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1.
J Hazard Mater ; 476: 135103, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38972203

RESUMO

An earlier study found that respiratory cadmium chloride (CdCl2) exposure caused COPD-like lung injury. This study aimed to explore whether mitochondrial dysfunction-mediated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury. Adult C57BL/6 mice were exposed to CdCl2 (10 mg/L) aerosol for six months. Beta-galactosidase-positive cells, p21 and p16 were increased in CdCl2-exposed mouse lungs. The in vitro experiments showed that γ-H2AX was elevated in CdCl2-exposed alveolar epithelial cells. The cGAS-STING pathway was activated in CdCl2-exposed alveolar epithelial cells and mouse lungs. Cxcl1, Cxcl9, Il-10, Il-1ß and Mmp2, several senescence-associated secretory phenotypes (SASP), were upregulated in CdCl2-exposed alveolar epithelial cells. Mechanistically, CdCl2 exposure caused SIRT3 reduction and mitochondrial dysfunction in mouse lungs and alveolar epithelial cells. The in vitro experiment found that Sirt3 overexpression attenuated CdCl2-induced alveolar epithelial senescence and SASP. The in vivo experiments showed that Sirt3 gene knockout exacerbated CdCl2-induced alveolar epithelial senescence, alveolar structure damage, airway inflammation and pulmonary function decline. NMN, an NAD+ precursor, attenuated CdCl2-induced alveolar epithelial senescence and SASP in mouse lungs. Moreover, NMN supplementation prevented CdCl2-induced COPD-like alveolar structure damage, epithelial-mesenchymal transition and pulmonary function decline. These results suggest that mitochondrial dysfunction-associated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury.

2.
Clin Exp Immunol ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990891

RESUMO

Growing evidence suggests that systemic immune and inflammatory responses may play a critical role in the formation and development of aneurysms. Exploring the differences between single intracranial aneurysm (SIA) and multiple IAs (MIAs) could provide insights for targeted therapies. However, there is a lack of comprehensive and detailed characterization of changes in circulating immune cells in MIAs. Peripheral blood mononuclear cell (PBMC) samples from patients with SIA (n = 16) or MIAs (n = 6) were analyzed using high-dimensional mass cytometry to evaluate the frequency and phenotype of immune cell subtypes. A total of 25 cell clusters were identified, revealing that the immune signature of MIAs included cluster changes. Compared to patients with SIA, patients with MIAs exhibited immune dysfunction and regulatory imbalance in T-cell clusters. They also had reduced numbers of CD8+ T cells and their subgroups CD8+ Te and CD8+ Tem cells, as well as reduced numbers of the CD4+ T-cell subgroup CD27-CD4+ Tem cells. Furthermore, compared to SIA, MIAs were associated with enhanced T-cell immune activation, with elevated expression levels of CD3, CD25, CD27, CCR7, GP130, and interleukin 10. This study provides insights into the circulating immune cell profiles in patients with MIAs, highlighting the similarities and differences between patients with SIA and those with MIAs. Furthermore, the study suggests that circulating immune dysfunction may contribute to development of MIAs.

3.
Hum Genomics ; 18(1): 79, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010135

RESUMO

The analysis of genomic variations in offspring after implantation has been infrequently studied. In this study, we aim to investigate the extent of de novo mutations in humans from developing fetus to birth. Using high-depth whole-genome sequencing, 443 parent-offspring trios were studied to compare the results of de novo mutations (DNMs) between different groups. The focus was on fetuses and newborns, with DNA samples obtained from the families' blood and the aspirated embryonic tissues subjected to deep sequencing. It was observed that the average number of total DNMs in the newborns group was 56.26 (54.17-58.35), which appeared to be lower than that the multifetal reduction group, which was 76.05 (69.70-82.40) (F = 2.42, P = 0.12). However, after adjusting for parental age and maternal pre-pregnancy body mass index (BMI), significant differences were found between the two groups. The analysis was further divided into single nucleotide variants (SNVs) and insertion/deletion of a small number of bases (indels), and it was discovered that the average number of de novo SNVs associated with the multifetal reduction group and the newborn group was 49.89 (45.59-54.20) and 51.09 (49.22-52.96), respectively. No significant differences were noted between the groups (F = 1.01, P = 0.32). However, a significant difference was observed for de novo indels, with a higher average number found in the multifetal reduction group compared to the newborn group (F = 194.17, P < 0.001). The average number of de novo indels among the multifetal reduction group and the newborn group was 26.26 (23.27-29.05) and 5.17 (4.82-5.52), respectively. To conclude, it has been observed that the quantity of de novo indels in the newborns experiences a significant decrease when compared to that in the aspirated embryonic tissues (7-9 weeks). This phenomenon is evident across all genomic regions, highlighting the adverse effects of de novo indels on the fetus and emphasizing the significance of embryonic implantation and intrauterine growth in human genetic selection mechanisms.


