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1.
Int J Biol Macromol ; 273(Pt 2): 132957, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38848837

RESUMO

Food waste resulting from perishable fruits and vegetables, coupled with the utilization of non-renewable petroleum-based packaging materials, presents pressing challenges demanding resolution. This study addresses these critical issues through the innovative development of a biodegradable functional plastic wrap. Specifically, the proposed solution involves the creation of a κ-carrageenan/carboxymethyl chitosan/arbutin/kaolin clay composite film. This film, capable of rapid in-situ formation on the surfaces of perishable fruits, adeptly conforms to their distinct shapes. The incorporation of kaolin clay in the composite film plays a pivotal role in mitigating water vapor and oxygen permeability, concurrently bolstering water resistance. Accordingly, tensile strength of the composite film experiences a remarkable enhancement, escalating from 20.60 MPa to 34.71 MPa with the incorporation of kaolin clay. The composite film proves its efficacy by preserving cherry tomatoes for an extended period of 9 days at 28 °C through the deliberate delay of fruit ripening, respiration, dehydration and microbial invasion. Crucially, the economic viability of the raw materials utilized in the film, coupled with the expeditious and straightforward preparation method, underscores the practicality of this innovative approach. This study thus introduces an easy and sustainable method for preserving perishable fruits, offering a cost-effective and efficient alternative to petroleum-based packaging materials.

2.
Food Chem X ; 22: 101502, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38872720

RESUMO

To determine the effect of cofermentation of Saccharomyces cerevisiae and different LABs on prune wine quality, this study compared phenolic compounds, organic acids, soluble sugars, biogenic amines and volatile flavor compounds among different treatments. The results showed that inoculation of LAB increased DPPH and total flavonoid content. Malic acid content was reduced in HS, HB and HF. Histamine content in S, F and B was lower than the limits in French and Australian wines. 15 phenolic compounds were identified. Yangmeilin and chlorogenic acid were detected only in HS, HF and HB. 51 volatile flavor compounds were identified, esters being the most diverse and abundant. 14 volatile flavor compounds with OAV > 1 contributed highly to the aroma of prune wine. 9 chemical markers including resveratrol, rutin, and catechin were screened to explain intergroup differences by OPLS-DA. This study provides new insights into the processing and quality analysis of prunes.

3.
Food Chem ; 452: 139616, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38759436

RESUMO

To investigate the effects of inoculating with three strains of lactic acid bacteria on prune wine quality during malolactic fermentation, this study determined its antioxidant activity, phenolic compounds, organic acids, and volatile/non-volatile metabolites. The results showed that inoculation with Lactobacillus paracasei SMN-LBK improved the antioxidant activity and phenolic compounds of prune wine. 73 VOCs were detected in prune wine by HS-SPME-GC-MS, and VOC content increased by 4.3% and 9.1% in MLFS and MLFB, respectively. Lactobacillus delbrueckii subsp. Bulgaricus showed better potential for winemaking, and citral and 5-nonanol, were detected in the MLF samples. 39 shared differential metabolites were screened and their metabolic pathways were investigated based on nontargeted metabolomics. Differences in amino acid and flavonoid content between strains reflected their specificity in flavonoid biosynthesis and amino acid biosynthesis. These findings will provide useful information for the biochemical study and processing of prune wine.


Assuntos
Fermentação , Compostos Orgânicos Voláteis , Vinho , Vinho/análise , Vinho/microbiologia , Compostos Orgânicos Voláteis/metabolismo , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/análise , Cromatografia Gasosa-Espectrometria de Massas , Fenóis/metabolismo , Fenóis/química , Fenóis/análise , Antioxidantes/metabolismo , Antioxidantes/química , Lactobacillales/metabolismo
4.
Nat Cardiovasc Res ; 3(3): 389-402, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38737787

RESUMO

The adult mouse heart responds to injury by scarring with consequent loss of contractile function, whereas the neonatal heart possesses the ability to regenerate. Activation of the immune system is among the first events upon tissue injury. It has been shown that immune response kinetics differ between regeneration and pathological remodeling, yet the underlying mechanisms of the distinct immune reactions during tissue healing remain unclear. Here we show that the immunomodulatory PD-1-PD-L1 pathway is highly active in regenerative neonatal hearts but rapidly silenced later in life. Deletion of the PD-1 receptor or inactivation of its ligand PD-L1 prevented regeneration of neonatal hearts after injury. Disruption of the pathway during neonatal cardiac injury led to increased inflammation and aberrant T cell activation, which ultimately impaired cardiac regeneration. Our findings reveal an immunomodulatory and cardioprotective role for the PD-1-PD-L1 pathway in heart regeneration and offer potential avenues for the control of adult tissue regeneration.

