Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 106
Filtrar
1.
Nat Methods ; 20(7): 1029-1036, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37231266

RESUMO

As a miniature RNA-guided endonuclease, IscB is presumed to be the ancestor of Cas9 and to share similar functions. IscB is less than half the size of Cas9 and thus more suitable for in vivo delivery. However, the poor editing efficiency of IscB in eukaryotic cells limits its in vivo applications. Here we describe the engineering of OgeuIscB and its corresponding ωRNA to develop an IscB system that is highly efficient in mammalian systems, named enIscB. By fusing enIscB with T5 exonuclease (T5E), we found enIscB-T5E exhibited comparable targeting efficiency to SpG Cas9 while showing reduced chromosome translocation effects in human cells. Furthermore, by fusing cytosine or adenosine deaminase with enIscB nickase, we generated miniature IscB-derived base editors (miBEs), exhibiting robust editing efficiency (up to 92%) to induce DNA base conversions. Overall, our work establishes enIscB-T5E and miBEs as versatile tools for genome editing.


Assuntos
Sistemas CRISPR-Cas , Desoxirribonuclease I , Animais , Humanos , Desoxirribonuclease I/genética , Desoxirribonuclease I/metabolismo , Edição de Genes , Citosina , RNA/genética , Mamíferos/genética , Mamíferos/metabolismo
2.
Nature ; 577(7788): 109-114, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31827280

RESUMO

Activation of RIPK1 controls TNF-mediated apoptosis, necroptosis and inflammatory pathways1. Cleavage of human and mouse RIPK1 after residues D324 and D325, respectively, by caspase-8 separates the RIPK1 kinase domain from the intermediate and death domains. The D325A mutation in mouse RIPK1 leads to embryonic lethality during mouse development2,3. However, the functional importance of blocking caspase-8-mediated cleavage of RIPK1 on RIPK1 activation in humans is unknown. Here we identify two families with variants in RIPK1 (D324V and D324H) that lead to distinct symptoms of recurrent fevers and lymphadenopathy in an autosomal-dominant manner. Impaired cleavage of RIPK1 D324 variants by caspase-8 sensitized patients' peripheral blood mononuclear cells to RIPK1 activation, apoptosis and necroptosis induced by TNF. The patients showed strong RIPK1-dependent activation of inflammatory signalling pathways and overproduction of inflammatory cytokines and chemokines compared with unaffected controls. Furthermore, we show that expression of the RIPK1 mutants D325V or D325H in mouse embryonic fibroblasts confers not only increased sensitivity to RIPK1 activation-mediated apoptosis and necroptosis, but also induction of pro-inflammatory cytokines such as IL-6 and TNF. By contrast, patient-derived fibroblasts showed reduced expression of RIPK1 and downregulated production of reactive oxygen species, resulting in resistance to necroptosis and ferroptosis. Together, these data suggest that human non-cleavable RIPK1 variants promote activation of RIPK1, and lead to an autoinflammatory disease characterized by hypersensitivity to apoptosis and necroptosis and increased inflammatory response in peripheral blood mononuclear cells, as well as a compensatory mechanism to protect against several pro-death stimuli in fibroblasts.


Assuntos
Caspase 8/metabolismo , Doenças Hereditárias Autoinflamatórias/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Adolescente , Adulto , Sequência de Aminoácidos , Animais , Sequência de Bases , Criança , Pré-Escolar , Feminino , Células HEK293 , Doenças Hereditárias Autoinflamatórias/genética , Doenças Hereditárias Autoinflamatórias/patologia , Humanos , Masculino , Camundongos , Camundongos Knockout , Proteína Serina-Treonina Quinases de Interação com Receptores/deficiência , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos
3.
Nano Lett ; 24(19): 5870-5878, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38608135

RESUMO

In the context of sustainable development, research on a biomass-based adhesive without chemical modification as a substitute for petroleum-based adhesive is now crucial. It turns out to be challenging to guarantee a simple and sustainable method to produce high-quality adhesives and subsequently manufacture multifunctional composites. Herein, the inherent properties of cellulose were exploited to generate an adhesive based on a cellulose aqueous solution. The adhesion is simple to prepare structurally and functionally complex materials in a single process. Cellulose-based daily necessities including straws, bags, and cups were prepared by adhering cellulose films, and smart devices like actuators and supercapacitors assembled by adhering hydrogels were also demonstrated. In addition, the composite boards bonded with natural biomass wastes, such as wood chips, displayed significantly stronger mechanical properties than the natural wood or commercial composite boards. Cellulose aqueous adhesives provide a straightforward, feasible, renewable, and inventive bonding technique for material shaping and the creation of multipurpose devices.

