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1.
Infect Drug Resist ; 17: 2089-2098, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828375

RESUMO

Background: Qiguiyin decoction (QGYD) is a traditional Chinese medicine (TCM) and its combined application with levofloxacin (LVFX) has been confirmed effective in the clinical treatment of multidrug-resistant Pseudomonas aeruginosa (MDR PA) infection. This study investigated the therapeutic effect and possible mechanism of QGYD in sensitizing LVFX against MDR PA infection. Materials and Methods: Pulmonary infections were induced in rats by MDR PA. The changes in pharmacokinetics-pharmacodynamics (PK-PD) parameters of LVFX after combined with QGYD were investigated in MDR PA-induced rats. Subsequently, the correlation between PK and PD was analyzed and PK-PD models were established to elucidate the relationship between QGYD-induced alterations in LVFX metabolism and its sensitization to LVFX. Antibody chip technology was used to detect the levels of inflammatory factors, suggesting the relationship between the beneficial effect of immune regulation and the sensitization of QGYD. Results: QGYD significantly enhanced the therapeutic efficacy of LVFX against MDR PA infection. The combination of QGYD changed the PK parameters of LVFX such as Tmax, t1/2, MRT, Vd/F, CL/F and PD parameters such as MIC, AUC0-24h/MIC. Predicted results from PK-PD models demonstrated that the antibacterial effect of LVFX was significantly enhanced with the combination of QGYD, consistent with experimental findings. Antibody chip results revealed that the combination of QGYD made IL-1 ß, IL-6, TNF- α, IL-10, and MCP-1 levels more akin to those of the blank group. Conclusion: These findings indicated that QGYD could change the PK-PD behaviors of LVFX and help the body restore immune balance faster. This implied that a potential drug interaction might occur between QGYD and LVFX, leading to improved clinical efficacy when combined.

2.
Chem Soc Rev ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833171

RESUMO

Photoelectrochemical (PEC) water splitting provides a scalable and integrated platform to harness renewable solar energy for green hydrogen production. The practical implementation of PEC systems hinges on addressing three critical challenges: enhancing energy conversion efficiency, ensuring long-term stability, and achieving economic viability. Metal-insulator-semiconductor (MIS) heterojunction photoelectrodes have gained significant attention over the last decade for their ability to efficiently segregate photogenerated carriers and mitigate corrosion-induced semiconductor degradation. This review discusses the structural composition and interfacial intricacies of MIS photoelectrodes tailored for PEC water splitting. The application of MIS heterostructures across various semiconductor light-absorbing layers, including traditional photovoltaic-grade semiconductors, metal oxides, and emerging materials, is presented first. Subsequently, this review elucidates the reaction mechanisms and respective merits of vacuum and non-vacuum deposition techniques in the fabrication of the insulator layers. In the context of the metal layers, this review extends beyond the conventional scope, not only by introducing metal-based cocatalysts, but also by exploring the latest advancements in molecular and single-atom catalysts integrated within MIS photoelectrodes. Furthermore, a systematic summary of carrier transfer mechanisms and interface design principles of MIS photoelectrodes is presented, which are pivotal for optimizing energy band alignment and enhancing solar-to-chemical conversion efficiency within the PEC system. Finally, this review explores innovative derivative configurations of MIS photoelectrodes, including back-illuminated MIS photoelectrodes, inverted MIS photoelectrodes, tandem MIS photoelectrodes, and monolithically integrated wireless MIS photoelectrodes. These novel architectures address the limitations of traditional MIS structures by effectively coupling different functional modules, minimizing optical and ohmic losses, and mitigating recombination losses.

3.
ACS Omega ; 9(22): 23613-23623, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38854533

RESUMO

Titanium dioxide nanoparticles (TiO2 NPs) have been extensively utilized in various applications. However, the regulatory mechanism behind the reproductive toxicity induced by TiO2 NP exposure remains largely elusive. In this study, we employed a Drosophila model to assess potential testicular injuries during spermatogenesis and conducted bulk RNA-Seq analysis to elucidate the underlying mechanisms. Our results reveal that while prolonged exposure to lower concentrations of TiO2 NPs (0.45 mg/mL) for 30 days did not manifest reproductive toxicity, exposure at concentrations of 0.9 and 1.8 mg/mL significantly impaired spermatid elongation in Drosophila testes. Notably, bulk RNA-seq analysis revealed that TiO2 NP exposure affected multiple metabolic pathways including carbohydrate metabolism and cytochrome P450. Importantly, the intervention of glutathione (GSH) significantly protected against reproductive toxicity induced by TiO2 NP exposure, as it restored the number of Orb-positive spermatid clusters in Drosophila testes. Our study provides novel insights into the specific detrimental effects of TiO2 NP exposure on spermatid elongation through multiple metabolic alterations in Drosophila testes and highlights the protective role of GSH in countering this toxicity.