5.
Small ; : e2401394, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709222

RESUMO

Transition metal silicates (TMSs) are attempted for the electrocatalyst of oxygen evolution reaction (OER) due to their special layered structure in recent years. However, defects such as low theoretical activity and conductivity limit their application. Researchers always prefer to composite TMSs with other functional materials to make up for their deficiency, but rarely focus on the effect of intrinsic structure adjustment on their catalytic activity, especially anion structure regulation. Herein, applying the method of interference hydrolysis and vacancy reserve, new silicate vacancies (anionic regulation) are introduced in cobalt silicate hydroxide (CoSi), named SV-CoSi, to enlarge the number and enhance the activity of catalytic sites. The overpotential of SV-CoSi declines to 301 mV at 10 mA cm-2 compared to 438 mV of CoSi. Source of such improvement is verified to be not only the increase of active sites, but also the positive effect on the intrinsic activity due to the enhancement of cobalt-oxygen covalence with the variation of anion structure by density functional theory (DFT) method. This work demonstrates that the feasible intrinsic anion structure regulation can improve OER performance of TMSs and provides an effective idea for the development of non-noble metal catalyst for OER.

6.
J Vis Exp ; (203)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38345262

RESUMO

The lethality of liver cancer and the resistance to chemical drugs have forced the search for effective prescriptions of traditional herbs for liver cancer. Animal models that are repeatable, easy to manipulate, and highly mimic the pathophysiological processes of liver cancer are the prerequisite for the successful screening of effective drug candidates. Meanwhile, reliable drug efficacy evaluation indicators and means are also the guarantee of anti-liver cancer drug research and development. Sanleng Jiashen formula, a representative prescription of traditional Chinese medicine containing Sparganium stoloni erum, Buch. -Ham. (Sanleng), Panax ginseng C. A. Mey. (ginseng), Rheum officinale Baill. (rhubarb), and Ligusticum chuanxiong Hort. (Chuanxiong), is prescribed to nourish the liver and clear heat, remove toxins, and promote blood circulation to treat liver cancer. This experimental protocol describes the preparation of lyophilized Sanleng Jiashen formula and the establishment process of in-situ liver cancer in BALB/c-nu mice. Histopathological staining, immunohistochemical detection of cancer markers, in vivo imaging of mice, and chick embryo chorioallantoic membrane test were used to explore the inhibition and anti-angiogenesis effect of Sanleng Jiashen formula on malignant proliferation of liver cancer tissue. The data show that the Sanleng Jiashen formula can effectively resist the malignant proliferation of liver cancer tissue, which is manifested by reduced tumor mass volume, improved pathological damage, and lower levels of the cancer marker ki67. The superior inhibition of angiogenesis also suggests that the Sanleng Jiashen formula may have the potential to treat and prevent the progression and deterioration of liver cancer. The whole experimental scheme shows a comprehensive process of traditional Chinese medicine components in the treatment of mouse liver cancer, which provides a reference for the establishment and optimization of a liver cancer model, as well as the research and development of drugs to prevent and treat liver cancer.


Assuntos
Carcinoma Hepatocelular , Medicamentos de Ervas Chinesas , Neoplasias Hepáticas , Embrião de Galinha , Camundongos , Animais , Camundongos Endogâmicos BALB C , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico
7.
Arch Insect Biochem Physiol ; 115(1): e22065, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38014596

