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1.
Inorg Chem ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829674

RESUMO

Ruddlesden-Popper oxyfluorides of the substitution series La2Ni1-xCuxO3F2 (0 ≤ x ≤ 1) were obtained by topochemical fluorination with polyvinylidene fluoride (PVDF) of oxide precursors La2Ni1-xCuxO4. The thermal stability and the temperature-dependent unit cell evolution of the oxyfluorides were investigated by high-temperature XRD measurements. The oxyfluoride with x = 0.6 shows the highest decomposition temperature of θdec ∼ 520 °C, which is significantly higher than the ones found for the end members La2NiO3F2 (x = 0) θdec ∼ 460 °C and La2CuO3F2 (x = 1) θdec ∼ 430 °C. The magnetic properties of all La2Ni1-xCuxO3F2 oxyfluorides were characterized by field- and temperature-dependent measurements as well as DFT calculations of the magnetic ground state. An antiferromagnetic ordering was derived for all substitution levels. For the Néel temperature (TN), a nonlinear dependence on the copper content was found, and comparably high values of TN in the region of 200-250 K were observed in the broad composition range of 0.3 ≤ x ≤ 0.8.

2.
Nat Prod Res ; : 1-7, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38752831

RESUMO

Polysaccharides and flavonoids have excellent antioxidant properties and tyrosinase inhibitory effects. In this paper, the antioxidant capacity of Inonotus sanghuang extract and its inhibition kinetics on mushroom tyrosinase were investigated to determine the preparation process of Inonotus sanghuang primary whitening gel. By conducting experimental studies on the effects of water extract and alcohol extract of Inonotus sanghuang on antioxidant capacity and tyrosinase activity, their inhibitory ability and types of inhibitory effects were determined. The single factor experiment was used to determine the preparation process of Sanghuang primary whitening gel. This study has proven that the extract of Inonotus sanghuang possesses antioxidant and tyrosinase inhibitory capabilities. It also identified the preparation process for the primary whitening gel of Inonotus sanghuang, thereby providing a theoretical and experimental basis for the development of whitening products utilising Inonotus sanghuang.

3.
Spectrochim Acta A Mol Biomol Spectrosc ; 318: 124469, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-38776671

RESUMO

Abnormal accumulation of mercury ions (Hg2+) in organisms can lead to severe central nervous system and other diseases. Therefore, the monitoring and detection of Hg2+ are of great significance for human health and environmental safety. Herein, we designed and synthesized a novel far-red to NIR emission fluorescent probe (Rho-Hg) based on rhodamine derivative as the fluorophore and thiospirolactone as the recognition site for turn-on detecting of Hg2+ in living cells and zebrafish. The probe Rho-Hg displayed superior sensitivity (detection limit = 17.5 nM), rapid response (<1 min), colorimetric change, high selectivity, and moderate pH stability. Leveraging this probe, we realized the real-time monitoring of Hg2+ in real samples, living cells and zebrafish. By fostering zebrafish embryos and larvae in Hg2+-containing nutrient solution, we noticed that Hg2+ was ingested into the zebrafish liver when zebrafish were grown up to 3 days old, and thus we successfully monitored the accumulation and changes of Hg2+ during zebrafish growth and development. Thus, the probe Rho-Hg could be a powerful tool for sensitive and real-time monitoring of Hg2+ in living systems.


Assuntos
Corantes Fluorescentes , Mercúrio , Peixe-Zebra , Animais , Peixe-Zebra/embriologia , Mercúrio/análise , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Humanos , Espectrometria de Fluorescência , Limite de Detecção , Células HeLa , Rodaminas/química , Concentração de Íons de Hidrogênio
4.
Inorg Chem ; 63(13): 6075-6081, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38506110