Assuntos
Feto , Humanos , Feminino , Gravidez , Recém-Nascido , Masculino , Adulto , Polimorfismo de Nucleotídeo Único/genética , Implantação do Embrião/genética , Genoma Humano/genética , Mutação INDEL/genética , Genômica , Sequenciamento Completo do Genoma , Sequenciamento de Nucleotídeos em Larga Escala , Mutação/genética , Desenvolvimento Fetal/genética
4.
Sci China Life Sci ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38951428

RESUMO

Cancer stem cells (CSCs) play an important role in metastasis development, tumor recurrence, and treatment resistance, and are essential for the eradication of cancer. Currently, therapies fail to eradicate CSCs due to their therapeutic stress-induced cellular escape, which leads to enhanced aggressive behaviors compared with CSCs that have never been treated. However, the underlying mechanisms regulating the therapeutic escape remain unknown. To this end, we established a model to isolate the therapeutic escaped CSCs (TSCSCs) from breast CSCs and performed the transcription profile to reveal the mechanism. Mechanistically, we demonstrated that the behavior of therapeutic escape was regulated through the p38/MAPK signaling pathway, resulting in TSCSCs exhibiting enhanced motility and metastasis. Notably, blocking the p38/MAPK signaling pathway effectively reduced motility and metastasis ability both in vitro and in vivo, which were further supported by downregulated motility-related genes and epithelial-mesenchymal transition (EMT)-related proteins vimentin and N-cadherin. The obtained findings reveal the p38/MAPK pathway as a potential therapeutic target for TSCSCs and would provide profound implications for cancer therapy.

5.
Nanomaterials (Basel) ; 14(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38998695

RESUMO

Co-N-CDs-based MXene nanocomposites (MXene@PDA/Co-N-CDs) were constructed by decorating Co-N-CDs on polydopamine-functionalized MXene nanosheets. Both Co-N-CDs and MXene nanosheets have peroxidase-like activity; when the two materials are combined to form MXene@PDA/Co-N-CDs nanocomposites, the peroxide-like activity can be further enhanced. MXene@PDA/Co-N-CDs could oxidize the substrate 3,3'5,5'-tetramethylbenziline (TMB) to form ox-TMB, as confirmed by detecting the absorption of the blue products. A highly selective colorimetric biosensor was developed for the determination of glutathione (GSH) in the concentration range of 0.3 to 20 µM with a lower detection limit (LOD) of 0.12 µM, which realized the accurate detection of GSH in human serum and urine samples. Moreover, in the tumor microenvironment, MXene@PDA/Co-N-CDs could catalyze hydrogen peroxide to produce hydroxyl free radicals and produce a photothermal effect under the exposure of NIR-I irradiation. The catalytic activity of MXene@PDA/Co-N-CD nanocomposites was fully achieved for the death of cancer cells through photothermal/photodynamic synergistic therapy. The MXene@PDA/Co-N-CDs nanozyme offers multiple applications in GSH detection and tumor therapy.

6.
Biomed Pharmacother ; 178: 117158, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39042963

RESUMO

Triple-negative breast cancer (TNBC) still one of the most challenging sub-type in breast cancer clinical. Caffeic acid (CA) derived from effective components of traditional Chinese herbal medicine has been show potential against TNBCs. Our research has found that CA can inhibit the proliferation of TNBC cells while also suppressing the size of cancer stem cell spheres. Additionally, it reduces reactive oxygen species (ROS) levels and disruption of mitochondrial membrane potential. Simultaneously, CA influences the stemness of TNBC cells by reducing the expression of the stem cell marker protein CD44. Furthermore, we have observed that CA can modulate the FOXO1/FIS signaling pathway, disrupting mitochondrial function, inducing mitochondrial autophagy, and exerting anti-tumor activity. Additionally, changes in the immune microenvironment were detected using a mass cytometer, we found that CA can induce M1 polarization of macrophages, enhancing anti-tumor immune responses to exert anti-tumor activity. In summary, CA can be considered as a lead compound for further research in targeting TNBC.