4.
Nat Mater ; 22(5): 619-626, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37037960

RESUMO

Methanol with 12.5 wt% H2 content is widely considered a liquid hydrogen medium. Taking into account water with 11.1 wt% H2 content, H2 synthesis from the mixture of water and methanol is a promising method for on-demand hydrogen production. We demonstrate an atomic-level catalyst design strategy using the synergy between single atoms and nanodots for H2 production. The PtCu-TiO2 sandwich photocatalyst achieves a remarkable H2 formation rate (2,383.9 µmol h-1) with a high apparent quantum efficiency (99.2%). Furthermore, the oxidation product is a high-value chemical formaldehyde with 98.6% selectivity instead of CO2, leading to a nearly zero-carbon-emission process. Detailed investigations indicate a dual role of the copper atoms: an electron acceptor to facilitate photoelectron transfer to Pt, and a hole acceptor for the selective oxidation of methanol to formaldehyde, thus avoiding over-oxidation to CO2. The synergy between Pt nanodots and Cu single atoms together reduces the activation energy of this process to 13.2 kJ mol-1.

5.
Phys Chem Chem Phys ; 26(22): 16337-16349, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38805067

RESUMO

SnSe has emerged as an outstanding thermoelectric material due to its exceptional performance. In this study, first-principles calculations are employed to investigate the thermoelectric properties of materials within the SnX family, where X can be either S, Se, or Te. Initially, we assessed the stability of SnX (X = S, Se, Te). We found that SnS exhibits better mechanical and thermal stability than SnSe and SnTe. We then conduct phonon and electronic transport analysis. Following the general rule that heavier atoms have lower thermal conductivity, SnTe demonstrates lower thermal conductivity due to its low group velocity compared with SnS and SnSe. Regarding electrical transport properties, the band gaps for SnS, SnSe, and SnTe are 0.56, 0.54, and 0.35 eV, respectively. Notably, the small band gap and higher degeneracy in its band valleys for SnTe make it more effective for achieving a high power factor. The maximum ZT values are determined to be 1.41, 1.41, and 1.87 for SnS, SnSe, and SnTe, respectively. Remarkably, ZTmax of SnTe exceeds that of SnSe by 32.6%. Overall, the results clearly demonstrate that SnTe exhibits superior thermoelectric properties compared to SnSe and SnS. This study provides valuable insights into the electronic structure, thermal conductivity, and mechanical and thermal stability of materials within the SnSe family, such as SnS or SnTe, without the need for extensive and costly experimental work.

