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1.
Colloids Surf B Biointerfaces ; 240: 113966, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38781846

RESUMO

Dental Implants are expected to possess both excellent osteointegration and antibacterial activity because poor osseointegration and infection are two major causes of titanium implant failure. In this study, we constructed layer-by-layer self-assembly films consisting of anionic casein phosphopeptides-amorphous calcium phosphate (CPP-ACP) and cationic poly (L-lysine) (PLL) on sandblasted and acid etched (SLA) titanium surfaces and evaluated their osseointegration and antibacterial performance in vitro and in vivo. The surface properties were examined, including microstructure, elemental composition, wettability, and Ca2+ ion release. The impact the surfaces had on the adhesion, proliferation and differentiation abilities of MC3T3-E1 cells were investigated, as well as the material's antibacterial performance after exposure to the oral microorganisms such as Porphyromonas gingivalis (P. g) and Actinobacillus actinomycetemcomitans (A. a). For the in vivo studies, SLA and Ti (PLL/CA-3.0)10 implants were inserted into the extraction socket immediately after extracting the rabbit mandibular anterior teeth with or without exposure to mixed bacteria solution (P. g & A. a). Three rabbits in each group were sacrificed to collect samples at 2, 4, and 6 weeks of post-implantation, respectively. Radiographic and histomorphometry examinations were performed to evaluate the implant osseointegration. The modified titanium surfaces were successfully prepared and appeared as a compact nano-structure with high hydrophilicity. In particular, the Ti (PLL/CA-3.0)10 surface was able to continuously release Ca2+ ions. From the in vitro and in vivo studies, the modified titanium surfaces expressed enhanced osteogenic and antibacterial properties. Hence, the PLL/CPP-ACP multilayer coating on titanium surfaces was constructed via a layer-by-layer self-assembly technology, possibly improving the biofunctionalization of Ti-based dental implants.

2.
Nat Commun ; 15(1): 4328, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773155

RESUMO

Parental experiences can affect the phenotypic plasticity of offspring. In locusts, the population density that adults experience regulates the number and hatching synchrony of their eggs, contributing to locust outbreaks. However, the pathway of signal transmission from parents to offspring remains unclear. Here, we find that transcription factor Forkhead box protein N1 (FOXN1) responds to high population density and activates the polypyrimidine tract-binding protein 1 (Ptbp1) in locusts. FOXN1-PTBP1 serves as an upstream regulator of miR-276, a miRNA to control egg-hatching synchrony. PTBP1 boosts the nucleo-cytoplasmic transport of pre-miR-276 in a "CU motif"-dependent manner, by collaborating with the primary exportin protein exportin 5 (XPO5). Enhanced nuclear export of pre-miR-276 elevates miR-276 expression in terminal oocytes, where FOXN1 activates Ptbp1 and leads to egg-hatching synchrony in response to high population density. Additionally, PTBP1-prompted nuclear export of pre-miR-276 is conserved in insects, implying a ubiquitous mechanism to mediate transgenerational effects.


Assuntos
Transporte Ativo do Núcleo Celular , Gafanhotos , MicroRNAs , Proteína de Ligação a Regiões Ricas em Polipirimidinas , Animais , MicroRNAs/metabolismo , MicroRNAs/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Gafanhotos/genética , Gafanhotos/metabolismo , Feminino , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Óvulo/metabolismo , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Núcleo Celular/metabolismo , Oócitos/metabolismo
3.
Adv Mater ; : e2404199, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38734974

RESUMO

External stimuli triggering chemical reactions in cancer cells to generate highly reactive chemical species are very appealing for cancer therapy, in which external irradiation activating sensitizers to transfer energy or electrons to surrounding oxygen or other molecules is critical for generating cytotoxic reactive species. However, poor light penetration into tissue, low activity of sensitizers, and reliance on oxygen supply restrict the generation of cytotoxic chemical species in hypoxic tumors, which lowers the therapeutic efficacy. Here, this work presents galvanic cell nanomaterials that can directly release highly reactive electrons in tumors without external irradiation or photosensitizers. The released reactive electrons directly react with surrounding biomolecules such as proteins and DNA within tumors to destroy them or react with other surrounding (bio)molecules to yield cytotoxic chemical species to eliminate tumors independent of oxygen. Administering these nanogalvanic cells to mice results in almost complete remission of subcutaneous solid tumors and deep metastatic tumors. The results demonstrate that this strategy can further arouse an immune response even in a hypoxic environment. This method offers a promising approach to effectively eliminate tumors, similar to photodynamic therapy, but does not require oxygen or irradiation to activate photosensitizers.

