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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 324: 125011, 2025 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-39213831

RESUMO

Thiols function as antioxidants in food, prolonging shelf life and enhancing flavor. Moreover, thiols are vital biomolecules involved in enzyme activity, cellular signal transduction, and protein folding among critical biological processes. In this paper, the fluorescent probe PYL-NBD was designed and synthesized, which utilized the fluorescent molecule pyrazoline, the lysosome-targeted morpholine moiety, and the sensing moiety NBD. Probe PYL-NBD was tailored for the recognition of biothiols through single-wavelength excitation, yielding distinct fluorescence emission signals: blue for Cys, Hcy, and GSH; green for Cys, Hcy. Probe PYL-NBD exhibited rapid reaction kinetics (<10 min), distinct fluorescence response signals, and low detection limits (15.7 nM for Cys, 14.4 nM for Hcy, and 12.6 nM for GSH). Probe PYL-NBD enabled quantitative determination of Cys content in food samples and L-cysteine capsules. Furthermore, probe PYL-NBD had been successfully applied for confocal imaging with dual-channel detection of biothiols in various biological specimens, including HeLa cells, zebrafish, tumor sections, and Arabidopsis thaliana.


Assuntos
Cisteína , Corantes Fluorescentes , Análise de Alimentos , Glutationa , Lisossomos , Espectrometria de Fluorescência , Peixe-Zebra , Humanos , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Lisossomos/química , Lisossomos/metabolismo , Células HeLa , Cisteína/análise , Animais , Análise de Alimentos/métodos , Glutationa/análise , Espectrometria de Fluorescência/métodos , Homocisteína/análise , Arabidopsis/química , Limite de Detecção , Microscopia Confocal
3.
Transplant Proc ; 56(8): 1870-1877, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39237387

RESUMO

AIM: The safety of liver transplantation and simultaneous splenectomy (LTSP) is still controversial. This study aimed to compare postoperative outcomes and infection in liver transplant recipients with and without simultaneous splenectomy. METHODS: Clinical data of patients who underwent liver transplantation (LT) from May 2015 to March 2023 in the First Affiliated Hospital of Anhui Medical University were retrospectively analyzed. The main parameters measured were culture results, infection incidence, pathogens, postoperative complications, and overall survival rates. RESULTS: Of 149 patients, 35 who underwent LTSP were assigned to the LTSP group, and the remaining 114 were assigned to the LT group. The postoperative infection incidence in the LTSP group was significantly higher than in the LT group within 1 month after transplantation. The two groups had no significant differences in pathogens details and overall survival rate. SP, postoperative days (POD) 3 Neutrophil to lymphocyte ratio (NLR), POD 7 NLR, and POD 7 Hemoglobin (HGB) were independent risk factors for postoperative infection in multivariate analysis. CONCLUSION: LTSP increases the risk of short-term postoperative infections, and postoperative NLR can be used as a marker of infection.


Assuntos
Transplante de Fígado , Complicações Pós-Operatórias , Esplenectomia , Humanos , Esplenectomia/efeitos adversos , Estudos Retrospectivos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Adulto , Complicações Pós-Operatórias/epidemiologia , Incidência , Infecções/epidemiologia , Infecções/etiologia , Neutrófilos
4.
Water Res X ; 25: 100253, 2024 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-39291147