6.
J Allergy Clin Immunol ; 152(5): 1292-1302, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37422272

RESUMO

BACKGROUND: Phospholipase C (PLC) γ1 is a critical enzyme regulating nuclear factor-κB (NF-κB), extracellular signal-related kinase, mitogen-activated protein kinase, and nuclear factor of activated T cells signaling pathways, yet germline PLCG1 mutation in human disease has not been reported. OBJECTIVE: We aimed to investigate the molecular pathogenesis of a PLCG1 activating variant in a patient with immune dysregulation. METHODS: Whole exome sequencing was used to identify the patient's pathogenic variants. Bulk RNA sequencing, single-cell RNA sequencing, quantitative PCR, cytometry by time of flight, immunoblotting, flow cytometry, luciferase assay, IP-One ELISA, calcium flux assay, and cytokine measurements in patient PBMCs and T cells and COS-7 and Jurkat cell lines were used to define inflammatory signatures and assess the impact of the PLCG1 variant on protein function and immune signaling. RESULTS: We identified a novel and de novo heterozygous PLCG1 variant, p.S1021F, in a patient presenting with early-onset immune dysregulation disease. We demonstrated that the S1021F variant is a gain-of-function variant, leading to increased inositol-1,4,5-trisphosphate production, intracellular Ca2+ release, and increased phosphorylation of extracellular signal-related kinase, p65, and p38. The transcriptome and protein expression at the single-cell level revealed exacerbated inflammatory responses in the patient's T cells and monocytes. The PLCG1 activating variant resulted in enhanced NF-κB and type II interferon pathways in T cells, and hyperactivated NF-κB and type I interferon pathways in monocytes. Treatment with either PLCγ1 inhibitor or Janus kinase inhibitor reversed the upregulated gene expression profile in vitro. CONCLUSIONS: Our study highlights the critical role of PLCγ1 in maintaining immune homeostasis. We illustrate immune dysregulation as a consequence of PLCγ1 activation and provide insight into therapeutic targeting of PLCγ1.


Assuntos
Mutação com Ganho de Função , NF-kappa B , Humanos , NF-kappa B/metabolismo , Transdução de Sinais , Proteínas Quinases Ativadas por Mitógeno/genética , Fosforilação , Fosfolipase C gama/genética
7.
J Environ Sci (China) ; 142: 33-42, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38527894

RESUMO

Biotoxicity assessment results of environmental waters largely depend on the sample extraction protocols that enrich pollutants to meet the effect-trigger thresholds of bioassays. However, more chemical mixture does not necessarily translate to higher combined biotoxicity. Thus, there is a need to establish the link between chemical extracting efficiency and biotoxicity outcome to standardize extraction methods for biotoxicity assessment of environmental waters. This study compares the performance of five different extraction phases in solid phase extraction (SPE), namely HLB, HLB+Coconut, C18 cartridge, C18 disk and Strata-X, and evaluated their chemical extracting efficiencies and biotoxicity outcomes. We quantitatively assessed cytotoxicity, acute toxicity, genotoxicity, estrogenic activity, and neurotoxicity of the extracts using in vitro bioassays and characterized the chemical extracting efficiencies of the SPE methods through chemical recoveries of 23 model compounds with different polarities and total organic carbon. Using Pareto ranking, we identified HLB+Coconut as the optimal SPE method, which exhibited the highest level of water sample biotoxicity and recovered the most chemicals in water samples. We found that the biotoxicity outcomes of the extracted water samples significantly and positively correlated with the chemical extracting efficiencies of the SPE methods. Moreover, we observed synchronous changing patterns in biotoxicity outcome and chemical extracting efficiencies in response to increasing sample volumes per cartridge (SVPC) during SPE. Our findings underscore that higher chemical extracting efficiency of SPE corresponds to higher biotoxicity outcome of environmental water samples, providing a scientific basis for standardization of SPE methods for adequate assessment of biotoxicities of environmental waters.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Águas Residuárias/toxicidade , Água/química , Extração em Fase Sólida/métodos , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise
8.
J Clin Immunol ; 43(4): 835-845, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36807221

RESUMO

PURPOSE: Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. METHODS: A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. RESULTS: Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. CONCLUSION: To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.


Assuntos
Adenosina Desaminase , Peptídeos e Proteínas de Sinalização Intercelular , Humanos , Adenosina Desaminase/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Estudos de Coortes , Estudos Retrospectivos , Mutação
9.
Small ; 19(21): e2300175, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36843265

RESUMO

The construction of a protective layer for stabilizing anion redox reaction is the key to obtaining long cycling stability for Li-rich Mn-based cathode materials. However, the protection of the exposed surface/interface of the primary particles inside the secondary particles is usually ignored and difficult, let alone the investigation of the impact of the surface engineering of the internal primary particles on the cycling stability. In this work, an efficient method to regulate cycling stability is proposed by simply adjusting the distribution state of the boron nickel complexes coating layer. Theoretical calculation and experimental results display that the full-surface boron nickel complexes coating layer can not only passivate the activity of interface oxygen and improve its stability but also play the role of sharing voltage and protective layer to gradually activate the oxygen redox reaction during cycling. As a result, the elaborately designed cobalt-free Li-rich Mn-based cathode displays the highest discharge-specific capacity retentions of 91.1% after 400 cycles at 1 C and 94.3% even after 800 cycles at 5 C. In particular, the regulation strategy has well universality and is suitable for other high-capacity Li-rich cathode materials.