4.
Toxicol Mech Methods ; : 1-7, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38736312

RESUMO

Although recent studies increasingly suggest the potential anti-cancer effect of quercetin, the exact underlying mechanism remains poorly demonstrated in oral squamous cell carcinoma (oSCC). Therefore, our research explored the impacts of quercetin on the ferroptosis and mTOR/S6KP70 axis in oSCC cell lines. After treating oSCC cells with quercetin or indicated compounds and transfection with SLC7A11- or S6KP70-overexpressing plasmid, cell viability was detected by CCK-8 assay. The level of ferroptosis in oSCC cells was assessed by measuring ROS and GSH levels. The activation of mTOR/S6KP70 axis was assessed by Western blotting. Quercetin promoted ferroptosis in an mTOR/S6KP70-dependent manner to inhibit tumor growth in oSCC cells. Mechanistically, we revealed that quercetin induced lipid peroxidation and reduced GSH levels by repressing SLC7A11 expression in oSCC cells. Specifically, the effects of quercetin on ferroptosis and mTOR and S6KP70 phosphorylation were partially blocked by both mTOR agonist and S6KP70 overexpression. Moreover, mTOR inhibitor promoted ferroptosis in quercetin-treated oSCC cells. Our findings showed that ferroptosis may be a new anti-tumor mechanism of quercetin. Additionally, we identified that quercetin can target mTOR/S6KP70 cascade to inhibit the growth of oSCC cells.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38761200

RESUMO

OBJECTIVE: To compare the clinical efficacy of the minimally invasive locking plate technique (Philos plate) and interlocking intramedullary nailing technique (TRIGEN intramedullary nail) in the treatment of Neer two-part and three-part proximal humeral fractures. METHODS AND MATERIALS: The clinical data of 60 patients with Neer two-part and three-part proximal humerus fractures admitted to the hospital from April 2017 to April 2021 were retrospectively analyzed. Thirty-two patients were treated with the minimally invasive locking plate technique (minimally invasive plate group), and 28 patients were treated with the interlocking intramedullary nailing technique (intramedullary nail group). The operation time, intraoperative blood loss, incision length, fracture healing time, and postoperative complications were compared between the two groups. The ASES score and Constant-Murley score were used to evaluate the shoulder joint function of the two groups one year after surgery. RESULTS: All 60 patients were followed up for 12 to 24 months, with an average of 16 months. There was no significant difference in operation time, intraoperative blood loss, incision length, or fracture healing time between the two groups (P > 0.05). The incidence of postoperative complications in the intramedullary nail group was significantly lower than that in the minimally invasive steel plate group, and the difference between the groups was statistically significant (P < 0.05). There was no significant difference in the ASES score or Constant-Murley score between the two groups one year after surgery (P > 0.05). CONCLUSION: The use of the minimally invasive locking plate technique and interlocking intramedullary nailing technique in the treatment of Neer two-part and three-part proximal humerus fractures has the advantages of a small incision, less blood loss, and a high fracture healing rate, and both can achieve satisfactory clinical effects. The internal nail technique is more convenient than the minimally invasive locking plate technique in controlling postoperative complications.