RESUMO

Efficient carbon use is crucial for biological nitrogen removal. Traditional aerobic processes can waste carbon sources, exacerbating carbon deficiency. This study explores an anaerobic/oxic/anoxic system with sludge double recirculation to improve nitrogen removal in low C/N wastewater. This system integrated aerobic nitrification after the carbon intracellular storage, separating carbon and nitrogen by denitrifying glycogen-accumulating organisms (DGAOs) with endogenous partial denitrification and Anammox within the anoxic units. A significant efficiency of 91.02±7.01% chemical oxygen demand (COD) was converted into intracellular carbon in anaerobic units, significantly reducing carbon futile oxidation in the aerobic units by effectively separating COD from ammonia. Intracellular storage of carbon sources and microbial adaptation to carbon scarcity prevent futile oxidation of COD in the aerobic units even with short-term high dissolved oxygen (DO), thereby enhancing nitrogen removal under anoxic conditions with sufficient intracellular carbon source. The microbial analysis identified Candidatus Brocadia as the dominant anammox bacteria, in combination with the activity of DGAOs and other related microbial communities, accounting for 37.0% of the TN removal. Consequently, the system demonstrated remarkable nitrogen removal efficiencies, achieving 81.3±3.3% for total nitrogen (TN) and 98.5±0.9% for ammonia nitrogen while maintaining an effluent COD concentration of 17.2±9.1 mg/L, treating the low C/N of 4.18 in the influent wastewater. The findings in this study provide a sustainable and energy-saving technique for conventional WWTPs to meet strict discharge standards by avoiding futile oxidation of COD and encouraging anammox contributions.

6.
Adv Mater ; : e2409949, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223931

RESUMO

High-entropy oxides (HEOs) exhibit distinctive catalytic properties owing to their diverse elemental compositions, garnering considerable attention across various applications. However, the preparation of HEO nanoparticles with different spatial structures remains challenging due to their inherent structural instability. Herein, ultrasmall high-entropy oxide nanoparticles (less than 5 nm) with different spatial structures are synthesized on carbon supports via the rapid thermal shock treatment. The low-symmetry HEO, BiSbInCdSn-O4, demonstrates exceptional performance for electrocatalytic carbon dioxide reaction (eCO2RR), including a lower overpotential, high Faraday efficiency across a wide electrochemical range (-0.3 to -1.6 V), and sustained stability for over100 h. In the membrane electrode assembly electrolyzer, BiSbInCdSn-O4 achieves a current density of 350 mA cm-2 while maintaining good stability for 24 h. Both experimental observations and theoretical calculations reveal that the electron donor-acceptor interactions between bismuth and indium sites in BiSbInCdSn-O4 enable the electron delocalization to facilitate the efficient adsorption of CO2 and hydrogenation reactions. Thus, the energy barrier of the rate-determining step is reduced to enhance the electrocatalytic activity and stability. This study elucidates that the spatial structure of metal sites in HEOs is able to regulate CO2 adsorption status for eCO2RR, paving the way for the rational design of efficient HEO catalysts.

7.
ACS Biomater Sci Eng ; 10(9): 5624-5631, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39107258

RESUMO

Poly(methyl methacrylate) (PMMA) bone cements have been widely used in orthopedics; thanks to their excellent mechanical properties, biocompatibility, and chemical stability. Barium sulfate and zirconia are usually added into PMMA bone cement to enhance the X-ray radiopacity, while the mechanical strength, radiopacity, and biocompatibility are not well improved. In this study, an insoluble and corrosion-resistant ceramic, tantalum carbide (TaC), was added into the PMMA bone cement as radiopacifies, significantly improving the mechanical, radiopaque, biocompatibility, and osteogenic performance of bone cement. The TaC-PMMA bone cement with varied TaC contents exhibits compressive strength over 100 MPa, higher than that of the commercial 30% BaSO4-PMMA bone cement. Intriguingly, when the TaC content reaches 20%, the radiopacity is equivalent to the commercial bone cement with 30% of BaSO4 in PMMA. The cytotoxicity and osteogenic performance indicate that the incorporation of TaC not only enhances the osteogenic properties of PMMA but also does not reduce cell viability. This study suggests that TaC could be a superior and multifunctional radio-pacifier for PMMA bone cement, offering a promising avenue for improving patient outcomes in orthopedic applications.