RESUMO

Suppressors of cytokine signaling (SOCS) play important roles in the regulation of growth, development, and immunity of eukaryotic organisms. SOCS7 is an important member of the SOCS family, but its physiological and pathological functions remain largely unknown in invertebrates including insects. Here, we first report the cloning of a SOCS7 gene from a domesticated silkworm (Bombyx mori), named BmSOCS7. We have characterized BmSOCS7 expression profiles in silkworm varieties susceptible or resistant to the infection of Bombyx mori nucleopolyhedrovirus (BmNPV) using the real-time fluorescence quantitative PCR. BmSOCS7 expresses highly in embryogenesis and lowly in metamorphosis in resistant silkworms but does in opposite contrast in susceptible silkworms. Its expression is at very low level in the fat body of resistant silkworms but is relatively high in the fat body of susceptible ones. BmNPV inoculation induces a transient downregulation and then a general upregulation of BmSOCS7 expression in BmN cells, while it induces a general downregulation in silkworm midgut, fat body and hemolymph with more pronounced effect in resistant silkworms than susceptible ones and more prominent in the fat body and hemolymph than the midgut. Together, our work reveals that downregulation of BmSOCS7 expression may be an important strategy for silkworm anti-BmNPV immune response, and BmSOCS7 may mainly function in the fat body and hemolymph rather than the midgut to participate in BmNPV infection process.


Assuntos
Bombyx , Nucleopoliedrovírus , Animais , Bombyx/metabolismo , Citocinas/metabolismo , Sistema Digestório , Clonagem Molecular
8.
Dev Cell ; 58(24): 2867-2880.e7, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-37972593

RESUMO

Cardiomyocytes are highly metabolic cells responsible for generating the contractile force in the heart. During fetal development and regeneration, these cells actively divide but lose their proliferative activity in adulthood. The mechanisms that coordinate their metabolism and proliferation are not fully understood. Here, we study the role of the transcription factor NFYa in developing mouse hearts. Loss of NFYa alters cardiomyocyte composition, causing a decrease in immature regenerative cells and an increase in trabecular and mature cardiomyocytes, as identified by spatial and single-cell transcriptome analyses. NFYa-deleted cardiomyocytes exhibited reduced proliferation and impaired mitochondrial metabolism, leading to cardiac growth defects and embryonic death. NFYa, interacting with cofactor SP2, activates genes linking metabolism and proliferation at the transcription level. Our study identifies a nodal role of NFYa in regulating prenatal cardiac growth and a previously unrecognized transcriptional control mechanism of heart metabolism, highlighting the importance of mitochondrial metabolism during heart development and regeneration.


Assuntos
Miócitos Cardíacos , Fatores de Transcrição , Animais , Camundongos , Proliferação de Células/fisiologia , Desenvolvimento Fetal , Coração Fetal/metabolismo , Coração/fisiologia , Miócitos Cardíacos/metabolismo , Fatores de Transcrição/metabolismo
9.
Jpn J Clin Oncol ; 53(11): 1068-1076, 2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37567587

RESUMO

PURPOSE: Cancer is the second leading cause of mortality worldwide. Cancer negatively affects individuals' quality of life and overall health. Mindfulness-based interventions appear to be promising in the reduction of cancer- and treatment-related symptoms. This review aimed to determine the effectiveness of online mindfulness-based interventions on distress, anxiety, depression, stress, mindfulness, sleep disturbance, quality of life, rumination, fear of cancer recurrence, fatigue and post-traumatic growth among adult cancer patients. METHODS: A literature search was conducted across five electronic databases. Only randomized controlled trials were eligible. Two reviewers independently screened the studies, extracted data, and performed quality assessment using the Cochrane risk of bias assessment tool. Meta-analyses were conducted using review manager software, and standardized mean difference was used to determine intervention effects. Heterogeneity was examined using the I2 statistics. RESULTS: Ten studies were included with a total of 962 participants. Analyses revealed that online mindfulness-based interventions was effective in reducing distress (I2 = 98%;standardized mean difference = -2.21,95% confidence interval: -3.84 to 0.57;P = 0.008), depression (I2 = 45%;standardized mean difference = -0.33,95% confidence interval: -0.64 to -0.03;P = 0.03), stress (I2 = 97%;standardized mean difference = -2.14,95% confidence interval: -4.24 to -0.03;P = 0.05) and sleep disturbance (I2 = 54%;standardized mean difference = -0.30,95% confidence interval: -0.59 to -0.01;P = 0.04), and improving quality of life (I2 = 94%;standardized mean difference = 0.92,95% confidence interval: 0.09-1.76;P = 0.03). The online mindfulness-based interventions had no significant effects on anxiety, mindfulness, rumination, fear of cancer recurrence, fatigue and post-traumatic growth. Subgroup analyses revealed that online mindfulness-based interventions resulted in higher effect sizes for distress when delivered by website than application, significantly higher effect sizes were also found for online mindfulness-based interventions with guidance, but not on treatment or cancer type. For sleep disturbance, and quality of life, no significant differences between subgroups were found. CONCLUSION: These results provide preliminary support that online mindfulness-based interventions may be feasible and acceptable, which can be used as an adjuvant therapy for the management of cancer-related symptoms among cancer patients.