4.
Angew Chem Int Ed Engl ; : e202408996, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38873975

RESUMO

Two-dimensional Ti3C2Tx MXene materials, with metal-like conductivities and versatile terminals, have been considered to be promising surface modification materials for Zn-metal-based aqueous batteries (ZABs). However, the oxygen-rich and hybridized terminations caused by conventional methods limit their advantages in inhibiting zinc dendrite growth and reducing corrosion-related side reactions. Herein, -O-depleted, -Cl-terminated Ti3C2Tx was precisely fabricated by the molten salt electrochemical etching of Ti3AlC2, and controlled in-situ terminal replacement from -Cl to unitary -S or -Se was achieved. The as-prepared -O-depleted and unitary-terminal Ti3C2Tx as Zn anode coatings provided excellent hydrophobicity and enriched zinc-ionophilic sites, facilitating Zn2+ horizontal transport for homogeneous deposition and effectively suppressing water-induced side reactions. The as-assembled Ti3C2Sx@Zn symmetric cell achieved a cycle life of up to 4200 h at a current density and areal capacity of 2 mA cm-2 and 1 mAh cm-2, respectively, with an impressive cumulative capacity of up to 7.25 Ah cm-2 at 5 mA cm-2 // 2 mAh cm-2. These findings provide an effective electrochemical strategy for tailoring -O-depleted and unitary Ti3C2Tx surface terminals and advancing the understanding of the role of specific Ti3C2Tx surface chemistry in regulating the plating/stripping behaviors of metal ions.

5.
Emerg Microbes Infect ; 13(1): 2320913, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38860446

RESUMO

Continuous emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enhanced transmissibility, significant immune escape, and waning immunity call for booster vaccination. We evaluated the safety, immunogenicity, and efficacy of heterologous booster with a SARS-CoV-2 mRNA vaccine SYS6006 versus an active control vaccine in a randomized, open-label, active-controlled phase 3 trial in healthy adults aged 18 years or more who had received two or three doses of SARS-CoV-2 inactivated vaccine in China. The trial started in December 2022 and lasted for 6 months. The participants were randomized (overall ratio: 3:1) to receive one dose of SYS6006 (N = 2999) or an ancestral receptor binding region-based, alum-adjuvanted recombinant protein SARS-CoV-2 vaccine (N = 1000), including 520 participants in an immunogenicity subgroup. SYS6006 boosting showed good safety profiles with most AEs being grade 1 or 2, and induced robust wild-type and Omicron BA.5 neutralizing antibody response on Days 14 and 28, demonstrating immunogenicity superiority versus the control vaccine and meeting the primary objective. The relative vaccine efficacy against COVID-19 of any severity was 51.6% (95% CI, 35.5-63.7) for any variant, 66.8% (48.6-78.5) for BA.5, and 37.7% (2.4-60.3) for XBB, from Day 7 through Month 6. In the vaccinated and infected hybrid immune participants, the relative vaccine efficacy was 68.4% (31.1-85.5) against COVID-19 of any severity caused by a second infection. All COVID-19 cases were mild. SYS6006 heterologous boosting demonstrated good safety, superior immunogenicity and high efficacy against BA.5-associated COVID-19, and protected against XBB-associated COVID-19, particularly in the hybrid immune population.Trial registration: Chinese Clinical Trial Registry: ChiCTR2200066941.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , Imunogenicidade da Vacina , SARS-CoV-2 , Vacinas de mRNA , Humanos , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , COVID-19/imunologia , COVID-19/virologia , Adulto , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Feminino , Masculino , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , China , Pessoa de Meia-Idade , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Adulto Jovem , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Adolescente , Eficácia de Vacinas , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , População do Leste Asiático
6.
Huan Jing Ke Xue ; 45(6): 3512-3522, 2024 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-38897771