6.
Fungal Genet Biol ; : 103899, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38802054

RESUMO

Fusarium head blight is a devastating disease that causes severe yield loses and mycotoxin contamination in wheat grain. Additionally, balancing the trade-off between wheat production and disease resistance has proved challenging. This study aimed to expand the genetic tools of the endophyte P. liquidambaris against Fusarium graminearum. Specifically, we engineered a UDP-glucosyltransferase-expressing P. liquidambaris strain (PL-UGT) using ADE1 as a selection marker and obtained a deletion mutant using an inducible promoter that drives Cas9 expression. Our PL-UGT strain converted deoxynivalenol (DON) into DON-3-G in vitro at a rate of 71.4 % after 36 h. DON inactivation can be used to confer tolerance in planta. Wheat seedlings inoculated with endophytic strain PL-UGT showed improved growth compared with those inoculated with wildtype P. liquidambaris. Strain PL-UGT inhibited the growth of Fusarium graminearum and reduced infection rate to 15.7 %. Consistent with this finding, DON levels in wheat grains decreased from 14.25 to 0.56 µg/g when the flowers were pre-inoculated with PL-UGT and then infected with Fusarium. The expression of UGT in P. liquidambaris was nontoxic and did not inhibit plant growth. Endophytes do not enter the seeds nor induce plant disease, thereby representing a novel approach to fungal disease control.

7.
Mikrochim Acta ; 191(5): 271, 2024 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632191

RESUMO

Pathogen infections including Shigella flexneri have posed a significant threat to human health for numerous years. Although culturing and qPCR were the gold standards for pathogen detection, time-consuming and instrument-dependent restrict their application in rapid diagnosis and economically less-developed regions. Thus, it is urgently needed to develop rapid, simple, sensitive, accurate, and low-cost detection methods for pathogen detection. In this study, an immunomagnetic beads-recombinase polymerase amplification-CRISPR/Cas12a (IMB-RPA-CRISPR/Cas12a) method was built based on a cascaded signal amplification strategy for ultra-specific, ultra-sensitive, and visual detection of S. flexneri in the laboratory. Firstly, S. flexneri was specifically captured and enriched by IMB (Shigella antibody-coated magnetic beads), and the genomic DNA was released and used as the template in the RPA reaction. Then, the RPA products were mixed with the pre-loaded CRISPR/Cas12a for fluorescence visualization. The results were observed by naked eyes under LED blue light, with a sensitivity of 5 CFU/mL in a time of 70 min. With no specialized equipment or complicated technical requirements, the IMB-RPA-CRISPR/Cas12a diagnostic method can be used for visual, rapid, and simple detection of S. flexneri and can be easily adapted to monitoring other pathogens.


Assuntos
Anticorpos , Shigella flexneri , Humanos , Luz Azul , Fluorescência , Recombinases
8.
J Colloid Interface Sci ; 668: 366-374, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38678891

RESUMO

Metal-functionalized porphyrin-like graphene structures are promising electrocatalysts for carbon dioxide reduction reaction (CO2RR) as their metal centers can modulate activity. Yet, the role of metal center of metalloporphyrins (MTPPs) in CO2 reaction activity is still lacking deep understanding. Here, CO2RR mechanism on MTPPs with five different metal centers (M = Fe, Co, Cu, Zn and Ni) are examined by first-principles calculations. The *COOH formation is the rate determined step on the five MTPP structures, and the CoTPP exhibits the best CO2RR activity while ZnTPP and NiTPP are the worst, which is also verified by our experiment. The CO2RR activity is controlled by adsorption states of intermediates (*CO, *COOH), i.e., chemisorption (e.g., on CoTPP) and physisorption (on ZnTPP and NiTPP) of intermediates will lead to good and poor activity, respectively. The deeper the d-band center of the porphyrin ring complexed metal atom, the weaker bonding of MTPP with CO and COOH. Theoretical calculations and experimental results indicate that MTPPs with Co and Fe centers lead to a reduction in the energy barriers for the two uphill reaction steps in the electrocatalytic CO2 reduction process, thereby enhancing CO2 reduction electrocatalytic activity. Faradaic efficiency of CO is correlated with the reaction energy barrier of the first proton-coupled electron reduction process, displaying a strong linear correlation. This work provides a fundamental understanding of MTPPs used as electrocatalysts for CO2RR.