Assuntos
Atenção Plena , Neoplasias , Transtornos do Sono-Vigília , Adulto , Humanos , Atenção Plena/métodos , Qualidade de Vida , Ansiedade , Neoplasias/terapia , Neoplasias/complicações , Fadiga/etiologia
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(4): 1019-1025, 2023 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-37551471

RESUMO

OBJECTIVE: To investigate the occurrence of CSF3R mutation in patients with t(8;21) acute myeloid leukemia (AML) and its correlation with some clinical parameters. METHODS: The clinical and laboratory data of 167 newly diagnosed AML patients with t(8;21) translocation were analyzed retrospectively. High-throughput DNA sequencing technology combined with Sanger sequencing method was used to detect 112 gene mutations. The occurrence of CSF3R gene mutation and its influence on the remission rate after chemotherapy were analyzed. RESULTS: Among 167 patients with t(8;21) AML, 15 patients (9.0%) carried CSF3R mutations, including 6 cases of membrane proximal region mutations and 9 cases of truncation mutations in the cytoplasmic tail. The most common coexisting mutations of CSF3R were KIT (40.0%), TET2 (33.3%), DNMT3A (26.7%), FLT3 (20.0%), CBL (20.0%), IDH1 (13.3%), etc. Compared with the wild type, the CSF3R mutant group had a higher mutation rate of DNA methylation-related genes(P <0.001). The median peripheral white blood cell (WBC) count of patients with CSF3R gene mutation was 5.80 (3.20-8.56)×109/L at initial diagnosis, which was significantly lower than 8.80 (5.26-19.92)×109/L of the CSF3R wild-type patients (P =0.017). There was no significant difference between the two groups in sex, median age, FAB classification, hemoglobin level, platelet count, etc. (P >0.05). The CR rate of the CSF3R gene mutation group (100%) was significantly higher than that of the wild-type group (86.8%), but the difference was not statistically significant (P >0.05). The CSF3R gene mutation group had a significantly higher CD19 positive rate and a higher -X rate than the wild group (86.7% vs 47.4%, P =0.004; 33.3% vs 13.2%, P =0.037). CONCLUSION: There is a high incidence of CSF3R mutation in t (8;21) AML patients. The clinical characteristics and coexisting mutation genes of CSF3R mutation-positive patients are different from those of wild-type patients.


Assuntos
Leucemia Mieloide Aguda , Humanos , Estudos Retrospectivos , Prognóstico , Leucemia Mieloide Aguda/genética , Mutação , Transdução de Sinais , Receptores de Fator Estimulador de Colônias/genética
11.
Z Naturforsch C J Biosci ; 78(9-10): 327-335, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37233326

RESUMO

Suppressors of cytokine signaling (SOCSs) are implicated in viral infection and host antiviral innate immune response. Recent studies demonstrate that viruses can hijack SOCSs to inhibit Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway, block the production and signaling of interferons (IFNs). At the same time, viruses can hijack SOCS to regulate non-IFN factors to evade antiviral response. Host cells can also regulate SOCSs to resist viral infection. The competition of the control of SOCSs may largely determine the fate of viral infection and the susceptibility or resistance of host cells, which is of significance for development of novel antiviral therapies targeting SOCSs. Accumulating evidence reveal that the regulation and function of SOCSs by viruses and host cells are very complicated, which is determined by characteristics of both viruses and host cell types. This report presents a systematic review to evaluate the roles of SOCSs in viral infection and host antiviral responses. One of messages worth attention is that all eight SOCS members should be investigated to accurately characterize their roles and relative contribution in each viral infection, which may help identify the most effective SOCS to be used in "individualized" antiviral therapy.


