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1.
Chem Asian J ; : e202400662, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095336

RESUMO

The design and development of new and efficient catalyst binder materials are important for improving cell performance in high-temperature proton-exchange membrane fuel cells (HT-PEMFCs). In this study, a series of tetrafluorophenyl phosphonic acid-based binder materials (PF-y-P, y = 1, 0.83, and 0.67) with rigid structures and controllable degrees of phosphonation were prepared and used in HT-PEMFCs using the ultra-strong acid-catalyzed Friedel-Crafts reaction and the combined Michaelis-Arbuzov reaction. The samples exhibited high stability, low water uptake, superior proton conductivity, and cell performance. In addition, the oxygen mass transport properties of the PF-1-P binder were investigated using high-temperature microelectrode electrochemical testing techniques. Compared with the phosphoric acid-doped polybenzimidazole (PBI) binder, the O2 solubility of PF-1-P binder material increased by 30% (5.36 × 10-6 mol cm-3) and the PF-1-P binder material exhibited better cell stability in HT-PEMFCs. After 10.5 h of discharge at a constant current of 0.12 A cm-2, the MEA voltage decreased by 7.1% and 20.8% in case of the PF-1-P and PBI binders, respectively.

2.
J Virol ; : e0086424, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39162567

RESUMO

Novel bat H17N10 and H18N11 influenza A viruses (IAVs) are incapable of reassortment with conventional IAVs during co-infection. To date, the underlying mechanisms that inhibit bat and conventional IAV reassortment remain poorly understood. Herein, we used the bat influenza M gene in the PR8 H1N1 virus genetic background to determine the molecular basis that restricts reassortment of segment 7. Our results showed that NEP and M1 from bat H17N10 and H18N11 can interact with PR8 M1 and NEP, resulting in mediating PR8 viral ribonucleoprotein (vRNP) nuclear export and formation of virus-like particles with single vRNP. Further studies demonstrated that the incompatible packaging signals (PSs) of H17N10 or H18N11 M segment led to the failure to rescue recombinant viruses in the PR8 genetic background. Recombinant PR8 viruses (rPR8psH18M and rPR8psH17M) containing bat influenza M coding region flanked with the PR8 M PSs were rescued but displayed lower replication in contrast to the parental PR8 virus, which is due to a low efficiency of recombinant virus uncoating correlating with the functions of the bat M2. Our studies reveal molecular mechanisms of the M gene that hinder reassortment between bat and conventional IAVs, which will help to understand the biology of novel bat IAVs. IMPORTANCE: Reassortment is one of the mechanisms in fast evolution of influenza A viruses (IAVs) and responsible for generating pandemic strains. To date, why novel bat IAVs are incapable of reassorting with conventional IAVs remains completely understood. Here, we attempted to rescue recombinant PR8 viruses with M segment from bat IAVs to understand the molecular mechanisms in hindering their reassortment. Results showed that bat influenza NEP and M1 have similar functions as respective counterparts of PR8 to medicating viral ribonucleoprotein nuclear export. Moreover, the incompatible packaging signals of M genes from bat and conventional IAVs and impaired bat M2 functions are the major reasons to hinder their reassortment. Recombinant PR8 viruses with bat influenza M open reading frames were generated but showed attenuation, which correlated with the functions of the bat M2 protein. Our studies provide novel insights into the molecular mechanisms that restrict reassortment between bat and conventional IAVs.

3.
Adv Mater ; : e2400060, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39126132

RESUMO

Band alignment engineering is crucial for facilitating charge separation and transfer in optoelectronic devices, which ultimately dictates the behavior of Van der Waals heterostructures (vdWH)-based photodetectors and light emitting diode (LEDs). However, the impact of the band offset in vdWHs on important figures of merit in optoelectronic devices has not yet been systematically analyzed. Herein, the regulation of band alignment in WSe2/Bi2Te3- xSex vdWHs (0 ≤ x ≤ 3) is demonstrated through the implementation of chemical vapor deposition (CVD). A combination of experimental and theoretical results proved that the synthesized vdWHs can be gradually tuned from Type I (WSe2/Bi2Te3) to Type III (WSe2/Bi2Se3). As the band alignment changes from Type I to Type III, a remarkable responsivity of 58.12 A W-1 and detectivity of 2.91×1012 Jones (in Type I) decrease in the vdWHs-based photodetector, and the ultrafast photoresponse time is 3.2 µs (in Type III). Additionally, Type III vdWH-based LEDs exhibit the highest luminance and electroluminescence (EL) external quantum efficiencies (EQE) among p-n diodes based on Transition Metal Dichalcogenides (TMDs) at room temperature, which is attributed to band alignment-induced distinct interfacial charge injection. This work serves as a valuable reference for the application and expansion of fundamental band alignment principles in the design and fabrication of future optoelectronic devices.

