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1.
Adv Sci (Weinh) ; : e2405077, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38959393

RESUMO

Energy and environmental issues have increasingly garnered significant attention for sustainable development. Flexible and shape-stable phase change materials display great potential in regulation of environmental temperature for energy saving and human comfort. Here, inspired by the water absorption behavior of salt-tolerant animals and plants in salinity environment and the Hofmeister theory, highly stable phase change salogels (PCSGs) are fabricated through in situ polymerization of hydrophilic monomers in molten salt hydrates, which can serve multiple functions including thermal management patches, smart windows, and ice blocking coatings. The gelation principles of the polymer in high ion concentration solution are explored through the density functional theory simulation and verified the feasibility of four types of salt hydrates. The high concentration chaotropic ions strongly interacted with polymer chains and promoted the gelation at low polymer concentrations which derive highly-stable and ultra-moisturizing PCSGs with high latent heat (> 200 J g-1). The synergistic adhesion and transparency switching abilities accompanied with phase transition enable their smart thermal management. The study resolves the melting leakage and thermal cycling stability of salt hydrates, and open an avenue to fabricate flexible PCM of low cost, high latent heat, and long-term durability for energy-saving, ice-blocking, and thermal management.

3.
J Integr Neurosci ; 23(6): 118, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38940085

RESUMO

BACKGROUND: Alcohol abuse, a prevalent global health issue, is associated with the onset of cognitive impairment and neurodegeneration. Actin filaments (F-actin) and microtubules (MTs) polymerized from monomeric globular actin (G-actin) and tubulin form the structural basis of the neuronal cytoskeleton. Precise regulation of the assembly and disassembly of these cytoskeletal proteins, and their dynamic balance, play a pivotal role in regulating neuronal morphology and function. Nevertheless, the effect of prolonged alcohol exposure on cytoskeleton dynamics is not fully understood. This study investigates the chronic effects of alcohol on cognitive ability, neuronal morphology and cytoskeleton dynamics in the mouse hippocampus. METHODS: Mice were provided ad libitum access to 5% (v/v) alcohol in drinking water and were intragastrically administered 30% (v/v, 6.0 g/kg/day) alcohol for six weeks during adulthood. Cognitive functions were then evaluated using the Y maze, novel object recognition and Morris water maze tests. Hippocampal histomorphology was assessed through hematoxylin-eosin (HE) and Nissl staining. The polymerized and depolymerized states of actin cytoskeleton and microtubules were separated using two commercial assay kits and quantified by Western blot analysis. RESULTS: Mice chronically exposed to alcohol exhibited significant deficits in spatial and recognition memory as evidenced by behavioral tests. Histological analysis revealed notable hippocampal damage and neuronal loss. Decreased ratios of F-actin/G-actin and MT/tubulin, along with reduced levels of polymerized F-actin and MTs, were found in the hippocampus of alcohol-treated mice. CONCLUSIONS: Our findings suggest that chronic alcohol consumption disrupted the assembly of the actin cytoskeleton and MTs in the hippocampus, potentially contributing to the cognitive deficits and pathological injury induced by chronic alcohol intoxication.


Assuntos
Citoesqueleto de Actina , Etanol , Hipocampo , Microtúbulos , Animais , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Citoesqueleto de Actina/efeitos dos fármacos , Citoesqueleto de Actina/metabolismo , Masculino , Etanol/farmacologia , Etanol/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Depressores do Sistema Nervoso Central/farmacologia , Depressores do Sistema Nervoso Central/administração & dosagem , Modelos Animais de Doenças , Comportamento Animal/efeitos dos fármacos
4.
Biomacromolecules ; 25(6): 3795-3806, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38781116

