RESUMO

Background: It is challenging for clinicians to distinguish adrenocortical carcinoma (ACC) from benign adrenocortical adenomas (ACA) in their early stages. This study explored the value of serum steroid profiling as a complementary biomarker for malignancy diagnosis of ACC other than diameter and explored the influence of sex and functional status. Methods: In this retrospective study, a matched cohort of patients diagnosed with either ACC or ACA based on histopathology was meticulously paired in a 1:1 ratio according to sex, age, and functional status. Eight serum steroids including 11-deoxycortisol, 11-deoxycorticosterone, progesterone, androstenedione, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone, and estradiol, were quantified by liquid chromatography tandem mass spectrometry. We conducted a comparative analysis of the clinical characteristics and serum steroid profiles of patients with ACC and ACA, with further subgroup analysis. Results: The study included 31 patients with ACC and 31 matched patients with ACA. Patients with ACC exhibited significantly larger tumor diameters, lower body mass index (BMI), and higher levels of 11-deoxycortisol, progesterone, and androstenedione than those with ACA. 11-deoxycortisol was the only valuable index for discriminating ACC from ACA, regardless of functional status and sex. Progesterone, DHEA, and DHEAS levels were higher in the functional ACC group than in the non-functional ACC group. Female ACC patients, especially in postmenopausal female exhibited higher levels of androstenedione than male patients. The area under the curve of tumor diameter, 11-deoxycortisol, and BMI was 0.947 (95% CI 0.889-1.000), with a sensitivity of 96.8% and specificity of 90.3%. Conclusion: Serum steroid profiling serves as a helpful discriminative marker for ACC and ACA, with 11-deoxycortisol being the most valuable marker. For other steroid hormones, consideration of sex differences and functional status is crucial.

Assuntos

Neoplasias do Córtex Suprarrenal , Adenoma Adrenocortical , Carcinoma Adrenocortical , Humanos , Masculino , Feminino , Neoplasias do Córtex Suprarrenal/sangue , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/sangue , Carcinoma Adrenocortical/diagnóstico , Pessoa de Meia-Idade , Estudos Retrospectivos , Adenoma Adrenocortical/sangue , Adenoma Adrenocortical/diagnóstico , Adenoma Adrenocortical/patologia , Adulto , Esteroides/sangue , Diagnóstico Diferencial , Idoso , Biomarcadores Tumorais/sangue , Fatores Sexuais

RESUMO

Objective: How to conduct objective and accurate individualized assessments of patients with disorders of consciousness (DOC) and carry out precision rehabilitation treatment technology is a major rehabilitation problem that needs to be solved urgently. Methods: In this study, a multi-layer brain network was constructed based on functional magnetic resonance imaging (fMRI) to analyze the structural and functional brain networks of patients with DOC at different levels and to find regulatory targets (imaging markers) with recovery potential for DOC. Then repeated transcranial magnetic stimulation (rTMS) was performed in DOC patients to clinically validate. Results: The brain network connectivity of DOC patients with different consciousness states is different, and the most obvious brain regions appeared in the olfactory cortex and precuneus. rTMS stimulation could effectively improve the consciousness level of DOC patients and stimulate the occipital lobe (specific regions found in this study) and the dorsolateral prefrontal cortex (DLPFC), and both parts had a good consciousness recovery effect. Conclusion: In clinical work, personalized stimulation regimen treatment combined with the brain network characteristics of DOC patients can improve the treatment effect.