Assuntos
Viroses , Humanos , Antivirais/farmacologia , Antivirais/uso terapêutico , Transdução de Sinais , Imunidade Inata
12.
Eur J Med Chem ; 254: 115353, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37068385

RESUMO

The type 2 small conductance Ca2+-activated K+ channels (SK2) have been considered as one of the most promising therapeutic targets for spinocerebellar ataxias type 2 (SCA2) by playing a critical role in the control of normal purkinje cells (PCs) pacemaking. Herein, a novel series of pyrrolopyrimidine derivatives were designed and synthesized from the lead compound NS13001 as subtype-selective modulators of SK channels. Among them, the halogen-substituted compound 12b (EC50 = 0.34 ± 0.044 µM) was identified with a ∼5.4-fold higher potency on potentiating SK2-a channels at submicromolar concentrations as compared to NS13001 (EC50 = 1.83 ± 0.50 µM). Furthermore, compound 12b exhibited selectivity on SK2-a/SK3 subtype by displaying 93.33 ± 3.26% efficacies on SK2-a channels, and 84.54% ± 7.49% on SK3 channels. In addition, compound 12b demonstrated the potential to cross the blood-brain barrier (BBB) with suitable pharmacokinetic properties and low cytotoxicity. Molecular docking study also unveiled the binding interactions of compound 12b with SK2-CaM protein complex. Overall, the novel pyrrolopyrimidines provide an insightful guidance for future structural optimization of SK channel agonists.


Assuntos
Pirimidinas , Canais de Potássio Ativados por Cálcio de Condutância Baixa , Canais de Potássio Ativados por Cálcio de Condutância Baixa/metabolismo , Simulação de Acoplamento Molecular , Pirimidinas/farmacologia , Pirróis/farmacologia
13.
Nat Med ; 29(2): 401-411, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36797478

RESUMO

The most common form of genetic heart disease is hypertrophic cardiomyopathy (HCM), which is caused by variants in cardiac sarcomeric genes and leads to abnormal heart muscle thickening. Complications of HCM include heart failure, arrhythmia and sudden cardiac death. The dominant-negative c.1208G>A (p.R403Q) pathogenic variant (PV) in ß-myosin (MYH7) is a common and well-studied PV that leads to increased cardiac contractility and HCM onset. In this study we identify an adenine base editor and single-guide RNA system that can efficiently correct this human PV with minimal bystander editing and off-target editing at selected sites. We show that delivery of base editing components rescues pathological manifestations of HCM in induced pluripotent stem cell cardiomyocytes derived from patients with HCM and in a humanized mouse model of HCM. Our findings demonstrate the potential of base editing to treat inherited cardiac diseases and prompt the further development of adenine base editor-based therapies to correct monogenic variants causing cardiac disease.


Assuntos
Cardiomiopatia Hipertrófica , Miócitos Cardíacos , Humanos , Animais , Camundongos , Edição de Genes , Miocárdio , Arritmias Cardíacas , Mutação
14.
Nurse Educ Today ; 120: 105633, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36436265

RESUMO

OBJECTIVES: This systematic review aimed to qualitatively synthesise existing literature to examine the clinical nursing experiences of final-year nursing students during the COVID-19 pandemic and provide recommendations for the effective management of clinical placement of nursing students. DESIGN: A qualitative systematic review was conducted and reported following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. DATA SOURCES: Five electronic databases were searched and qualitative studies were included for analysis if they focussed on the clinical nursing experiences of final-year nursing students during the COVID-19 pandemic. REVIEW METHODS: Data synthesis was conducted by extracting all findings, developing categories, and producing synthesised findings. RESULTS: Four synthesised findings were concluded: 1) facing the unknown and willingness to help, 2) challenging the clinical environment, 3) transition improving professional identity, and 4) finding ways out of the pandemic. CONCLUSIONS: The transition of nursing students to clinical nursing practice during the pandemic is a personally and professionally challenging process, while nursing students try to adapt to the changing clinical environment and enhance their professional identity. Nursing managers and health policymakers should acknowledge the challenges encountered by nursing students during the pandemic and support the professional growth of future nursing teams by providing high-quality supervision.