RESUMO

Heavy metal pollution in farmland soil can affect the growth, development, and yield of vegetable crops, as well as the quality and taste of vegetables, and can be continuously transmitted and enriched through the food chain, which ultimately poses a certain hazard to human health in the long term. Therefore, in order to investigate the distribution characteristics of soil heavy metals after years of multi-crop planting of vegetables supplied to Hong Kong, predict their ecological risks, and analyze the causes of pollution formation, 477 surface soil samples of vegetable fields supplied to Hong Kong in Ningxia were collected for three consecutive years from 2019 to 2021, and the contents and distribution characteristics of eight heavy metals, namely, As, Cd, Cr, Hg, Pb, Cu, Zn, and Ni were analyzed. The soil heavy metal pollution status of vegetable fields supplied to Hong Kong in Ningxia was evaluated using the single-factor pollution index method, Nemero's comprehensive pollution index method, land accumulation index method, and potential ecological risk index method, and the sources of heavy metals in vegetable fields supplied to Hong Kong in Ningxia were analyzed using the Pearson's correlation analysis and the principal component analysis method. The results showed that the mean values of As, Cd, Cr, Hg, Cu, and Zn in the soils of Ningxia's vegetable fields were higher than the background values of Ningxia soils, but the contents of all eight heavy metals were lower than the risk screening values of domestic agricultural soils; in terms of spatial distribution, As, Cr, and Ni showed contiguous high values in the northwestern, central, and southern parts of the study area, whereas Pb, Zn, Cd, Hg, and Cu showed high values in the northwestern and southern parts of the study area. The single-factor index method and the Nemero's comprehensive pollution index method showed that the soil of Ningxia's vegetable farmland for Hong Kong was at the clean level as a whole. The results of the ground accumulation index method showed that the pollution in the study area was mainly Hg and Cd pollution, and the pollution areas were mainly concentrated in the northwest and south of the study area. The potential ecological risk index showed that Hg and Cd were the main risk elements, among which Hg was dominated by moderate, strong, and very strong ecological risks, accounting for 44.65 %, 44.65 %, and 1.26 %, respectively, and Cd was dominated by moderate and strong risks, accounting for 65.83 % and 3.56 %. The comprehensive Pearson correlation analysis and principal component analysis showed that the pollution sources of eight heavy metals could be divided into three categories, namely, natural sources:Cu, Zn, Pb, As, Ni, and Cr; agricultural sources:Cd; and industrial and agricultural sources:Hg. From a comprehensive point of view, the heavy metals of the soil in the fields of vegetables supplied to Hong Kong had not exceeded the standard, and the environmental conditions of the soil were good, such that the production of vegetables supplied to Hong Kong by Ningxia was at a safe level overall. The results of the study can provide a theoretical basis for the safe utilization of soil in vegetable fields and the green production of vegetables supplied to Hong Kong in Ningxia, which were aimed to provide help for the safe production of vegetable fields supplied to Hong Kong, the rational application of fertilizers, agronomic planning, and the adjustment of planting structure.


Assuntos
Monitoramento Ambiental , Metais Pesados , Poluentes do Solo , Verduras , Metais Pesados/análise , Poluentes do Solo/análise , Verduras/crescimento & desenvolvimento , Verduras/química , Hong Kong , Medição de Risco , China , Solo/química
7.
Ecotoxicol Environ Saf ; 279: 116460, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38781888

RESUMO

Furan-containing compounds distribute widely in food, herbal medicines, industrial synthetic products, and environmental media. These compounds can undergo oxidative metabolism catalyzed by cytochrome P450 enzymes (CYP450) within organisms, which may produce reactive products, possibly reacting with biomolecules to induce toxic effects. In this work, we performed DFT calculations to investigate the CYP450-mediated metabolic mechanism of furan-ring oxidation using 2-methylfuran as a model substrate, meanwhile, we studied the regioselective competition of another hydroxylation reaction involving methyl group of 2-methylfuran. As a result, we found the toxicological-relevant cis-enedione product can be produced from O-addition directly via a concerted manner without formation of an epoxide intermediate as traditionally believed. Moreover, our calculations demonstrate the kinetic and thermodynamic feasibility of both furan-ring oxidation and methyl hydroxylation pathways, although the former pathway is a bit more favorable. We then constructed a linear model to predict the rate-limiting activation energies (ΔE*) of O-addition with 11 diverse furan substates based on their adiabatic ionization potentials (AIPs) and condensation Fukui functions (CFFs). The results show a good predictive ability (R2=0.94, Q2CV=0.87). Therefore, AIP and CFF with clear physichem meanings relevant to the mechanism, emerge as pivotal molecular descriptors to enable the fast prediction of furan-ring oxidation reactivities for quick insight into the toxicological risk of furans, using just ground-state calculations.