RESUMO

Ruddlesden-Popper oxyfluorides La2Ni1-xCuxO3F2 (0 ≤ x ≤ 1) were obtained by topochemical reaction of oxide precursors La2Ni1-xCuxO4, prepared by citrate-based soft chemistry synthesis, with polyvinylidene fluoride (PVDF) as the fluorine source. Systematic changes of the crystal structure in the oxide as well as the oxyfluoride substitution series were investigated. For 0.2 ≤ x ≤ 0.9, the oxyfluorides adopt the monoclinic (C2/c) structural distortion previously solved for the x = 0.8 compound based on neutron powder diffraction data, whereas the sample with a lower Cu content of x = 0.1 crystallizes in the orthorhombic (Cccm) structure variant of La2NiO3F2. The orthorhombic-to-monoclinic structural transition was found to be the result of an additional tilt component of the Jahn-Teller elongated CuO4F2 octahedra. The structural transitions were additionally studied by DFT calculations, confirming the monoclinic space group symmetry. The "channel-like" anionic ordering of the endmembers La2NiO3F2 and La2CuO3F2 was checked by 19F MAS NMR experiments and was found to persist throughout the entire substitution series.

5.
J Am Chem Soc ; 146(14): 10206-10216, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38536205

RESUMO

The attractive interactions between aromatic rings, also known as π-π interactions, have been widely used for decades. However, the origin of π-π interactions remains controversial due to the difficulties in experimentally measuring the weak interactions between π-systems. Here, we construct an elaborate system to accurately compare the strength of the π-π interactions between phenylalanine derivatives via molecular exchange processes inside a protein nanopore. Based on quantitative comparison of binding strength, we find that in most cases, the π-π interaction is primarily driven by dispersive attraction, with the electrostatic interaction playing a secondary role and tending to be repulsive. However, in cases where electronic effects are particularly strong, electrostatic induction may exceed dispersion forces to become the primary driving force for interactions between π-systems. The results of this study not only deepen our understanding of π-stacking but also have potential implications in areas where π-π interactions play a crucial role.

7.
Appl Environ Microbiol ; 90(3): e0211023, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38391210

RESUMO

Ultraviolet (UV) A radiation (315-400 nm) is the predominant component of solar UV radiation that reaches the Earth's surface. However, the underlying mechanisms of the positive effects of UV-A on photosynthetic organisms have not yet been elucidated. In this study, we investigated the effects of UV-A radiation on the growth, photosynthetic ability, and metabolome of the edible cyanobacterium Nostoc sphaeroides. Exposures to 5-15 W m-2 (15-46 µmol photons m-2 s-1) UV-A and 4.35 W m-2 (20 µmol photons m-2 s-1) visible light for 16 days significantly increased the growth rate and biomass production of N. sphaeroides cells by 18%-30% and 15%-56%, respectively, compared to the non-UV-A-acclimated cells. Additionally, the UV-A-acclimated cells exhibited a 1.8-fold increase in the cellular nicotinamide adenine dinucleotide phosphate (NADP) pool with an increase in photosynthetic capacity (58%), photosynthetic efficiency (24%), QA re-oxidation, photosystem I abundance, and cyclic electron flow (87%), which further led to an increase in light-induced NADPH generation (31%) and ATP content (83%). Moreover, the UV-A-acclimated cells showed a 2.3-fold increase in ribulose-1,5-bisphosphate carboxylase/oxygenase activity, indicating an increase in their carbon-fixing capacity. Gas chromatography-mass spectrometry-based metabolomics further revealed that UV-A radiation upregulated the energy-storing carbon metabolism, as evidenced by the enhanced accumulation of sugars, fatty acids, and citrate in the UV-A-acclimated cells. Therefore, our results demonstrate that UV-A radiation enhances energy flow and carbon assimilation in the cyanobacterium N. sphaeroides.IMPORTANCEUltraviolet (UV) radiation exerts harmful effects on photo-autotrophs; however, several studies demonstrated the positive effects of UV radiation, especially UV-A radiation (315-400 nm), on primary productivity. Therefore, understanding the underlying mechanisms associated with the promotive effects of UV-A radiation on primary productivity can facilitate the application of UV-A for CO2 sequestration and lead to the advancement of photobiological sciences. In this study, we used the cyanobacterium Nostoc sphaeroides, which has an over 1,700-year history of human use as food and medicine, to explore its photosynthetic acclimation response to UV-A radiation. As per our knowledge, this is the first study to demonstrate that UV-A radiation increases the biomass yield of N. sphaeroides by enhancing energy flow and carbon assimilation. Our findings provide novel insights into UV-A-mediated photosynthetic acclimation and provide a scientific basis for the application of UV-A radiation for optimizing light absorption capacity and enhancing CO2 sequestration in the frame of a future CO2 neutral, circular, and sustainable bioeconomy.