RESUMO

BACKGROUND: When considering hepatectomy for elderly HCC patients, it's essential to assess surgical safety and survival benefits. This study investigated the impact of preoperative frailty, assessed with the Clinical Frailty Scale (CFS), on outcomes for octogenarians undergoing HCC hepatectomy. METHODS: A retrospective cohort study of octogenarians who had hepatectomy for HCC between 2010 and 2022 at 16 hepatobiliary centers was conducted. Patients were categorized as frail or non-frail based on preoperative CFS, with frailty defined as CFS ≥5. The primary endpoints were overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS), with perioperative outcomes as secondary endpoints. RESULTS: Among 240 octogenarians, 105 were characterized as being frail. Frail patients had a higher incidence of postoperative 30-day morbidity and postoperative 30-day and 90-day mortality versus non-frail patients. Meanwhile, 5-year OS, RFS and CSS among frail patients were lower compared with non-frail patients. Univariable and multivariable analysis revealed that preoperative frailty was an independent risk factor of postoperative 30-day morbidity (OR: 2.060), OS (HR: 2.384), RFS (HR: 2.190) and CSS (HR: 2.203). CONCLUSION: Preoperative frailty, as assessed by the CFS, was strongly associated with both short-term outcomes and long-term survival among octogenarians undergoing hepatectomy for HCC. Incorporating frailty assessment into the preoperative evaluation may help optimize patient selection and perioperative care.

RESUMO

High-grade B-cell lymphoma with 11q aberration (HGBL-11q) is a distinct lymphoma entity according to the 5th edition of the WHO classification of hematolymphoid tumors. It lacks MYC translocation but carries proximal gains and/or telomeric losses of chromosome 11q. This rare type of B-cell lymphoma is less frequently reported in people living with HIV (PLWH), and its exact frequency remains unclear. Our goal was to retrospectively analyze its frequency in a cohort of aggressive B-cell lymphomas in PLWH, including Burkitt lymphoma (BL, n = 35), diffuse large B-cell lymphoma (DLBCL, n = 48), high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS, n = 13), which was diagnosed as AIDS-related lymphoma (ARL) at our institution. In total, 10/96 (10.4%) cases harbored the typical 11q aberration pattern, predominantly those that had been classified as BL (6/35, 17.1%), DLBCL (2/48, 4.2%), and HGBL, NOS (2/13, 15.4%). We also evaluated 7 cases of AIDS-related HGBL-11q (AR-HGBL-11q) reported in the literature. The median age of our cohort was 35 years, and all the patients were male. Most cases (70%) had a history of HIV infection for over 1 year, and all were involved in lymph nodes (100%), frequently involved extranodal sites (60%), and Ann Arbor stage III/IV. In histomorphology, the cases exhibited diverse cytological features, reminiscent of BL (6 cases), DLBCL (2 cases), and HGBL (2 cases). A comparison of the combined cohort of 17 AR-HGBL-11q cases with 11 ARL cases that lacked both MYC rearrangement and 11q aberration at our institution showed that HGBL-11q cases were characterized by strikingly coarse apoptotic debris (P < 0.001), background rich in eosinophils (P = 0.002), higher expression of the germinal centre marker LMO2 (P = 0.080), lower expression of MUM1 (P = 0.004), BCL2 (P = 0.007), and LEF1 (P = 0.080), and lower positivity for EBER in situ hybridisation (P = 0.027). Notably, one case in our series was EBV-positive, a finding not previously reported in the literature. Furthermore, comparing the prognosis between these two groups, AR-HGBL-11q showed a relatively favorable prognosis (P = 0.15), although the difference was not statistically significant. We analyzed this rare lymphoma entity in the HIV setting and highlighted the importance of integrating histomorphological and immunophenotypic features in its diagnosis and classification.

