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1.
Biophys J ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38475997

RESUMO

This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been withdrawn at the request of the Editor and Publisher, after being inadvertently published due to an editorial error. This error bears no reflection on the article or its authors. The Publisher apologizes for any inconvenience this may cause.

2.
Biophys J ; 123(13): 1804-1814, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38783604

RESUMO

To realize a low-cost neuromorphic visual system, employing an artificial neuron capable of mimicking the retinal neuron functions is essential. A photoresponsive single transistor neuron composed of a vertical silicon nanowire is proposed. Similar to retinal neurons, various photoresponsive characteristics of the single transistor neuron can be modulated by light intensity as well as wavelength and have a high responsivity to green light like the human eye. The device is designed with a cylindrical surrounding double-gate structure, enclosed by an independently controlled outer gate and inner gate. The outer gate has the function of selectively inhibiting neuron activity, which can mimic lateral inhibition of amacrine cells to ganglion cells, and the inner gate can be utilized for the adjustment of the firing threshold voltage, which can be used to mimic the regulation of photoresponsivity by horizontal cells for adaptive visual perception. Furthermore, a myelination function that controls the speed of information transmission is obtained according to the inherent asymmetric source/drain structure of a vertical silicon nanowire. This work can enable photoresponsive neuronal function using only a single transistor, providing a promising hardware implementation for building miniaturized neuromorphic vision systems at low cost.


Assuntos
Nanofios , Silício , Transistores Eletrônicos , Nanofios/química , Silício/química , Neurônios Retinianos/fisiologia , Luz , Humanos
3.
Breast Cancer Res Treat ; 205(2): 403-411, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38441847

RESUMO

PURPOSE: The recent findings from the DESTINY-Breast04 trial highlighted the clinical importance of distinguishing between HER2 immunohistochemistry (IHC) scores 0 and 1 + in metastatic breast cancer (BC). However, pathologist interpretation of HER2 IHC scoring is subjective, and standardized methodology is needed. We evaluated the consistency of HER2 IHC scoring among pathologists and the accuracy of digital image analysis (DIA) in interpreting HER2 IHC staining in cases of HER2-low BC. METHODS: Fifty whole-slide biopsies of BC with HER2 IHC staining were evaluated, comprising 25 cases originally reported as IHC score 0 and 25 as 1 +. These slides were digitally scanned. Six pathologists with breast expertise independently reviewed and scored the scanned images, and DIA was applied. Agreement among pathologists and concordance between pathologist scores and DIA results were statistically analyzed using Kendall coefficient of concordance (W) tests. RESULTS: Substantial agreement among at least five of the six pathologists was found for 18 of the score 0 cases (72%) and 15 of the score 1 + cases (60%), indicating excellent interobserver agreement (W = 0.828). DIA scores were highly concordant with pathologist scores in 96% of cases (47/49), indicating excellent concordance (W = 0.959). CONCLUSION: Although breast subspecialty pathologists were relatively consistent in evaluating BC with HER2 IHC scores of 0 and 1 +, DIA may be a reliable supplementary tool to enhance the standardization and quantification of HER2 IHC assessment, especially in challenging cases where results may be ambiguous (i.e., scores 0-1 +). These findings hold promise for improving the accuracy and consistency of HER2 testing.


Assuntos
Neoplasias da Mama , Imuno-Histoquímica , Variações Dependentes do Observador , Receptor ErbB-2 , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Feminino , Imuno-Histoquímica/métodos , Reprodutibilidade dos Testes , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Processamento de Imagem Assistida por Computador/métodos
4.
Proc Natl Acad Sci U S A ; 118(44)2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34711680

RESUMO

SrMn2P2 and CaMn2P2 are insulators that adopt the trigonal CaAl2Si2-type structure containing corrugated Mn honeycomb layers. Magnetic susceptibility χ and heat capacity versus temperature T data reveal a weak first-order antiferromagnetic (AFM) transition at the Néel temperature [Formula: see text] K for SrMn2P2 and a strong first-order AFM transition at [Formula: see text] K for CaMn2P2 Both compounds exhibit isotropic and nearly T-independent [Formula: see text], suggesting magnetic structures in which nearest-neighbor moments are aligned at [Formula: see text] to each other. The 31P NMR measurements confirm the strong first-order transition in CaMn2P2 but show critical slowing down above [Formula: see text] for SrMn2P2, thus also evidencing second-order character. The 31P NMR measurements indicate that the AFM structure of CaMn2P2 is commensurate with the lattice whereas that of SrMn2P2 is incommensurate. These first-order AFM transitions are unique among the class of (Ca, Sr, Ba)Mn2 (P, As, Sb, Bi)2 compounds that otherwise exhibit second-order AFM transitions. This result challenges our understanding of the circumstances under which first-order AFM transitions occur.