RESUMO

Biodegradable polymers with shape memory effects (SMEs) offer promising solutions for short-term medical interventions, facilitating minimally invasive procedures and subsequent degradation without requiring secondary surgeries. However, achieving a good balance among desirable SMEs, mechanical performance, degradation rate, and bioactivities remains a significant challenge. To address this issue, we established a strategy to develop a versatile biodegradable polyurethane (PPDO-PLC) with tunable hierarchical structures via precise chain segment control. Initial copolymerization of l-lactide and ε-caprolactone sets a tunable Tg close to body temperature, followed by block copolymerization with poly(p-dioxanone) to form a hard domain. This yields a uniform microphase-separation morphology, ensuring robust SME and facilitating the development of roughly porous surface structures in alkaline environments. Cell experiments indicate that these rough surfaces significantly enhance cellular activities, such as adhesion, proliferation, and osteogenic differentiation. Our approach provides a methodology for balancing biodegradability, SMEs, three-dimensional (3D) printability, and bioactivity in materials through hierarchical structure regulation.


Assuntos
Poliuretanos , Poliuretanos/química , Poliuretanos/farmacologia , Proliferação de Células/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Animais , Porosidade , Adesão Celular/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Camundongos , Poliésteres/química , Diferenciação Celular/efeitos dos fármacos , Lactonas/química , Lactonas/farmacologia , Humanos , Caproatos/química , Dioxanos/química , Polímeros
5.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2783-2797, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812179

RESUMO

Dihuang Baoyuan Granules is a prescription endorsed by HU Tianbao, a renowned and elderly Chinese medicine practitioner from Beijing, and has demonstrated definite clinical efficacy. The composition of this prescription is intricate as it includes 7 distinct herbal medicines. This study aims to analyze the chemical composition of Dihuang Baoyuan Granules, evaluate its efficacy in the treatment of diabetes and analyze the distribution of the drug components in the plasma, liver, and kidney after administration. The findings will serve as a reference for future research on pharmacodynamic substances of this prescription. UHPLC-LTQ-Orbitrap MS was employed to analyze the main chemical components of Dihuang Baoyuan Granules. A Waters ACQUITY Premier HSS T3 column(2.1 mm×100 mm, 1.8 µm) was used for chromatographic separation with 0.1% formic acid(A)-acetonitrile(B) as the mobile phases in a gradient elution at a flow rate of 0.3 mL·min~(-1). Electrospray ionization(ESI) source was used to acquire data in positive and negative ion modes. Furthermore, a rat model of diabetes mellitus was established by feeding with a high-sugar high-fat diet, and injection with streptozocin at a dose of 35 mg·kg~(-1), and the modeled rats were then administrated with Dihuang Baoyuan Granules. The fasting blood glucose, hemoglobin A1c, and other relevant indicators were measured, and the substances present in the plasma, liver, and kidney were identified. By reference to quasi-molecular ions, MS/MS fragment ions, MS spectra of reference substances, and compound information in available reports, 191 components were identified in Dihuang Baoyuan Granules, including 29 alkaloids, 24 flavonoids, 22 organic acids, 16 amino acids, 12 terpenes, 11 steroid saponins, 9 sugars, 8 phenylethanoid glycosides, 8 nucleosides, 2 phenylpropanoids, and 49 others compounds. Eighty-three chemical components were identified in rat plasma, 109 in the liver, and 98 in the kidney. Component identification and characterization of Dihuang Baoyuan Granules in vitro and in vivo provide efficacy information and guidance for the basic research on the pharmacodynamic substances and further clinical application of this prescription.


Assuntos
Medicamentos de Ervas Chinesas , Ratos Sprague-Dawley , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Animais , Ratos , Masculino , Humanos , Fígado/efeitos dos fármacos , Fígado/química , Fígado/metabolismo , Espectrometria de Massas/métodos , Rim/efeitos dos fármacos , Rim/química , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus/tratamento farmacológico
6.
Oncol Lett ; 27(6): 239, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38623571

RESUMO

[This retracts the article DOI: 10.3892/ol.2018.8797.].