Assuntos
Materiais Biocompatíveis , Cimentos Ósseos , Osteogênese , Polimetil Metacrilato , Tantálio , Cimentos Ósseos/química , Tantálio/química , Polimetil Metacrilato/química , Osteogênese/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Teste de Materiais , Sobrevivência Celular/efeitos dos fármacos , Humanos , Animais , Força Compressiva , Camundongos
8.
Plant Commun ; : 101072, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39192582

RESUMO

Plants utilize plasma membrane-localized pattern recognition receptors (PRRs) to perceive pathogen-associated molecular patterns (PAMPs) to activate broad-spectrum pattern-triggered immunity (PTI). However, the regulatory mechanism ensuring robust broad-spectrum plant immunity remains largely unknown. Here, we reveal the dual roles of the transcription factor WRKY8 in transcriptional regulation of PRR genes: repressing the nlp20/nlp24 receptor gene RLP23 whereas promoting the chitin receptor gene CERK1. Remarkably, SsNLP1 and SsNLP2, two nlp24 type PAMPs in the destructive fungal pathogen Sclerotinia sclerotiorum, activate two calcium-elicited kinases, CPK4 and CPK11 to phosphorylate WRKY8 and consequently release its inhibition on RLP23 expression to accumulate RLP23. Meanwhile, SsNLPs activate a RLCK type kinase, PBL19 to phosphorylate WRKY8 and consequently enhance the accumulation of CERK1. Intriguingly, RLP23 is repressed at late stage by PBL19-mediated phosphorylation of WRKY8, to avoid excessive immunity for normal growth. Our findings unveil a "killing two birds with one stone" strategy employed by plants to elicit robust broad-spectrum immunity, which is based on PAMP-triggered fine-tuning of a dual-role transcription factor to simultaneously amplify two PRRs recognizing PAMPs well conserved in a wide range of pathogens. Moreover, our results reveal a novel plant strategy based on fine-tuning of multiple PRR gene expression to balance the trade-off between growth and immunity.

9.
Heliyon ; 10(12): e32617, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39183881

RESUMO

Objective: The present investigation was designed to devise a rapid and straightforward technique for the isolation of rat precartilaginous stem cells (PCSCs) that eschews the use of immunomagnetic bead sorting. Method: Rat neonates within 24 h of birth were selected for this study. Microsurgical techniques were used to harvest the femur, tibia, and the musculature of the knee joint. The ring of LaCroix between the metaphysis of the femur and the epiphysis was excised and divided into fragments of approximately 1 mm³. Tissue sections were cultured in Dulbecco's modified Eagle's medium(DMEM)/F12 medium supplemented with 20 % fetal bovine serum and 1 % penicillin-streptomycin. Cell digestion and passaging were performed using trypsin when cells reached 70%-80 % confluence. Third-generation cells underwent immunofluorescence staining and flow cytometry to evaluate fibroblast growth factor receptor-3(FGFR-3) and proliferating cell nuclear antigen(PCNA) expression, while ß-galactosidase staining was used to determine cellular senescence. Results: Within two days of isolation, numerous short spindle-shaped cells exhibiting distinct refractive properties were observed around the tissue fragments. These cells began to proliferate within 2-3 days and displayed ample cytoplasm. Adherent cells adopted various morphologies, including angular, triangular, and elongated spindles. By the fifth day, more than 80 % of the culture dish surface was covered with elongated cells, with some arranged in patterns reminiscent of whirlpools. Significant FGFR-3 and PCNA expression was confirmed via immunofluorescence in the third-generation cells. Additionally, flow cytometry identified that the proportion of cells positive for FGFR-3 and PCNA exceeded 98 %. Notably, the cells preserved their proliferative capacity through nine passages in vitro, with a marginal proportion showing senescence as indicated by ß-galactosidase staining alone. Conclusion: The developed tissue adherence protocol was used to successfully isolate PCSCs with positive FGFR-3 and PCNA expression, rendering the immunomagnetic bead sorting superfluous. The expression of FGFR-3 and PCNA in the isolated cells persisted through the ninth passage in vitro with minimal senescence.