5.
Breast Cancer Res Treat ; 199(3): 457-469, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37061619

RESUMO

PURPOSE: Neoadjuvant anti-PD-(L)1 therapy improves the pathological complete response (pCR) rate in unselected triple-negative breast cancer (TNBC). Given the potential for long-term morbidity from immune-related adverse events (irAEs), optimizing the risk-benefit ratio for these agents in the curative neoadjuvant setting is important. Suboptimal clinical response to initial neoadjuvant therapy (NAT) is associated with low rates of pCR (2-5%) and may define a patient selection strategy for neoadjuvant immune checkpoint blockade. We conducted a single-arm phase II study of atezolizumab and nab-paclitaxel as the second phase of NAT in patients with doxorubicin and cyclophosphamide (AC)-resistant TNBC (NCT02530489). METHODS: Patients with stage I-III, AC-resistant TNBC, defined as disease progression or a < 80% reduction in tumor volume after 4 cycles of AC, were eligible. Patients received atezolizumab (1200 mg IV, Q3weeks × 4) and nab-paclitaxel (100 mg/m2 IV,Q1 week × 12) as the second phase of NAT before undergoing surgery followed by adjuvant atezolizumab (1200 mg IV, Q3 weeks, × 4). A two-stage Gehan-type design was employed to detect an improvement in pCR/residual cancer burden class I (RCB-I) rate from 5 to 20%. RESULTS: From 2/15/2016 through 1/29/2021, 37 patients with AC-resistant TNBC were enrolled. The pCR/RCB-I rate was 46%. No new safety signals were observed. Seven patients (19%) discontinued atezolizumab due to irAEs. CONCLUSION: This study met its primary endpoint, demonstrating a promising signal of activity in this high-risk population (pCR/RCB-I = 46% vs 5% in historical controls), suggesting that a response-adapted approach to the utilization of neoadjuvant immunotherapy should be considered for further evaluation in a randomized clinical trial.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Antraciclinas/uso terapêutico , Neoplasias de Mama Triplo Negativas/patologia , Terapia Neoadjuvante , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
6.
J Transl Med ; 21(1): 132, 2023 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-36803784

RESUMO

BACKGROUND: Osteosarcoma is the most common malignant tumor in bone and its prognosis has reached a plateau in the past few decades. Recently, metabolic reprogramming has attracted increasing attention in the field of cancer research. In our previous study, P2RX7 has been identified as an oncogene in osteosarcoma. However, whether and how P2RX7 promotes osteosarcoma growth and metastasis through metabolic reprogramming remains unexplored. METHODS: We used CRISPR/Cas9 genome editing technology to establish P2RX7 knockout cell lines. Transcriptomics and metabolomics were performed to explore metabolic reprogramming in osteosarcoma. RT-PCR, western blot and immunofluorescence analyses were used to determine gene expression related to glucose metabolism. Cell cycle and apoptosis were examined by flowcytometry. The capacity of glycolysis and oxidative phosphorylation were assessed by seahorse experiments. PET/CT was carried out to assess glucose uptake in vivo. RESULTS: We demonstrated that P2RX7 significantly promotes glucose metabolism in osteosarcoma via upregulating the expression of genes related to glucose metabolism. Inhibition of glucose metabolism largely abolishes the ability of P2RX7 to promote osteosarcoma progression. Mechanistically, P2RX7 enhances c-Myc stabilization by facilitating nuclear retention and reducing ubiquitination-dependent degradation. Furthermore, P2RX7 promotes osteosarcoma growth and metastasis through metabolic reprogramming in a predominantly c-Myc-dependent manner. CONCLUSIONS: P2RX7 plays a key role in metabolic reprogramming and osteosarcoma progression via increasing c-Myc stability. These findings provide new evidence that P2RX7 might be a potential diagnostic and/or therapeutic target for osteosarcoma. Novel therapeutic strategies targeting metabolic reprogramming appear to hold promise for a breakthrough in the treatment of osteosarcoma.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Osteossarcoma/genética , Osteossarcoma/patologia , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Glucose , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Receptores Purinérgicos P2X7/genética , Receptores Purinérgicos P2X7/metabolismo , Receptores Purinérgicos P2X7/uso terapêutico
7.
J Nanobiotechnology ; 21(1): 27, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36694219