7.
Adv Sci (Weinh) ; 11(23): e2309031, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38553794

RESUMO

Chiral conjugated polymer has promoted the development of the efficient circularly polarized electroluminescence (CPEL) device, nevertheless, it remains a challenge to develop chiral polymers with high electroluminescence performance. Herein, by the acceptor copolymerization of axially chiral biphenyl emitting skeleton and benzophenone, a pair of axially chiral conjugated polymers namely R-PAC and S-PAC are synthesized. The target polymers exhibit obvious thermally activated delayed fluorescence (TADF) activities with high photoluminescence quantum yields of 81%. Moreover, the chiral polymers display significant circularly polarized luminescence features, with luminescence dissymmetry factor (|glum|) of nearly 3 × 10-3. By using the chiral polymers as emitters, the corresponding circularly polarized organic light-emitting diodes (CP-OLEDs) exhibit efficient CPEL signals with electroluminescence dissymmetry factor |gEL| of 3.4 × 10-3 and high maximum external quantum efficiency (EQEmax) of 17.8%. Notably, considering both EQEmax and |gEL| comprehensively, the device performance of R-PAC and S-PAC is the best among all the reported CP-OLEDs with chiral conjugated polymers as emitters. This work provides a facile approach to constructing chiral conjugated TADF polymers and discloses the potential of axially chiral conjugated luminescent skeletons in architecting high-performance CP-OLEDs.

8.
Phytomedicine ; 127: 155461, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38452697

RESUMO

BACKGROUND: The active ingredients of the Chinese medical herb Paris polyphylla, P. polyphylla ethanol extract (PPE) and polyphyllin I (PPI), potentially inhibit epithelial-mesenchymal transition (EMT) in tumors. However, the roles of these ingredients in inhibiting EMT in adenomyosis (AM) remain to be explored. PURPOSE: The primary goal of the study was to uncover the underlying molecular processes through which PPE and PPI suppress EMT in AM, alongside assessing the safety profiles of these substances. METHODS: To assess the suppressive impact of PPE on adenomyosis-derived cells (AMDCs), we employed Transwell and wound healing assays. The polyphyllins (PPI, PPII, PPVII) contained in PPE were characterized using high-performance liquid chromatography (HPLC). Then, bioinformatics techniques were performed to pinpoint potential PPI targets that could be effective in treating AM. Immunoblotting was used to verify the key proteins and pathways identified via bioinformatics. Furthermore, we examined the efficacy of PPE and PPI in treating Institute of Cancer Research (ICR) mice with AM by observing the morphological and pathological features of the uterus and performing immunohistochemistry. In addition, we assessed safety by evaluating liver, kidney and spleen pathologic features and serum test results. RESULTS: Three major polyphyllins of PPE were revealed by HPLC, and PPI had the highest concentration. In vitro experiments indicated that PPE and PPI effectively prevent AMDCs invasion and migration. Bioinformatics revealed that the primary targets E-cadherin, N-cadherin and TGFß1, as well as the EMT biological process, were enriched in PPI-treated AM. Immunoblotting assays corroborated the hypothesis that PPE and PPI suppress the TGFß1/Smad2/3 pathway in AMDCs to prevent EMT from progressing. Additionally, in vivo studies showed that PPE (3 mg/kg and 6 mg/kg) and PPI (3 mg/kg and 6 mg/kg), successfully suppressed the EMT process through targeting the TGFß1/Smad2/3 signaling pathway. Besides, it was observed that lower doses of PPE (3 mg/kg) and PPI (3 mg/kg) exerted minimal effects on the liver, kidneys, and spleen. CONCLUSIONS: PPE and PPI efficiently impede the development of EMT by inhibiting the TGFß1/Smad2/3 pathway, revealing an alternative pathway for the pharmacological treatment of AM.


Assuntos
Adenomiose , Antineoplásicos , Diosgenina/análogos & derivados , Liliaceae , Humanos , Feminino , Animais , Camundongos , Adenomiose/tratamento farmacológico , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Transição Epitelial-Mesenquimal
9.
Trials ; 25(1): 200, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509589

