, and conducted screening based on inclusion and exclusion criteria. Characteristics of the included RCTs were extracted. The heterogeneity of the trials was assessed using the I2 statistic. Meta-analysis was performed using Stata 17 software. Bias risk and methodological quality were evaluated using the Cochrane RoB 2 tool and the Pedro scale. Results: A total of six randomized controlled trials involving 288 patients met our inclusion criteria. In our analysis, rTMS was more effective in treating patients with CPSP compared to the placebo group (SMD=-1.15, 95% CI: -1.69, -0.61, P < 0.001). Furthermore, results from subgroup analysis indicated no statistically significant difference in the improvement of pain for durations exceeding 6 months when comparing rTMS to conventional treatment (SMD=-0.80, 95% CI: -1.63, 0.03, P = 0.059). Conclusion: TMS can alleviate pain in CPSP patients and improve their motor function, but its effects on depression, anxiety, and MEP-latency are not significant. Systematic review registration: https://www.crd.york.ac.uk/prospero/, CRD42024497530.

15.
BMC Genomics ; 25(1): 626, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902625

RESUMO

BACKGROUND: Wheat grain endosperm is mainly composed of proteins and starch. The contents and the overall composition of seed storage proteins (SSP) markedly affect the processing quality of wheat flour. Polyploidization results in duplicated chromosomes, and the genomes are often unstable and may result in a large number of gene losses and gene rearrangements. However, the instability of the genome itself, as well as the large number of duplicated genes generated during polyploidy, is an important driving force for genetic innovation. In this study, we compared the differences in starch and SSP, and analyzed the transcriptome and metabolome among Aegilops sharonensis (R7), durum wheat (Z636) and amphidiploid (Z636×R7) to reveal the effects of polyploidization on the synthesis of seed reserve polymers. RESULTS: The total starch and amylose content of Z636×R7 was significantly higher than R7 and lower than Z636. The gliadin and glutenin contents of Z636×R7 were higher than those in Z636 and R7. Through transcriptome analysis, there were 21,037, 2197, 15,090 differentially expressed genes (DEGs) in the three comparison groups of R7 vs Z636, Z636 vs Z636×R7, and Z636×R7 vs R7, respectively, which were mainly enriched in carbon metabolism and amino acid biosynthesis pathways. Transcriptome data and qRT-PCR were combined to analyze the expression levels of genes related to storage polymers. It was found that the expression levels of some starch synthase genes, namely AGP-L, AGP-S and GBSSI in Z636×R7 were higher than in R7 and among the 17 DEGs related to storage proteins, the expression levels of 14 genes in R7 were lower than those in Z636 and Z636×R7. According to the classification analysis of all differential metabolites, most belonged to carboxylic acids and derivatives, and fatty acyls were enriched in the biosynthesis of unsaturated fatty acids, niacin and nicotinamide metabolism, one-carbon pool by folate, etc. CONCLUSION: After allopolyploidization, the expression of genes related to starch synthesis was down-regulated in Z636×R7, and the process of starch synthesis was inhibited, resulting in delayed starch accumulation and prolongation of the seed development process. Therefore, at the same development time point, the starch accumulation of Z636×R7 lagged behind that of Z636. In this study, the expression of the GSe2 gene in Z636×R7 was higher than that of the two parents, which was beneficial to protein synthesis, and increased the protein content. These results eventually led to changes in the synthesis of seed reserve polymers. The current study provided a basis for a greater in-depth understanding of the mechanism of wheat allopolyploid formation and its stable preservation, and also promoted the effective exploitation of high-value alleles.