10.
Genes (Basel) ; 15(8)2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39202382

RESUMO

Spodoptera frugiperda poses a severe threat to crops, causing substantial economic losses. The increased use of chemical pesticides has led to resistance in S. frugiperda populations. Micro ribonucleic acids (MicroRNAs or miRNAs) are pivotal in insect growth and development. This study aims to identify miRNAs across different developmental stages of S. frugiperda to explore differential expression and predict target gene functions. High-throughput sequencing of miRNAs was conducted on eggs, 3rd instar larvae, pupae, and adults. Bioinformatics analyses identified differentially expressed miRNAs specifically in larvae, with candidate miRNAs screened to predict target genes, particularly those involved in detoxification pathways. A total of 184 known miRNAs and 209 novel miRNAs were identified across stages. Comparative analysis revealed 54, 15, and 18 miRNAs differentially expressed in larvae, compared to egg, pupa, and adult stages, respectively. Eight miRNAs showed significant differential expression across stages, validated by quantitative reverse transcription PCR (qRT-PCR). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses predicted target genes' functions, identifying eight differentially expressed miRNAs targeting 10 gene families associated with detoxification metabolism, including P450s, glutathione S-transferase (GSTs), ATP-binding cassette (ABC) transporters, and sodium channels. These findings elucidate the species-specific miRNA profiles and regulatory mechanisms of detoxification-related genes in S. frugiperda larvae, offering insights and strategies for effectively managing this pest.


Assuntos
Inativação Metabólica , Larva , MicroRNAs , Spodoptera , Animais , Spodoptera/genética , Spodoptera/metabolismo , Spodoptera/crescimento & desenvolvimento , MicroRNAs/genética , MicroRNAs/metabolismo , Larva/genética , Larva/metabolismo , Larva/crescimento & desenvolvimento , Inativação Metabólica/genética , Sequenciamento de Nucleotídeos em Larga Escala , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica no Desenvolvimento , Glutationa Transferase/genética , Glutationa Transferase/metabolismo
11.
ACS Appl Mater Interfaces ; 16(34): 44636-44644, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39146398

RESUMO

Bismuth-based compounds based on conversion-alloying reactions of multielectron transfer have attracted extensive attention as alternative anode candidates for rechargeable magnesium batteries (rMBs). However, the inadequate magnesium storage capability induced by the sluggish kinetics, poor reversibility, and terrible structural stability impedes their practical utilization. Herein, monodispersed Bi2S3 anchored on MXene has been prepared via a simple self-assembly strategy to induce the interfacial bonding of Ti-S and Ti-O-Bi. Unique superiority, including good electrical conductivity, high mechanical strength, and rapid charge transfer, is cleverly integrated together in the Bi2S3/MXene heterostructures, which endowed heterostructures with enhanced magnesium storage performance. Density functional theory calculations combined with kinetic behavior analyses confirm the favorable charge transfer and low ion diffusion barrier in hybrids. Furthermore, a stepwise insertion-conversion-alloying reaction mechanism is revealed in depth by ex situ investigations, which may also account for promoting performance. This work provides significant inspirations for constructing ingenious multicompositional hybrids by strong interfacial coupling engineering toward high-performance energy storage devices.

12.
Int J Biol Macromol ; 279(Pt 1): 135029, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39197618

RESUMO

Conductive hydrogels with excellent mechanical properties, a broad detection range, and stability in complex environments have remained a significant challenge for the development of flexible sensors. In this study, a straightforward freeze-thaw cycles strategy was developed to fabricate a polyvinyl alcohol (PVA)/carrageenan (CA)/calcium chloride (CaCl2)/MXene-based double network organohydrogel (PCCME) for highly flexible and responsive strain detection across a broad temperature spectrum. The PCCME organohydrogel features multiple interactive forces including hydrogen bonding, ionic interactions, and microphase crystallization, which contribute to the organohydrogel's exceptional mechanical and electrical performance. The PCCME organohydrogel exhibited excellent performance in a load-unload test repeated 100 times after being maintained at room temperature for 7 days, with a minimal mechanical decay of only 2.6%. Furthermore, the repaired PCCME organohydrogel retained its robust stability after storage at low temperatures followed by placement at room temperature. The organohydrogel sensor not only detects various movement amplitudes of the human body but also recognizes arrays of pressure signals and converts these into digital images, highlighting its significant potential for applications in rehabilitation monitoring, pressure sensing, and human-computer interaction.