RESUMO

BACKGROUND: The neural cells in the brains of patients with Parkinson's disease (PWP) display aberrant synchronized oscillatory activity within the beta frequency range. Additionally, enhanced gamma oscillations may serve as a compensatory mechanism for motor inhibition mediated by beta activity and also reinstate plasticity in the primary motor cortex affected by Parkinson's disease. Transcranial alternating current stimulation (tACS) can synchronize endogenous oscillations with exogenous rhythms, thereby modulating cortical activity. The objective of this study is to investigate whether the addition of tACS to multidisciplinary intensive rehabilitation treatment (MIRT) can improve symptoms of PWP so as to enhance the quality of life in individuals with Parkinson's disease based on the central-peripheral-central theory. METHODS: The present study was a randomized, double-blind trial that enrolled 60 individuals with Parkinson's disease aged between 45 and 70 years, who had Hoehn-Yahr scale scores ranging from 1 to 3. Participants were randomly assigned in a 1:1 ratio to either the tACS + MIRT group or the sham-tACS + MIRT group. The trial consisted of a two-week double-blind treatment period followed by a 24-week follow-up period, resulting in a total duration of twenty-six weeks. The primary outcome measured the change in PDQ-39 scores from baseline (T0) to 4 weeks (T2), 12 weeks (T3), and 24 weeks (T4) after completion of the intervention. The secondary outcome assessed changes in MDS-UPDRS III scores at T0, the end of intervention (T1), T2, T3, and T4. Additional clinical assessments and mechanistic studies were conducted as tertiary outcomes. DISCUSSION: The objective of this study is to demonstrate that tACS can enhance overall functionality and improve quality of life in PWP, based on the framework of MIRT. Additionally, it seeks to establish a potential correlation between these therapeutic effects and neuroplasticity alterations in relevant brain regions. The efficacy of tACS will be assessed during the follow-up period in order to optimize neuroplasticity and enhance its potential impact on rehabilitation efficiency for PWP. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300071969. Registered on 30 May 2023.


Assuntos
Doença de Parkinson , Estimulação Transcraniana por Corrente Contínua , Humanos , Pessoa de Meia-Idade , Idoso , Doença de Parkinson/diagnóstico , Doença de Parkinson/terapia , Doença de Parkinson/complicações , Estimulação Transcraniana por Corrente Contínua/efeitos adversos , Estimulação Transcraniana por Corrente Contínua/métodos , Qualidade de Vida , Terapia por Exercício/métodos , Método Duplo-Cego , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
NPJ Parkinsons Dis ; 10(1): 70, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548756

RESUMO

This study aimed to investigate the association between irritable bowel syndrome (IBS) and Parkinson's disease (PD) utilizing prospective cohort study and Mendelian randomization. The dataset contained a substantial cohort of 426,911 participants from the UK Biobank, discussing the association between IBS and PD with Cox proportional hazards models and case-control analysis while adjusting for covariates such as age, gender, ethnicity and education level. In univariate Cox regression model, the risk of PD was reduced in IBS patients (HR: 0.774, 95%CI: 0.625-0.956, P = 0.017), but the statistical significance diminished in the three models after adjusting for other variables. In a few subgroup analyses, IBS patients are less likely to develop into PD, and patients diagnosed with IBS after 2000 also had a lower risk (HR: 0.633, 95%CI: 0.403-0.994, P = 0.047) of subsequently developing PD. In addition, we matched five healthy control participants based on gender and age at the end of the study for each IBS patient diagnosed during the follow-up period, and logistic regression results (OR:1.239, 95%CI: 0.896-1.680, P = 0.181) showed that IBS was not associated with the risk of PD. Mendelian randomization did not find significant evidence of the causal relationship between IBS and Parkinson's disease (OR: 0.801, 95%CI: 0.570-1.278, P = 0.204). Overall, we suggest that IBS status is not associated with the risk of developing PD, and that these findings provide valuable insights into the clinical management and resource allocation of patients with IBS.