Assuntos
Nostoc , Raios Ultravioleta , Humanos , Biomassa , Carbono/metabolismo , Dióxido de Carbono/metabolismo , Nostoc/metabolismo , Fotossíntese/fisiologia
8.
BMC Musculoskelet Disord ; 25(1): 37, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38183070

RESUMO

BACKGROUND: Quadriceps training is necessary in function and activity of daily living for patients with knee osteoarthritis (KOA). However, it did not reduce the rate of surgical treatment for end-stage KOA in the long term. This may be related to brain structure changes and maladaptive plasticity in KOA patients. Transcranial Magnetic Stimulation (TMS) could enhance the functional connectivity of brain regions and improves maladaptive plasticity. However, the synergistic effect of the combination of the two for treat KOA is still unclear. Therefore, the purpose of this study is to investigate whether the High-Frequency rTMS combined with quadriceps strength training can improve the pain and function in KOA more effectively than quadriceps training alone and explore the mechanism of action. METHODS: This study is an assessor-blind, sham-controlled, randomized controlled trial involving 12 weeks of intervention and 6 months follow-up. 148 participants with KOA will receive usual care management and be randomized into four subgroups equally, including quadriceps strength training, high-frequency rTMS training, sham rTMS and quadriceps strength training, high-frequency rTMS and quadriceps strength training. The rehabilitation interventions will be carried out 5 days per week for a total of 12 weeks. All outcomes will be measured at baseline, 4 weeks, 8 weeks, and 12 weeks during the intervention and 1 month, 3 months and 6 months during the follow-up period. The effectiveness outcomes will be included visual analog scale, isokinetic knee muscle strength, Knee Injury and Osteoarthritis Outcome score and 36-Item Short-Form Health Survey score; The act mechanism outcomes will be included motor evoked potential, grey matter density, white matter, subcortical nuclei volumes, cortical thickness and functional connectivity by MRI. Two-way of variance with repeated measures will be used to test the group and time effect for outcome measures. DISCUSSION: The study will be the first protocol to examine whether there are synergistic effects following high-frequency rTMS combined with quadriceps strength training for treat KOA and clarify the mechanism of action. High-frequency rTMS can be added into the training program for KOA patients if it is proven effective. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300067617. Registered on Jan.13,2023.


Assuntos
Osteoartrite do Joelho , Treinamento Resistido , Humanos , Osteoartrite do Joelho/terapia , Estimulação Magnética Transcraniana , Músculo Quadríceps , Encéfalo , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Sleep Breath ; 28(1): 123-131, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37428352