Assuntos
Aegilops , Sementes , Triticum , Triticum/genética , Triticum/metabolismo , Aegilops/genética , Aegilops/metabolismo , Sementes/genética , Sementes/metabolismo , Hibridização Genética , Poliploidia , Amido/biossíntese , Amido/metabolismo , Transcriptoma , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Proteômica/métodos , Multiômica
16.
Angew Chem Int Ed Engl ; : e202405781, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38782734

RESUMO

Synthesis of bicyclic scaffolds has gained significant attention in drug discovery due to their potential to mimic benzene bioisosteres. Here, we present a mild and scalable Sc(OTf)3-catalyzed [3+2] cycloaddition of bicyclo[1.1.0]butanes (BCBs) with ynamides, yielding a diverse array of polysubstituted 2-amino-bicyclo[2.1.1]hexenes in good to excellent yields. These products offer valuable starting materials for the construction of novel functionalized bicyclo[1.1.0]butanes. Preliminary mechanistic studies indicate that the reaction involves a nucleophilic addition of ynamides to bicyclo[1.1.0]butanes, followed by an intramolecular cyclization of in situ generated enolate and keteniminium ion. We expect that these findings will encourage utilization of complex bioisosteres and foster further investigation into BCB-based cycloaddition chemistry.

17.
MedComm (2020) ; 5(5): e553, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38737469

RESUMO

The generation of chimeric antigen receptor-modified natural killer (CAR-NK) cells using induced pluripotent stem cells (iPSCs) has emerged as one of the paradigms for manufacturing off-the-shelf universal immunotherapy. However, there are still some challenges in enhancing the potency, safety, and multiple actions of CAR-NK cells. Here, iPSCs were site-specifically integrated at the ribosomal DNA (rDNA) locus with interleukin 24 (IL24) and CD19-specific chimeric antigen receptor (CAR19), and successfully differentiated into iPSC-derived NK (iNK) cells, followed by expansion using magnetic beads in vitro. Compared with the CAR19-iNK cells, IL24 armored CAR19-iNK (CAR19-IL24-iNK) cells showed higher cytotoxic capacity and amplification ability in vitro and inhibited tumor progression more effectively with better survival in a B-cell acute lymphoblastic leukaemia (B-ALL) (Nalm-6 (Luc1))-bearing mouse model. Interestingly, RNA-sequencing analysis showed that IL24 may enhance iNK cell function through nuclear factor kappa B (NFκB) pathway-related genes while exerting a direct effect on tumor cells. This study proved the feasibility and potential of combining IL24 with CAR-iNK cell therapy, suggesting a novel and promising off-the-shelf immunotherapy strategy.

18.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2478-2488, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812147

RESUMO

In order to analyze the similarities and differences of chemical compositions between the roots and stems and leaves of Isodon japonicus(IJ), this study utilized UPLC-Q-TOF-MS technology to systematically characterize its chemical compositions, analyzed and identified the structure of its main compounds, and established a method for simultaneous determination of its content by refe-rence substance. A total of 34 major compounds in IJ, including 14 reference compounds, were identified or predicted online. Moreover, an UPLC-UV content determination method was developed for 11 compounds [danshensu, caffeic acid, vicenin-2,(1S,2S)-globoidnan B, rutin,(+)-rabdosiin,(-)-rabdosiin,(1S,2S)-rabdosiin, shimobashiric acid C, rosmarinic acid, and pedalitin]. The method exhibited excellent separation, stability, and repeatability, with a wide linear range(0.10-520.00 µg·mL~(-1)) and high linearity(R~2>0.999). The average recovery rates ranged from 94.72% to 104.2%. The principal component analysis(PCA) demonstrated a clear difference between the roots and stems and leaves of IJ, indicating good separation by cluster. Furthermore, the orthogonal partial least squares discriminant analysis(OPLS-DA) model was employed, and six main differentially identified compounds were identified: rosmarinic acid, shimobashiric acid C, epinodosin, pedalitin, rutin, and(1S,2S)-rabdosiin. In summary, this study established a strategy and method for distinguishing different parts of IJ, providing a valuable tool for quality control of IJ and a basis for the ratio-nal utilization and sustainable development of IJ.