9.
ACS Biomater Sci Eng ; 10(5): 2925-2934, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38587986

RESUMO

Spider dragline (major ampullate) silk is one of the toughest known fibers in nature and exhibits an excellent combination of high tensile strength and elasticity. Increasing evidence has indicated that preassembly plays a crucial role in facilitating the proper assembly of silk fibers by bridging the mesoscale gap between spidroin molecules and the final strong fibers. However, it remains challenging to control the preassembly of spidroins and investigate its influence on fiber structural and mechanical properties. In this study, we explored to bridge this gap by modulating the polyalanine (polyA) motifs in repetitive region of spidroins to tune their preassemblies in aqueous dope solutions. Three biomimetic silk proteins with varying numbers of alanine residues in polyA motif and comparable molecular weights were designed and biosynthesized, termed as N16C-5A, N15C-8A, and N13C-12A, respectively. It was found that all three proteins could form nanofibril assemblies in the concentrated aqueous dopes, but the size and structural stability of the fibrils were distinct from each other. The silk protein N15C-8A with 8 alanine residues in polyA motif allowed for the formation of stable nanofibril assemblies with a length of approximately 200 nm, which were not prone to disassemble or aggregate as that of N16C-5A and N13C-12A. More interestingly, the stable fibril assembly of N15C-8A enabled spinning of simultaneously strong (623.3 MPa) and tough (107.1 MJ m-3) synthetic fibers with fine molecular orientation and close interface packing of fibril bundles. This work highlights that modulation of polyA motifs is a feasible way to tune the morphology and stability of the spidroin preassemblies in dope solutions, thus controlling the structural and mechanical properties of the resulting fibers.


Assuntos
Fibroínas , Peptídeos , Resistência à Tração , Fibroínas/química , Fibroínas/genética , Peptídeos/química , Seda/química , Animais , Motivos de Aminoácidos , Nanofibras/química , Aranhas/química
10.
11.
Sci Total Environ ; 931: 172795, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38677429

RESUMO

The ubiquitous presence of micro-and nanoplastics (MNPs) in the environment and everyday products has attracted attention due to their hazardous risks. However, the effects of MNPs on reproduction and the underlying mechanisms remain unclear. The present study investigated the impact of polystyrene (PS) nanoplastics of 80, 200 and 500 nm diameters on zebrafish reproduction at an environmentally relevant concentration of 0.5 mg/L. Exposure to PS delayed spermatogenesis and caused aberrant follicular growth, resulting in dysgenesis in F0 adults and impacting F1 embryo development. Notably, the reproductive toxicity exhibited size-dependency, with the 500 nm PS being the most detrimental. Combined analyses of transcriptomics and metabolomics in ovary tissue revealed that treatment with 500 nm PS affected the peroxisome proliferator-activated receptor (PPAR) signaling pathway, dysregulated lipid transport, binding and activity processes, and led to dysgenesis in zebrafish. Specifically, the ovulatory dysfunction induced by PS exposure resembled clinical manifestations of polycystic ovary syndrome (PCOS) and can be attributed to lipid metabolism disorder involving glycerophospholipid, sphingolipid, arachidonic acid, and alpha-linolenic acid. Collectively, our results provide new evidence revealing the molecular mechanisms of PS-induced reproductive toxicity, highlighting that MNPs may pose a risk to female reproductive health.


Assuntos
Transtornos do Metabolismo dos Lipídeos , Receptores Ativados por Proliferador de Peroxissomo , Poliestirenos , Reprodução , Poluentes Químicos da Água , Peixe-Zebra , Animais , Poliestirenos/toxicidade , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Reprodução/efeitos dos fármacos , Transtornos do Metabolismo dos Lipídeos/induzido quimicamente , Poluentes Químicos da Água/toxicidade , Feminino , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Microplásticos/toxicidade
13.
Clin Lab ; 70(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38623667