7.
Mol Ther Nucleic Acids ; 35(2): 102223, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38948330

RESUMO

The development of messenger RNA (mRNA) vaccines and therapeutics necessitates the production of high-quality in vitro-transcribed mRNA drug substance with specific critical quality attributes (CQAs), which are closely tied to the uniformity of linear DNA template. The supercoiled plasmid DNA is the precursor to the linear DNA template, and the supercoiled DNA percentage is commonly regarded as a key in-process control (IPC) during the manufacturing of linear DNA template. In this study, we investigate the influence of supercoiled DNA percentage on key mRNA CQAs, including purity, capping efficiency, double-stranded RNA (dsRNA), and distribution of poly(A) tail. Our findings reveal a significant impact of supercoiled DNA percentage on mRNA purity and in vitro transcription yield. Notably, we observe that the impact on mRNA purity can be mitigated through oligo-dT chromatography, alleviating the tight range of DNA supercoiled percentage to some extent. Overall, this study provides valuable insights into IPC strategies for DNA template chemistry, manufacturing, and controls (CMC) and process development for mRNA drug substance.

8.
MedComm (2020) ; 5(8): e637, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39015556

RESUMO

Previous studies have found that the peripheral immune environment is closely related to the occurrence and development of intracranial aneurysms. However, it remains unclear how the metabolism of peripheral blood mononuclear cells (PBMCs) and the composition of polymorphonuclear leukocytes (PMNs) changes in the process of intracranial aneurysm rupture. This study utilized cytometry by time of flight technology to conduct single-cell profiling analysis of PBMCs and PMNs from 72 patients with IAs. By comparing the expression differences of key metabolic enzymes in PBMCs between patients with ruptured intracranial aneurysms (RIAs) and unruptured intracranial aneurysms, we found that most PBMCs subsets from RIA group showed upregulation of rate-limiting enzymes related to the glycolytic pathway. By comparing the composition of PMNs, it was found that the proinflammatory CD101+HLA DR+ subsets were increased in the RIA group, accompanied by a decrease in the anti-inflammatory polymorphonuclear myeloid-derived suppressor cells. In conclusion, this study showed the changes in the peripheral immune profile of RIAs, which is helpful for our understanding of the mechanisms underlying peripheral changes and provides a direction for future related research.

9.
ACS Appl Mater Interfaces ; 16(28): 37073-37086, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38958638

RESUMO

Isoporous membranes produced from diblock copolymers commonly display a poor mechanical property that shows many negative impacts on their separation application. It is theoretically predicted that dense films produced from symmetric triblock copolymers show much stronger mechanical properties than those of homologous diblock copolymers. However, to the best of our knowledge, symmetric triblock copolymers have rarely been fabricated into isoporous membranes before, and a full understanding of separation as well as mechanical properties of membranes prepared from triblock copolymers and homologous diblock copolymers has not been conducted, either. In this work, a cleavable symmetric triblock copolymer with polystyrene as the side block and poly(4-vinylpyridine) (P4VP) as the middle block was synthesized and designed by the RAFT polymerization using the symmetric chain transfer agent, which located at the center of polymer chains and could be removed to produce homologous diblock copolymers with half-length while having the same composition as that found in triblock copolymers. The self-assembly of these two copolymers in thin films and casting solutions was first investigated, observing that they displayed similar self-organized structures under these two conditions. When fabricated into isoporous membranes, they showed similar pore sizes (5-7% difference) and comparable rejection performance (∼10% difference). However, isoporous membranes produced from triblock copolymers showed significantly improved mechanical strength and higher toughness (2-10 times larger) as evidenced by the compacting resistance, strain-stress determination, and nanoindentation testing, suggesting the unique and novel structure-performance relationship in the isoporous membranes produced from symmetric triblock copolymers. The above finding will guide the way to fabricate mechanically robust isoporous membranes without notably changing the separation performance from rarely used symmetric triblock copolymers, which can be synthesized by the controlled polymerization as facilely as that found for diblock copolymers.