13.
Ecotoxicol Environ Saf ; 284: 116944, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39208575

RESUMO

Aristolochic acid (AA) exposure is a severe public health concern worldwide. AAs damage the kidney with an inevitable acute phase that is similar to acute kidney injury (AKI). Gasdermin E (GSDME) is abundant in the kidney; thus; it-mediated pyroptosis might be essential in connecting cell death and inflammation and promoting AAs-AKI. However, the role and exact mechanism of pyroptosis in AAs-AKI have not been investigated. In this study, aristolochic acid I (AAI) was used to establish AKI models. The expression and translocation results showed GSDME-mediated pyroptosis in AAI-AKI. Knocking down GSDME attenuated AAI-induced cell death and transcription of proinflammatory cytokines. Mechanistic research inhibiting caspase (casp) 3, casp 8, and casp 9 with specific chemical antagonists demonstrated that GSDME was activated by cleaved casp 3. Furthermore, the kinase activity of upstream receptor-interacting protein kinase 1 (RIPK1) was significantly elevated, and inhibiting RIPK1 with specific inhibitors markedly improved AAI-induced cell damage. In addition, the level of autophagy was obviously increased. Pretreatment with a specific autophagic inhibitor (3-methyladenine) or knockdown of autophagic genes (Atg5 or Atg7) evidently reduced the activity of RIPK1 and downstream apoptosis and pyroptosis, thus attenuating AA-induced cell injury, which suggested that RIPK1 was a novel link conferring autophagic promotion of pyroptosis. These findings reveal GSDME-mediated pyroptosis for the first time in AAI-induced AKI, propose its novel role in the transcription of cytokines, and demonstrate that autophagy promotes pyroptosis via the RIPK1-dependent apoptotic pathway. This study promotes the understanding of the toxic effects and exact mechanisms of AAs. This will contribute to evaluating the environmental risk of AA exposure and might provide potential therapeutic targets for AA-AKI.

14.
Protein Expr Purif ; 223: 106562, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39094814

RESUMO

Previous studies have demonstrated the presence of chitinase in Bacillus velezensis through extensive genomic sequencing and experimental analyses. However, the detailed structure, functional roles, and antifungal activity of these chitinases remain poorly characterized. In this study, genomic screening identified three genes-chiA, chiB, and lpmo10-associated with chitinase degradation in B. velezensis S161. These genes encode chitinases ChiA and ChiB, and lytic polysaccharide monooxygenase LPMO10. Both ChiA and ChiB contain two CBM50 binding domains and one catalytic domain, whereas LPMO10 includes a signal peptide and a single catalytic domain. The chitinases ChiA, its truncated variant ChiA2, and ChiB were heterologously expressed in Escherichia coli. The purified enzymes efficiently degraded colloidal chitin and inhibited the spore germination of Penicillium digitatum. Notably, even after losing one CBM50 domain, the resultant enzyme, consisting of the remaining CBM50 domain and the catalytic domain, maintained its colloidal chitin hydrolysis and antifungal activity, indicating commendable stability. These results underscore the role of B. velezensis chitinases in suppressing plant pathogenic fungi and provide a solid foundation for developing and applying chitinase-based biocontrol strategies.


Assuntos
Antifúngicos , Bacillus , Quitinases , Penicillium , Antifúngicos/farmacologia , Antifúngicos/química , Bacillus/enzimologia , Bacillus/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/farmacologia , Quitina/química , Quitinases/química , Quitinases/farmacologia , Escherichia coli , Penicillium/efeitos dos fármacos , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacologia
15.
Front Immunol ; 15: 1430571, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39131156