RESUMO

BACKGROUND: This study aims to investigate the application value of serum cytokeratin 19 fragment (CYFRA21-1) combined with nerve-specific enolase (NSE), carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCC-Ag) in the diagnosis of lung cancer (LC). METHODS: A total of 831 cases of LC, 360 cases of benign lung disease (BLD) and 102 healthy controls, were enrolled. The data were processed using SPSS, GraphPad Prism, and MedCalc software. RESULTS: The tumor marker (TM) levels in the LC and BLD groups were significantly higher than those in the control group; the CYFRA21-1, NSE, and CEA levels in the patients with LC were higher than in those with BLD. In particular, the increase was predominantly observed for the levels of CEA and CYFRA21-1 in adenocarcinoma (LUAD), CYFRA21-1 and SCC-Ag in squamous cell carcinoma (LUSC), and NSE in small cell carcinoma (SCLC). The CYFRA21-1, NSE, and CEA levels were significantly higher in stage IV than in other stages in LC. Univariate binary logistic analysis showed that increased levels of all four TMs were risk factors for BLD and LC. The area under the curve (AUC) of CYFRA21-1 was most effective in distinguishing patients with BLD or LC from the controls and in distinguishing patients with BLD and LC. The AUCs of combined CYFRA21-1, NSE, and CEA were increased to 0.755, 0.922, and 0.783, respectively, with no significant difference with the AUC of the four combined tests. In the histological classification, the best predictors were CEA, for LUAD, CYFRA21-1 for LUSC, and NSE for SCLC. Moreover, the expression levels of CYFRA21-1, NSE, and CEA significantly decreased after each treatment course. CONCLUSIONS: The combined assay of CYFRA21-1, NSE, and CEA addresses the aspects of accuracy, sensitivity, specificity, and economic cost and should be considered as a potential diagnostic test in LC.


Assuntos
Neoplasias Pulmonares , Serpinas , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/diagnóstico , Antígeno Carcinoembrionário , Biomarcadores Tumorais , Antígenos de Neoplasias , Queratina-19 , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Fosfopiruvato Hidratase
14.
JACS Au ; 4(4): 1480-1488, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38665676

RESUMO

Biomolecular condensates are dynamic subcellular compartments that lack surrounding membranes and can spatiotemporally organize the cellular biochemistry of eukaryotic cells. However, such dynamic organization has not been realized in prokaryotes that naturally lack organelles, and strategies are urgently needed for dynamic biomolecular compartmentalization. Here we develop a light-switchable condensate system for on-demand dynamic organization of functional cargoes in the model prokaryotic Escherichia coli cells. The condensate system consists of two modularly designed and genetically encoded fusions that contain a condensation-enabling scaffold and a functional cargo fused to the blue light-responsive heterodimerization pair, iLID and SspB, respectively. By appropriately controlling the biogenesis of the protein fusions, the condensate system allows rapid recruitment and release of cargo proteins within seconds in response to light, and this process is also reversible and repeatable. Finally, the system is demonstrated to dynamically control the subcellular localization of a cell division inhibitor, SulA, which enables the reversible regulation of cell morphologies. Therefore, this study provides a new strategy to dynamically control cellular processes by harnessing light-controlled condensates in prokaryotic cells.

15.
J Med Virol ; 96(3): e29533, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38483048

RESUMO

Cytidine/uridine monophosphate kinase 2 (UMP-CMP kinase 2, CMPK2) has been reported as an antiviral interferon-stimulated gene (ISG). We previously observed that the expression of CMPK2 was significantly upregulated after Zika Virus (ZIKV) infection in A549 cells. However, the association and the underlying mechanisms between CMPK2 induction and ZIKV replication remain to be determined. We investigated the induction of CMPK2 during ZIKV infection and the effect of CMPK2 on ZIKV replication in A549, U251, Vero, IFNAR-deficient U5A and its parental 2fTGH cells, Huh7 and its RIG-I-deficient derivatives Huh7.5.1 cells. The activation status of Jak-STAT signaling pathway was determined by detecting the phosphorylation level of STAT1, the activity of interferon stimulated response element (ISRE) and the expression of several interferon stimulated genes (ISGs). We found that ZIKV infection induced CMPK2 expression through an IFNAR and RIG-I dependent manner. Overexpression of CMPK2 inhibited while CMPK2 knockdown promoted ZIKV replication in A549 and U251 cells. Mechanically, we found that CMPK2 overexpression increased IFNß expression and activated Jak/STAT signaling pathway as shown by the increased level of p-STAT1, enhanced activity of ISRE, and the upregulated expression of downstream ISGs. These findings suggest that ZIKV infection induced CMPK2 expression, which inhibited ZIKV replication and serves as a positive feedback regulator for IFN-Jak/STAT pathway.