RESUMO

BACKGROUND: Magnetofection-mediated gene delivery shows great therapeutic potential through the regulation of the direction and degree of differentiation. Lumbar degenerative disc disease (DDD) is a serious global orthopaedic problem. However, even though intervertebral fusion is the gold standard for the treatment of DDD, its therapeutic effect is unsatisfactory. Here, we described a novel magnetofection system for delivering therapeutic miRNAs to promote osteogenesis and angiogenesis in patients with lumbar DDD. RESULTS: Co-stimulation with electromagnetic field (EMF) and iron oxide nanoparticles (IONPs) enhanced magnetofection efficiency significantly. Moreover, in vitro, magnetofection of miR-21 into bone marrow mesenchymal stem cells (BMSCs) and human umbilical endothelial cells (HUVECs) influenced their cellular behaviour and promoted osteogenesis and angiogenesis. Then, gene-edited seed cells were planted onto polycaprolactone (PCL) and hydroxyapatite (HA) scaffolds (PCL/HA scaffolds) and evolved into the ideal tissue-engineered bone to promote intervertebral fusion. Finally, our results showed that EMF and polyethyleneimine (PEI)@IONPs were enhancing transfection efficiency by activating the p38 MAPK pathway. CONCLUSION: Our findings illustrate that a magnetofection system for delivering miR-21 into BMSCs and HUVECs promoted osteogenesis and angiogenesis in vitro and in vivo and that magnetofection transfection efficiency improved significantly under the co-stimulation of EMF and IONPs. Moreover, it relied on the activation of p38 MAPK pathway. This magnetofection system could be a promising therapeutic approach for various orthopaedic diseases.


Assuntos
Campos Eletromagnéticos , Degeneração do Disco Intervertebral , MicroRNAs , Osteogênese , Humanos , Diferenciação Celular , Células Endoteliais , Nanopartículas Magnéticas de Óxido de Ferro , MicroRNAs/genética , Osteogênese/genética , Osteogênese/fisiologia , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/terapia
8.
Vet Med (Praha) ; 68(3): 106-115, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37981902

RESUMO

Porcine deltacoronavirus (PDCoV) and porcine sapelovirus (PSV) are two viruses that can cause diarrhoea in pigs and bring great economic loss to the pig industry. In this research, a duplex real-time quantitative polymerase chain reaction (qPCR) assay based on SYBR Green I was developed to simultaneously detect PDCoV and PSV. No specific melting peaks were found in other porcine diarrhoea-associated viruses, indicating that the method developed in this study had good specificity. The detection limits of PDCoV and PSV were 1.0 × 101 copies µl-1 and 1.0 × 102 copies µl-1, respectively. The duplex real-time qPCR assay tested two hundred and three (203) intestinal and faecal samples collected from diarrhoeal and asymptomatic pigs. The positive rates of PDCoV and PSV were 20.2% and 23.2%, respectively. The co-infection rate of PDCoV and PSV was 13.8%. To evaluate the accuracy of the developed method, conventional PCR and singular TaqMan real-time qPCR assays for PDCoV/PSV were also used to detect the samples. The results showed that the duplex real-time qPCR assay was consistent with the singular assays, but its sensitivity was higher than conventional PCR methods. This duplex real-time qPCR assay provides a rapid, sensitive and reliable method in a clinic to simultaneously detect PDCoV and PSV.