Assuntos
COVID-19 , Enfermeiros Administradores , Estudantes de Enfermagem , Humanos , Pandemias , Pesquisa Qualitativa
15.
Immunol Lett ; 253: 1-7, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36460232

RESUMO

BACKGROUND: Preeclampsia is a major cause of increased maternal and fetal morbidity and mortality, which is closely related to the abnormal maternal immune response. The skew of decidual macrophage polarization toward M1 phenotype has been proved to promote the pathogenesis of preeclampsia. However, it's not easy to monitor the change of decidual macrophage subtypes. The current study aims to examine the distribution of different circulating monocyte subtypes and analyze whether certain monocyte subtypes act as potential clinical indicators for preeclampsia. METHODS: A total of 50 pregnant women [mild preeclampsia (n = 20); severe preeclampsia (n = 15); healthy pregnancy (n = 15)] and 15 healthy donors were included in the study. Medical information such as BMI, blood pressure, ALT, creatinine, thrombocyte, etc., were recorded. The frequency of different monocyte subtypes in venous blood were measured by flow cytometry. Serum level of IL-6 was detected using Roche-Hitachi cobas 8000. Serum concentration of inflammatory cytokines (IL-1ß, IL-4, IL-10 and TNF-α) were measured by ELISA. RESULTS: A circulating monocyte subset with both M1 and M2 markers (CD14+CD16+CD163+) was found to occupy an obvious higher proportion in the preeclampsia group than in the normal pregnancy group. The ratio of CD206+/CD206- M2-like monocytes was also increased in the preeclampsia group, and meanwhile, it had statistic difference between the mild- and the severe-preeclampsia group. Furthermore, the serum levels of IL-1ß and TNF-α were positively correlated with the frequency of CD14+CD16+CD163+ intermediate monocytes in the preeclampsia group. CONCLUSIONS: The increased proportion of CD14+C16+CD163+ circulating monocytes and the high ratio of CD206+/CD206- M2-like monocytes may act as potential clinical indicators for preeclampsia, with the superiority of convenience and dynamic monitoring.


Assuntos
Monócitos , Pré-Eclâmpsia , Feminino , Humanos , Gravidez , Receptores de Lipopolissacarídeos , Fenótipo , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/patologia , Fator de Necrose Tumoral alfa
17.
Fundam Res ; 3(2): 288-297, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38932920

RESUMO

Over the past few years, the flexible quasi-solid-state zinc-ion hybrid supercapacitors (FQSS ZHSCs) have been found to be ideal for wearable electronics applications due to their high areal capacitance and energy density. The assembly of desirable ZHSCs devices that have promising practical applications is of high importance, whereas it is still challenging to assemble ZHSCs devices. In this study, a ZHSC that exhibited ultrahigh areal capacitance and high stability was developed by using an active carbon cloth (ACC) cathode, which could improve ionic adsorption. The as-obtained ACC cathode had an energy storage mechanism due to the electrical double-layer capacitive behavior of Zn2+, which was accompanied by the dissolution/deposition of Zn4SO4(OH)6·5H2O. The ACC//Zn@ACC ZHSC device exhibited an areal capacitance of 2437 mF cm-2 (81 F cm-3, 203 F g-1 under the mass of ACC with ∼12 mg cm-2) at 1 mA cm-2, an areal energy density of 1.354 mWh cm-2 at 1 mW cm-2, as well as high stability (with an insignificant capacitance decline after 20000 cycles), which was demonstrated to outperform the existing ZHSCs. Furthermore, the assembled flexible device still had competitive capacitance, energy density and service life when integrated into a FQSS ZHSC. When applied in practice, the device could achieve high mechanical flexibility, wearable stability and output. This study can inspire the development of the FQSS ZHSC device to satisfy the demands for wearable energy storage devices with high performance.