RESUMO

OBJECTIVE: The aim of the present study was to assess the therapeutic impact of diosgenin derivative ML5 on Parkinson's disease (PD) and explore the mechanism underlying mitochondrial biogenesis and fusion/fission. METHODS: We established 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse models and N-methyl-4-phenylpyridinium iodide (MPP+)-induced cell models of PD. The pole test and forced swimming test were used to detect the motor coordination and depressive symptoms in mice. The influence of ML5 on dopaminergic neuronal injury was investigated. Meanwhile, adenosine triphosphate (ATP) content, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) production were measured to evaluate mitochondrial function. Confocal and transmission electron microscopy were used to detect mitochondrial morphology of cell. The expression of mitochondrial biogenesis-related proteins was measured by Western blotting. RESULTS: The administration of ML5 showed the neuroprotection against MPTP-induced damage in vivo and in vitro. The levels of ATP, MMP, and ROS were restored after ML5 administration. In addition, we observed that ML5 preserved the mitochondrial network morphology and inhibited mitochondrial fission. Furthermore, the amelioration of mitochondrial dysfunction was mediated by enhancing 5'-monophosphate-activated protein kinase (AMPK) and peroxisome proliferators-activated receptor γ coactivator-l alpha (PGC-1α) expression, which activated its downstream modulators leading to the enhancing of mitochondrial biogenesis and the balance of mitochondrial fusion/fission. CONCLUSION: ML5 can protect the PD models against MPTP/MPP+-induced mitochondrial dysfunction and neuronal injury via promoting AMPK/PGC-1α signaling activation and be used as a therapeutic drug for PD treatment.

RESUMO

A series of heterogeneous catalysts, designated as POP-n-Pd (where n = 1, 2, 3, or 4), were synthesized by polymerizing a six-membered N-heterocyclic compound with an alkyl substituted group monomer (S1), using divinylbenzene (DVB) as crosslinkers. This process was followed by the incorporation of palladium (Pd) nanoparticles. The impact of the substituted group and the S1:DVB ratio in the catalysts, together with the reaction conditions, was investigated to assess their influence on the catalytic performance in converting propylamine, carbon dioxide (CO2) and 4-iodoanisole to oxazolidinones. The POP-1-Pd catalyst, featuring a methyl substituted group and a S1:DVB ratio of 1:4, exhibited remarkable efficiency, resulting in an excellent yield of 96 % under room temperature and ambient pressure conditions. Furthermore, it has demonstrated wide applicability across a variety of substrates and in the treatment of lime kiln exhaust gas. Additionally, POP-1-Pd can be used in a gram-scale reaction and maintains its performance after six recycles, with no significant decline in yield. The possible catalytic mechanism is proposed as follows: the catalyst's pores adsorb both CO2 and substrates, creating a high concentration reactant enrichment microenvironment. This facilitates the activation of both CO2 and substrates by the imidazole moiety and Pd nanoparticles in the catalyst, thereby generating oxazolidinones.

RESUMO

Yellow nail syndrome (YNS) is a rare clinical syndrome characterized by nail bed changes, pulmonary involvement, and lymphatic drainage disorders. Pulmonary involvement usually manifests as bronchiectasis, bronchiolitis, and pleural effusion. There are few studies on yellow nail syndrome combined with opportunistic infection. Here, we report a case of clinically diagnosed YNS combined with Nocardia cyriacigeorgica infection and the course of treatment used, which can provide some useful information for clinicians to better understand this rare illness.

RESUMO

Carbon monoxide (CO) functions as a significant endogenous cell signaling molecule and is strongly associated with many physiological and pathological processes. However, conventional fluorescence imaging in the visible and near-infrared (NIR) I regions suffers autofluorescence background and photon scattering, hindering the accurate detection of CO in vivo. In addition, the complexity of physiological environments leads to fluctuating fluorescence emission. To solve these problems, herein, the NIR-II fluorescent nanoprobe NP-Pd for in vivo ratiometric bioimaging of CO is developed. In the presence of CO, NP-Pd exhibits responsive enhancement in absorption at 808 nm, which amplifies the fluorescence signal of down-conversion nanoparticles (DCNP) at 1060 nm under 808 nm excitation, while the fluorescence signal of DCNP at 1525 nm under 980 nm excitation remains unchanged and serves as an internal standard. Through this orthogonally ratiometric fluorescence strategy, accurate CO bioimaging and precise diagnosis of acute liver injury diseases are achieved in the mouse model experiments, providing a novel tool for the in vivo detection of CO-related diseases.