4.
Molecules ; 29(15)2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39124934

RESUMO

CdS quantum dots (CdS QDs) are regarded as a promising photocatalyst due to their remarkable response to visible light and suitable placement of conduction bands and valence bands. However, the problem of photocorrosion severely restricts their application. Herein, the CdS QDs-Co9S8 hollow nanotube composite photocatalyst has been successfully prepared by loading Co9S8 nanotubes onto CdS QDs through an electrostatic self-assembly method. The experimental results show that the introduction of Co9S8 cocatalyst can form a stable structure with CdS QDs, and can effectively avoid the photocorrosion of CdS QDs. Compared with blank CdS QDs, the CdS QDs-Co9S8 composite exhibits obviously better photocatalytic hydrogen evolution performance. In particular, CdS QDs loaded with 30% Co9S8 (CdS QDs-30%Co9S8) demonstrate the best photocatalytic performance, and the H2 production rate reaches 9642.7 µmol·g-1·h-1, which is 60.3 times that of the blank CdS QDs. A series of characterizations confirm that the growth of CdS QDs on Co9S8 nanotubes effectively facilitates the separation and migration of photogenerated carriers, thereby improving the photocatalytic hydrogen production properties of the composite. We expect that this work will facilitate the rational design of CdS-based photocatalysts, thereby enabling the development of more low-cost, high-efficiency and high-stability composites for photocatalysis.

5.
Food Chem ; 461: 140009, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-39167943

RESUMO

A label-free electrochemical immunosensor was developed to rapidly detect tilmicosin (TMC) residues in pork and milk. The immunosensor was constructed by immobilizing a high-affinity monoclonal antibody against TMC on an rGO-PEI-Ag nanocomposite-modified electrode. The rGO-PEI-Ag nanocomposites were prepared by mixing polyethyleneimine (PEI) modified reduced graphene oxide (rGO) with AgNO3 solution. The prepared rGO-PEI-Ag nanocomposites showed good redox activity and conductivity, as characterized by ultraviolet-visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), and X-ray diffraction (XRD). During the preparation process, staphylococcal protein A (SPA) was added to targetedly bind the Fc segment of the monoclonal antibody. The immunosensor showed a low detection limit (LOD) of 0.0013 ng/mL, a linear range of 0.01-100 ng/mL, and recoveries ranging from 92.77 to 100.02% in pork and 92.26-101.23% in milk. Furthermore, the immunosensor exhibited good stability, reproducibility, and specificity in detecting TMC in pork and milk real samples.

6.
Environ Sci Pollut Res Int ; 31(35): 48062-48072, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39017865

RESUMO

Microalgae can promote antibiotic removal, which has attracted growing attention. However, its synergistic removal performance with bacteria in antibiotic pollutants is still poorly understood. In this study, firstly, we selected two green algae (Dictyosphaerium sp. and Chlorella sp.) and exposed them to Enrofloxacin (ENR) to observe their extracellular polysaccharides (EPS) concentration dynamic and the removal of antibiotics. Secondly, EPS was extracted and added to in situ lake water (no algae) to investigate its combined effect with bacteria. The results indicate that both Dictyosphaerium sp. and Chlorella sp. exhibited high tolerance to ENR stress. When the biomass of microalgae was low, ENR could significantly stimulate algae to produce EPS. The removal rates of Dictyosphaerium sp. and Chlorella sp. were 15.8% and 10.5%, respectively. The addition of EPS can both alter the microbial community structure in the lake water and promote the removal of ENR. The LEfSe analysis showed that there were significant differences in the microbial marker taxa, which promoted the increase of special functional bacteria for decomposing ENR, between the EPS-added group and the control group. The EPS of Dictyosphaerium sp. increased the abundance of Moraxellaceae and Spirosomaceae, while the EPS of Chlorella sp. increased the abundance of Sphingomonadaceae and Microbacteriaceae. Under the synergistic effect, Chlorella sp. achieved a maximum removal rate of 24.2%, while Dictyosphaerium sp. achieved a maximum removal rate of 28.9%. Our study provides new insights into the removal performance and mechanism of antibiotics by freshwater microalgae in water bodies and contribute to the development of more effective water treatment strategies.