Assuntos
Sistema Enzimático do Citocromo P-450 , Teoria da Densidade Funcional , Furanos , Oxirredução , Furanos/química , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/química , Hidroxilação , Cinética , Termodinâmica
8.
Mol Med ; 30(1): 69, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783226

RESUMO

BACKGROUND: The Enoyl-CoA hydratase/isomerase family plays a crucial role in the metabolism of tumors, being crucial for maintaining the energy balance and biosynthetic needs of cancer cells. However, the enzymes within this family that are pivotal in gastric cancer (GC) remain unclear. METHODS: We employed bioinformatics techniques to identify key Enoyl-CoA hydratase/isomerase in GC. The expression of ECHDC2 and its clinical significance were validated through tissue microarray analysis. The role of ECHDC2 in GC was further assessed using colony formation assays, CCK8 assay, EDU assay, Glucose and lactic acid assay, and subcutaneous tumor experiments in nude mice. The mechanism of action of ECHDC2 was validated through Western blotting, Co-immunoprecipitation, and immunofluorescence experiments. RESULTS: Our analysis of multiple datasets indicates that low expression of ECHDC2 in GC is significantly associated with poor prognosis. Overexpression of ECHDC2 notably inhibits aerobic glycolysis and proliferation of GC cells both in vivo and in vitro. Further experiments revealed that overexpression of ECHDC2 suppresses the P38 MAPK pathway by inhibiting the protein level of MCCC2, thereby restraining glycolysis and proliferation in GC cells. Ultimately, it was discovered that ECHDC2 promotes the ubiquitination and subsequent degradation of MCCC2 protein by binding with NEDD4. CONCLUSIONS: These findings underscore the pivotal role of the ECHDC2 in regulating aerobic glycolysis and proliferation in GC cells, suggesting ECHDC2 as a potential therapeutic target in GC.


Assuntos
Proliferação de Células , Ubiquitina-Proteína Ligases Nedd4 , Neoplasias Gástricas , Animais , Feminino , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Enoil-CoA Hidratase/metabolismo , Enoil-CoA Hidratase/genética , Regulação Neoplásica da Expressão Gênica , Glicólise , Camundongos Nus , Ubiquitina-Proteína Ligases Nedd4/metabolismo , Ubiquitina-Proteína Ligases Nedd4/genética , Ligação Proteica , Proteólise , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Ubiquitinação , Efeito Warburg em Oncologia
9.
Se Pu ; 42(5): 474-480, 2024 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-38736391

RESUMO

A method was established for the simultaneous detection of 12 prohibited veterinary drugs, including ß2-receptor agonists, nitrofuran metabolites, nitroimidazoles, chlorpromazine, and chloramphenicol, in pig urine. The sample was pretreated by enzymolysis, acid hydrolysis/derivatization, and liquid-liquid extraction combined with solid-phase extraction. Detection was performed using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Ammonium acetate solution (0.2 mol/L, 4.5 mL) and ß-glucuronidase/aryl sulfatase (40 µL) were added to the sample, which was subsequently enzymolized at 37 ℃ for 2 h. Then, 1.5 mL of 1.0 mol/L hydrochloric acid solution and 100 µL of 0.1 mol/L o-nitrobenzaldehyde solution were added to the sample. The mixture was incubated at 37 ℃ for 16 h, and the analytes were extracted with 8 mL of ethyl acetate by liquid-liquid extraction. The lower aqueous phase obtained after extraction was extracted and purified using a mixed cation-exchange solid-phase extraction column. The extracts were combined, the extraction solution was blow-dried with nitrogen, and the residue was redissolved for determination. The samples were analyzed under multiple-reaction monitoring mode with both positive and negative electrospray ionization, and quantified using an isotope internal standard method. The correlation coefficients (r) of the 12 compounds were >0.99. The limits of detection (LODs) and quantification (LOQs) of chloramphenicol were 0.05 and 0.1 µg/L, respectively, and the LODs and LOQs of the other compounds were 0.25 and 0.5 µg/L, respectively. The mean recoveries and RSDs at 1, 2, and 10 times the LOQ were 83.6%-115.3% and 2.20%-12.34%, respectively. The proposed method has the advantages of high sensitivity, good stability, and accurate quantification; thus, it is suitable for the simultaneous determination of the 12 prohibited veterinary drug residues in pig urine.


Assuntos
Resíduos de Drogas , Espectrometria de Massas em Tandem , Drogas Veterinárias , Animais , Espectrometria de Massas em Tandem/métodos , Suínos , Cromatografia Líquida de Alta Pressão/métodos , Drogas Veterinárias/urina , Drogas Veterinárias/análise , Resíduos de Drogas/análise , Cloranfenicol/urina , Cloranfenicol/análise
10.
J Clin Nurs ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38757751