10.
Hepatol Commun ; 8(8)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39023343

RESUMO

BACKGROUND: When massive necrosis occurs in acute liver failure (ALF), rapid expansion of HSCs called liver progenitor cells (LPCs) in a process called ductular reaction is required for survival. The underlying mechanisms governing this process are not entirely known to date. In ALF, high levels of retinoic acid (RA), a molecule known for its pleiotropic roles in embryonic development, are secreted by activated HSCs. We hypothesized that RA plays a key role in ductular reaction during ALF. METHODS: RNAseq was performed to identify molecular signaling pathways affected by all-trans retinoid acid (atRA) treatment in HepaRG LPCs. Functional assays were performed in HepaRG cells treated with atRA or cocultured with LX-2 cells and in the liver tissue of patients suffering from ALF. RESULTS: Under ALF conditions, activated HSCs secreted RA, inducing RARα nuclear translocation in LPCs. RNAseq data and investigations in HepaRG cells revealed that atRA treatment activated the WNT-ß-Catenin pathway, enhanced stemness genes (SOX9, AFP, and others), increased energy storage, and elevated the expression of ATP-binding cassette transporters in a RARα nuclear translocation-dependent manner. Further, atRA treatment-induced pathways were confirmed in a coculture system of HepaRG with LX-2 cells. Patients suffering from ALF who displayed RARα nuclear translocation in the LPCs had significantly better MELD scores than those without. CONCLUSIONS: During ALF, RA secreted by activated HSCs promotes LPC activation, a prerequisite for subsequent LPC-mediated liver regeneration.


Assuntos
Falência Hepática Aguda , Células-Tronco , Tretinoína , Humanos , Tretinoína/farmacologia , Células-Tronco/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Fígado/efeitos dos fármacos , Receptor alfa de Ácido Retinoico/genética , Receptor alfa de Ácido Retinoico/metabolismo , Técnicas de Cocultura , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo
11.
Int J Biol Markers ; : 3936155241262045, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38887052

RESUMO

OBJECTIVES: This study aimed to explore the value of D-dimer levels in predicting the treatment efficacy and prognosis of advanced esophageal squamous cell carcinoma (ESCC) treated with programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors. METHODS: The study retrospectively analyzed 233 ESCC patients who received PD-1/PD-L1 inhibitors. The optimal cut-off values for platelets, fibrinogen, and D-dimer were calculated based on maximally selected rank statistics for patients' overall survival. Univariate and multivariate analyses of progression-free survival and overall survival were conducted by Cox proportional hazards regression model. Subgroup analyses of D-dimer levels in different fibrinogen levels were performed by log-rank test. RESULTS: The multivariate Cox regression analyses demonstrated that ESCC patients with D-dimer levels > 236 ng/mL exhibited both poorer progression-free survival (P = 0.004) and overall survival (P < 0.0001) compared to those with low D-dimer levels. The subgroup analyses further indicated that in the group of low fibrinogen levels, the higher D-dimer levels of ESCC patients exhibited significantly shorter progression-free survival (P = 0.0021) and overall survival (P < 0.0001). CONCLUSIONS: The study revealed that the D-dimer levels possess predictive value for the treatment efficacy and prognosis of ESCC patients treated with PD-1/PD-L1 inhibitors.

12.
J Med Chem ; 67(12): 10035-10056, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38885173

RESUMO

Triple-negative breast cancer (TNBC) represents a highly aggressive and heterogeneous malignancy. Currently, effective therapies for TNBC are very limited and remain a significant unmet clinical need. Targeting the transcription-regulating cyclin-dependent kinase 9 (CDK9) has emerged as a promising avenue for therapeutic treatment of TNBC. Herein, we report the design, synthesis, optimization, and evaluation of a new series of aminopyrazolotriazine compounds as orally bioavailable, potent, and CDK9/2 selectivity-improved inhibitors, enabling efficacious inhibition of TNBC cell growth, as well as notable antitumor effect in TNBC models. The compound C35 demonstrated low-nanomolar potency with substantially improved CDK9/2 selectivity, downregulated the CDK9-downstream targets (e.g., MCL-1), and induced apoptosis in TNBC cell lines. Moreover, with the desired oral bioavailability, oral administration of C35 could significantly suppress the tumor progression in two TNBC mouse models. This study demonstrates that target transcriptional regulation is an effective strategy and holds promising potential as a targeted therapy for the treatment of TNBC.