Assuntos
Enrofloxacina , Microalgas , Poluentes Químicos da Água , Poluentes Químicos da Água/metabolismo , Antibacterianos , Chlorella/metabolismo , Lagos/microbiologia , Microbiota
7.
Expert Rev Anticancer Ther ; 24(9): 881-891, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38970210

RESUMO

OBJECTIVES: Due to its anti-angiogenic properties, trebananib is frequently employed in the treatment of cancer patients, particularly those with ovarian cancer. We conducted a meta-analysis to assess the efficacy and safety profile of trebananib in combination with other drugs for treating both ovarian and non-ovarian cancer patients. METHODS: Our search encompassed PubMed, Medline, Cochrane, and Embase databases, with a focus on evaluating study quality. Data extraction was conducted from randomized controlled trials (RCTs), and RevMan 5.3 facilitated result analysis. RESULTS: Combining trebananib with other drugs extended progression-free survival (PFS) [HR 0.81, (95%CI: 0.65, 0.99), p = 0.04] and overall survival (OS) [HR 0.88, (95%CI: 0.79, 1.00), p = 0.04] in ovarian cancer patients. Ovarian cancer patients exhibited a higher objective response rate (ORR) with trebananib compared to non-ovarian cancer cohorts. Moreover, the incorporation of trebananib into the standard treatment regimen for malignant tumors did not significantly elevate drug-related adverse events [RR 1.05, (95% CI: 1.00, 1.11), p = 0.05]. CONCLUSION: Trebananib plus other drugs can improve the PFS, OS and ORR in patients with cancer, especially ovarian cancer. Our recommendation is to use trebananib plus other drugs to treat advanced cancer, and to continuously monitor and manage drug-related adverse events. REGISTRATION: PROSPERO (No. CRD42023466988).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Ovarianas , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/farmacologia , Taxa de Sobrevida , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Proteínas Recombinantes de Fusão
8.
Sci Total Environ ; 946: 174340, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-38950633

RESUMO

The growing demand for natural rubber products has driven the expansion of rubber plantations in recent decades. While much attention has been given to studying the long-term effects of rubber and rubber-based agroforestry systems on surface soil properties, there has been a tendency to overlook changes in soil properties in deeper layers. Our study addresses this gap by examining alterations in nitrogen (N), phosphorus (P), and metal ion levels in deep soil layers resulting from the prolonged cultivation of rubber and rubber-based agroforestry systems. We found notable shifts in soil NH4+ and NO3- concentrations within the 0-30 cm soil layer across different-aged rubber and rubber-based agroforestry systems. Particularly in mature systems, NO3- and available P levels were close to zero below 30 cm soil depth. Introducing Flemingia macrophylla into young rubber plantations increased soil NH4+ and NO3- in the 0-90 cm soil layer and available P in the 0-10 cm soil layer. Over the long term, cultivation of rubber plantations increased the depletion of total P in the 0-50 cm soil layer, available iron (Fe) and manganese (Mn) in the 30-90 cm soil layer, available copper (Cu) and zinc (Zn) in the 0-90 cm soil layer, accompanied by a decrease in soil pH and increase in exchangeable aluminum (Al) in the 0-90 cm soil layer. Notably, soil exchangeable Al levels exceeding 2.0 cmol kg-1 appeared to induce aluminum toxicity. Furthermore, soil pH below 5.2 triggered a sharp release of exchangeable Al within the 0-90 cm soil layer of rubber plantations, with soil available P nearing zero when exchangeable Al levels assed 7.3 cmol kg-1. Our findings underscore the profound impact of long-term rubber plantation cultivation on surface and deep soil properties. Addressing soil degradation in these deep soil layers poses significant challenges for future soil restoration efforts.