10.
Small ; 19(47): e2303256, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37501313

RESUMO

High-capacity Li-rich layered oxides (LLOs) suffer from severe structure degradation due to the utilization of hybrid anion- and cation-redox activity. The native post-cycled structure, composed of progressively densified defective spinel layer (DSL) and intrinsic cations mixing, is deemed as the hindrance of the rapid and reversible de/intercalation of Li+ . Herein, the artificial post-cycled structure consisting of artificial DSL and inner cations mixing is in situ constructed, which would act as a shield against the irreversible oxygen emission and undesirable transition metal migration by suppressing anion redox activity and modulating cation mixing. Eventually, the modified DSL-2% Li-rich cathode demonstrates remarkable electrochemical properties with a high discharge capacity of 187 mAh g-1 after 500 cycles at 2 C, and improved voltage stability. Even under harsh operating conditions of 50 °C, DSL-2% can provide a high discharge capacity of 168 mAh g-1 after 250 cycles at 2 C, which is much higher than that of pristine LLO (92 mAh g-1 ). Furthermore, the artificial post-cycled structure provides a novel perspective on the role of native post-cycled structure in sustaining the lattice structure of the lithium-depleted region and also provides an insightful universal design principle for highly stable intercalated materials with anionic redox activity.

11.
Sensors (Basel) ; 23(4)2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36850840

RESUMO

Value chain collaboration management is an effective means for enterprises to reduce costs and increase efficiency to enhance competitiveness. Vertical and horizontal collaboration have received much attention, but the current collaboration model combining the two is weak in terms of task assignment and node collaboration constraints in the whole production-distribution process. Therefore, in the enterprise dynamic alliance, this paper models the MVC (multi-value-chain) collaboration process for the optimization needs of the MVC collaboration network in production-distribution and other aspects. Then a MVC collaboration network optimization model is constructed with the lowest total production-distribution cost as the optimization objective and with the delivery cycle and task quantity as the constraints. For the high-dimensional characteristics of the decision space in the multi-task, multi-production end, multi-distribution end, and multi-level inventory production-distribution scenario, a genetic algorithm is used to solve the MVC collaboration network optimization model and solve the problem of difficult collaboration of MVC collaboration network nodes by adjusting the constraints among genes. In view of the multi-level characteristics of the production-distribution scenario, two chromosome coding methods are proposed: staged coding and integrated coding. Moreover, an algorithm ERGA (enhanced roulette genetic algorithm) is proposed with enhanced elite retention based on a SGA (simple genetic algorithm). The comparative experiment results of SGA, SEGA (strengthen elitist genetic algorithm), ERGA, and the analysis of the population evolution process show that ERGA is superior to SGA and SEGA in terms of time cost and optimization results through the reasonable combination of coding methods and selection operators. Furthermore, ERGA has higher generality and can be adapted to solve MVC collaboration network optimization models in different production-distribution environments.

12.
Zhonghua Nan Ke Xue ; 29(3): 275-281, 2023 Mar.
Artigo em Zh | MEDLINE | ID: mdl-38597711

RESUMO

Prostate cancer (PCa) is one of the most common tumors of the male urogenital system, ranking the second among male malignancies worldwide. Age is a major risk factor for PCa, and population aging leads to an increasing incidence of the malignancy. Androgen-deprivation therapy (ADT) is currently the first-line treatment of PCa, but with the advance of the tumor, many of the patients become resistant to ADT and develop castration-resistant prostate cancer (CRPC), which marks a transition of PCa to a hormone-refractory state associated with a poor prognosis. Metastatic CRPC (mCRPC) is the terminal stage of the disease and a leading cause of death. Despite many new advances in the treatment of mCRPC, its prognosis remains poor. For patients with mCRPC, classical treatment options with chemotherapy and androgen-blocking agents have limited survival benefit, and radionuclide therapy has become a novel therapeutic option for mCRPC. This paper focuses on the development of the radionuclide therapy for mCRPC in recent years.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Androgênios/uso terapêutico , Prognóstico , Radioisótopos/uso terapêutico
13.
Zhonghua Nan Ke Xue ; 29(4): 364-368, 2023 Apr.
Artigo em Zh | MEDLINE | ID: mdl-38598223