RESUMO

AIMS AND OBJECTIVES: To investigate knowledge, attitudes, and practices regarding the application of the Injury Severity Score (ISS) among emergency department nurses in China and the factors influencing these variables. BACKGROUND: ISS is the first trauma scoring method to be developed and the most widely used in clinical practice. The correct application of the ISS by emergency department nurses plays an important role in assisting in the diagnosis and treatment of trauma patients, and it is crucial to understand nurses' knowledge, attitudes and practices. DESIGN: A cross-sectional multicentre study. METHODS: Nurses from the emergency departments of 25 grade II and grade III hospitals in Gansu Province, China participated in this study. Data was collected online using a self-administered questionnaire. Student's t-test or analysis of variance was performed to compare the differences between the groups. Multiple logistic regression analysis identified factors influencing nurses' knowledge, attitudes and practices regarding applying ISS. A STROBE checklist was used to report findings. RESULTS: Among 459 nurses, a good level of attitude and passing levels of knowledge and practice regarding applying the ISS were revealed. Nurses in higher hospital grades, who had been exposed to ISS and received training had higher levels of knowledge and practices. Previous exposure to the ISS and training related to it were factors that influenced nurses' attitudes. CONCLUSIONS: Chinese emergency department nurses' knowledge, attitudes and practices of applying the ISS still need to be improved. Hospitals and nursing managers should provide training opportunities for nurses about ISS knowledge and practices, while grade II hospitals should pay more attention to training and continuing education in this area. RELEVANCE TO CLINICAL PRACTICE: In hospitals, nursing managers may benefit from enhancing related education and training to promote the emergency department nurses' knowledge and practice of the ISS, by developing specific curricula and providing continuing education and training opportunities, while grade II hospitals should pay more attention to training and continuing education in this area. NO PATIENT OR PUBLIC CONTRIBUTIONS: This study focused on emergency department nurses' knowledge, attitudes, and practices regarding the application of the ISS. The research questions and design were derived from clinical nursing practice, literature review, and expert panel review, and patients or the public are temporarily not involved.

11.
J Sport Health Sci ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38719184

RESUMO

The discovery that contracting skeletal muscle generates reactive oxygen species (ROS) was first reported over 40 years ago. The prevailing view in the 1980s was that exercise-induced ROS production promotes oxidation of proteins and lipids resulting in muscle damage. However, a paradigm shift occurred in the 1990s as growing research revealed that ROS are signaling molecules, capable of activating transcriptional activators/coactivators and promoting exercise-induced muscle adaptation. Growing evidence supports the notion that reduction-oxidation (redox) signaling pathways play an important role in the muscle remodeling that occurs in response to endurance exercise training. This review examines the specific role that redox signaling plays in this endurance exercise-induced skeletal muscle adaptation. We begin with a discussion of the primary sites of ROS production in contracting muscle fibers followed by a summary of the antioxidant enzymes involved in the regulation of ROS levels in the cell. We then discuss which redox-sensitive signaling pathways promote endurance exercise-induced muscle adaptation and debate the strength of the evidence supporting the notion that redox signaling plays an essential role in muscle adaptation to endurance exercise training. In hopes of stimulating future research, we highlight several important unanswered questions in this field.

12.
Mikrochim Acta ; 191(6): 330, 2024 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744738

RESUMO

In view of a large number of people infected with Helicobacter pylori (H. pylori) with great harm followed, there is an urgent need to develop a non-invasive, easy-to-operate, and rapid detection method, and to identify effective sterilization strategies. In this study, highly specific nanoprobes with nanozyme activity, Ag@Pt nanoparticles (NPs) with the antibody, were utilized as a novel lateral flow immunoassay (LFIA). The optical label (Ag@Pt NPs) was enhanced by the introduction of the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB) and compared with a gold nanoparticles (Au NPs) optical label. Under the optimal condition, Ag@Pt-LFIA and TMB-enhanced Ag@Pt-LFIA for H. pylori were successfully established, two of which were over twofold and 100-fold more sensitive than conventional visual Au NP-based LFIA, respectively. Furthermore, Ag@Pt NPs with the antibody irradiated with NIR laser (808 nm) at a power intensity of 550 mW/cm2 for 5 min exhibited a remarkable antibacterial effect. The nanoprobes could close to bacteria through effective interactions between antibodies and bacteria, thereby benefiting photothermal sterilization. Overall, Ag@Pt NPs provide promising applications in pathogen detection and therapeutic applications.