Assuntos
Antineoplásicos , Quinase 9 Dependente de Ciclina , Inibidores de Proteínas Quinases , Neoplasias de Mama Triplo Negativas , Quinase 9 Dependente de Ciclina/antagonistas & inibidores , Quinase 9 Dependente de Ciclina/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Humanos , Animais , Feminino , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacocinética , Antineoplásicos/química , Antineoplásicos/síntese química , Administração Oral , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Camundongos , Linhagem Celular Tumoral , Relação Estrutura-Atividade , Disponibilidade Biológica , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Descoberta de Drogas , Transcrição Gênica/efeitos dos fármacos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Anal Chem ; 96(28): 11611-11618, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38943567

RESUMO

Citrus Huanglongbing (HLB) is known as the cancer of citrus, where Candidatus Liberibacter asiaticus (CLas) is the most prevalent strain causing HLB. In this study, we report a novel electrochemiluminescence (ECL) biosensor for the highly sensitive detection of the CLas outer membrane protein (Omp) gene by coupling rolling circle amplification (RCA) with a CRISPR/Cas12a-responsive smart DNA hydrogel. In the presence of the target, a large number of amplicons are generated through RCA. The amplicons activate the trans-cleavage activity of CRISPR/Cas12a through hybridizing with crRNA, triggering the response of smart DNA hydrogel to release the encapsulated AuAg nanoclusters (AuAg NCs) on the electrode and therefore leading to a decreased ECL signal. The ECL intensity change (I0 - I) is positively correlated with the concentration of the target in the range 50 fM to 5 nM, with a limit of detection of 40 fM. The performance of the sensor has also been evaluated with 10 samples of live citrus leaves (five HLB negative and five HLB positive), and the result is in excellent agreement with the gold standard qPCR result. The sensing strategy has expanded the ECL versatility for detecting varying levels of dsDNA or ssDNA in plants with high sensitivity.


Assuntos
Proteínas da Membrana Bacteriana Externa , Citrus , Técnicas Eletroquímicas , Medições Luminescentes , Técnicas Eletroquímicas/métodos , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/química , Citrus/microbiologia , Citrus/química , Hidrogéis/química , Técnicas Biossensoriais/métodos , DNA/química , DNA/genética , Sistemas CRISPR-Cas/genética , Liberibacter/genética , Liberibacter/química , Técnicas de Amplificação de Ácido Nucleico , Doenças das Plantas/microbiologia , Ouro/química , Nanopartículas Metálicas/química , Limite de Detecção
14.
J Environ Manage ; 365: 121565, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38917539

RESUMO

Animals manure and chemical fertilizers are widely applied to agricultural soils to mitigate soil fertility decline resulting from intensive farming practices. However, the use of antibiotics such as ciprofloxacin (CIP) and enrofloxacin (ENR) in these manures introduces certain environmental risks. The sorption of CIP and ENR in soil is influenced by various factors. Soil cations (i.e., Na+, K+, Mg2+, and Ca2+) and artificially introduced ions (NH4+) can affect the sorption behavior of CIP and ENR in alkaline agricultural soils through mechanisms such as ion exchange and competitive sorption. To investigate the effects of ionic strength and ion type on the sorption of antibiotics in alkaline agricultural soil, batch equilibrium experiments were conducted in this study. The results showed that the affinity of alkaline farmland soil to CIP and ENR was poor, and Kd was only 159 L/kg and 89 L/kg, respectively. Increases in temperature and pH inhibited CIP and ENR sorption on soil. Mineral elements in the soil strongly inhibited CIP and ENR sorption. Conversely, NH4+ promoted the Kd values of CIP and ENR by 46% and 221%, respectively. Additionally, under different influencing factors, both the sorption affinity (Kd) and sorption amount of ENR were lower than those of CIP. These findings indicate that ENR has a greater migration potential and poses a greater environmental risk in agricultural soils. Alkaline soil and mineral elements increase the migration potential of CIP, ENR, but the introduction of NH4+ in agricultural production can weaken the migration potential of them.