RESUMO

Erectile dysfunction (ED) is the inability of men to consistently obtain and maintain sufficient penile erections to complete a satisfactory sex activity, significantly affecting men's quality of life. In recent years, a large number of studies have shown that low-intensity extracorporeal shock wave therapy (Li-ESWT) may improve erectile function by inducing angiogenesis and reversing the pathological process of the erectile tissue, and is a safe, effective and tolerable method for the treatment of vascular ED. This article reviews the pathophysiological mechanism and clinical application of Li-ESWT in the treatment of ED.


Assuntos
Disfunção Erétil , Tratamento por Ondas de Choque Extracorpóreas , Masculino , Humanos , Disfunção Erétil/terapia , Qualidade de Vida , Comportamento Sexual
14.
Zhonghua Nan Ke Xue ; 29(10): 910-915, 2023 Oct.
Artigo em Zh | MEDLINE | ID: mdl-38639661

RESUMO

OBJECTIVE: To compare the efficacy and complications of radical surgery (RP) and radical radiotherapy (RRT). METHODS: The clinical data of patients diagnosed with localized prostate cancer in General Hospital of Eastern Theater Command with RP and RRT from January 2015 to December 2019, Observed and recorded patient preoperative and postoperative PSA levels, biochemical Relapse-free Survival and clinical Relapse-free Survival,and the occurrence of hematuria, urinary incontinence, erectile dysfunction, ankylurethria, diarrhea, hemoproctia and radiocystitis. RESULTS: A total of 150 patients with localized prostate cancer were included in this study, including 105 patients with RP and 45 patients undergoing RRT. There was no significant difference between the complication rates of hematuria, urinary incontinence, erectile dysfunction and ankylurethria(P>0.05).Patients in the RRT group had higher rates of diarrhea(20.00% vs 2.86%), hemoproctia(15.56% vs 1.90%) and radiocystitis(13.33% vs 0%) than those in the RP group, with significant differences (P<0.05). The 5-year bRFS was lower than that in the RP group (95.1% vs 90.7%), with no statistical significance (P=0.832); the 5-year cRFS in the RP group was lower than that in the RRT group (91.2% vs 89.6%), with no significant difference (P=0.971). CONCLUSION: The incidence of diarrhea, hemoproctia and radiocystitis was lower in the RP group than in the RRT group, and the recurrence-free survival was not significantly different between the two groups.


Assuntos
Disfunção Erétil , Neoplasias da Próstata , Incontinência Urinária , Masculino , Humanos , Disfunção Erétil/etiologia , Hematúria/etiologia , Recidiva Local de Neoplasia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Incontinência Urinária/etiologia , Diarreia/etiologia , Diarreia/cirurgia , Prostatectomia/efeitos adversos , Estudos Retrospectivos
15.
Zhonghua Nan Ke Xue ; 29(3): 239-243, 2023 Mar.
Artigo em Zh | MEDLINE | ID: mdl-38597705