RESUMO

OBJECTIVE: To investigate the role of TWIK-related acid-sensitive potassium channels TASK-1 and TASK-3 in the mechanism of asthma combined with obstructive sleep apnea (OSA) in mice. METHOD: C57BL/6 mice were randomly divided into four groups: control group (NS-RA), asthma group (OVA-RA), OSA group (NS-IH), and asthma combined with OSA group (OVA-IH). After monitoring lung function in each group, the expression levels of TASK-1 and TASK-3 mRNA and protein in lung tissues were measured, and the correlation between the changes of both and lung function was analyzed. RESULTS: A total of 64 male mice were studied. Penh, serum IgE concentrations, and the percentage of eosinophils in bronchoalveolar lavage fluid (BALF) were higher in OVA-RA and OVA-IH mice compared with NS-RA (P < 0.05),while the above indexes were slightly elevated in NS-IH mice compared with NS-RA (P > 0.05), where the Penh and the percentage of eosinophils in BALF was higher in OVA-IH mice than NS-IH (P < 0.05).Increased TASK-3 mRNA expression (P < 0.05) as well as TASK-1 and TASK-3 protein expression (P > 0.05) in lung tissues of OVA-RA and NS-IH mice compared with NS-RA, and TASK-3 mRNA expression was slightly more in the OVA-IH group compared with NS-RA (P > 0.05), but less compared with OVA-RA (P < 0.05) or NS-IH (P > 0.05), while TASK-1 and TASK-3 protein expression was increased in the OVA-IH group compared with the remaining three groups, and TASK-3 protein expression was associated with lung function impairment was positively correlated with the degree of lung function impairment (P < 0.05). CONCLUSION: Task-1 and Task-3 may be involved in the pathogenesis of asthma with OSA by affecting lung function.


Assuntos
Asma , Animais , Masculino , Camundongos , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Pulmão/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , RNA Mensageiro
10.
Perit Dial Int ; 44(1): 27-36, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37408329

RESUMO

OBJECTIVE: Peritoneal dialysis (PD)-related peritonitis is independently associated with low serum 25-hydroxy vitamin D [25(OH)D] levels. Our objective is to examine the feasibility of conducting a large, randomised controlled trial to determine the effects of vitamin D supplementation on the risk of PD-related peritonitis. DESIGN: Pilot, prospective, open-label randomised controlled trial. SETTING: Peking University First Hospital, China. PARTICIPANTS: Patients receiving PD who had recovered from a recent episode of peritonitis between 30 September 2017 and 28 May 2020. INTERVENTIONS: Oral natural vitamin D supplementation (2000 IU per day) versus no vitamin D supplementation for 12 months. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were feasibility (recruitment success, retention, adherence, safety) and fidelity (change in serum 25(OH)D level during follow-up) for a large, randomised controlled trial in the future to determine the effects of vitamin D on PD-related peritonitis. Secondary outcomes were time to peritonitis occurrence and outcome of subsequent peritonitis. RESULTS: Overall, 60 among 151 patients were recruited (recruitment rate was 39.7%, 95% CI 31.9-47.5%, recruitment rate among eligible patients was 61.9%, 95% CI 52.2-71.5%). Retention and adherence rates were 100.0% (95% CI 100.0-100.0%) and 81.5% (95% CI 66.8-96.1%), respectively. During follow-up, serum 25(OH)D levels increased in the vitamin D (VD) group (from 19.25 ± 10.11 nmol/L to 60.27 ± 23.29 nmol/L after 6 months, p < 0.001, n = 31), and remained higher (p < 0.001) than those in the control group (n = 29). No differences were observed between the two groups with respect to time to subsequent peritonitis (hazard ratio 0.85, 95% CI 0.33-2.17) or any of the peritonitis outcomes. Adverse events were uncommon. CONCLUSIONS: A randomised controlled trial of the effect of vitamin D supplementation on peritonitis occurrence in patients receiving PD is feasible, safe and results in adequate serum 25(OH)D levels.


Assuntos
Diálise Peritoneal , Peritonite , Deficiência de Vitamina D , Humanos , Estudos Prospectivos , Projetos Piloto , Diálise Peritoneal/efeitos adversos , Vitamina D , Peritonite/etiologia , Peritonite/prevenção & controle , Suplementos Nutricionais , Deficiência de Vitamina D/etiologia , Método Duplo-Cego
11.
Nat Methods ; 21(1): 102-109, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37957431

RESUMO

Direct protein sequencing technologies with improved sensitivity and throughput are still needed. Here, we propose an alternative method for peptide sequencing based on enzymatic cleavage and host-guest interaction-assisted nanopore sensing. We serendipitously discovered that the identity of any proteinogenic amino acid in a particular position of a phenylalanine-containing peptide could be determined via current blockage during translocation of the peptide through α-hemolysin nanopores in the presence of cucurbit[7]uril. Building upon this, we further present a proof-of-concept demonstration of peptide sequencing by sequentially cleaving off amino acids from C terminus of a peptide with carboxypeptidases, and then determining their identities and sequence with a peptide probe in nanopore. With future optimization, our results point to a different way of nanopore-based protein sequencing.