Assuntos
Ciprofloxacina , Enrofloxacina , Poluentes do Solo , Solo , Ciprofloxacina/química , Solo/química , Concentração de Íons de Hidrogênio , Enrofloxacina/química , Concentração Osmolar , Poluentes do Solo/química , Adsorção , Agricultura , Antibacterianos/química
15.
Talanta ; 278: 126485, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38943767

RESUMO

Although nanozyme engineering has made tremendous progress, there is a huge gap between them and natural enzymes due to the enormous challenge of precisely adjusting the geometric and electronic structure of active sites. Considering that intentionally adjusting the metal-carrier interactions may bring the promising catalytic activity, in this work, a novel Mo atom nanocluster is successfully synthesized using nitrogen-doped Mxene (MoACs/N-MXene) nanozymes as carriers. The constructed MoACs/N-MXene displays excellent peroxidase-like catalytic activity and kinetics, outweighing its N-MXene and Mo nanoparticles (NPs)-MXene references and natural horse radish peroxidase. This work not only reports a successful example of MoACs/N-MXene nanozyme as a guide for achieving peroxidase-mimic performance of nanozymes for colorimetric glutathione sensing at 0.29 µM, but also expands the application prospects of two-dimensional MXene nanosheets by reasonably introducing metal atomic clusters and nonmetal atom doping and exploring related nanozyme properties.

16.
Emerg Infect Dis ; 30(7): 1434-1437, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38916639

RESUMO

We investigated Alongshan virus infection in reindeer in northeastern China. We found that 4.8% of the animals were viral RNA-positive, 33.3% tested positive for IgG, and 19.1% displayed neutralizing antibodies. These findings suggest reindeer could serve as sentinel animal species for the epidemiologic surveillance of Alongshan virus infection.


Assuntos
Anticorpos Antivirais , Rena , Animais , Rena/virologia , China/epidemiologia , Anticorpos Antivirais/sangue , Anticorpos Neutralizantes/sangue , Infecções por Bunyaviridae/veterinária , Infecções por Bunyaviridae/epidemiologia , Infecções por Bunyaviridae/virologia , RNA Viral , Imunoglobulina G/sangue
17.
Spectrochim Acta A Mol Biomol Spectrosc ; 320: 124612, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-38857548

RESUMO

High fructose intake is an important cause of metabolic disease. Due to the increasing prevalence of metabolic diseases worldwide, the development of an accurate and efficient tool for monitoring fructose in food is urgently needed to control the intake of fructose. Herein, a new fluorescent probe NBD-PQ-B with 7-nitrobenz-2-oxa-1, 3-diazole (NBD) as the fluorophore, piperazine (PQ) as the bridging group and phenylboronic acid (B) as the recognition receptor, was synthesized to detect fructose. The fluorescence of NBD-PQ-B increased linearly at 550 nm at an excitation wavelength of 497 nm with increasing fructose concentration from 0.1 to 20 mM. The limit of detection (LOD) of fructose was 40 µM. The pKa values of NBD-PQ-B and its fructose complexes were 4.1 and 10.0, respectively. In addition, NBD-PQ-B bound to fructose in a few seconds. The present technique was applied to determine the fructose content in beverages, honey, and watermelon with satisfactory results. Finally, the system could not only be applied in an aqueous solution with a spectrophotometer, but also be fabricated as a NBD-PQ-B/polyvinyl oxide (PEO) film by electrospinning for on-site food analysis simply with the assistance of a smartphone.


Assuntos
Corantes Fluorescentes , Análise de Alimentos , Frutose , Espectrometria de Fluorescência , Frutose/análise , Corantes Fluorescentes/química , Espectrometria de Fluorescência/métodos , Análise de Alimentos/métodos , Limite de Detecção , Mel/análise , Bebidas/análise , 4-Cloro-7-nitrobenzofurazano/química
18.
Int J Biol Macromol ; 273(Pt 2): 132854, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38838879

RESUMO

Depression is a neuropsychiatric disorder characterized by persistent pleasure loss and behavioral despair. However, the potential mechanisms and therapeutic targets for depression treatment remain unclear. Therefore, identifying the underlying pathogenesis of depression would promote the development of novel treatment and provide effective targets for antidepressant drugs. In this study, proteomics analysis showed that the expression level of phosphatase and actin regulator 4 (Phactr4) was significantly increased in the CA1 hippocampus of depressed rats. The upregulated Phactr4 might induce dysfunction of the synaptic structure via suppressing the p-LIMK/p-Cofilin signaling pathway, and promote neuroinflammation via activating the NF-κB/NLRP3 pathway, which ultimately contributes to the pathogenesis of depression. In contrast, the downregulation of Phactr4 in hippocampal CA1 of depressed rats alleviated depression-like behaviors, along with reducing neuroinflammation and improving synaptic plasticity. In conclusion, these findings provide evidence that Phactr4 plays an important role in regulating neuroinflammatory response and impairment of synaptic plasticity, effects seem to involve in the pathogenesis of depression, and Phactr4 may serve as a potential target for antidepressant treatment.