9.
J Orthop Traumatol ; 24(1): 28, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37328665

RESUMO

BACKGROUND: Pipkin type III femoral head fractures are relatively rare injuries. Few studies have explored and described the treatment and outcomes of Pipkin type III femoral head fractures. The purpose of this study was to evaluate the efficacy of open reduction and internal fixation (ORIF) in treating Pipkin type III femoral head fractures. METHODS: We retrospectively reviewed 12 patients with Pipkin type III femoral head fractures who underwent ORIF from July 2010 and January 2018. The complications and reoperations were recorded. The visual analog scale (VAS) pain score, Harris hip score (HHS), Thompson-Epstein criteria, and SF-12 score [including the physical component summary (PCS) and the mental component summary (MCS)] were used for functional assessment. RESULTS: Among the 12 patients, ten were males and two were females, with a mean age of 34.2 ± 11.9 years. The median follow-up time was 6 years (range 4-8 years). Five patients (42%) developed osteonecrosis of the femoral head, and one patient (8%) developed nonunion. These six patients (50%) underwent total hip arthroplasty (THA). One patient (8%) developed heterotopic ossification and underwent ectopic bone excision; this patient also presented with post-traumatic arthritis. The mean final VAS pain score and HHS were 4.1 ± 3.1 points and 62.8 ± 24.4 points, respectively. According to the Thompson-Epstein criteria, there was one patient (8%) with excellent, four patients (33%) with good, one patient (8%) with fair, and six patients (50%) with poor outcomes. The PCS score and MCS score were 41.7 ± 34.7 points and 63.2 ± 14.5 points, respectively. CONCLUSION: Limited by the high incidence of osteonecrosis of the femoral head, it is difficult to achieve satisfactory functional outcomes when treating Pipkin type III femoral head fractures using ORIF, and a primary THA may be considered. However, for younger patients, considering the survivorship of prosthesis, ORIF may be recommended with the proviso that the patient is fully informed of the high complication rate associated with this procedure. LEVEL OF EVIDENCE: IV.


Assuntos
Fraturas do Fêmur , Fraturas do Quadril , Osteonecrose , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Cabeça do Fêmur/cirurgia , Cabeça do Fêmur/lesões , Estudos Retrospectivos , Resultado do Tratamento , Fraturas do Fêmur/cirurgia , Fixação Interna de Fraturas/métodos , Dor , Fraturas do Quadril/cirurgia
10.
Biol Reprod ; 106(5): 1011-1021, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35238896

RESUMO

Preeclampsia (PE) is a common pregnancy disorder, and mounting evidence has revealed that circular RNA participates in PE development. However, the detailed molecular mechanism of circ_0007611 in PE progression remains unknown. RNA expressions of circ_0007611, microRNA-558 (miR-558), and IL-1 receptor accessory protein (IL1RAP) were detected by quantitative real-time polymerase chain reaction. Cell proliferation was investigated by clonogenicity, 5-Ethynyl-29-deoxyuridine, and DNA content quantitation assays. Cell apoptotic rate and angiogenesis were analyzed by cell apoptosis and tube formation assays, respectively. Protein expression was detected by western blot. The binding relationship between miR-558 and circ_0007611 or IL1RAP was identified by a dual-luciferase reporter or RNA immunoprecipitation assay. Circ_0007611 and IL1RAP expressions were significantly upregulated, while miR-558 was downregulated in the placental tissues of PE women in comparison with normal placental tissues. Functionally, circ_0007611 overexpression inhibited trophoblast cell proliferation and angiogenesis and induced cell apoptosis; however, circ_0007611 downregulation showed the opposite effects. Mechanistically, circ_0007611 acted as a miR-558 sponge, and miR-558 bound to IL1RAP. Besides, miR-558 overexpression or IL1RAP absence relieved circ_0007611-induced trophoblast cell dysfunction. Moreover, miR-558 contributed to cell proliferation and tube formation and inhibited cell apoptosis by reducing IL1RAP expression in trophoblast cells. Circ_0007611 aggravated trophoblast cell disorders by the miR-558/IL1RAP pathway in PE.


Assuntos
MicroRNAs , Pré-Eclâmpsia , Apoptose/genética , Proliferação de Células/fisiologia , Feminino , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neovascularização Patológica/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Gravidez , Receptores de Interleucina-1/metabolismo , Trofoblastos/metabolismo
11.
New Phytol ; 234(4): 1278-1293, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35224735