Assuntos
Ligas , Helicobacter pylori , Nanopartículas Metálicas , Platina , Prata , Helicobacter pylori/efeitos da radiação , Helicobacter pylori/efeitos dos fármacos , Prata/química , Nanopartículas Metálicas/química , Platina/química , Ligas/química , Antibacterianos/farmacologia , Antibacterianos/química , Imunoensaio/métodos , Benzidinas/química , Ouro/química , Humanos , Esterilização/métodos , Limite de Detecção
13.
Int J Nanomedicine ; 19: 4339-4356, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774026

RESUMO

Background: The in vivo barriers and multidrug resistance (MDR) are well recognized as great challenges for the fulfillment of antitumor effects of current drugs, which calls for the development of novel therapeutic agents and innovative drug delivery strategies. Nanodrug (ND) combining multiple drugs with distinct modes of action holes the potential to circumvent these challenges, while the introduction of photothermal therapy (PTT) can give further significantly enhanced efficacy in cancer therapy. However, facile preparation of ND which contains dual drugs and photothermal capability with effective cancer treatment ability has rarely been reported. Methods: In this study, we selected curcumin (Cur) and doxorubicin (Dox) as two model drugs for the creation of a cocktail ND (Cur-Dox ND). We utilized polyvinylpyrrolidone (PVP) as a stabilizer and regulator to prepare Cur-Dox ND in a straightforward one-pot method. Results: The size of the resulting Cur-Dox ND can be easily adjusted by tuning the charged ratios. It was noted that both loaded drugs in Cur-Dox ND can realize their functions in the same target cell. Especially, the P-glycoprotein inhibition effect of Cur can synergistically cooperate with Dox, leading to enhanced inhibition of 4T1 cancer cells. Furthermore, Cur-Dox ND exhibited pH-responsive dissociation of loaded drugs and a robust photothermal translation capacity to realize multifunctional combat of cancer for photothermal enhanced anticancer performance. We further demonstrated that this effect can also be realized in 3D multicellular model, which possibly attributed to its superior drug penetration as well as photothermal-enhanced cellular uptake and drug release. Conclusion: In summary, Cur-Dox ND might be a promising ND for better cancer therapy.


Assuntos
Curcumina , Doxorrubicina , Povidona , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Povidona/química , Curcumina/química , Curcumina/farmacologia , Curcumina/farmacocinética , Linhagem Celular Tumoral , Animais , Camundongos , Humanos , Nanopartículas/química , Tamanho da Partícula , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Terapia Fototérmica/métodos , Liberação Controlada de Fármacos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Portadores de Fármacos/química , Sobrevivência Celular/efeitos dos fármacos
14.
Front Med (Lausanne) ; 11: 1357260, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38784230

RESUMO

Background: Pulmonary alveolar microlithiasis (PAM) is a rare disease whose clinical and imaging manifestations are non-specific, characterized by the deposition of microliths, which primarily consist of calcium and phosphorus, within the alveoli. In the cases of PAM, patients combined with calcification of other organs such as gastric mucosal calcification are less common. Case presentation: A 59-year-old woman was admitted to our hospital due to cough producing white, foamy sputum, accompanied by dyspnea and fever for 20 days. The CT scan showed diffuse ground-glass opacities and calcification of the gastric mucosa. Lung tissue biopsy revealed the presence of calcification and granulomatous foreign bodies in the interstitium and alveolar cavity. In the later stages, she developed painful skin petechiae. For this patient, the diagnosis of PAM, gastric mucosal calcification, and purpura fulminans was made. However, the genetic test results hinted that the patient and her son had a heterozygous mutation in the FBN1 gene, but her daughter's genetic test results were normal. Although the patient received anti-infection treatment, steroids, and oxygen therapy, her condition did not improve. Conclusion: We reported a rare case of PAM combined with calcification of other organs and purpura fulminans. Treatment of steroids did not show any benefit. The causative mechanism and effective treatment of this disease remain unclear. More treatments need to be explored.

15.
Carbohydr Polym ; 337: 122188, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38710565

RESUMO

Growing plants in karst areas tends to be difficult due to the easy loss of water and soil. To enhance soil agglomeration, water retention, and soil fertility, this study developed a physically and chemically crosslinked hydrogel prepared from quaternary ammonium guar gum and humic acid. The results showed that non-covalent dynamic bonds between the two components delayed humic acid release into the soil, with a release rate of only 35 % after 240 h. The presence of four hydrophilic groups (quaternary ammonium, hydroxyl, carboxyl, and carbonyl) in the hydrogel more than doubled the soil's water retention capacity. The interaction between hydrogel and soil minerals (especially carbonate and silica) promoted hydrogel-soil and soil­carbonate adhesion, and the adhesion strength between soil particles was enhanced by 650 %. Moreover, compared with direct fertilization, this degradable hydrogel not only increased the germination rate (100 %) and growth status of mung beans but also reduced the negative effects of excessive fertilization on plant roots. The study provides an eco-friendly, low-cost, and intelligent system for soil improvement in karst areas. It further proves the considerable application potential of hydrogels in agriculture.