RESUMO

Mycelium polysaccharide (MPP) from Monascus pilosus with the compositions of glucose, galactose, mannose, glucosamine hydrochloride, rhamnose and arabinose, was obtained using alkaline extracting, and subsequently three purified components (MPP-0, MPP-0.1 and MPP-0.3) were separated. The purity and extraction volume of the MPP-0.1 fraction surpassed those of the other two groups, thus warranting its selection for subsequent experimental investigations. The sample MPP-0.1, with an average molecular weight of 3.7776 × 104 Da, exhibited exceptional thermal stability up to 170 °C. The main glycosidic linkage pattern of MPP-0.1 was structured as→[4)-α-D-Glcp-(1]6 â†’ 4)-α-D-Glcp-(1 â†’ [2)-α-D-Manp-(1]5 â†’ 2)-α-D-Manp-(1 â†’ 5)-ß-D-Galf-(1 â†’ 3)-ß-D-Galf (1 â†’ 3)-ß-D-Galf-(1 â†’ 3)-ß-D-Galf-(1→, and branched Glcp, Manp, Galf fragments were connected with the main chain through →4, 6)-α-D-Glcp-(1→, →2, 6)-α-D-Manp-(1 â†’ and →3, 6)-ß-D-Galf-(1→. Besides, the up-regulated levels of Nitric oxide (NO), Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-1ß (IL-1ß) and other pro-inflammatory cytokines along with increased phagocytic activity revealed that MPP-0.1 has significant immunomodulatory effect, and can significantly enhance the proliferation and activation of RAW264.7 cells. Finally, the gene UGE (UDP-glucose 4-epimerase) was overexpressed in M. pilosus to increase the MPP production. Results showed that the biomass of the recombinant strain exhibited a remarkable increase of approximately 62.56 ± 1.50 % compared to that of the parental strain, and the extraction yield of MPP increased significantly by 83.19 ± 4.56 %.

RESUMO

It is a great challenge for effective treatment of shale gas produced water (SGPW), a typical industrial wastewater with complex composition. Single forward osmosis (FO) or membrane distillation (MD) process has been widely used for desalination of SGPW, with membrane fouling not well addressed. Fertilizer draw solution (DS) with high osmotic pressure is less likely to cause FO fouling and can be used for irrigation. An integrated process using fertilizer-driven FO (FDFO) and MD process was proposed for the first time for SGPW treatment, and characteristics of fertilizer DS and powdered activated carbon (PAC) enhancement were assessed. The DS using KCl and (NH4)2SO4 had high MD fluxes (36.8-38.8 L/(m2·h)) and low permeate conductivity (below 50 µS/cm), increasing the contact angle of the MD membrane by 113 % than that without FO, while the DS using MgCl2 and NH4H2PO4 produced a lower reverse salt flux (0.9-3.2 g/(m2·h)). When diluted DS was treated using PAC, the MD permeate conductivity was further reduced to 35 µS/cm without ammonia, and the membrane hydrophobicity was maintained to 71-83 % of the original. The mechanism of the FDFO-MD integrated process for mitigating MD fouling and improving permeate quality was analyzed, providing guidance for efficient SGPW treatment.

RESUMO

To reveal the effect of wheat flour particle size on the quality deterioration of quick-frozen dumpling wrappers (QFDW) during freeze-thawed (F/T) cycles, the components and physicochemical properties of wheat flours with five different particle sizes were determined and compared, along with the changes in texture and sensory properties, water status, and microstructure of QFDW during F/T cycles. Results showed that as particle size decreased, the damaged starch content and B-type starch content increased, the water absorption increased, and the gluten strength decreased. Furthermore, F/T cycles negatively impacted the quality of QFDW, evidenced by decreased texture properties and sensory evaluation score, water redistribution, higher freezable water content, and disruption of gluten network. Notably, QFDW made from larger particle size wheat flours required the shortest duration when traversing the maximum ice crystal formation zone. The QFDW made from larger particle size wheat flours formed a more stable starch-gluten matrix, which resisted the damage caused by ice recrystallization, demonstrating better water binding capacity and F/T resistance. The results may provide theoretical guidance for the study of QFDW quality and the moderate processing of wheat flour in actual production.