Assuntos
Nanoporos , Peptídeos , Sequência de Aminoácidos , Proteínas Hemolisinas/química
12.
Chinese Journal of School Health ; (12): 346-352, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013503

RESUMO

Objective@#To analyze the status of health risk behaviors among middle school students in Beijing City from 2018 to 2022, in order to provide reference for scientific and effective intervention.@*Methods@#Using multi stage stratified cluster random sampling method,data of student health and associated factors monitoring among 84 712 middle school students from 16 districts of Beijing during 2018 to 2022 were compared regarding the differences of health risk behaviors among students in different groups by Chi quare test. And their change trends were evaluated by annual percentage change (APC). @*Results@#In the five surveys during 2018 to 2022,reporting rates of unhealthy diet, unintentional injury, intentional injury, substance abuse and Internet addiction (only in 2018 and 2020) behaviors were higher in boys than in girls ( χ 2=4.91-297.52, P <0.05).Reporting rate of physical inactivity behavior in girls was higher than that in boys ( χ 2=56.49-160.88, P <0.05). Reporting rates of unhealthy diet, physical inactivity, unintentional injury (except 2021), substance abuse and Internet addiction (only in 2018 and 2019) behaviors were the highest in vocational high school, followed by general high school, and the lowest in junior middle school ( χ 2=23.30-1 285.98, P <0.01). Intentional injury behavior was highest in junior high school, followed by vocational high school, and lowest in general high school ( χ 2=96.18-378.32, P <0.01).Reporting rate of Internet addiction (2020-2022) behavior was highest in general high school, followed by vocational high school, and lowest in junior high school ( χ 2=16.93-60.11, P<0.01). Reporting rates of unhealthy diet, intentional injury (2020 and 2022) and substance abuse (except 2018) behaviors were higher in suburban areas than in urban areas (χ 2=6.70-117.56, P<0.05). Reporting rates of physical inactivity, unintentional injury, intentional injury (2018 and 2019) and Internet addiction behaviors were higher in urban areas than in suburban areas (χ2=3.90-130.80, P<0.05). Standardized rates of unintentional injury, intentional injury, substance abuse and Internet addiction behaviors showed a statistically significant downward trend from 2018 to 2022 (APC=-14.16, -13.43, -16.03, -8.48, t =-6.94, -4.46, -11.98, -4.36, P <0.05).@*Conclusions@#During 2018-2022, unintentional injury, intentional injury, substance abuse and Internet addiction behaviors of middle school students in Beijing City have improved, and the reporting rates of unhealthy diet and physical inactivity behaviors are high and don t show a downward trend. Efforts should be made to strengthen intervention in unhealthy diet and physical inactivity behaviors among middle school students, in order to reduce the occurrence of health risk behaviors.

13.
Front Oncol ; 13: 1276907, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38023214

RESUMO

Tertiary lymphoid structures (TLSs), referred to as tertiary lymphoid organs and lymphoid tissue neogenesis, are aggregates of immune cells that occur in nonlymphoid tissues. In recent years, it has been found that TLSs within the tumor microenvironment have been associated with local adaptive immune immunity against cancer and favorable prognosis in several human solid tumors, including gynecological cancers. The issue of the prognosis of gynecological cancers, including endometrial, cervical, and ovarian cancer, is an enormous challenge that many clinical doctors and researchers are now facing. Concerning the predictive prognostic role of TLSs, effective evaluation, and quantification of TLSs in human tissues may be used to assist gynecologists in assessing the clinical outcome of gynecological cancer patients. This review summarizes the current knowledge of TLSs in gynecological cancers, mainly focusing on the potential mechanism of TLS neogenesis, methods for evaluating TLSs, their prognostic value, and their role in antitumor immune immunity. This review also discusses the new therapeutic methods currently being explored in gynecological cancers to induce the formation of TLSs.