18.
Sci Transl Med ; 14(672): eade1633, 2022 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-36417486

RESUMO

Mutations in RNA binding motif protein 20 (RBM20) are a common cause of familial dilated cardiomyopathy (DCM). Many RBM20 mutations cluster within an arginine/serine-rich (RS-rich) domain, which mediates nuclear localization. These mutations induce RBM20 mis-localization to form aberrant ribonucleoprotein (RNP) granules in the cytoplasm of cardiomyocytes and abnormal alternative splicing of cardiac genes, contributing to DCM. We used adenine base editing (ABE) and prime editing (PE) to correct pathogenic p.R634Q and p.R636S mutations in the RS-rich domain in human isogenic induced pluripotent stem cell (iPSC)-derived cardiomyocytes. Using ABE to correct RBM20R634Q human iPSCs, we achieved 92% efficiency of A-to-G editing, which normalized alternative splicing of cardiac genes, restored nuclear localization of RBM20, and eliminated RNP granule formation. In addition, we developed a PE strategy to correct the RBM20R636S mutation in iPSCs and observed A-to-C editing at 40% efficiency. To evaluate the potential of ABE for DCM treatment, we also created Rbm20R636Q mutant mice. Homozygous (R636Q/R636Q) mice developed severe cardiac dysfunction, heart failure, and premature death. Systemic delivery of ABE components containing ABEmax-VRQR-SpCas9 and single-guide RNA by adeno-associated virus serotype 9 in these mice restored cardiac function as assessed by echocardiography and extended life span. As seen by RNA sequencing analysis, ABE correction rescued the cardiac transcriptional profile of treated R636Q/R636Q mice, compared to the abnormal gene expression seen in untreated mice. These findings demonstrate the potential of precise correction of genetic mutations as a promising therapeutic approach for DCM.


Assuntos
Cardiomiopatia Dilatada , Humanos , Camundongos , Animais , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/patologia , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Mutação/genética , Miócitos Cardíacos/metabolismo , Genômica
19.
Biosens Bioelectron ; 217: 114692, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36150325

RESUMO

Circulating tumor cells (CTCs) are important markers for cancer diagnosis and monitoring. However, CTCs detection remains challenging due to their scarcity, where most of the detection methods are compromised by the loss of CTCs in pre-enrichment, and by the lack of universal antibodies for capturing different kinds of cancer cells. Herein, we report a single-chain based nano lock (SCNL) polymer incorporating dually stimulative dynamic ligands that can bind with a broad spectrum of cancer cells and CTCs overexpressing sialic acid (SA) with high sensitivity and selectivity. The high sensitivity is realized by the polymeric single chain structure and the multi-valent functional moieties, which improve the accessibility and binding stability between the target cells and the SCNL. The highly selective targeting of cancer cells is achieved by the dynamic and dually stimulative nano lock structures, which can be unlocked and functionalized upon simultaneous exposure to overexpressed SA and acidic microenvironment. We applied the SCNL to detecting cancer cells and CTCs in clinical samples, where the detection threshold of SCNL reached 4 cells/mL. Besides CTCs enumeration, the SCNL approach could also be extended to metastasis assessment through monitoring the expressing level of surface SA on cancer cells.


Assuntos
Técnicas Biossensoriais , Células Neoplásicas Circulantes , Anticorpos/química , Linhagem Celular Tumoral , Humanos , Ácido N-Acetilneuramínico , Células Neoplásicas Circulantes/patologia , Polímeros , Microambiente Tumoral
20.
Lab Invest ; 102(11): 1170-1181, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35922478

RESUMO

Proteomics plays a vital role in biomedical research in the post-genomic era. With the technological revolution and emerging computational and statistic models, proteomic methodology has evolved rapidly in the past decade and shed light on solving complicated biomedical problems. Here, we summarize scientific research and clinical practice of existing and emerging high-throughput proteomics approaches, including mass spectrometry, protein pathway array, next-generation tissue microarrays, single-cell proteomics, single-molecule proteomics, Luminex, Simoa and Olink Proteomics. We also discuss important computational methods and statistical algorithms that can maximize the mining of proteomic data with clinical and/or other 'omics data. Various principles and precautions are provided for better utilization of these tools. In summary, the advances in high-throughput proteomics will not only help better understand the molecular mechanisms of pathogenesis, but also to identify the signature signaling networks of specific diseases. Thus, modern proteomics have a range of potential applications in basic research, prognostic oncology, precision medicine, and drug discovery.


Assuntos
Genômica , Proteômica , Proteômica/métodos , Espectrometria de Massas , Genômica/métodos , Medicina de Precisão , Análise Serial de Proteínas
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