9.
Clin Epigenetics ; 16(1): 94, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39026267

RESUMO

INTRODUCTION: Walking stands as the most prevalent physical activity in the daily lives of individuals and is closely associated with physical functioning and the aging process. Nonetheless, the precise cause-and-effect connection between walking and aging remains unexplored. The epigenetic clock emerges as the most promising biological indicator of aging, capable of mirroring the biological age of the human body and facilitating an investigation into the association between walking and aging. Our primary objective is to investigate the causal impact of walking with epigenetic age acceleration (EAA). METHODS: We conducted a two-sample two-way Mendelian randomization (MR) study to investigate the causal relationship between walking and EAA. Walking and Leisure sedentary behavior data were sourced from UK Biobank, while EAA data were gathered from a total of 28 cohorts. The MR analysis was carried out using several methods, including the inverse variance weighted (IVW), weighted median, MR-Egger, and robust adjusted profile score (RAPS). To ensure the robustness of our findings, we conducted sensitivity analyses, which involved the MR-Egger intercept test, Cochran's Q test, and MR-PRESSO, to account for and mitigate potential pleiotropy. RESULTS: The IVW MR results indicate a significant impact of usual walking pace on GrimAge (BETA = - 1.84, 95% CI (- 2.94, - 0.75)), PhenoAge (BETA = - 1.57, 95% CI (- 3.05, - 0.08)), Horvath (BETA = - 1.09 (- 2.14, - 0.04)), and Hannum (BETA = - 1.63, 95% CI (- 2.70, - 0.56)). Usual walking pace is significantly associated with a delay in epigenetic aging acceleration (EAA) (P < 0.05). Moreover, the direction of effect predicted by the gene remained consistent across RAPS outcomes and sensitivity MR analyses. There is a lack of robust causal relationships between other walking conditions, such as walking duration and walking frequency, on EAA (P > 0.05). CONCLUSION: Our evidence demonstrates that a higher usual walking pace is associated with a deceleration of the acceleration of all four classical epigenetic clocks acceleration.


Assuntos
Envelhecimento , Epigênese Genética , Análise da Randomização Mendeliana , Caminhada , Humanos , Análise da Randomização Mendeliana/métodos , Caminhada/fisiologia , Epigênese Genética/genética , Envelhecimento/genética , Envelhecimento/fisiologia , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Reino Unido , Comportamento Sedentário , Metilação de DNA/genética
10.
BMC Pediatr ; 24(1): 449, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997661

RESUMO

BACKGROUND: Language delay affects near- and long-term social communication and learning in toddlers, and, an increasing number of experts pay attention to it. The development of prosody discrimination is one of the earliest stages of language development in which key skills for later stages are mastered. Therefore, analyzing the relationship between brain discrimination of speech prosody and language abilities may provide an objective basis for the diagnosis and intervention of language delay. METHODS: In this study, all cases(n = 241) were enrolled from a tertiary women's hospital, from 2021 to 2022. We used functional near-infrared spectroscopy (fNIRS) to assess children's neural prosody discrimination abilities, and a Chinese communicative development inventory (CCDI) were used to evaluate their language abilities. RESULTS: Ninety-eight full-term and 108 preterm toddlers were included in the final analysis in phase I and II studies, respectively. The total CCDI screening abnormality rate was 9.2% for full-term and 34.3% for preterm toddlers. Full-term toddlers showed prosody discrimination ability in all channels except channel 5, while preterm toddlers showed prosody discrimination ability in channel 6 only. Multifactorial logistic regression analyses showed that prosody discrimination of the right angular gyrus (channel 3) had a statistically significant effect on language delay (odd ratio = 0.301, P < 0.05) in full-term toddlers. Random forest (RF) regression model presented that prosody discrimination reflected by channels and brain regions based on fNIRS data was an important parameter for predicting language delay in preterm toddlers, among which the prosody discrimination reflected by the right angular gyrus (channel 4) was the most important parameter. The area under the model Receiver operating characteristic (ROC) curve was 0.687. CONCLUSIONS: Neural prosody discrimination ability is positively associated with language development, assessment of brain prosody discrimination abilities through fNIRS could be used as an objective indicator for early identification of children with language delay in the future clinical application.


Assuntos
Transtornos do Desenvolvimento da Linguagem , Desenvolvimento da Linguagem , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Feminino , Masculino , Pré-Escolar , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Lactente , Percepção da Fala/fisiologia , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem
11.
Nanotechnology ; 35(36)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38861963

RESUMO

Optimizing the width of depletion region is a key consideration in designing high performance photovoltaic photodetectors, as the electron-hole pairs generated outside the depletion region cannot be effectively separated, leading to a negligible contribution to the overall photocurrent. However, currently reported photovoltaic mid-infrared photodetectors based on two-dimensional heterostructures usually adopt a single pn junction configuration, where the depletion region width is not maximally optimized. Here, we demonstrate the construction of a high performance broadband mid-infrared photodetector based on a MoS2/b-AsP/MoS2npn van der Waals heterostructure. The npn heterojunction can be equivalently represented as two parallel-stacked pn junctions, effectively increasing the thickness of the depletion region. Consequently, the npn device shows a high detectivity of 1.3 × 1010cmHz1/2W-1at the mid-infrared wavelength, which is significantly improved compared with its single pn junction counterpart. Moreover, it exhibits a fast response speed of 12 µs, and a broadband detection capability ranging from visible to mid-infrared wavelengths.