RESUMO

Salt tolerance during seed germination is essential for seedling establishment under salt stress. Sirtuin-like proteins, NAD+ -dependent histone deacetylases, are involved in plant responses to abiotic stresses; however, the regulatory mechanism remains unknown. We elucidated the mechanism underlying AtSRT2 (a sirtuin-like protein)-mediated regulation of salt tolerance during seed germination in Arabidopsis. The AtSRT2 mutant srt2 exhibited significantly reduced seed germination percentages under salt stress; its targets were identified via chromatin immunoprecipitation coupled with ultra-high-throughput parallel DNA sequencing (ChIP-Seq) assay. Epistasis analysis was performed to identify AtSRT2-related pathways. Overexpression of SRT2.7, an AtSRT2 splice variant, rescued the salt-sensitive phenotype of mutant srt2. AtSRT2 histone deacetylation activity was important for salt tolerance during seed germination. The acetylation level of histone H4K8 locus in srt2-1 increased significantly under salt treatment. Vesicle-associated membrane protein 714 (VAMP714), a negative regulator of hydrogen peroxide (H2 O2 )-containing vesicle trafficking in cells, was identified as a target of AtSRT2. AtSRT2 regulated histone acetylation in the promoter region of VAMP714 and inhibited VAMP714 transcription under salt treatment. Seed germination percentage of double-mutant srt2-1vamp714 was close to that of single-mutant vamp714, and higher than that of single-mutant srt2 under salt stress. Hydrogen peroxide content and DNA damage increased after salt treatment in srt2 during seed germination. AtSRT2 regulates salt tolerance during seed germination through VAMP714 in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Sirtuínas , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Germinação , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Histonas/metabolismo , Peróxido de Hidrogênio/metabolismo , Proteínas R-SNARE/genética , Tolerância ao Sal/genética , Sementes/metabolismo , Sirtuínas/genética , Sirtuínas/metabolismo , Estresse Fisiológico/genética
12.
Glob Chang Biol ; 28(6): 2066-2080, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34918427

RESUMO

The accurate assessment of the global gross primary productivity (GPP) of vegetation is the key to estimating the global carbon cycle. Temperature (Ts) and soil moisture (SM) are essential for vegetation growth. It is acknowledged that the global Ts has shown an increasing trend, yet SM has shown a decreasing trend. However, the importance of SM and Ts changes on the productivity of global ecosystems remains unclear, as SM and Ts are strongly coupled through soil-atmosphere interactions. Using solar-induced chlorophyll fluorescence (SIF) as a proxy for GPP and by decoupling SM and Ts changes, our investigation shows Ts plays a more important role in SIF in 60% of the vegetation areas. Overall, increased Ts promotes SIF by mitigating the resistance from SM's reduction. However, the importance of SM and Ts varies, given different vegetation types. The results show that in the humid zone, the variation of Ts plays a more important role in SIF, but in the arid and semi-arid zones, the variation of SM plays a more important role; in the semi-humid zone, the disparity in the importance of SM and Ts is difficult to unravel. In addition, our results suggest that SIF is very sensitive to aridity gradients in arid and semi-arid ecosystems. By decoupling the intertwined SM-Ts impact on SIF, our study provides essential evidence that benefits future investigation on the factors the influence ecosystem productivity at regional or global scales.


Assuntos
Ecossistema , Solo , Clorofila , Fluorescência , Fotossíntese , Temperatura
13.
BMC Biotechnol ; 21(1): 5, 2021 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-33422076

RESUMO

BACKGROUND: At present, microorganism has been considered as important factors that threaten to buried pipelines with disbonded coatings. Aiming at the problem of unknown corrosion mechanism of sulfate-reducing bacteria (SRB), a series of studies have been carried out in this paper. Spectrophotometer and fluorescent labeling technology are used to study the growth and attachment of SRB in the simulated soil solution. The corrosion behavior of X80 pipeline steel with or without SRB was researched by electrochemical methods such as open circuit potential, dynamic potential polarization curve, and electrochemical impedance spectroscopy. The microscopic morphology of the corrosion products on the surface was observed with a scanning electron microscope (SEM), and the element content of the corrosion products on the surface of the sample after corrosion was observed using X-ray energy spectrum (EDS) analysis. RESULTS: The results showed that the growth and reproduction of SRB caused the pH of the soil simulated solution to increase, which may promote the corrosion of X80 steel. In addition, the cathode reaction of X80 steel in a sterile environment is the reduction of H+, and the main corrosion product is iron oxide. When the soil simulation solution contains SRB, the cathodic reaction is controlled by both H+ reduction and sulfide depolarization reactions, and FeS appears in the corrosion products. CONCLUSION: Although the life cycle of SRB is only about 14 days, the corrosion of X80 steel is greatly promoted by SRB, and even causes corrosion perforation, which will bring huge economic losses and serious safety hazards.