RESUMO

Background: Intermediate-stage (BCLC-B) hepatocellular carcinoma (HCC) beyond the up-to-11 criteria represent a significant therapeutic challenge due to high and heterogeneous tumor burden. This study evaluated the effectiveness and safety of transarterial chemoembolization (TACE) in combination with lenvatinib and tislelizumab for these patients. Methods: In this retrospective cohort study, patients with unresectable intermediate-stage HCC beyond the up-to-11 criteria were enrolled and divided into TACE monotherapy (T), TACE combined with lenvatinib (TL), or TACE plus lenvatinib and tislelizumab (TLT) group based on the first-line treatment, respectively. The primary endpoint was overall survival (OS). The secondary outcomes included progression-free survival (PFS), tumor response according to RESIST1.1 and modified RECIST, and adverse events (AEs). Results: There were 38, 45, and 66 patients in the T, TL, and TLT groups, respectively. The TLT group exhibited significantly higher ORR and DCR than the other two groups, as assessed by either mRECIST or RECIST 1.1 (all P<0.05). Median PFS and OS were significantly longer in the TLT group compared with the T group (PFS: 8.5 vs. 4.4 months; OS: 31.5 vs. 18.5 months; all P<0.001) and TL group (PFS: 8.5 vs. 5.5 months; OS: 31.5 vs. 20.5 months; all P<0.05). The incidence of TRAEs was slightly higher in the TLT and TL groups than in the T group, while all the toxicities were tolerable. No treatment-related death occurred in all groups. Conclusions: TACE combined with lenvatinib and tislelizumab significantly improved the survival benefit compared with TACE monotherapy and TACE plus lenvatinib in patients with intermediate-stage HCC beyond the up-to-11 criteria, with an acceptable safety profile.


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Compostos de Fenilureia , Quinolinas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/tratamento farmacológico , Quinolinas/uso terapêutico , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Quimioembolização Terapêutica/métodos , Compostos de Fenilureia/uso terapêutico , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Estudos Retrospectivos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Estadiamento de Neoplasias , Resultado do Tratamento
16.
J Hepatocell Carcinoma ; 11: 1473-1479, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39105210

RESUMO

Purpose: The combination of sorafenib and hepatic arterial infusion chemotherapy (SoHAIC) has shown to enhance overall survival rates in patients with advanced hepatocellular carcinoma and major portal vein tumor thrombosis (HCC-Vp3-4) compared to sorafenib alone. Our objective was to evaluate the cost-effectiveness of SoHAIC versus sorafenib for the treatment of HCC-Vp3-4, taking into account the viewpoint of Chinese healthcare payers. Methods: This pharmacoeconomic study employed a Markov model to assess the cost-effectiveness of treating HCC-Vp3-4 with SoHAIC in comparison to sorafenib. The patient characteristics were drawn from individuals from the trial conducted between June 2017 and November 2019, with cost and health value data sourced from published literature. The primary outcome measure in this research was the incremental cost-effectiveness ratio (ICER), which indicates the additional cost per quality-adjusted life year (QALY). The willingness-to-pay (WTP) threshold per QALY was set at $30,492.00. Furthermore, 1-way sensitivity and probabilistic sensitivity analyses were carried out to validate the consistency of the results. Results: In the baseline scenario, sorafenib resulted in 0.42 QALY at a cost of $10,507.89, while SoHAIC generated 1.66 QALY at a cost of $32,971.56. When comparing SoHAIC to sorafenib, the ICER was $18,237.20 per QALY, which was below the WTP threshold per QALY. Furthermore, the 1-way sensitivity analysis demonstrated that the ICER remained within the WTP threshold despite fluctuations in variables. In the probabilistic sensitivity analysis, SoHAIC had a 98.8% probability of being cost-effective at the WTP threshold, considering a wide range of parameters. Conclusion: In this cost-effectiveness evaluation, SoHAIC demonstrated cost-effectiveness over sorafenib for HCC with major portal vein tumor thrombosis, as observed from the perspective of a Chinese payer.

17.
Nano Lett ; 24(34): 10458-10466, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39146031

RESUMO

Rechargeable magnesium batteries (rMBs) are promising candidates for next-generation batteries in which sulfides are widely used as cathode materials. The slow kinetics, low redox reversibility, and poor magnesium storage stability induced by the large Coulombic resistance and ionic polarization of Mg2+ ions have obstructed the development of high-performance rMBs. Herein, a Cu1.8S1-xSex cathode material with a two-dimensional sheet structure has been prepared by an anion-tuning strategy, achieving improved magnesium storage capacity and cycling stability. Element-specific synchrotron radiation analysis is evidence that selenium incorporation has indeed changed the chemical state of Cu species. Density functional theory calculations combined with kinetics analysis reveal that the anionic substitution endows the Cu1.8S1-xSex electrode with favorable charge-transfer kinetics and low ion diffusion barrier. The principal magnesium storage mechanisms and structural evolution process have been revealed in details based on a series of ex situ investigations. Our findings provide an effective heteroatom-tuning tactic of optimizing electrode structure toward advanced energy storage devices.