11.
Ann Med Surg (Lond) ; 86(3): 1590-1600, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38463086

RESUMO

Background: Playing an exemplary role, frailty have crucial effect on the preoperative evaluation of elderly patients. Previous studies have shown that frailty is associated with complications and mortality in patients with gastric cancer (GC). However, with the development of the concept of "patient-centered", the range of health-related outcomes is broad. The differences in relation between frailty and various adverse outcomes will be further explored. Method: The PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wan Fang, and Chinese Biomedical Literature databases were searched for keywords, including frailty (such as frail) and gastric cancer (such as stomach neoplasms or stomach cancer or gastrectomy or gastric surgery). The search period is until August 2023. The included studies were observational or cohort studies with postoperative related adverse outcomes as primary or secondary outcome measures. Valid assessment tools were used. The Quality Assessment Tool for Observational Cohort and Cross-sectional Studies was used to assess methodological quality in the included literature. Result: Fifteen studies were included, including 4 cross-sectional studies, 8 retrospective cohort studies, and 3 prospective cohort studies. Among them, 6 studies were rated as "Good" and 9 studies were rated as "Fair," indicating that the quality of the literature was high. Then, 10 frailty assessment tools were summarized and classified into two broad categories in accordance with frailty models. Results of the included studies indicated that frailty in elderly patients with GC was associated with postoperative complications, mortality, hospital days, readmissions, quality of life, non-home discharge, and admission to the intensive care unit. Conclusion: This scoping review concludes that high levels of preoperative frailty increase the risk of adverse outcomes in elderly patients with GC. Frailty will be widely used in the future clinical evaluation of elderly gastric cancer patients, precise risk stratification should be implemented for patients, and frailty management should be implemented well to reduce the occurrence of adverse treatment outcomes.

12.
World J Diabetes ; 15(2): 220-231, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38464364

RESUMO

BACKGROUND: The effects of viral hepatitis (VH) on type 2 diabetes (T2D) remain controversial. AIM: To analyze the causal correlation between different types of VH and T2D using Mendelian randomization (MR). METHODS: Single nucleotide polymorphisms of VH, chronic hepatitis B (CHB), chronic hepatitis C (CHC) and T2D were obtained from the BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Inverse variance weighted, MR-Egger, and weighted median were used to test exposure-outcome associations. The MR-Egger intercept analysis and Cochran's Q test were used to assess horizontal pleiotropy and heterogeneity, respectively. Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results. RESULTS: The MR analysis showed no significant causal relationship between VH and T2D in Europeans [odds ratio (OR) = 1.028; 95% confidence interval (CI): 0.995-1.062, P = 0.101]. There was a negative causal association between CHB and T2D among East Asians (OR = 0.949; 95%CI: 0.931-0.968, P < 0.001), while there was no significant causal association between CHC and T2D among East Asians (OR = 1.018; 95%CI: 0.959-1.081, P = 0.551). Intercept analysis and Cochran's Q test showed no horizontal pleiotropy or heterogeneity (P > 0.05). Sensitivity analysis showed that the results were robust. CONCLUSION: Among East Asians, CHB is associated with a reduced T2D risk, but this association is limited by HBV load and cirrhosis. Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D, focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHC-mediated pathways of hepatic steatosis, liver fibrosis, and cirrhosis.

13.
Zhongguo Zhong Yao Za Zhi ; 49(2): 361-369, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38403312

RESUMO

The 4-coumarate: CoA ligase(4CL) is a key enzyme in the upstream pathway of phenylpropanoids such as flavonoids, soluble phenolic esters, lignans, and lignins in plants. In this study, 13 4CL family members of Arabidopsis thaliana were used as reference sequences to identify the 4CL gene family candidate members of Isatis indigotica from the reported I. indigotica genome. Further bioinformatics analysis and analysis of the expression pattern of 4CL genes and the accumulation pattern of flavonoids were carried out. Thirteen 4CL genes were obtained, named Ii4CL1-Ii4CL13, which were distributed on chromosomes 1, 2, 3, 4, and 6. The analysis of the gene structure and conserved structural domains revealed the intron number of I. indigotica 4CL genes was between 1 and 12 and the protein structural domains were highly conserved. Cis-acting element analysis showed that there were multiple response elements in the promoter sequence of I. indigotica 4CL gene family, and jasmonic acid had the largest number of reaction elements. The collinearity analysis showed that there was a close relationship between the 4CL gene family members of I. indigotica and A. thaliana. As revealed by qPCR results, the expression analysis of the 4CL gene family showed that 10 4CL genes had higher expression levels in the aboveground part of I. indigotica. The content assay of flavonoids in different parts of I. indigotica showed that flavonoids were mainly accumulated in the aboveground part of plants. This study provides a basis for further investigating the roles of the 4CL gene family involved in the biosynthesis of flavonoids in I. indigotica.