Assuntos
Bactérias/metabolismo , Aço/química , Sulfatos/metabolismo , Corrosão , Técnicas Eletroquímicas , Eletroquímica , Compostos Férricos , Solo , Microbiologia do Solo
14.
Nat Chem Biol ; 15(12): 1223-1231, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31659317

RESUMO

PARP1 inhibitors (PARPi) are known to kill tumor cells via two mechanisms (PARP1 catalytic inhibition and PARP1 trapping). The relative contribution of these two pathways in mediating the cytotoxicity of PARPi, however, is not well understood. Here we designed a series of small molecule PARP degraders. Treatment with one such compound iRucaparib-AP6 results in highly efficient and specific PARP1 degradation. iRucaparib-AP6 blocks the enzymatic activity of PARP1 in vitro, and PARP1-mediated poly-ADP-ribosylation signaling in intact cells. This strategy mimics PARP1 genetic depletion, which enables the pharmacological decoupling of PARP1 inhibition from PARP1 trapping. Finally, by depleting PARP1, iRucaparib-AP6 protects muscle cells and primary cardiomyocytes from DNA-damage-induced energy crisis and cell death. In summary, these compounds represent 'non-trapping' PARP1 degraders that block both the catalytic activity and scaffolding effects of PARP1, providing an ideal approach for the amelioration of the various pathological conditions caused by PARP1 hyperactivation.


Assuntos
Poli(ADP-Ribose) Polimerase-1/metabolismo , Animais , Humanos , Camundongos , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Proteólise
15.
BMC Musculoskelet Disord ; 22(1): 660, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362341

RESUMO

BACKGROUND: The purpose of this study was to investigate the efficacy of gelatin sponge impregnated with ropivacaine on postoperative pain after transforaminal lumbar interbody fusion (TLIF) in patients with lumbar degenerative diseases. METHODS: We retrospectively reviewed patients who underwent TLIF in our department between August 2018 and January 2020. Patients were divided to ropivacaine group and saline group. A ropivacaine group whom received gelatin sponge impregnated with ropivacaine during operation, and a saline group whom were intraoperatively administered by gelatin sponge impregnated with saline. The two groups were compared in reference to postoperative hospital stay, postoperative complications and visual analog scale (VAS) scores. The consumption of postoperative diclofenac sodium suppository use was also recorded. The Oswestry Disability Index (ODI) scores and Japanese Orthopedic Association (JOA) scores were used for functional evaluation at 1 year postoperatively. RESULT: A total of 127 patients were evaluated in this retrospective study. The mean postoperative hospital stay in the ropivacaine group was significantly lower than saline group. The VAS score was significantly lower in patients receiving gelatin sponge impregnated with ropivacaine as compared with patients in saline group on postoperative day 1, 2, 3 and 4. The number of patients who need the administration of diclofenac sodium suppository and the mean consumption of postoperative diclofenac sodium suppository was significantly lower in the ropivacaine group as compared with saline group. CONCLUSION: The application of gelatin sponge impregnated with ropivacaine around the nerve root in patients undergoing TLIF can effectively control the postoperative pain and reduce postoperative hospital stay.


Assuntos
Gelatina , Fusão Vertebral , Humanos , Vértebras Lombares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Estudos Retrospectivos , Ropivacaina , Fusão Vertebral/efeitos adversos , Resultado do Tratamento
16.
Zhongguo Zhong Yao Za Zhi ; 46(6): 1410-1416, 2021 Mar.
Artigo em Zh | MEDLINE | ID: mdl-33787139