12.
Immunity ; 57(6): 1187-1189, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38865963

RESUMO

A major barrier to antitumor immunity in solid tumors is T cell exclusion. In this issue of Immunity, De Sanctis et al.1 elucidate how CLDN18 on pancreatic and lung cancer cells enhances infiltration, immunological synapse formation, and activation of cytotoxic T lymphocytes.


Assuntos
Claudinas , Humanos , Claudinas/metabolismo , Claudinas/imunologia , Claudinas/genética , Neoplasias/imunologia , Animais , Linfócitos T Citotóxicos/imunologia , Neoplasias Pancreáticas/imunologia , Neoplasias Pulmonares/imunologia , Ativação Linfocitária/imunologia , Sinapses Imunológicas/imunologia , Sinapses Imunológicas/metabolismo
14.
Front Oncol ; 14: 1375648, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706591

RESUMO

Background: For patients with hilar cholangiocarcinoma (HC) undergoing hemi-hepatectomy, there are controversies regarding the requirement of, indications for, and timing of preoperative biliary drainage (PBD). Dynamic three-dimensional volume reconstruction could effectively evaluate the regeneration of liver after surgery, which may provide assistance for exploring indications for PBD and optimal preoperative bilirubin value. The purpose of this study was to explore the indications for PBD and the optimal preoperative bilirubin value to improve prognosis for HC patients undergoing hemi-hepatectomy. Methods: We retrospectively analyzed the data of HC patients who underwent hemi-hepatectomy in the First Affiliated Hospital of China Medical University from 2012 to 2023. The liver regeneration rate was calculated using three-dimensional volume reconstruction. We analyzed the factors affecting the liver regeneration rate and occurrence of postoperative liver insufficiency. Results: This study involved 83 patients with HC, which were divided into PBD group (n=36) and non-PBD group (n=47). The preoperative bilirubin level may be an independent risk factor affecting the liver regeneration rate (P=0.014) and postoperative liver insufficiency (P=0.016, odds ratio=1.016, ß=0.016, 95% CI=1.003-1.029). For patients whose initial bilirubin level was >200 µmol/L (n=45), PBD resulted in better liver regeneration in the early stage (P=0.006) and reduced the incidence of postoperative liver insufficiency [P=0.012, odds ratio=0.144, 95% confidence interval (CI)=0.031-0.657]. The cut-off value of bilirubin was 103.15 µmol/L based on the liver regeneration rate. Patients with a preoperative bilirubin level of ≤103.15 µmol/L shown a better liver regeneration (P<0.01) and lower incidence of postoperative hepatic insufficiency (P=0.011, odds ratio=0.067, 95% CI=0.008-0.537). Conclusion: For HC patients undergoing hemi-hepatectomy whose initial bilirubin level is >200 µmol/L, PBD may result in better liver regeneration and reduce the incidence of postoperative liver insufficiency. Preoperative bilirubin levels ≤103.15 µmol/L maybe recommended for leading to a better liver regeneration and lower incidence of postoperative hepatic insufficiency.

15.
Front Pharmacol ; 15: 1322473, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694912

RESUMO

Context: Cabozantinib combined with immune checkpoint inhibitors (ICIs) has brought a new therapeutic effect for the medical treatment of renal cell carcinoma (RCC). Objectives: We performed a meta-analysis of randomized controlled trials and single-arm trials to evaluate the efficacy and safety of cabozantinib plus ICIs in RCC. Methods: We extracted data from PubMed, Cochrane, Medline and Embase databases, and rated literature quality through Cochrane risk of bias tool and MINORS. RevMan5.3 software was used to analyze the results of randomized controlled trials and single-arm trials. Results: A total of 7 studies were included. Treatment with cabozantinib plus ICIs improved PFS [HR 0.75, (95%CI: 0.52, 1.08), p = 0.12] and the OS [HR 0.80, (95%CI: 0.60, 1.07), p = 0.13] in randomized controlled trials. Meanwhile, the result of the ORR in randomized controlled trials was [risk ratio (RR) 1.37, (95%CI: 1.21, 1.54), p < 0.00001] and in single-arm trials was [risk difference (RD) 0.49, (95%CI: 0.26, 0.71), p < 0.0001]. Conclusion: Cabozantinib plus ICIs prolonged the PFS and OS, and improved ORR in patients with RCC. Our recommendation is to use cabozantinib plus ICIs to treat advanced RCC, and to continuous monitor and manage the drug-related adverse events. Systematic Review Registration: identifier CRD42023455878.