Assuntos
Isatis , Ligases , Ligases/genética , Isatis/genética , Regiões Promotoras Genéticas , Plantas/metabolismo , Flavonoides , Coenzima A Ligases/genética , Coenzima A Ligases/química , Coenzima A Ligases/metabolismo
14.
Angew Chem Int Ed Engl ; 63(18): e202401835, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38380835

RESUMO

The intrinsic helical π-conjugated skeleton makes helicenes highly promising for circularly polarized electroluminescence (CPEL). Generally, carbon helicenes undergo low external quantum efficiency (EQE), while the incorporation of a multi-resonance thermally activated delayed fluorescence (MR-TADF) BN structure has led to an improvement. However, the reported B,N-embedded helicenes all show low electroluminescence dissymmetry factors (gEL), typically around 1×10-3. Therefore, the development of B,N-embedded helicenes with both a high EQE and gEL value is crucial for achieving highly efficient CPEL. Herein, a facile approach to synthesize B,N-embedded hetero[9]helicenes, BN[9]H, is presented. BN[9]H shows a bright photoluminescence with a maximum at 578 nm with a high luminescence dissymmetry factor (|glum|) up to 5.8×10-3, attributed to its inherited MR-TADF property and intrinsic helical skeleton. Furthermore, circularly polarized OLED devices incorporating BN[9]H as an emitter show a maximum EQE of 35.5 %, a small full width at half-maximum of 48 nm, and, more importantly, a high |gEL| value of 6.2×10-3. The Q-factor (|EQE×gEL|) of CP-OLEDs is determined to be 2.2×10-3, which is the highest among helicene analogues. This work provides a new approach for the synthesis of higher helicenes and paves a new way for the construction of highly efficient CPEL materials.

15.
Arch Microbiol ; 206(3): 125, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38411841

RESUMO

Non-specific endonucleases can be used for the digestion of nucleic acids because they hydrolyze DNA/RNA into 3-5 base pairs (bp) length oligonucleotide fragments without strict selectivity. In this work, a novel non-specific endonuclease from Pseudomonas fluorescens (PfNuc) with high activities for both DNA and RNA was successfully cloned and expressed in Escherichia coli. The production of PfNuc in flask scale could be achieved to 1.73 × 106 U/L and 4.82 × 106 U/L for DNA and RNA by investigation of the culture and induction conditions. The characterization of PfNuc indicated that it was Mg2+-dependent and the catalytic activity was enhanced by 3.74 folds for DNA and 1.06 folds for RNA in the presence of 5 mM Mg2+. The specific activity of PfNuc for DNA was 1.44 × 105 U/mg at pH 8.0 and 40 °C, and 3.93 × 105 U/mg for RNA at pH 8.5 and 45 °C. The Km of the enzyme for both DNA and RNA was close to 43 µM. The Vmax was 6.40 × 105 U/mg and 1.11 × 106 U/mg for DNA and RNA, respectively. There was no observed activity loss when PfNuc was stored at 4 °C and - 20 °C after 28 days or 10 repeated freeze-thaw cycles at - 80 °C. Molecular docking revealed that PfNuc formed 17 and 19 hydrogen bonds with single-stranded RNA and double-stranded DNA, respectively. These results could explain the high activity and stability of PfNuc, suggesting its great potential applications in the industry and clinic.