14.
World J Gastroenterol ; 29(39): 5435-5451, 2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37900996

RESUMO

Small extracellular vesicles (exosomes) are important components of the tumor microenvironment. They are small membrane-bound vesicles derived from almost all cell types and play an important role in intercellular communication. Exosomes transmit biological molecules obtained from parent cells, such as proteins, lipids, and nucleic acids, and are involved in cancer development. MicroRNAs (miRNAs), the most abundant contents in exosomes, are selectively packaged into exosomes to carry out their biological functions. Recent studies have revealed that exosome-delivered miRNAs play crucial roles in the tumorigenesis, progression, and drug resistance of hepatocellular carcinoma (HCC). In addition, exosomes have great industrial prospects in the diagnosis, treatment, and prognosis of patients with HCC. This review summarized the composition and function of exosomal miRNAs of different cell origins in HCC and highlighted the association between exosomal miRNAs from stromal cells and immune cells in the tumor microenvironment and the progression of HCC. Finally, we described the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Exossomos , Vesículas Extracelulares , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/metabolismo , Exossomos/genética , Exossomos/metabolismo , Vesículas Extracelulares/metabolismo , Microambiente Tumoral/genética
15.
J Phys Chem Lett ; 14(44): 9969-9977, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37905788

RESUMO

We study two-dimensional noble metal chalcogenides, with compositions {Cu, Ag, Au}2{S, Se, Te}, crystallizing in a snub-square lattice. This is a semiregular two-dimensional tesselation formed by triangles and squares that exhibits geometrical frustration. We use for comparison a square lattice, from which the snub-square tiling can be derived by a simple rotation of the squares. The monolayer snub-square chalcogenides are very close to thermodynamic stability, with the most stable system (Ag2Se) a mere 7 meV/atom above the convex hull of stability. All compounds studied in the square and snub-square lattice are semiconductors, with band gaps ranging from 0.1 to more than 2.5 eV. Excitonic effects are strong, with an exciton binding energy of around 0.3 eV. We propose the Cu (001) surface as a possible substrate to synthesize Cu2Se, although many other metal and semiconducting surfaces can be found with very good lattice matching.

16.
Medicine (Baltimore) ; 102(34): e34623, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37653768

RESUMO

BACKGROUND: Evaluate efficacy and safety of paliperidone palmitate 6-monthly (PP6M) for patients with schizophrenia in the Asian subgroup of a global, multicenter, noninferiority phase-3 study (NCT03345342). METHODS: Patients received paliperidone palmitate 1-monthly (PP1M, 100/150 mg eq.) or paliperidone palmitate 3-monthly (PP3M, 350/525 mg eq.) during the maintenance phase and entered a 12-month double-blind (DB) phase, wherein they were randomized (2:1) to PP6M (700/1000 mg. eq.) or PP3M (350/525 mg eq.). Subgroup analysis was performed for 90 (12.7%) patients from Asia region (India, Taiwan, Malaysia, Hong Kong, and Korea). Primary endpoint was time-to-relapse during DB phase (Kaplan-Meier estimates). Secondary endpoints were changes from baseline in Positive and Negative Syndrome Scale, Clinical Global Impression-Severity scale, Personal and Social Performance (PSP) scale score. RESULTS: In Asian subgroup, 91.9% (82/90) of patients completed DB phase (PP6M: 54/62 [87%]; PP3M: 28/28 [100%]). Median time-to-relapse was "not-estimable" due to low relapse rates in both groups. Estimated difference (95% confidence interval [CI]) between relapse-free patients in PP6M and PP3M groups of Asian subgroup was -0.1% [-8.5%, 8.4%] (global study population: -2.9% [-6.8%, 1.1%]). Mean change from baseline in secondary efficacy parameters was comparable between both groups, similar to the global study population. The incidence of extrapyramidal symptoms was higher in the Asian subgroup than in the global study population. CONCLUSION: Consistent with the global study population, PP6M was noninferior to PP3M in preventing relapse in patients with schizophrenia from the Asia region. Findings suggest the possibility of switching from PP1M/PP3M to twice-yearly PP6M without loss of efficacy and with no unexpected safety concerns.