RESUMO

OBJECTIVE: To verify the effect and safety of low-intensity extracorporeal shockwave therapy (Li-ESWT) in improving the symptoms of ED, and provide some reference for further related large-scale clinical trials. METHODS: Twenty-six patients diagnosed with ED received Li-ESWT with an energy of 0.09 mJ/mm2 for 20 minutes once a week for 6 four-week courses. Before and at 3, 6, 9, and 12 months after treatment, we obtained the IIEF-5 and Erectile Hardness Scale (EHS) scores of the patients using questionnaires, recorded the incidence of treatment-related adverse reactions, compared the erectile function of the patients before and after treatment, and evaluated the effect and safety of Li-ESWT in improving ED-related symptoms. RESULTS: Compared with the baseline, the IIEF-5 scores of the patients were significantly increased (P < 0.01) while the EHS scores slightly increased at 3 months after Li-ESWT treatment (P > 0.05), both IIEF-5 and EHS scores were dramatically increased at 6 months (P < 0.01), and both significantly higher than at 3 months. At 9 months, EHS scores remained remarkably higher than the baseline (P < 0.01) although IIEF-5 scores slightly lower than at 6 months. At 12 months, however, IIEF-5 scores decreased, though still significantly higher than the baseline (P < 0.01), and EHS scores became lower than at 6 and 9 months (P < 0.05) but still markedly higher than before treatment (P < 0.05). Adverse reactions observed during the intervention mainly included pruritus (4.35%), pain (2.90%), paresthesia (2.17%), and petechiae/ecchymosis (2.90%). CONCLUSION: Li-ESWT can increase the IIEF-5 and EHS scores and improve the clinical symptoms of ED patients, with a low incidence of adverse reactions during the treatment.


Assuntos
Disfunção Erétil , Tratamento por Ondas de Choque Extracorpóreas , Masculino , Humanos , Disfunção Erétil/terapia , Ereção Peniana , Equimose , Dor , Resultado do Tratamento
16.
Zhonghua Nan Ke Xue ; 29(12): 992-999, 2023 Dec.
Artigo em Zh | MEDLINE | ID: mdl-38639951

RESUMO

OBJECTIVE: To analyze the influential factors of erectile dysfunction (ED) in patients with localized prostate cancer (LPC) after radical surgery. METHODS: The clinical data of 150 male patients diagnosed with LPC and normal erectile function (EF) before surgery admitted to the Department of Urology of the Eastern Theatre General Hospital from January 2021 to January 2023 were retrospectively analyzed. The EF status of the patients 6 months after surgery was assessed using the International Erectile Function Index -5(IIEF-5). Age, Gleason score, PSA level, TNM stage, preoperative International prostatic symptom score (IPSS), preoperative prostate volume, smoking index, alcohol consumption index, educational level, comorbidities, operation mode, and psychosexual state were used as influencing factors to analyze their effects on postoperative ED. RESULTS: Of the 150 patients, 88 had ED and 62 had normal EF. Univariate analysis showed that age, preoperative IPSS, preoperative prostate volume, comorbidities and sexual and psychological status were significantly correlated with postoperative ED. Further multivariate logistic regression analysis showed that age, preoperative prostate volume, comorbidities and sexual and psychological status were independent factors influencing the occurrence of ED after RP in LPC patients. CONCLUSION: The recovery of sexual function of patients with localized prostate cancer after radical surgery is generally poor, and the incidence of ED is high. Its independent influencing factors include age, preoperative prostate volume, comorbidities and sexual psychological state, etc. Correct intervention of different influencing factors is required in clinical work. In order to provide a better diagnosis and treatment scheme for LPC patients undergoing radical treatment, reduce the incidence of postoperative ED and improve the quality of life of patients after surgery.


Assuntos
Disfunção Erétil , Neoplasias da Próstata , Humanos , Masculino , Disfunção Erétil/epidemiologia , Disfunção Erétil/etiologia , Disfunção Erétil/tratamento farmacológico , Qualidade de Vida , Estudos Retrospectivos , Prostatectomia/efeitos adversos , Ereção Peniana , Neoplasias da Próstata/complicações , Neoplasias da Próstata/cirurgia
17.
Proteins ; 90(2): 589-600, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34599611