Assuntos
Pseudomonas fluorescens , Pseudomonas fluorescens/genética , Simulação de Acoplamento Molecular , RNA , Endonucleases/genética , Escherichia coli/genética , DNA , Clonagem Molecular
16.
Zookeys ; 1189: 287-325, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38314111

RESUMO

Eleven leptonetid species belonging to four genera collected in Jiangxi and Fujian Provinces, China are presented. Ten new species of midget cave spiders from southern China are diagnosed, described, and illustrated: Leptoneteladawu Yao & Liu, sp. nov., L.yuanhaoi Yao & Liu, sp. nov. and L.zuojiashanensis Yao & Liu, sp. nov. from Jiangxi; Longileptonetaguadunensis Yao & Liu, sp. nov., L.huboliao Yao & Liu, sp. nov., L.jiaxiani Yao & Liu, sp. nov., L.letuensis Yao & Liu, sp. nov., L.renzhouensis Yao & Liu, sp. nov., L.tianmenensis Yao & Liu, sp. nov., and Pararanamingxuani Yao & Liu, sp. nov. from Fujian. Furthermore, Falcileptonetamonodactyla (Yin, Wang & Wang, 1984) is recorded from Jiangxi province for the first time. Distributions records are given for all investigated species.

17.
Zookeys ; 1190: 195-212, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38323097

RESUMO

Taxonomic notes on the Talaus species from China are provided. Two new species, T.yuyang Yao & Liu, sp. nov. and T.zhangjiangkou Yao & Liu, sp. nov. are described and illustrated, and a further three species are redescribed based on their genitalic characters: T.dulongjiang Tang, Yin, Ubick & Peng, 2008, T.niger Tang, Yin, Ubick & Peng, 2008, and T.sulcus Tang & Li, 2010. The species T.xiphosus Zhu & Ono, 2007 is considered a junior synonym of T.triangulifer Simon, 1886 based on an examination of many recently collected female and male specimens from Guangxi Province, China. Diagnoses, detailed illustrations and a map of distributional records of the six treated species of Talaus in China are provided.

18.
Support Care Cancer ; 32(2): 115, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38240829

RESUMO

BACKGROUND AND AIM: Previous studies reported inconsistent results on the prevalence and prognostic implications of frailty among older adults with gastric cancer. This systematic review synthesized available literature pertaining on this topic to establish the prevalence and unfavorable outcomes of frailty in older adults with gastric cancer. METHODS: A comprehensive search was conducted across multiple English databases including PubMed, Cochrane Library, CINAHL, Embase, and Web of Science as well as Chinese databases, namely, CNKI, Wan Fang, and CBM, from inception to July 4, 2023, to identify potential studies. Data related to the incidence of frailty and its unfavorable outcomes in older adults with gastric cancer were extracted. RevMan5.3 and R 4.2.2 were used to evaluate pooled prevalence, hazard ratios (HR), and 95% confidence interval (CI). RESULTS: This review comprehensively selected 13 studies, comprising 9 cohort studies and 4 cross-sectional studies, on 44,117 older adults diagnosed with gastric cancer. The incidence of frailty among older adults with gastric cancer ranged from 10 to 71%. The pooled prevalence of frailty was 29% (95% CI 0.21-0.39). Frailty was found to be associated with an elevated risk of postoperative complications (HR = 1.99, 95% CI 1.45-2.73), prolonged postoperative hospital stay (HR = 2.68, 95% CI 2.38-3.02), likelihood of readmission (HR = 3.28, 95% CI 1.77-6.08), and an increased mortality risk (HR = 1.60, 95% CI 1.36-1.90). CONCLUSIONS: Frailty was associated with a poor prognosis in older adults with gastric cancer. Clinical medical staff should focus on the frailty of older adults with gastric cancer, conduct large-scale, multicenter, and prospective studies and early screening of patients, and provide guidance for the implementation of prevention and treatment strategies.