Assuntos
Interferon Tipo I , Núcleosídeo-Fosfato Quinase , Infecção por Zika virus , Zika virus , Humanos , Zika virus/metabolismo , Transdução de Sinais , Janus Quinases/metabolismo , Fatores de Transcrição STAT/metabolismo , Fatores de Transcrição STAT/farmacologia , Interferon Tipo I/genética , Replicação Viral , Receptores Imunológicos
16.
World J Gastrointest Surg ; 16(2): 307-317, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38463380

RESUMO

BACKGROUND: Gallstones are common lesions that often require surgical intervention. Laparoscopic cholecystectomy is the treatment of choice for symptomatic gallstones. Preoperatively, the anatomical morphology of the cystic duct (CD), needs to be accurately recognized, especially when anatomical variations occur in the CD, which is otherwise prone to bile duct injury. However, at present, there is no optimal classification system for CD morphology applicable in clinical practice, and the relationship between anatomical variations in CDs and gallstones remains to be explored. AIM: To create a more comprehensive clinically applicable classification of the morphology of CD and to explore the correlations between anatomic variants of CD and gallstones. METHODS: A total of 300 patients were retrospectively enrolled from October 2021 to January 2022. The patients were divided into two groups: The gallstone group and the nongallstone group. Relevant clinical data and anatomical data of the CD based on magnetic resonance cholangiopancreatography (MRCP) were collected and analyzed to propose a morphological classification system of the CD and to explore its relationship with gallstones. Multivariate analysis was performed using logistic regression analyses to identify the independent risk factors using variables that were significant in the univariate analysis. RESULTS: Of the 300 patients enrolled in this study, 200 (66.7%) had gallstones. The mean age was 48.10 ± 13.30 years, 142 (47.3%) were male, and 158 (52.7%) were female. A total of 55.7% of the patients had a body mass index (BMI) ≥ 24 kg/m2. Based on the MRCP, the CD anatomical typology is divided into four types: Type I: Linear, type II: n-shaped, type III: S-shaped, and type IV: W-shaped. Univariate analysis revealed differences between the gallstone and nongallstone groups in relation to sex, BMI, cholesterol, triglycerides, morphology of CD, site of CD insertion into the extrahepatic bile duct, length of CD, and angle between the common hepatic duct and CD. According to the multivariate analysis, female, BMI (≥ 24 kg/m2), and CD morphology [n-shaped: Odds ratio (OR) = 10.97, 95% confidence interval (95%CI): 5.22-23.07, P < 0.001; S-shaped: OR = 4.43, 95%CI: 1.64-11.95, P = 0.003; W-shaped: OR = 7.74, 95%CI: 1.88-31.78, P = 0.005] were significantly associated with gallstones. CONCLUSION: The present study details the morphological variation in the CD and confirms that CD tortuosity is an independent risk factor for gallstones.

17.
Artigo em Inglês | MEDLINE | ID: mdl-38548389

RESUMO

Objective To investigate the effects of platelet-rich plasma-derived exosomes (PRP-Exos) on the proliferation and migration of tendon stem/progenitor cell (TSPC). Methods PRP-Exos were extracted through the combination of polymer-based precipitation and ultracentrifugation.The morphology,concentration,and particle size of PRP-Exos were identified by transmission electron microscopy and nanoparticle tracking analysis.The expression levels of surface marker proteins on PRP-Exos and platelet membrane glycoproteins were determined by Western blot analysis.Rat TSPC was extracted and cultured,and the expression of surface marker molecules on TSPC was detected using flow cytometry and immunofluorescence staining.The proliferation of TSPC influenced by PRP-Exos was evaluated using CCK-8 assay and EdU assay.The effect of PRP-Exos on the migration of TSPC was evaluated by cell scratch assay and Transwell assay. Results The extracted PRP-Exos exhibit typical saucer-like structures,with a concentration of 4.9×1011 particles/mL,an average particle size of (132.2±56.8) nm,and surface expression of CD9,CD63 and CD41.The extracted TSPC expressed the CD44 protein.PRP-Exos can be taken up by TSPC,and after co-cultured for 48 h,concentrations of 50 and 100 µg/mL of PRP-Exos significantly promoted the proliferation of TSPC (both P<0.001),with no statistical difference between the two concentrations (P=0.283).Additionally,after co-cultured for 24 h,50 µg/mL of PRP-Exos significantly promoted the migration of TSPC (P<0.001). Conclusion Under in vitro culture conditions,PRP-Exos significantly promote the proliferation and migration of rat TSPC.