Assuntos
Depressão , Doenças Neuroinflamatórias , Plasticidade Neuronal , Estresse Psicológico , Animais , Plasticidade Neuronal/efeitos dos fármacos , Ratos , Depressão/tratamento farmacológico , Depressão/metabolismo , Depressão/etiologia , Masculino , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Estresse Psicológico/complicações , Estresse Psicológico/metabolismo , Proteínas dos Microfilamentos/metabolismo , Ratos Sprague-Dawley , Comportamento Animal/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Modelos Animais de Doenças , Antidepressivos/farmacologia , Hipocampo/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , NF-kappa B/metabolismo
19.
PLoS One ; 19(6): e0300656, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38865385

RESUMO

BACKGROUND: Acute kidney injury (AKI) remains a common complication of coronary revascularization and increases poor outcomes in critically ill surgical patients. Compared to the plasma volume status (PVS), estimated plasma volume status (ePVS) has the advantages of being noninvasive and simple and has been shown to be associated with worse prognosis in patients undergoing coronary revascularization. This study was to evaluate the association of ePVS with the risk of AKI in patients who underwent coronary revascularization. METHODS: In this retrospective cohort study, data of patients who underwent coronary revascularization were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database (2008-2019). The outcome was the occurrence of AKI after ICU admission. The covariates were screened via the LASSO regression method. Univariate and multivariate Logistic regression models were performed to assess the association of ePVS and PVS and the odds of AKI in patients who underwent coronary revascularization, with results shown as odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses of age, surgery, and anticoagulation agents and sequential organ failure assessment (SOFA) score were performed to further explore the association of ePVS with AKI. RESULTS: A total of 3,961 patients who underwent coronary revascularization were included in this study, of whom 2,863 (72.28%) had AKI. The high ePVS was associated with the higher odds of AKI in patients who received coronary revascularization (OR = 1.06, 95%CI: 1.02-1.10), after adjusting for the covariates such as age, race, SAPS-II score, SOFA score, CCI, weight, heart rate, WBC, RDW-CV, PT, BUN, glucose, calcium, PH, PaO2, mechanical ventilation, vasopressors, and diuretic. Similar results were found in patients who underwent the CABG (OR = 1.07, 95%CI: 1.02-1.11), without anticoagulation agents use (OR = 1.07, 95%CI: 1.03-1.12) and with high SOFA score (OR = 1.10, 95%CI: 1.04-1.17). No relationship was found between PVS and the odds of AKI in patients who underwent the coronary revascularization. CONCLUSION: The ePVS may be a promising parameter to evaluate the risk of AKI in patients undergoing coronary revascularization, which provides a certain reference for the risk stratification management of ICU patients who underwent coronary revascularization.


Assuntos
Injúria Renal Aguda , Volume Plasmático , Humanos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/epidemiologia , Feminino , Masculino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Bases de Dados Factuais , Fatores de Risco , Revascularização Miocárdica/efeitos adversos , Prognóstico , Unidades de Terapia Intensiva , Intervenção Coronária Percutânea/efeitos adversos
20.
Opt Express ; 32(8): 13384-13395, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38859310

RESUMO

We introduce a unique dual-function detector with an asymmetric light illumination based on the black silicon co-hyperdoped with sulfur and nitrogen for light and gas detection, and the properties in NO2 gas sensing and photoelectric detection are studied under various light and gas environments, respectively. Enhanced performance of the device under certain light and gas conditions is observed. When illuminated at the optimal wavelength, the gas sensors' responsivity to NO2 can be enhanced by approximately 5 to 200 times over 730 nm illumination, respectively. The photodetectors' photoresponsivity increases 15 to 200 times in a 300 ppm NO2 gas environment compared to air. Such mutual enhancement achieved through the clever combination of light and gas implies a novel approach to improve the performance of the black silicon detectors in both gas sensing and photoelectric detection.

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