16.
Chin J Cancer Res ; 36(2): 124-137, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38751436

RESUMO

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2 (HER2)-positive (+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is unknown. Methods: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to trastuzumab. Results: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and rat sarcoma virus (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase (MAPK)/extracellular-signal regulated kinase (ERK) pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft model. Conclusions: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance to trastuzumab. These findings support clinical testing of the therapeutic efficacy of dual anti-HER2 treatment combining an intracellular small molecule with an extracellular antibody.

17.
Gen Psychiatr ; 37(3): e101389, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38808176

RESUMO

Background: Anorexia nervosa (AN) has been characterised as a psychiatric disorder associated with increased control. Currently, it remains difficult to predict treatment response in patients with AN. Their cognitive abilities are known to be resistant to treatment. It has been established that the frontoparietal control network (FPCN) is the direct counterpart of the executive control network. Therefore, the resting-state brain activity of the FPCN may serve as a biomarker to predict treatment response in AN. Aims: The study aimed to investigate the association between resting-state functional connectivity (RSFC) of the FPCN, clinical symptoms and treatment response in patients with AN. Methods: In this case-control study, 79 female patients with AN and no prior treatment from the Shanghai Mental Health Center and 40 matched healthy controls (HCs) were recruited from January 2015 to March 2022. All participants completed the Questionnaire Version of the Eating Disorder Examination (version 6.0) to assess the severity of their eating disorder symptoms. Additionally, RSFC data were obtained from all participants at baseline by functional magnetic resonance imaging. Patients with AN underwent routine outpatient treatment at the 4th and 12th week, during which time their clinical symptoms were evaluated using the same measures as at baseline. Results: Among the 79 patients, 40 completed the 4-week follow-up and 35 completed the 12-week follow-up. The RSFC from the right posterior parietal cortex (PPC) and dorsolateral prefrontal cortex (dlPFC) increased in 79 patients with AN vs 40 HCs after controlling for depression and anxiety symptoms. By multiple linear regression, the RSFC of the PPC to the inferior frontal gyrus was found to be a significant factor for self-reported eating disorder symptoms at baseline and the treatment response to cognitive preoccupations about eating and body image, after controlling for age, age of onset and body mass index. The RSFC in the dlPFC to the middle temporal gyrus and the superior frontal gyrus may be significant factors in the treatment response to binge eating and loss of control/overeating in patients with AN. Conclusions: Alterations in RSFC in the FPCN appear to affect self-reported eating disorder symptoms and treatment response in patients with AN. Our findings offer new insight into the pathogenesis of AN and could promote early prevention and treatment.

18.
Adv Sci (Weinh) ; 11(25): e2400730, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38654621

RESUMO

Metal-enzyme integrated catalysts (MEICs) that combine metal and enzyme offer great potential for sustainable chemoenzymatic cascade catalysis. However, rational design and construction of optimal microenvironments and accessible active sites for metal and enzyme in individual nanostructures are necessary but still challenging. Herein, Pd nanoparticles (NPs) and Candida antarctica lipase B (CALB) are co-immobilized into the pores and surfaces of covalent organic frameworks (COFs) with tunable functional groups, affording Pd/COF-X/CALB (X = ONa, OH, OMe) MEICs. This strategy can regulate the microenvironment around Pd NPs and CALB, and their interactions with substrates. As a result, the activity of the COF-based MEICs in catalyzing dynamic kinetic resolution of primary amines is enhanced and followed COF-OMe > COF-OH > COF-ONa. The experimental and simulation results demonstrated that functional groups of COFs modulated the conformation of CALB, the electronic states of Pd NPs, and the affinity of the integrated catalysts to the substrate, which contributed to the improvement of the catalytic activity of MEICs. Further, the MEICs are prepared using COF with hollow structure as support material, which increased accessible active sites and mass transfer efficiency, thus improving catalytic performance. This work provides a blueprint for rational design and preparation of highly active MEICs.