Assuntos
Palmitato de Paliperidona , Esquizofrenia , Humanos , Asiático , Hong Kong , Palmitato de Paliperidona/administração & dosagem , Palmitato de Paliperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico
17.
Bioeng Transl Med ; 8(5): e10558, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37693059

RESUMO

High positive charge-induced toxicity, easy lysosomal degradation of nucleic acid drugs, and poor lesion sites targeting are major problems faced in the development of gene carriers. Herein, we proposed the concept of self-escape non-cationic gene carriers for targeted delivery and treatment of photocontrolled hepatocellular carcinoma (HCC) with sufficient lysosome escape and multiple response capacities. Functional DNA was bound to the surface of biotin-PEG2000-modified graphitic carbon nitride (Bio-PEG-CN) nanosheets to form non-cationic nanocomplexes Bio-PEG-CN/DNA. These nanocomposites could actively target HCC tissue. Once these nanocomplexes were taken up by tumor cells, the accumulated reactive oxygen species (ROS) generated by Bio-PEG-CN under LED irradiation would disrupt the lysosome structure, thereby facilitating nanocomposites escape. Due to the acidic microenvironment and lipase in the HCC tissue, the reversible release of DNA could be promoted to complete the transfection process. Meanwhile, the fluorescence signal of Bio-PEG-CN could be monitored in real time by fluorescence imaging technology to investigate the transfection process and mechanism. In vitro and in vivo results further demonstrated that these nanocomplexes could remarkably upregulate the expression of tumor suppressor protein P53, increased tumor sensitivity to ROS generated by nanocarriers, and realized effective gene therapy for HCC via loading P53 gene.

18.
Biogerontology ; 24(5): 753-769, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37289374

RESUMO

We investigated the effects of lifelong aerobic exercise and 8 months of detraining after 10 months of aerobic training on circulation, skeletal muscle oxidative stress, and inflammation in aging rats. Sprague-Dawley rats were randomly assigned to the control (CON), detraining (DET), and lifelong aerobic training (LAT) groups. The DET and LAT groups began aerobic treadmill exercise at the age of 8 months and stopped training at the 18th and 26th month, respectively; all rats were sacrificed when aged 26 months. Compared with CON, LAT remarkably decreased serum and aged skeletal muscle 4-hydroxynonenal (4-HNE) and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. Superoxide dismutase 2(SOD2) levels were higher in the LAT group than in the CON group in skeletal muscle. However, DET remarkably decreased SOD2 protein expression and content in the skeletal muscle and increased malondialdehyde (MDA) level compared with LAT. Compared with LAT, DET remarkably downregulated adiponectin and upregulated tumor necrosis factor alpha (TNF-α) expression, while phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and 70-kDa ribosomal protein S6 kinase (P70S6K) protein expression decreased, and that of FoxO1 and muscle atrophy F-box (MAFbX) proteins increased in the quadriceps femoris. Adiponectin and TNF-α expression in the soleus muscle did not change between groups, whereas that of AKT, mammalian target of rapamycin (mTOR), and P70S6K was lower in the soleus in the DET group than in that in the LAT group. Compared with that in the LAT group, sestrin1 (SES1) and nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression in the DET group was lower, whereas Keap1 mRNA expression was remarkably upregulated in the quadriceps femoris. Interestingly, the protein and mRNA levels of SES1, Nrf2, and Keap1 in soleus muscle did not differ between groups. LAT remarkably upregulated ferritin heavy polypeptide 1(FTH), glutathione peroxidase 4(GPX4), and solute carrier family 7member 11 (SLC7A11) protein expression in the quadriceps femoris and soleus muscles, compared with CON. However, compared with LAT, DET downregulated FTH, GPX4, and SLC7A11 protein expression in the quadriceps femoris and soleus muscles. Long-term detraining during the aging phase reverses the improvement effect of lifelong exercise on oxidative stress, inflammation, ferroptosis, and muscle atrophy in aging skeletal muscle. The quadriceps femoris is more evident than the soleus, which may be related to the different changes in the Keap1/Nrf2 pathway in different skeletal muscles.