Assuntos

Farinha , Manipulação de Alimentos , Congelamento , Glutens , Tamanho da Partícula , Amido , Triticum , Água , Farinha/análise , Triticum/química , Amido/química , Amido/análise , Manipulação de Alimentos/métodos , Água/química , Glutens/análise , Glutens/química , Humanos

RESUMO

BACKGROUND: Despite increasing awareness, silica dust-induced silicosis still contributes to the huge disease burden in China. Worryingly, recent silica dust exposure levels and silicosis risk in Chinese noncoal mines remain unclear. OBJECTIVE: We aimed to determine recent silica dust exposure levels and assess the risk of silicosis in Chinese noncoal mines. METHODS: Between May and December 2020, we conducted a retrospective cohort study on 3 noncoal mines and 1 public hospital to establish, using multivariable Cox regression analyses, prediction formulas of the silicosis cumulative hazard ratio (H) and incidence (I) and a cross-sectional study on 155 noncoal mines in 10 Chinese provinces to determine the prevalence of silica dust exposure (PDE), free silica content, and total dust and respirable dust concentrations. The qualitative risk of silicosis was assessed using the International Mining and Metals Commission's risk-rating table and the occupational hazard risk index; the quantitative risk was assessed using prediction formulas. RESULTS: Kaplan-Meier survival analysis revealed significant differences in the silicosis probability between silica dust-exposed male and female miners (log-rank test χ21=7.52, P=.01). A total of 126 noncoal mines, with 29,835 miners and 4623 dust samples, were included; 13,037 (43.7%) miners were exposed to silica dust, of which 12,952 (99.3%) were male. The median PDE, free silica content, total dust concentration, and respirable dust concentration were 61.6%, 27.6%, 1.30 mg/m3, and 0.58 mg/m3, respectively, indicating that miners in nonmetal, nonferrous metal, small, and open-pit mines suffer high-level exposure to silica dust. Comprehensive qualitative risk assessment showed noncoal miners had a medium risk of silicosis, and the risks caused by total silica dust and respirable silica dust exposure were high and medium, respectively. When predicting H and I over the next 10, 20, and 30 years, we assumed that the miner gender was male. Under exposure to current total silica dust concentrations, median I10, I20, and I30 would be 6.8%, 25.1%, and 49.9%, respectively. Under exposure to current respirable silica dust concentrations, median I10, I20, and I30 would be 6.8%, 27.7%, and 57.4%, respectively. These findings showed that miners in nonmetal, nonferrous metal, small, and open-pit mines have a higher I and higher qualitative silicosis risk. CONCLUSIONS: Chinese noncoal miners, especially those in nonmetal, nonferrous metal, small, and open-pit mines, still suffer high-level exposure to silica dust and a medium-level risk of silicosis. Data of both total silica dust and respirable silica dust are vital for occupational health risk assessment in order to devise effective control measures to reduce noncoal mine silica dust levels, improve miners' working environment, and reduce the risk of silicosis.

Assuntos

Poeira , Mineração , Exposição Ocupacional , Dióxido de Silício , Silicose , Humanos , Silicose/epidemiologia , Silicose/etiologia , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Exposição Ocupacional/estatística & dados numéricos , Dióxido de Silício/análise , Dióxido de Silício/efeitos adversos , Poeira/análise , Masculino , China/epidemiologia , Feminino , Medição de Risco/métodos , Estudos Retrospectivos , Mineração/estatística & dados numéricos , Adulto , Pessoa de Meia-Idade , Estudos Transversais , Estudos de Coortes