18.
Anal Bioanal Chem ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39191938

RESUMO

Biothiols, characterized by their unique sulfhydryl (-SH) groups, possess excellent antioxidant properties, effectively neutralizing the damage to cellular structures caused by reactive oxygen species (ROS) in living organisms. Additionally, lysosomes play a crucial role in decomposing damaged biomolecules through the action of their internal enzymes, regulating the cellular redox state, and mitigating oxidative stress. To facilitate rapid monitoring of intracellular biothiols, particularly within lysosomes, we constructed a lysosome-targeted biothiol fluorescent probe, PHL-DNP, in this study. PHL-DNP exhibited excellent photophysical properties in an aqueous test system, including strong fluorescence enhancement response, excellent selectivity, and low detection limits (Cys 16.5 nM, Hcy 16.8 nM, GSH 21.3 nM, Cap 26.6 nM). These attributes enabled easy and efficient qualification of Cys on test strips and accurate determination of the effective content of captopril tablets. Notably, PHL-DNP demonstrated low cytotoxicity and precise lysosomal targeting. Through bioimaging, PHL-DNP not only monitored changes in biothiol levels under oxidative stress but also assessed biothiols in complex biological systems such as live HeLa cells, zebrafish, tumor tissue sections, and radish roots. This provides a promising tool for quantitative analysis of biothiols, disease marker detection, and drug testing.

19.
Spectrochim Acta A Mol Biomol Spectrosc ; 323: 124944, 2024 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-39128308

RESUMO

As a type of reactive oxygen species, hypochlorous acid (ClO-) plays an important role in sterilization, disinfection and protection in organisms. However, excessive production of ClO- is closely related to various diseases. In this work, we have designed a robust ratiometric fluorescent probe, RDB-ClO, using the excited-state intramolecular proton transfer (ESIPT) strategy. RDB-ClO was achieved by modifying 2-(2-(benzo[d]thiazol-2-yl)-6-(diethylamino)-3-oxo-3H-xanthen-9-yl) benzoic acid (RDB-OH) with a 1-naphthoyl chloride group, specifically for the sensitive detection of ClO-. In the presence of ClO-, RDB-ClO demonstrated relatively good performance, showing swift response time (35 s), low detection limit of 5.1 nM and high selectivity towards ClO-. Notably, the convenience and accessibility detection of ClO- has been implemented using test strip and agarose probe. RDB-ClO effectively tracked both endogenous and exogenous ClO- in HeLa cells, HepG2 cells and zebrafish. Additionally, it is successfully applied to detect changes of exogenous ClO- content in E. coli. and acetaminophen (APAP)-induced liver injury in mice. The development of RDB-ClO represents a promising molecular tool for studying the pathogenesis of DILI and biotransformation of ClO- in bacteria.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Corantes Fluorescentes , Ácido Hipocloroso , Peixe-Zebra , Corantes Fluorescentes/química , Animais , Humanos , Células HeLa , Ácido Hipocloroso/análise , Ácido Hipocloroso/metabolismo , Células Hep G2 , Camundongos , Escherichia coli/efeitos dos fármacos , Espectrometria de Fluorescência , Limite de Detecção
20.
Neuroimage ; : 120811, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39214436

RESUMO

This paper proposes a data-driven analysis method to accurately partition large-scale resting-state functional brain networks from fMRI data. The method is based on a spectral clustering algorithm and combines eigenvector direction selection with Pearson correlation clustering in the spectral space. The method is an improvement on available spectral clustering methods, capable of robustly identifying active brain networks consistent with those from model-driven methods at different noise levels, even at the noise level of real fMRI data.

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