Assuntos
Ferroptose , Fator 2 Relacionado a NF-E2 , Ratos , Animais , Ratos Sprague-Dawley , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adiponectina , Fosfatidilinositol 3-Quinases , Músculo Esquelético/fisiologia , Envelhecimento , Atrofia Muscular/metabolismo , RNA Mensageiro/genética , Inflamação/metabolismo , Mamíferos/genética , Mamíferos/metabolismo
20.
BMC Psychiatry ; 23(1): 365, 2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-37226150

RESUMO

BACKGROUND: Psychotic symptoms are prevalent in patients with bipolar disorder (BD). However, nearly all previous studies on differences in sociodemographic and clinical factors between patients with (BD P +) and without (BD P-) psychotic symptoms were conducted in Western populations, and limited information is known in China. METHOD: A total of 555 patients with BD from seven centers across China were recruited. A standardized procedure was used to collect patients' sociodemographic and clinical characteristics. The patients were divided into BD P + or BD P- groups based on the presence of lifetime psychotic symptoms. Mann-Whitney U test or chi-square test was used to analyze differences in sociodemographic and clinical factors between patients with BD P + and BD P-. Multiple logistic regression analysis was conducted to explore factors that were independently correlated with psychotic symptoms in BD. All the above analyses were re-conducted after the patients were divided into BD I and BD II group according to their types of diagnosis. RESULTS: A total of 35 patients refused to participate, and the remaining 520 patients were included in the analyses. Compared with patients with BD P-, those with BD P + were more likely to be diagnosed with BD I and mania/hypomania/mixed polarity in the first mood episode. Moreover, they were more likely to be misdiagnosed as schizophrenia than major depressive disorder, were hospitalized more often, used antidepressants less frequently, and used more antipsychotics and mood stabilizers. Multivariate analyses revealed that diagnosis of BD I, more frequent misdiagnosis as schizophrenia and other mental disorders, less frequent misdiagnosis as major depressive disorder, more frequent lifetime suicidal behavior, more frequent hospitalizations, less frequent use of antidepressants, more frequent use of antipsychotics and mood stabilizers were independently correlated with psychotic symptoms in BD. After dividing the patients into BD I and BD II groups, we observed notable differences in sociodemographic and clinical factors, as well as clinicodemographic correlates of psychotic features between the two groups. CONCLUSIONS: Differences in clinical factors between patients with BD P + and BD P- showed cross-cultural consistency, but results on the clinicodemographic correlates of psychotic features were not. Notable differences between patients with BD I and BD II were found. Future work exploring the psychotic features of BD needs to take types of diagnosis and cultural differences into consideration. TRIAL REGISTRATION: This study was first registered on the website of the ClinicalTrials.gov ( https://clinicaltrials.gov/ ) on 18/01/2013. Its registration number is NCT01770704.


Assuntos
Antipsicóticos , Transtorno Bipolar , Transtorno Depressivo Maior , Humanos , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/epidemiologia , Antipsicóticos/uso terapêutico , Afeto , Anticonvulsivantes , Antimaníacos , China/epidemiologia
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