Assuntos
Quimiometria , Medicamentos de Ervas Chinesas , Isodon , Espectrometria de Massas , Folhas de Planta , Cromatografia Líquida de Alta Pressão/métodos , Isodon/química , Espectrometria de Massas/métodos , Quimiometria/métodos , Folhas de Planta/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Raízes de Plantas/química , Caules de Planta/química
19.
Food Chem ; 453: 139633, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-38781896

RESUMO

Smilax glabra Roxb. (SGR) is known for its high nutritional and therapeutic value. However, the frequent appearance of counterfeit products causes confusion and inconsistent quality among SGR varieties. Herein, this study collected the proportion of SGR adulteration and used high-performance liquid chromatography (HPLC) to measure the astilbin content of SGR. Then Fourier-transform near-infrared (FT-NIR) technology, combined with multivariate intelligent algorithms, was used to establish partial least squares regression quantitative models for detecting SGR adulteration and measuring astilbin content, respectively. The method conducted a quantitative analysis of dual indicators through single-spectrum data acquisition (QADS) to comprehensively evaluate the authenticity and superiority of SGR. The coefficients of determination (R2) for both the calibration and prediction sets exceeded 0.96, which successfully leverages FT-NIR combined with multivariate intelligent algorithms to considerably enhance the accuracy and reliability of quantitative models. Overall, this research holds substantial value in the comprehensive quality evaluation in functional health foods.


Assuntos
Algoritmos , Smilax , Espectroscopia de Luz Próxima ao Infravermelho , Smilax/química , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Cromatografia Líquida de Alta Pressão , Controle de Qualidade , Espectroscopia de Infravermelho com Transformada de Fourier , Extratos Vegetais/química , Extratos Vegetais/análise , Análise dos Mínimos Quadrados
20.
ACS Nano ; 18(21): 13885-13898, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38757565

RESUMO

Severe acute pancreatitis (SAP), characterized by pancreatic acinar cell death, currently lacks effective targeted therapies. Ellagic acid (EA), rich in pomegranate, shows promising anti-inflammatory and antioxidant effects in SAP treatment. However, the roles of other forms of EA, such as plant extracellular vesicles (EVs) extracted from pomegranate, and Urolithin A (UA), converted from EA through gut microbiota metabolism in vivo, have not been definitively elucidated. Our research aimed to compare the effects of pomegranate-derived EVs (P-EVs) and UA in the treatment of SAP to screen an effective formulation and to explore its mechanisms in protecting acinar cells in SAP. By comparing the protective effects of P-EVs and UA on injured acinar cells, UA showed superior therapeutic effects than P-EVs. Subsequently, we further discussed the mechanism of UA in alleviating SAP inflammation. In vivo animal experiments found that UA could not only improve the inflammatory environment of pancreatic tissue and peripheral blood circulation in SAP mice but also revealed that the mechanism of UA in improving SAP might be related to mitochondria and endoplasmic reticulum (ER) through the results including pancreatic tissue transcriptomics and transmission electron microscopy. Further research found that UA could regulate ER-mitochondrial calcium channels and reduce pancreatic tissue necroptosis. In vitro experiments of mouse pancreatic organoids and acinar cells also confirmed that UA could improve pancreatic inflammation by regulating the ER-mitochondrial calcium channel and necroptosis pathway proteins. This study not only explored the therapeutic effect of plant EVs on SAP but also revealed that UA could alleviate SAP by regulating ER-mitochondrial calcium channel and reducing acinar cell necroptosis, providing insights into the pathogenesis and potential treatment of SAP.


Assuntos
Cumarínicos , Retículo Endoplasmático , Mitocôndrias , Pancreatite , Animais , Cumarínicos/farmacologia , Cumarínicos/química , Pancreatite/tratamento farmacológico , Pancreatite/metabolismo , Pancreatite/patologia , Camundongos , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Canais de Cálcio/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Punica granatum/química , Células Acinares/efeitos dos fármacos , Células Acinares/metabolismo , Células Acinares/patologia , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/química
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