RESUMO

In the realm of intracellular drug delivery, overcoming the barrier of endosomal entrapment stands as a critical factor influencing the effectiveness of nanodrug delivery systems. This study focuses on the synthesis of an acid-sensitive fatty acid derivative called imidazole-stearic acid (IM-SA). Leveraging the proton sponge effect attributed to imidazole groups, IM-SA was anticipated to play a pivotal role in facilitating endosomal escape. Integrated into the lipid core of solid lipid nanoparticles (SLNs), IM-SA was paired with hyaluronic acid (HA) coating on the surface of SLNs loading with curcumin (CUR). The presence of IM-SA and HA endowed HA-IM-SLNs@CUR with dual functionalities, enabling the promotion of endosomal escape, and specifical targeting of liver cancer. HA-IM-SLNs@CUR exhibited a particle size of ∼228 nm, with impressive encapsulation efficiencies (EE) of 87.5 % ± 2.3 % for CUR. Drugs exhibit significant pH sensitive release behavior. Cellular experiments showed that HA-IM-SLN@CUR exhibits enhanced drug delivery capability. The incorporation of IM-SA significantly improved the endosomal escape of HA-IM-SLN@CUR, facilitating accelerated intracellular drug release and increasing intracellular drug concentration, exhibiting excellent growth inhibitory effects on HepG2 cells. Animal experiments revealed a 3.4-fold increase in CUR uptake at the tumor site with HA-IM-SLNs@CUR over the free CUR, demonstrating remarkable tumor homing potential with the tumor growth inhibition rate of 97.2 %. These findings indicated the significant promise of HA-IM-SLNs@CUR in the realm of cancer drug delivery.

Assuntos

Antineoplásicos , Curcumina , Endossomos , Nanopartículas , Tamanho da Partícula , Curcumina/farmacologia , Curcumina/química , Humanos , Nanopartículas/química , Animais , Endossomos/metabolismo , Endossomos/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Células Hep G2 , Liberação Controlada de Fármacos , Camundongos , Lipídeos/química , Sistemas de Liberação de Medicamentos , Proliferação de Células/efeitos dos fármacos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Propriedades de Superfície , Portadores de Fármacos/química , Ácidos Esteáricos/química , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Imidazóis/química , Imidazóis/farmacologia , Camundongos Nus , Ácido Hialurônico/química , Camundongos Endogâmicos BALB C , Lipossomos

RESUMO

Background: Tuberculosis and chronic obstructive pulmonary disease (COPD) are significant public health challenges, with pulmonary tuberculosis recognized as a pivotal risk factor for the development of COPD. Tuberculosis-associated COPD is increasingly recognized as a distinct phenotype of COPD that potentially exhibits unique clinical features. A thorough understanding of the precise definition, clinical manifestations, prognosis, and most effective pharmacological strategies for tuberculosis-associated COPD warrants further investigation. Methods: This prospective, observational cohort study aims to enroll over 135 patients with tuberculosis-associated COPD and 405 patients with non-tuberculosis-associated COPD, across seven tertiary hospitals in mainland China. The diagnosis of tuberculosis-associated COPD will be established based on the following criteria: (1) history of pulmonary tuberculosis with standard antituberculosis treatment; (2) suspected pulmonary tuberculosis with radiological evidence indicative of tuberculosis sequelae; (3) no definitive history of pulmonary tuberculosis but with positive interferon-gamma release assay results and radiological signs suggestive of tuberculosis. At baseline, demographic information, medical history, respiratory questionnaires, complete blood count, interferon-gamma release assays, medications, spirometry, and chest computed tomography (CT) scans will be recorded. Participants will be followed for one year, with evaluations at six-month intervals to track the longitudinal changes in symptoms, treatment, lung function, and frequencies of COPD exacerbations and hospitalizations. At the final outpatient visit, additional assessments will include chest CT scans and total medical costs incurred. Discussion: The findings of this study are expected to delineate the specific characteristics of tuberculosis-associated COPD and may propose potential treatment options for this particular phenotype, potentially leading to improved clinical management and patient outcomes.