19.
J Ethnopharmacol ; 329: 118098, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38582152

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Major Depressive Disorder (MDD) emerges as a complex psychosomatic condition, notable for its considerable suicidality and mortality rates. Increasing evidence suggests the efficacy of Chinese herbal medicine in mitigating depression symptoms and offsetting the adverse effects associated with conventional Western therapeutics. Notably, clinical trials have revealed the adjunctive antidepressant potential of Kaiyu Zhishen Decoction (KZD) alongside Western medication. However, the standalone antidepressant efficacy of KZD and its underlying mechanisms merit in-depth investigation. AIM OF THE STUDY: This research aims to elucidate the impact of KZD on MDD and delineate its mechanistic pathways through integrated network pharmacological assessments and empirical in vitro and in vivo analyses. MATERIALS AND METHODS: To ascertain the optimal antidepressant dosage and mechanism of KZD, a Chronic Unpredictable Mild Stress (CUMS)-induced depression model in mice was established to evaluate depressive behaviors. High-Performance Liquid Chromatography (HPLC) and network pharmacological approaches were employed to predict KZD's antidepressant mechanisms. Subsequently, hippocampal samples were subjected to 4D-DIA proteomic sequencing and validated through Western blot, immunofluorescence, Nissl staining, and pathway antagonist applications. Additionally, cortisol-stimulated PC12 cells were utilized to simulate neuronal damage, analyzing protein and mRNA levels of MAPK-related signals and cell proliferation markers. RESULTS: The integration of network pharmacology and HPLC identified kaempferol and quercetin as KZD's principal active compounds for MDD treatment. Proteomic and network pharmacological KEGG pathway analyses indicated the MAPK signaling pathway as a critical regulatory mechanism for KZD's therapeutic effect on MDD. KZD was observed to mitigate CUMS-induced upregulation of p-ERK/ERK, CREB, and BDNF protein expressions in hippocampal cells by attenuating oxidative stress, thereby ameliorating neuronal damage and exerting antidepressant effects. The administration of PD98059 counteracted KZD's improvements in depression-like behaviors and downregulated p-ERK/ERK and BDNF protein expressions in the hippocampus. CONCLUSIONS: This investigation corroborates KZD's pivotal, dose-dependent role in antidepressant activity. Both in vivo and in vitro experiments demonstrate KZD's capacity to modulate the ERK-CREB-BDNF signaling pathway by diminishing ROS expression induced by oxidative stress, enhancing neuronal repair, and thus, manifesting antidepressant properties. Accordingly, KZD represents a promising herbal candidate for further antidepressant research.


Assuntos
Antidepressivos , Fator Neurotrófico Derivado do Encéfalo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Medicamentos de Ervas Chinesas , Farmacologia em Rede , Transdução de Sinais , Animais , Antidepressivos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Camundongos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Masculino , Transdução de Sinais/efeitos dos fármacos , Células PC12 , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ratos , Transtorno Depressivo Maior/tratamento farmacológico , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Depressão/tratamento farmacológico , Depressão/metabolismo , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Comportamento Animal/efeitos dos fármacos
20.
Nanoscale ; 16(16): 7862-7873, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38568087

RESUMO

Recent years have witnessed advances in chemical vapor deposition growth of graphene films on metal foils with fine scalability and thickness controllability. However, challenges for obtaining wrinkle-free, defect-free and large-area uniformity remain to be tackled. In addition, the real commercial applications of graphene films still require industrially compatible transfer techniques with reliable performance of transferred graphene, excellent production capacity, and suitable cost. Transferred graphene films, particularly with a large area, still suffer from the presence of transfer-related cracks, wrinkles and contaminants, which would strongly deteriorate the quality and uniformity of transferred graphene films. Potential applications of graphene films include moisture barrier films, transparent conductive films, electromagnetic shielding films, and optical communications; such applications call different requirements for the performance of transferred graphene, which, in turn, determine the suitable transfer techniques. Besides the reliable transfer process, automatic machines should be well developed for the future batch transfer of graphene films, ensuring the repeatability and scalability. This mini-review provides a summary of recent advances in the transfer of graphene films and offers a perspective for future directions of transfer techniques that are compatible for industrial batch transfer.

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