RESUMO

The extract rates, multicomponent content and fingerprint were determined in this study to investigate the quality diffe-rence between standard decoction of raw Paeoniae Radix Alba and fried Paeoniae Radix Alba. UPLC fingerprint was established for 17 batches of standard decoction of raw and fried Paeoniae Radix Alba, and the contents of gallic acid, catechin, albiflorin, paeoniflorin and benzoyl paeoniflorin were determined. The peak areas of standard decoction were analyzed by the independent t-test and orthogonal partial least squares discriminant analysis. There was no significant difference in extract rates between the standard decoction of raw and fried Paeoniae Radix Alba. After fried processing, the content of albiflorin increased by 0.26%, while the contents of gallic acid, catechin, paeoniflorin and benzoyl paeoniflorin decreased by 13.04%, 27.97%, 10.30% and 18.79% respectively. There were 14 common peaks in the fingerprint of standard decoction of raw Paeoniae Radix Alba, and 16 common peaks in the fried Paeoniae Radix Alba. Peak 1 and peak 3 were new ones after processing, among which the peak 3 was 5-hydroxymethylfurfural. The results showed that peak 1, peak 3, peak 11 and peak 15 were the key compounds to distinguish standard decoction of raw and fried Paeoniae Radix Alba. In conclusion, this method is stable and can be used for the study of quantity transfer and quality control in the preparation process of standard decoction, granules and other dosage forms for raw and fried Paeoniae Radix Alba, providing reference for the identification of raw and fried Paeoniae Radix Alba and related preparations.


Assuntos
Medicamentos de Ervas Chinesas , Paeonia , Cromatografia Líquida de Alta Pressão , Controle de Qualidade , Padrões de Referência
17.
Am J Transplant ; 20(1): 52-63, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31355483

RESUMO

IL-10+ regulatory B cells (Bregs) inhibit immune responses in various settings. While Bregs appear to inhibit inflammatory cytokine expression by CD4+ T cells and innate immune cells, their reported impact on CD8+ T cells is contradictory. Moreover, it remains unclear which effects of Bregs are direct versus indirect. Finally, the subanatomical localization of Breg suppressive function and the nature of their intercellular interactions remain unknown. Using novel tamoxifen-inducible B cell-specific IL-10 knockout mice, we found that Bregs inhibit CD8+ T cell proliferation and inhibit inflammatory cytokine expression by both CD4+ and CD8+ T cells. Sort-purified Bregs from IL-10-reporter mice were adoptively transferred into wild-type hosts and examined by live-cell imaging. Bregs localized to the T:B border, specifically entered the T cell zone, and made more frequent and longer contacts with both CD4+ and CD8+ T cells than did non-Bregs. These Breg:T cell interactions were antigen-specific and reduced subsequent T:DC contacts. Thus, Bregs inhibit T cells through direct cognate interactions that subsequently reduce DC:T cell interactions.


Assuntos
Linfócitos B Reguladores/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Comunicação Celular , Células Dendríticas/imunologia , Interleucina-10/fisiologia , Linfócitos T Reguladores/imunologia , Animais , Linfócitos B Reguladores/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Células Dendríticas/metabolismo , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Interleucina-10/metabolismo , Linfócitos T Reguladores/metabolismo
18.
Waste Manag Res ; 38(11): 1295-1300, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32308154

RESUMO

Residual electrolyte is the main pollution source in the lithium ion battery disassembly process. A practical detoxified approach is studied using the lithium hexafluorophosphate in the decommissioned power battery with dimethyl carbonate as a solvent. The pH measurement, Fourier transform infrared spectroscopy, micromorphology and phase structure characterization techniques showed that the process in this study is capable of removing lithium hexafluorophosphate from decommissioned power batteries, while controlling the proper ratio of NaOH can also completely precipitate F- into CaF2 crystal and allows recycling of the organic solvents. This process scheme of residual electrolyte treatment effectively reduces environmental pollution during the decommissioned power batteries recycling process, and has the benefit of resource reuse for valuable elements.


Assuntos
Fontes de Energia Elétrica , Lítio , Eletrólitos , Reciclagem , Solventes
20.
Nanotechnology ; 30(36): 365202, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31151116

RESUMO

We demonstrate the possibility of designing plasmonic structures that extend, and even further concentrate the field enhancement in the feed-gap region of single-layer Au bowtie nanoantennas (BNAs) hundreds of nanometers away from the initial metal-dielectric interface. The design is based on a stack of Au BNAs with progressively reduced gap distances sandwiched by thin dielectric layers. We find that this stacked BNA geometry also behaves as a near-field focusing lens of nanometer focal length. By merely controlling the number of BNAs in a stack and thickness of the accompanying dielectric layers, we show that the usual fast-damping field enhancement right above a 50 nm thick base BNA can be relayed and maintained at >104 over a distance of at least up to 200 nm above the base BNA surface. Our novel plasmonic structures offer an approach to design plasmonic nanostructures for applications in metamaterial engineering, SERS, and nonlinear optics.

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