Assuntos

Antituberculosos , Pulmão , Doença Pulmonar Obstrutiva Crônica , Tuberculose Pulmonar , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/complicações , Estudos Prospectivos , China/epidemiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , Antituberculosos/uso terapêutico , Pulmão/fisiopatologia , Pulmão/diagnóstico por imagem , Pulmão/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Fatores de Risco , Prognóstico , Projetos de Pesquisa , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Progressão da Doença

RESUMO

Effective endosomal escape is crucial for enhancing the efficiency of nanodrug delivery systems. In this study, we developed a novel liposomal system utilizing acid-sensitive N-(3-amino-propyl) imidazole cholesterol (IM-Chol), specifically designed for the targeted co-delivery of doxorubicin (DOX) and curcumin (CUR) to hepatocellular carcinoma (HCC). Designated as GA-IM-LIP@DOX/CUR, this liposomal system incorporates glycyrrhetinic acid (GA) to improve target specificity toward HCC cells. Notably, both drugs exhibited pH-sensitive release profiles, facilitating precise drug release within acidic environments. Our investigation into cellular uptake demonstrated that modified liposomes, GA-IM-LIP@FITC and IM-LIP@FITC, achieved progressively enhanced intracellular accumulation of FITC compared to unmodified liposomes. Competitive inhibition assays utilizing free GA further validated the targeting efficacy of GA. Moreover, the GA-IM-LIP@FITC and IM-LIP@FITC groups exhibited rapid endosomal escape of FITC within the first two hours, in contrast to delayed escape observed in the LIP@FITC group, confirming that the protonation of IM-Chol promotes drug release into the cytosol. In vivo studies substantiated that GA-IM-LIP@DOX/CUR effectively inhibited tumor growth. This research provides significant insights into the design and functionality of the GA-IM-LIP@DOX/CUR liposomal system, underscoring its potential to enhance drug delivery strategies in the treatment of HCC.

RESUMO

Nowadays, the overconsumption of artificial sweeteners and their related adverse health impacts have proposed an urgent need to develop safe and healthy alternatives. Herein, we introduce ChemSweet, an AI-based platform for the rapid discovery of potential sweet molecules (http://chemsweet.ddai.tech) with the consideration of their physicochemical properties, sweetness profile, and health risks at the same time. Machine learning prediction models of four important physicochemical and four toxicity properties were established and integrated with the platform to evaluate the candidate molecules' biosafety and stability during the processing processes. Then, a new sweet taste prediction system was developed which ensures the sweet evaluation of six specific kinds of sweeteners. To facilitate the practical application of ChemSweet, the SuperNatural database was integrated for the rational screening of promising new sweeteners. We successfully identified 294 potential sweeteners that simultaneously meet the multiple anticipated criteria. We believe that ChemSweet will serve as a useful tool for identifying safe and healthy sweeteners while reducing the timeframe and high experimental costs.

RESUMO

The study of antibiotic resistance in the silage microbiome has attracted initial attention. However, the influences of lactic acid bacteria inoculants and dry matter (DM) content on antibiotic resistance genes (ARGs) reduction in whole-plant corn silage remain poorly studied. This study accessed the ARGs' risk and transmission mechanism in whole-plant corn silage with different DM levels and treated with Lactiplantibacillus plantarum or Lentilactobacillus buchneri. The macrolide and tetracycline were the main ARGs in corn silage. The dominant species (Lent. buchneri and Lactobacillus acetotolerans) were the main ARGs carriers in whole-plant corn silage. The application of Lent. buchneri increased total ARGs abundance regardless of corn DM. Whole-plant corn silage with 30 % DM reduced the abundances of integrase and plasmid compared with 40 % DM. The correlation and structural equation model analysis demonstrated that bacterial community succession, resulting from changes in DM content, was the primary driving factor influencing the ARGs distribution in whole-plant corn silage. Interestingly, whole-plant corn silage inoculated with Lent. buchneri reduced abundances of high-risk ARGs (mdtG, mepA, tetM, mecA, vatE and tetW) by regulating pathogens (Escherichia coli), mobile genetic elements (MGEs) genes (IS3 and IS1182), and this effect was more pronounced at 30 % DM level. In summary, although whole-plant corn silage inoculated with Lent. buchneri increased the total ARGs abundance at both DM levels, it decreased the abundance of high-risk ARGs by reducing the abundances of the pathogens and MGEs, and this effect was more noticeable at 30 % DM level.