Assuntos
Fragilidade , Neoplasias Gástricas , Humanos , Idoso , Fragilidade/epidemiologia , Fragilidade/complicações , Idoso Fragilizado , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/complicações , Estudos Prospectivos , Prevalência , Estudos Transversais , Fatores de Risco , Estudos Multicêntricos como Assunto
19.
Acta Pharmacol Sin ; 45(3): 609-618, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38030799

RESUMO

Leveraging the specificity of antibody to deliver cytotoxic agent into tumor, antibody-drug conjugates (ADCs) have become one of the hotspots in the development of anticancer therapies. Although significant progress has been achieved, there remain challenges to overcome, including limited penetration into solid tumors and potential immunogenicity. Fully human single-domain antibodies (UdAbs), with their small size and human nature, represent a promising approach for addressing these challenges. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a glycosylated cell surface protein that rarely expressed in normal adult tissues but overexpressed in diverse cancers, taking part in tumorigenesis, progression, and metastasis. In this study, we investigated the therapeutic potential of UdADC targeting CEACAM5. We performed biopanning in our library and obtained an antibody candidate B9, which bound potently and specifically to CEACAM5 protein (KD = 4.84 nM) and possessed excellent biophysical properties (low aggregation tendency, high homogeneity, and thermal stability). The conjugation of B9 with a potent cytotoxic agent, monomethyl auristatin E (MMAE), exhibited superior antitumor efficacy against CEACAM5-expressing human gastric cancer cell line MKN-45, human pancreatic carcinoma cell line BxPC-3 and human colorectal cancer cell line LS174T with IC50 values of 38.14, 25.60, and 101.4 nM, respectively. In BxPC-3 and MKN-45 xenograft mice, administration of UdADC B9-MMAE (5 mg/kg, i.v.) every 2 days for 4 times markedly inhibited the tumor growth without significant change in body weight. This study may have significant implications for the design of next-generation ADCs.


Assuntos
Antineoplásicos , Imunoconjugados , Anticorpos de Domínio Único , Humanos , Animais , Camundongos , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Imunoconjugados/farmacologia , Imunoconjugados/uso terapêutico , Moléculas de Adesão Celular , Citotoxinas , Ensaios Antitumorais Modelo de Xenoenxerto , Antígeno Carcinoembrionário , Proteínas Ligadas por GPI
20.
J Colloid Interface Sci ; 656: 177-188, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-37989051

RESUMO

The effectiveness of chemotherapeutic agents for hepatocellular carcinoma (HCC) is unsatisfactory because of tumor heterogeneity, multidrug resistance, and poor target accumulation. Therefore, multimodality-treatment with accurate drug delivery has become increasingly popular. Herein, a cell penetrating peptide-aptamer dual modified-nanocomposite (USILA NPs) was successfully constructed by coating a cell penetrating peptide and aptamer onto the surface of sorafenib (Sora), ursolic acid (UA) and indocyanine green (ICG) condensed nanodrug (USI NPs) via one-pot assembly for targeted and synergistic HCC treatment. USILA NPs showed higher cellular uptake and cytotoxicity in HepG2 and H22 cells, with a high expression of epithelial cell adhesion molecule (EpCAM). Furthermore, these NPs caused more significant mitochondrial membrane potential reduction and cell apoptosis. These NPs could selectively accumulate at the tumor site of H22 tumor-bearing mice and were detected with the help of ICG fluorescence; moreover, they retarded tumor growth better than monotherapy. Thus, USILA NPs can realize the targeted delivery of dual drugs and the integration of diagnosis and treatment. Moreover, the effects were more significant after co-administration of iRGD peptide, a tumor-penetrating peptide with better penetration promoting ability or programmed cell death ligand 1 (PD-L1) antibody for the reversal of the immunosuppressive state in the tumor microenvironment. The tumor inhibition rates of USILA NPs + iRGD peptide or USILA NPs + PD-L1 antibody with good therapeutic safety were 72.38 % and 67.91 % compared with control, respectively. Overall, this composite nanosystem could act as a promising targeted tool and provide an effective intervention strategy for enhanced HCC synergistic treatment.


Assuntos
Carcinoma Hepatocelular , Peptídeos Penetradores de Células , Neoplasias Hepáticas , Nanopartículas , Camundongos , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Preparações Farmacêuticas , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Peptídeos Penetradores de Células/química , Antígeno B7-H1/uso terapêutico , Nanopartículas/química , Linhagem Celular Tumoral , Microambiente Tumoral
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