Assuntos
Galactanos , Substâncias Húmicas , Hidrogéis , Mananas , Gomas Vegetais , Compostos de Amônio Quaternário , Solo , Gomas Vegetais/química , Galactanos/química , Mananas/química , Hidrogéis/química , Solo/química , Compostos de Amônio Quaternário/química , Fertilizantes , Preparações de Ação Retardada/química , Germinação/efeitos dos fármacos , Água/química
16.
Microb Ecol ; 87(1): 66, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700528

RESUMO

Despite the importance of wood-inhabiting fungi on nutrient cycling and ecosystem functions, their ecology, especially related to their community assembly, is still highly unexplored. In this study, we analyzed the wood-inhabiting fungal richness, community composition, and phylogenetics using PacBio sequencing. Opposite to what has been expected that deterministic processes especially environmental filtering through wood-physicochemical properties controls the community assembly of wood-inhabiting fungal communities, here we showed that both deterministic and stochastic processes can highly contribute to the community assembly processes of wood-inhabiting fungi in this tropical forest. We demonstrated that the dynamics of stochastic and deterministic processes varied with wood decomposition stages. The initial stage was mainly governed by a deterministic process (homogenous selection), whereas the early and later decomposition stages were governed by the stochastic processes (ecological drift). Deterministic processes were highly contributed by wood physicochemical properties (especially macronutrients and hemicellulose) rather than soil physicochemical factors. We elucidated that fine-scale fungal-fungal interactions, especially the network topology, modularity, and keystone taxa of wood-inhabiting fungal communities, strongly differed in an initial and decomposing deadwood. This current study contributes to a better understanding of the ecological processes of wood-inhabiting fungi in tropical regions where the knowledge of wood-inhabiting fungi is highly limited.


Assuntos
Florestas , Fungos , Micobioma , Madeira , Madeira/microbiologia , Fungos/genética , Fungos/classificação , Fungos/isolamento & purificação , Clima Tropical , Filogenia , Sequenciamento de Nucleotídeos em Larga Escala , Biodiversidade
17.
mSystems ; 9(6): e0138523, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38752789

RESUMO

A dysfunction of human host genes and proteins in coronavirus infectious disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key factor impacting clinical symptoms and outcomes. Yet, a detailed understanding of human host immune responses is still incomplete. Here, we applied RNA sequencing to 94 samples of COVID-19 patients with and without hematological tumors as well as COVID-19 uninfected non-tumor individuals to obtain a comprehensive transcriptome landscape of both hematological tumor patients and non-tumor individuals. In our analysis, we further accounted for the human-SARS-CoV-2 protein interactome, human protein interactome, and human protein complex subnetworks to understand the mechanisms of SARS-CoV-2 infection and host immune responses. Our data sets enabled us to identify important SARS-CoV-2 (non-)targeted differentially expressed genes and complexes post-SARS-CoV-2 infection in both hematological tumor and non-tumor individuals. We found several unique differentially expressed genes, complexes, and functions/pathways such as blood coagulation (APOE, SERPINE1, SERPINE2, and TFPI), lipoprotein particle remodeling (APOC2, APOE, and CETP), and pro-B cell differentiation (IGHM, VPREB1, and IGLL1) during COVID-19 infection in patients with hematological tumors. In particular, APOE, a gene that is associated with both blood coagulation and lipoprotein particle remodeling, is not only upregulated in hematological tumor patients post-SARS-CoV-2 infection but also significantly expressed in acute dead patients with hematological tumors, providing clues for the design of future therapeutic strategies specifically targeting COVID-19 in patients with hematological tumors. Our data provide a rich resource for understanding the specific pathogenesis of COVID-19 in immunocompromised patients, such as those with hematological malignancies, and developing effective therapeutics for COVID-19. IMPORTANCE: A majority of previous studies focused on the characterization of coronavirus infectious disease 2019 (COVID-19) disease severity in people with normal immunity, while the characterization of COVID-19 in immunocompromised populations is still limited. Our study profiles changes in the transcriptome landscape post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hematological tumor patients and non-tumor individuals. Furthermore, our integrative and comparative systems biology analysis of the interactome, complexome, and transcriptome provides new insights into the tumor-specific pathogenesis of COVID-19. Our findings confirm that SARS-CoV-2 potentially tends to target more non-functional host proteins to indirectly affect host immune responses in hematological tumor patients. The identified unique genes, complexes, functions/pathways, and expression patterns post-SARS-CoV-2 infection in patients with hematological tumors increase our understanding of how SARS-CoV-2 manipulates the host molecular mechanism. Our observed differential genes/complexes and clinical indicators of normal/long infection and deceased COVID-19 patients provide clues for understanding the mechanism of COVID-19 progression in hematological tumors. Finally, our study provides an important data resource that supports the increasing value of the application of publicly accessible data sets to public health.