Assuntos

Silagem , Zea mays , Zea mays/microbiologia , Silagem/microbiologia , Genes Bacterianos , Sequências Repetitivas Dispersas , Resistência Microbiana a Medicamentos/genética , Farmacorresistência Bacteriana/genética , Antibacterianos/farmacologia , Lactobacillus/genética , Lactobacillus/efeitos dos fármacos , Fermentação

RESUMO

In this work, a design of transimpedance amplifier (TIA) for cryogenic scanning tunneling microscope (CryoSTM) is proposed. TIA with the tip-sample component in CryoSTM is called as CryoSTM-TIA. With transimpedance gain of 1 GΩ, the bandwidth of the CryoSTM-TIA is larger than 200 kHz. The distinctive feature of the proposed CryoSTM-TIA is that its pre-amplifier is made of a single cryogenic high electron mobility transistor (HEMT), so the apparatus equivalent input noise current power spectral density at 100 kHz is lower than 6 (fA)2/Hz. In addition, "bias-cooling method" can be used to in-situ control the density of the frozen DX- centers in the HEMT doping area, changing its structure to reduce the device noises. With this apparatus, fast scanning tunneling spectra measurements with high-energy-resolution are capable to be performed. And, it is capable to measure scanning tunneling shot noise spectra (STSNS) at the atomic scale for various quantum systems, even if the shot noise is very low. It provides a powerful tool to investigate novel quantum states by measuring STSNS, such as detecting the existence of Majorana bound states in the topological quantum systems.

RESUMO

Artificial ionic sensory systems, bridging the divide between biological systems and electronics, mimic human skin functions but face critical challenges with biocompatibility, comfort, signal stability, and simplifying packaging. Here, we present a simple and permeable skin-interfaced iontronic mechanosensing (SIIM) architecture that integrates human skin as natural ionic material and hierarchically porous MXene-fiber composite membranes as sensing electrodes. The SIIM system eliminates complex ionic material design and multilayer matrix, exhibiting ultrahigh pressure sensitivities (5.4 kPa-1, <75 Pa), a low detection limit (6 Pa), excellent output stability along with high permeability to minimize the impact of sweating on sensing. The noncytotoxic nature of SIIM electrodes ensures excellent biocompatibility (>97% cell coincubational viability), facilitating long-term wearability and high biosafety. Furthermore, the scalable SIIM configuration integrated with matrix smart gloves, effectively monitors human physical movements. This SIIM-based sensor with marked sensing capabilities, structural simplicity, and scalability, holds promising potential in diverse wearable applications.

Assuntos

Materiais Biocompatíveis , Pele , Dispositivos Eletrônicos Vestíveis , Humanos , Materiais Biocompatíveis/química , Membranas Artificiais , Eletrodos , Permeabilidade , Técnicas Biossensoriais/instrumentação , Porosidade

RESUMO

Dual-single-atom catalysts (DSACs) are the next paradigm shift in single-atom catalysts because of the enhanced performance brought about by the synergistic effects between adjacent bimetallic pairs. However, there are few methods for synthesizing DSACs with precise bimetallic structures. Herein, a pre-coordination strategy is proposed to precisely synthesize a library of DSACs. This strategy ensures the selective and effective coordination of two metals via phthalocyanines with specific coordination sites, such as -F- and -OH-. Subsequently, in-situ confinement inhibits the migration of metal pairs during high-temperature pyrolysis, and obtains the DSACs with precisely constructed metal pairs. Despite changing synthetic parameters, including transition metal centers, metal pairs, and spatial geometry, the products exhibit similar atomic metal pairs dispersion properties, demonstrating the universality of the strategy. The pre-coordination strategy synthesized DSACs shows significant CO2 reduction reaction performance in both flow-cell and practical rechargeable Zn-CO2 batteries. This work not only provides new insights into the precise synthesis of DSACs, but also offers guidelines for the accelerated discovery of efficient catalysts.