18.
Org Lett ; 26(12): 2376-2380, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38484337

RESUMO

A short scalable biomimetic route to bioactive natural product bimagnolignan (1) was accomplished. Compound 1 was successfully prepared through a three-step metal-free synthesis from honokiol (2). Alternatively, 1 was also synthesized by biomimetic transformations that mimic tyrosinase in four steps. The key reactions feature a regioselective acetylation, a highly efficient C(sp2)-H oxidation, a cascade aerobic oxidative cyclization/coupling, and a Cu-catalyzed direct oxidative coupling. In addition, cell-based assays validate that 1 is a promising natural lead for HER2-positive breast cancer treatment.


Assuntos
Biomimética , Neoplasias da Mama , Humanos , Feminino , Ciclização , Oxirredução , Acoplamento Oxidativo , Neoplasias da Mama/tratamento farmacológico
19.
Chem Res Toxicol ; 37(4): 528-539, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38507288

RESUMO

Quinoxaline 1,4-di-N-Oxides (QdNOs) have been used as synthetic antimicrobial agents in animal husbandry and aquaculture. The metabolism and potential toxicity have been also concerns in recently years. The metabolism investigations showed that there were 8 metabolites of Carbadox (CBX), 34 metabolites of Cyadox (CYA), 33 metabolites of Mequindox (MEQ), 35 metabolites of Olaquindox (OLA), and 56 metabolites of Quinocetone (QCT) in different animals. Among them, Cb3 and Cb8, M6, and O9 are metabolic residual markers of CBX, MEQ and OLA, which are associated with N → O reduction. Toxicity studies revealed that QdNOs exhibited severe tumorigenicity, cytotoxicity, and adrenal toxicity. Metabolic toxicology showed that toxicity of QdNOs metabolites might be related to the N → O group reduction, and some metabolites exhibited higher toxic effects than the precursor, which could provide guidance for further research on the metabolic toxicology of QdNOs and provide a wealth of information for food safety evaluation.


Assuntos
Óxidos , Quinoxalinas , Animais , Quinoxalinas/toxicidade , Quinoxalinas/metabolismo , Carbadox , Estresse Oxidativo
20.
J Environ Manage ; 354: 120205, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38359623

RESUMO

Formation and extinction of thermal stratifications impact the reservoir ecosystems and have been closely influenced by meteorological and hydrological factors. However, quantifying the relative importance of these crucial environmental factors and mechanisms in reservoir regions characterized by various depths remain comparatively uninvestigated. Tianbao Reservoir is a typical monomictic warm and drinking water source reservoir in Southwest China. This study supplemented field observations with a three-dimensional numerical simulation model to quantitatively analyze mixing and turnover events. Air temperature and wind were two important meteorological factors resulting in hydrodynamics during stratification and mixing processes. Air temperature led to variations in stratification strength and wind-induced fluctuations of thermocline depth. A 10% rise in air temperature increased stratification strength by 18%, and a 3 m/s rise in wind speed induced the deepening of the thermocline by 2.09 m. Two hydrodynamics involved penetrative convection caused by temperature plummets and wind-induced mixing during winter turnover events were identified. Penetrative convection was the main driving force, and wind shear mixed the upper 21% of the mixed layer, which was contributed by convection. Response of water temperature to air temperature in shallow regions was faster (58 d), and the mixing depth caused by the wind was smaller than that in deep regions. Research on physical processes during stratification and mixing processes can provide support for further study on water quality deterioration distributions.


Assuntos
Ecossistema , Qualidade da Água , Estações do Ano , Temperatura , Vento , China , Monitoramento Ambiental
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