Assuntos
COVID-19 , Hospedeiro Imunocomprometido , SARS-CoV-2 , Transcriptoma , Humanos , COVID-19/genética , COVID-19/imunologia , COVID-19/virologia , Transcriptoma/genética , SARS-CoV-2/genética , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/imunologia , Masculino , Feminino , Mapas de Interação de Proteínas/genética , Pessoa de Meia-Idade , Perfilação da Expressão Gênica/métodos
18.
Nat Immunol ; 25(5): 834-846, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38561495

RESUMO

Cancer remains one of the leading causes of mortality worldwide, leading to increased interest in utilizing immunotherapy strategies for better cancer treatments. In the past decade, CD103+ T cells have been associated with better clinical prognosis in patients with cancer. However, the specific immune mechanisms contributing toward CD103-mediated protective immunity remain unclear. Here, we show an unexpected and transient CD61 expression, which is paired with CD103 at the synaptic microclusters of T cells. CD61 colocalization with the T cell antigen receptor further modulates downstream T cell antigen receptor signaling, improving antitumor cytotoxicity and promoting physiological control of tumor growth. Clinically, the presence of CD61+ tumor-infiltrating T lymphocytes is associated with improved clinical outcomes, mediated through enhanced effector functions and phenotype with limited evidence of cellular exhaustion. In conclusion, this study identified an unconventional and transient CD61 expression and pairing with CD103 on human immune cells, which potentiates a new target for immune-based cellular therapies.


Assuntos
Antígenos CD , Apirase , Cadeias alfa de Integrinas , Receptores de Antígenos de Linfócitos T , Transdução de Sinais , Animais , Humanos , Camundongos , Antígenos CD/metabolismo , Antígenos CD/imunologia , Linhagem Celular Tumoral , Citotoxicidade Imunológica , Cadeias alfa de Integrinas/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias/imunologia , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T/imunologia , Transdução de Sinais/imunologia , Linfócitos T Citotóxicos/imunologia
19.
Environ Int ; 186: 108636, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38593692

RESUMO

The uncommon metabolic pathways of organic pollutants are easily overlooked, potentially leading to idiosyncratic toxicity. Prediction of their biotransformation associated with the toxic effects is the very purpose that this work focuses, to develop a de novo method to mechanistically predict the reactive toxicity pathways of uncommon metabolites from start aliphatic amine molecules, which employed sertraline triggered by CYP450 enzymes as a model system, as there are growing concerns about the effects on human health posed by antidepressants in the aquatic environment. This de novo prediction strategy combines computational and experimental methods, involving DFT calculations upon sequential growth, in vitro and in vivo assays, dissecting chemically reactive mechanism relevant to toxicity, and rationalizing the fundamental factors. Significantly, desaturation and debenzylation-aromatization as the emerging metabolic pathways of sertraline have been elucidated, with the detection of DNA adducts of oxaziridine metabolite in mice, highlighting the potential reactive toxicity. Molecular orbital analysis supports the reactivity preference for toxicological-relevant C-N desaturation over N-hydroxylation of sertraline, possibly extended to several other aliphatic amines based on the Bell-Evans-Polanyi principle. It was further validated toward some other wide-concerned aliphatic amine pollutants involving atrazine, ε-caprolactam, 6PPD via in silico and in vitro assays, thereby constituting a complete path for de novo prediction from case study to general applications.


Assuntos
Aminas , Sertralina , Sertralina/metabolismo , Aminas/metabolismo , Animais , Camundongos , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade , Humanos , Biotransformação
20.
Angew Chem Int Ed Engl ; 63(23): e202405315, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38588049

RESUMO

The surface and interface chemistry are critical for controlling the properties of two-dimensional transition metal carbides and nitrides (MXenes). Numerous efforts have been devoted to the functionalization of MXenes with small inorganic ligands; however, few etching methods have been reported on the direct bonding of organic groups to MXene surfaces. In this work, we demonstrated an efficient and rapid strategy for the direct synthesis of 2D Ti3C2Tx MXene nanosheets with organic terminal groups in an organic Lewis acid (trifluoromethanesulfonic acid) solvent, without introducing additional intercalations. The dissolution of aluminum and the subsequent in situ introduction of trifluoromethanesulfonic acid resulted in the extraction of Ti3C2Tx MXene (T=CF3SO3 -) (denoted as CF3SO3H-Ti3C2Tx) flakes with sizes reaching 15 µm and high productivity (over 70 %) of monolayers or few layers. More importantly, the large CF3SO3H-Ti3C2Tx MXene nanosheets had high colloidal stability, making them promising as efficient electrocatalysts for the hydrogen evolution reaction.

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