RESUMO

Transactive response DNA binding protein 43 (TDP-43), an alternative-splicing regulator, can specifically bind long UG-rich RNAs, associated with a range of neurodegenerative diseases. Upon binding RNA, TDP-43 undergoes a large conformational change with two RNA recognition motifs (RRMs) connected by a long linker rearranged, strengthening the binding affinity of TDP-43 with RNA. We extend the equally weighted multiscale elastic network model (ewmENM), including its Gaussian network model (ewmGNM) and Anisotropic network model (ewmANM), with the multiscale effect of interactions considered, to the characterization of the dynamics of binding interactions of TDP-43 and RNA. The results reveal upon RNA binding a loss of flexibility occurs to TDP-43's loop3 segments rich in positively charged residues and C-terminal of high flexibility, suggesting their anchoring RNA, induced fit and conformational adjustment roles in recognizing RNA. Additionally, based on movement coupling analyses, it is found that RNA binding strengthens the interactions among intra-RRM ß-sheets and between RRMs partially through the linker's mediating role, which stabilizes RNA binding interface, facilitating RNA binding efficiency. In addition, utilizing our proposed thermodynamic cycle method combined with ewmGNM, we identify the key residues for RNA binding whose perturbations induce a large change in binding free energy. We identify not only the residues important for specific binding, but also the ones critical for the conformational rearrangement between RRMs. Furthermore, molecular dynamics simulations are also performed to validate and further interpret the ENM-based results. The study demonstrates a useful avenue to utilize ewmENM to investigate the protein-RNA interaction dynamics characteristics.


Assuntos
Proteínas de Ligação a DNA/metabolismo , DNA/metabolismo , Humanos , Ligação Proteica
18.
J Am Chem Soc ; 144(50): 22831-22837, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36417425

RESUMO

Phosphine ligands are the most important class of ligands for cross-coupling reactions due to their unique electronic and steric properties. However, metalloproteins generally rely on nitrogen, sulfur, or oxygen ligands. Here, we report the genetic incorporation of P3BF, which contains a biocompatible borane-protected phosphine, into proteins. This step is followed by a straightforward one-pot strategy to perform deboronation and palladium coordination in aqueous and aerobic conditions. The genetically encoded phosphine ligand P3BF should significantly expand our ability to design functional metalloproteins.


Assuntos
Metaloproteínas , Fosfinas , Metaloproteínas/genética , Metaloproteínas/metabolismo , Ligantes , Paládio
19.
Opt Express ; 30(19): 33603-33612, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36242391

RESUMO

A dynamically reconfigurable liquid crystal (LC) photonic device is an important research field in modern LC photonics. We present a type of continuously tunable distributed Bragg reflector (DBR) based on LC polymer composites modulated via a novel optofluidic method. LC-templated DBR films are fabricated by photopolymerization under visible standing wave interference. The influences of the incident angle, incident light intensity, and content of ethanol as a pore-forming additive on the reflection behavior are discussed in detail. Then, the LC-templated DBR films are integrated into microfluidic channels and reversibly refilled by different organic solvents. The reconfigurable characteristics of optofluidic DBRs were demonstrated by changing the average refractive index (RI) of the mixed liquids and adjusting the flow rates, resulting in the dynamic and continuous variation of the reflection band within a specific visible light band. It is anticipated that the prototype optofluidic LC device will hopefully be applied to some specific scenarios where conventional means of regulation, such as electric, optical, and temperature fields, are unsuitable and possibly boost the development of microfluidic analysis techniques based on structural color.

20.
Entropy (Basel) ; 24(10)2022 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37420380

RESUMO

This paper concentrates on the study of logic-based switching adaptive control. Two different cases will be considered. In the first case, the finite time stabilization problem for a class of nonlinear system is studied. Based on the recently developed adding a barrier power integrator technique, a new logic-based switching adaptive control method is proposed. In contrast with the existing results, finite time stability can be achieved when the considered systems contain both fully unknown nonlinearties and unknown control direction. Moreover, the proposed controller has a very simple structure and no approximation methods, e.g., neural networks/fuzzy logic, are needed. In the second case, the sampled-data control for a class of nonlinear system is investigated. New sampled-data logic-based switching mechanism is proposed. Compared with previous works, the considered nonlinear system has an uncertain linear growth rate. The control parameters and the sampling time can be adjusted adaptively to render the exponential stability of the closed loop system. Applications in robot manipulators are conducted to verify the proposed results.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA