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1.
Int J Hyperthermia ; 40(1): 2165728, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36653176

RESUMO

PURPOSE: To determine the effects of tract embolization with gelatin sponge particles on the prevention of pneumothorax after percutaneous microwave ablation (MWA) in rabbit lungs. MATERIALS AND METHODS: Twenty-four New Zealand white rabbits were randomly divided into Group A (MWA followed by tract embolization with gelatin sponge particles, n = 12) and Group B (MWA without tract embolization, n = 12). For each group, CT images were reviewed for the occurrence of pneumothorax within 30 min after MWA. The rate of pneumothorax was compared by Chi-square Test. Lung tissue around the needle tract was harvested after the rabbits were euthanized, and histopathological examinations were performed and studied with hematoxylin and eosin stains. RESULTS: Twenty-four animals underwent 47 sessions of MWA (24 sessions in Group A and 23 sessions in Group B). Group A had a statistically lower rate of pneumothorax than Group B (25.0 vs. 56.5%; p = 0.028). The pathological examinations of both groups demonstrated thermal injury of the needle tract characterized by a rim of the coagulated lung parenchyma, which might be responsible for pneumothorax after MWA. Gelatin sponge particles could be arranged in irregular flakes densely to effectively seal the needle tract, thus reducing the occurrence of pneumothorax. The gelatin sponge particles could be almost completely absorbed about 14 days later. CONCLUSION: Results of the present study showed needle tract embolization with gelatin sponge particles after CT-guided pulmonary MWA can significantly reduce the incidence of pneumothorax. Gelatin sponge particles can effectively seal the needle tract after ablation and can be completely absorbed in the body with good safety.


Assuntos
Ablação por Cateter , Neoplasias Pulmonares , Pneumotórax , Animais , Coelhos , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Gelatina , Pulmão/cirurgia , Pulmão/patologia , Neoplasias Pulmonares/cirurgia , Micro-Ondas/uso terapêutico , Pneumotórax/etiologia , Pneumotórax/patologia , Estudos Retrospectivos
2.
Neuroimmunomodulation ; : 1-14, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36599309

RESUMO

INTRODUCTION: Inflammation in early life is a risk factor for the development of neuropsychiatric diseases later in adolescence and adulthood, yet the underlying mechanism remains elusive. In the present study, we performed an integrated proteomic and phosphoproteomic analysis of the hippocampus to identify potential molecular mechanisms of early life inflammation-induced cognitive impairment. METHODS: Both female and male mice received a single intraperitoneal injection of 100 µg/kg lipopolysaccharide (LPS) on postnatal day 10 (P10). Behavioral tests, including open field, elevated plus-maze, and Y-maze tests, were performed on P39, P40, and P41, respectively. After behavioral tests, male mice were sacrificed. The whole brain tissues and the hippocampi were harvested on P42 for proteomic, phosphoproteomic, Western blot, and Golgi staining. RESULTS: Early life LPS exposure induced cognitive impairment in male mice but not in female mice, as assessed by the Y-maze test. Therefore, following biochemical tests were conducted on male mice. By proteomic analysis, 13 proteins in LPS group exhibited differential expression. Among these, 9 proteins were upregulated and 4 proteins were downregulated. For phosphoproteomic analysis, a total of 518 phosphopeptides were identified, of which 316 phosphopeptides were upregulated and 202 phosphopeptides were downregulated in the LPS group compared with the control group. Furthermore, KEGG analysis indicated that early life LPS exposure affected the glutamatergic synapse and neuroactive ligand-receptor interaction, which were associated with synaptic function and energy metabolism. Increased level of brain protein i3 (Bri3), decreased levels of PSD-95 and mGLUR5, and dendritic spine loss after early life LPS exposure further confirmed the findings of proteomic and phosphoproteomic analysis. CONCLUSIONS: Our findings demonstrated that neuroinflammation and impaired synapse may be involved in early life inflammation-induced cognitive impairment. Future studies are required to confirm our preliminary results.

3.
Mol Psychiatry ; 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36690792

RESUMO

Long-term sequelae clustering phenotypes are important for precise health care management in COVID-19 survivors. We reported findings for 1000 survivors 20 months after diagnosis of COVID-19 in a community-based cohort in China. Sequelae symptoms were collected from a validated questionnaire covering 27 symptoms involved in five organ systems including self-reported physical condition, dyspnea, cognitive function and mental health. The generalized symptoms were reported with the highest rate (60.7%), followed by the mental (48.3%), cardiopulmonary (39.8%), neurological (37.1%; cognitive impairment, 15.6%), and digestive symptoms (19.1%). Four clusters were identified by latent class analysis: 44.9% no or mild group (cluster 1), 29.2% moderate group with mainly physical impairment (cluster 2), 9.6% moderate group with mainly cognitive and mental health impairment (cluster 3), and 16.3% severe group (cluster 4). Physical comorbidities or history of mental disorders, longer hospitalization periods and severe acute illness predicted severe group. For moderate group, adults less than 60 years, with physical comorbidities and severe acute illness were more likely to have physical symptoms, while adult women with longer hospitalization stays had increased risk of cognitive and mental health impairment. Overall, among more than half of community COVID-19 survivors who presented moderate or severe sequelae 20 months after recovery, three-tenth had physical vulnerability that may require physical therapy aiming to improve functioning, one-tenth mental or cognitive vulnerable cases need psychotherapy and cognitive rehabilitation, and one-sixth severe group needs multidisciplinary clinical management. The remaining half is free to clinical intervention. Our findings introduced an important framework to map numerous symptoms to precise classification of the clinical sequelae phenotype and provide information to guide future stratified recovery interventions.

4.
Environ Sci Technol ; 2023 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36617724

RESUMO

Electrochemical reduction (ER) is a promising approach to safely remove pollutants. However, sluggish reaction kinetics and significant side reactions considerably limit the applicability of this green process. Herein, we uncovered the previously ignored role of interfacial hydrophilicity in determining the ER performance through electron microscopy observations, contact angle (CA) analysis, and electrochemical measurements. A Pd/C electrocatalyst forms dense nanopores on the electrode surface, rendering it highly hydrophobic and achieving a CA of up to 145°. This imposes a large mass-transfer barrier for the diffusion of water and pollutants into Pd sites. Moreover, the release of H2 is suppressed, which changes the solid-liquid (Pd-polluted water) interface into a solid-gas (H2)-liquid interface. This further slows down mass transfer and the decontamination process. This dilemma can be easily alleviated by adding hydrophilic polymers like polyethylene glycol to increase hydrophilicity and improve mass transfer. By this way, the activity and Faraday efficiency of Pd/C in the electrochemical hydrodehalogenation of 2,4-dichlorophenol could be increased by 4-5 times. Moreover, this interfacial microenvironment modulation strategy is parallel to other approaches, such as Pd structural engineering, and therefore these strategies can be combined to further increase the electrochemical decontamination performance of electrocatalysts.

5.
ACS Nano ; 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36622112

RESUMO

Directly integrating the bifunctional photoelectrode into Li-O2 batteries has been considered an effective way to reduce the overpotential and promote electric energy saving. However, more regular investigations on various bifunctional photocatalysts have still been desired for high-performance photoassisted Li-O2 batteries. Herein, a systematic exploration of various-sized siloxene photocatalysts affected by Li-O2 batteries has been introduced. Compared with the utilization of larger-sized siloxene nanosheets (SNSs), the photoassisted Li-O2 battery with a siloxene quantum dot (SQD) photoelectrode delivers a superior round-trip efficiency of 230% based on the highest discharge potential up to 3.72 V and lowest charge potential of 1.60 V and enables the maintenance of a long-term cycling life with only 13% efficiency attenuation after 200 cycles at 0.075 mA/cm2. Furthermore, this system exhibits a record-high rate-cycling performance (162% round-trip efficiency, even at 3 mA/cm2) and a high discharge capacity of 2212 mAh/g at 1 mA/cm2. These ground-breaking performances could be attributed to the synergistic effect of the photocatalytic and electrocatalytic activities of SQD photocatalysts with the ideal conduction band/valence band values, the abundant defective sites, and the stronger O2 and lower LiO2 adsorption strengths of SQD photocatalysts. These systematic research studies highlight the significance of SQD bifunctional photocatalysts and could be extended to other photocatalysts for further high-efficiency photoelectric conversion and storage.

6.
Integr Cancer Ther ; 22: 15347354221147499, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36625232

RESUMO

BACKGROUND: At present, simple reminiscence has been widely used in the field of neurocognitive disorders, life review/life review therapy has been widely used in the field of cancer, and both simple reminiscence and life review/life review therapy are suitable for psychological disorders such as depression and anxiety. However, the efficacy of reminiscence in treating cancer-related symptom has not been fully assessed. OBJECTIVES: To evaluate the effect of reminiscence therapy (RT) on relieving cancer-related symptoms such as anxiety and depression in cancer survivals. METHODS: China National Knowledge Infrastructure (CNKI), VIP database, Wanfang Data Knowledge Service Platform, China Biomedical Database, PubMed, Cochrane Library, Embase, EBSCO, Scopus, and Ovid databases were searched. To collect clinical randomized controlled trials (RCT) on RT and cancer-related studies published from the establishment of the database to October 05, 2021. Two researchers independently evaluated the articles that met the inclusion criteria, meta-analysis was performed using RevMan5.4 software. RESULTS: A total of 20 RCTs published in 2010 to 2021 were included, with a total of 1853 cancer patients. Meta-analysis results showed that the anxiety scale (HADS-A and HAMA and SAS) and depression scale (HADS-D and HAMD and SDS) scores of the RT group were significantly lower than those of the control group (HADS-A: P = .0002; HAMA: P < .00001; SAS: P = .0010; HADS-D: P = .01; HAMD: P < .00001; SDS: P = .0001). Meta-analysis results showed that RT can improve overall quality of life of cancer patients of RT group to a certain extent hope (P < .00001). Meta-analysis results showed that the scores on the hope and dignity were significantly increased, and the difference were statistically significant (P < .001). CONCLUSION: This review indicates that RT has significant efficacy on cancer-related symptoms such as anxiety and depression. RT for cancer survivals can effectively improve quality of life, self-hope, and self-esteem. The findings of this meta-analysis can provide direction for future symptom management research.


Assuntos
Ansiedade , Neoplasias , Humanos , Ansiedade/etiologia , Ansiedade/terapia , Transtornos de Ansiedade , Neoplasias/terapia , Neoplasias/psicologia , China , Depressão/etiologia , Depressão/terapia
7.
BMC Psychiatry ; 23(1): 17, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624454

RESUMO

BACKGROUND: Maladaptation of the HPA (hypothalamic-pituitary-adrenal) axis plays an important role in depression-like behaviour, but the specific molecular mechanisms are unknown. Here, we determined the roles of CRHR1 (corticotrophin releasing hormone receptor 1) and nectin3 in LPS (lipopolysaccharide)-induced depression-like behaviour in mice. METHODS: C57BL/6 male mice were intraperitoneally injected with LPS (0.83 g/kg), and the open field, novelty-suppressed feeding, forced swimming, and tail suspension tests were performed after intraperitoneal injections of saline or antalarmin (20 mg/kg). The hippocampal mRNA levels of CRHR1 and nectin3 were determined by quantitative reverse transcription-PCR. The hippocampal protein levels of CRHR1, nectin3, and calbindin were measured by western blotting. The CORT (corticosterone) levels in the blood were measured by ELISA kits. RESULTS: Antalarmin alleviated LPS-induced depression-like behaviour in male mice. Furthermore, antalarmin significantly inhibited changes in CRHR1, nectin3 and calbindin levels in the hippocampus and reduced the increase in CORT levels in LPS-treated mice. CONCLUSION: CRHR1antagonist showed antidepressant effects in LPS-induced depressive mice, and CRHR1/nectin3 signalling may play a crucial role in this process.


Assuntos
Depressão , Receptores de Hormônio Liberador da Corticotropina , Animais , Masculino , Camundongos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Modelos Animais de Doenças , Hipocampo , Sistema Hipotálamo-Hipofisário/metabolismo , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Sistema Hipófise-Suprarrenal/metabolismo , Receptores de Hormônio Liberador da Corticotropina/antagonistas & inibidores
8.
IUCrJ ; 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36692859

RESUMO

Multicomponent crystals of a chiral drug with non-chiral components have attracted increasing attention in the application of enantiomer purification and regulation of the physicochemical properties of crystalline materials. Crystalline solid solutions provide opportunities for fine-tuning material properties because of continuously adjustable component stoichiometry ratios. The synthesis, crystal structure, thermodynamics and solid-state enantioselectivity of a series of multicomponent crystals of chiral dihydromyricetin (DMY) with caffeine (CAF) or theophylline (THE) were investigated and the results reveal how the subtle change of molecular structure of the coformer dictates the enantiomer selectivity in multicomponent cocrystals. A series of multicomponent cocrystal solvates of chiral DMY with CAF and THE were synthesized by the slurry cocrystallization method in acetonitrile. Although most racemic mixtures crystallize as racemic compounds or conglomerates, both DMY-CAF and DMY-THE crystallize as chiral solid solutions, unveiled by pseudo-binary melt phase diagrams and pseudo-ternary solution phase diagrams. Crystal structures of Rac-DMY-CAF, R,R-DMY-CAF, Rac-DMY-THE and R,R-DMY-THE are reported for the first time via single-crystal X-ray diffraction, displaying two distinct types of solid solution differing in mixing scale of enantiomers spanning several orders of magnitude. Surprisingly, this remarkable impact on enantiomer discrimination was simply achieved by the reduction of a methyl group of CAF to the THE coformer, which was further rationalized from their crystal structures and intermolecular interactions. Collectively, this work has demonstrated that a subtle change in the molecular structure of a coformer can regulate enantioselectivity in crystalline materials, guiding the purification of chiral racemic compounds via the cocrystallization method and the design of solid-solution crystalline materials.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36693010

RESUMO

Nanofibrillated cellulose paper (nanopaper) has gained growing interest as one promising substrate material for paper-based microfluidics, thanks to its ultrasmooth surface, high optical transparency, uniform nanofiber matrix with nanoscale porosity, and tunable chemical properties. Recently, research on nanopaper-based microfluidics has quickly advanced; however, the current technique of patterning microchannels on nanopaper (i.e., 3D printing, spray coating, or manual cutting and sticking), that is fundamental for application development, still has some limitations, such as ease-of-contamination, and more importantly, only enabling millimeter-scale channels. This paper reports a facile process that leverages the simple operations of microembossing with the convenient plastic micro-molds, for the first time, patterning nanopaper microchannels downing to 200 µm, which is 4 times better than the existing methods and is time-saving (<45 mins). We also optimized the patterning parameters and provided one quick look-up table as the guideline for application developments. As proof-of-concept, we first demonstrated two fundamental microfluidic devices on nanopaper, the laminar-mixer and droplet generator, and two functional nanopaper-based analytical devices (NanoPADs) for glucose and Rhodamine B (RhB) sensing based on optical colorimetry and surface-enhanced Raman spectroscopy, respectively. The two NanoPADs showed outstanding performance with low limits of detection (2 mM for glucose and 19fM for RhB), which are 1.25× and 500× fold improvement compared to the previously reported values. This can be attributed to our newly developed highly accurate microchannel patterning process that enables high integration and fine-tunability of the NanoPADs along with the superior optical properties of nanopaper.

10.
Viruses ; 15(1)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36680259

RESUMO

Genital herpes (GH) has become one of the most common sexually transmitted diseases worldwide, and it is spreading rapidly in developing countries. Approximately 90% of GH cases are caused by HSV-2. Therapeutic HSV-2 vaccines are intended for people already infected with HSV-2 with the goal of reducing clinical recurrences and recurrent virus shedding. In our previous work, we evaluated recombinant adenovirus-based vaccines, including rAd-gD2ΔUL25, rAd-ΔUL25, and rAd-gD2, for their potency as prophylactic vaccines. In this study, we evaluated these three vaccines as therapeutic vaccines against acute and recurrent diseases in intravaginal challenged guinea pigs. Compared with the control groups, the recombinant vaccine rAd-gD2ΔUL25 induced a higher titer of the binding antibody, and rAd-gD2 + rAd-ΔUL25 induced a higher titer of the neutralizing antibody. Both rAd-gD2ΔUL25 and rAd-gD2 + rAd-ΔUL25 vaccines significantly enhanced the survival rate by 50% compared to rAd-gD2 and reduced viral replication in the genital tract and recurrent genital skin disease. Our findings provide a new perspective for HSV-2 therapeutic vaccine research and provide a new technique to curtail the increasing spread of HSV-2.


Assuntos
Infecções por Adenoviridae , Vacinas contra Adenovirus , Herpes Genital , Vacinas contra o Vírus do Herpes Simples , Cobaias , Animais , Herpesvirus Humano 2/genética , Adenoviridae/genética , Proteínas do Envelope Viral/genética , Herpes Genital/prevenção & controle , Vacinas Sintéticas/genética , Anticorpos Antivirais
11.
J Org Chem ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36648061

RESUMO

A palladium-catalyzed cyclization coupling of iodoarene-tethered alkynes with cyclobutanone-derived N-tosylhydrazones is reported, providing a convenient and efficient approach to benzofuran-3-cyclobutylidenes. On this basis, spirocyclobutanes can be generated smoothly in an efficient cascade manner by the addition of dienophiles. Good yields and scalability are demonstrated. Sequential intramolecular carbopalladation, palladium-carbene migratory insertion, δ-hydride elimination, and cycloaddition processes are involved.

12.
Leuk Lymphoma ; : 1-12, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36657437

RESUMO

THZ1, a CDK7 inhibitor, has potent antitumor effects in several cancers; however, its role in Acute myeloid leukemia (AML) is unclear. We explored the effects and potential mechanisms of THZ1, alone and in combination with azacitidine (AZA), in AML cells and xenograft models. THZ1 decreased cell viability, induced apoptosis in a dose and time-dependent manner, induced G0/G1 cell cycle arrest, decreased phosphorylated CDK1 and CDK2 expression, and inhibited RNA Pol II phosphorylation at multiple serine sites. The combination of AZA and THZ1 exhibited synergistic antileukemic effects in AML cell lines and primary cells with MCL1 and c-MYC downregulation. Moreover, the combination therapy significantly decreased tumor burden and prolonged animal survival in xenograft mice models. Our data demonstrate that CDK7 inhibition induces the apoptosis of AML cells and exerts a synergistic antileukemia effect with AZA in vitro and in vivo, which supports future exploration of this combination in clinical studies.

13.
Neurosci Lett ; 796: 137049, 2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36608926

RESUMO

BACKGROUND: Elderly patients after surgery are prone to cognitive decline known as postoperative cognitive dysfunction (POCD). Several studies have shown that the microglial activation and the increase of complement protein expression in hippocampus induced by surgery may be related to the pathogenesis of POCD. The purpose of this study was to determine whether microglia and complement system were involved in cognitive dysfunction in aged mice. METHODS: The POCD model was established by exploratory laparotomy in 15-month-old male C57BL/6J mice and animal behavioral tests were performed to test hippocampal-dependent memory capacity. Minocycline was used to suppress the activation of microglia, and complement 3 receptor inhibitor was used to suppress the association between microglia and complement 3. Western blot and immunofluorescence were used to detect the microglial activation, complement protein, and synaptic protein expressions. RESULTS: Operation induced hippocampal-dependent memory impairment (P < 0.01), which was accompanied by microglial activation (P < 0.01). There was also a significant reduction in inhibitory synaptic protein expression in the hippocampus of mice in the surgery group (P < 0.01). However, minocycline, a microglia inhibitor, rescued all the above changes. In addition, C3RI intervention inhibited the phagocytosis of inhibitory synapses by microglia (P < 0.05) and improved the cognitive function of mice (P < 0.01). CONCLUSION: Microglia participate in postoperative cognitive dysfunction by mediating inhibitory synaptic loss through the complement pathway.


Assuntos
Disfunção Cognitiva , Complicações Cognitivas Pós-Operatórias , Masculino , Camundongos , Animais , Complicações Cognitivas Pós-Operatórias/metabolismo , Microglia/metabolismo , Minociclina/farmacologia , Camundongos Endogâmicos C57BL , Hipocampo/metabolismo , Sinapses
14.
Micromachines (Basel) ; 14(1)2023 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36677222

RESUMO

An MEMS resonant accelerometer is a temperature-sensitive device because temperature change affects the intrinsic resonant frequency of the inner silicon beam. Most classic temperature compensation methods, such as algorithm modeling and structure design, have large errors under rapid temperature changing due to the hysteresis of the temperature response of the accelerometer. To address this issue, we propose a novel reservoir computing (RC) structure based on a nonlinear silicon resonator, which is specifically improved for predicting dynamic information that is referred to as the input-output-improved reservoir computing (IOI-RC) algorithm. It combines the polynomial fitting with the RC on the input data mapping ensuring that the system always resides in the rich nonlinear state. Meanwhile, the output layer is also optimized by vector concatenation operation for higher memory capacity. Therefore, the new system has better performance in dynamic temperature compensation. In addition, the method is real-time, with easy hardware implementation that can be integrated with MEMS sensors. The experiment's result showed a 93% improvement in IOI-RC compared to raw data in a temperature range of -20-60 °C. The study confirmed the feasibility of RC in realizing dynamic temperature compensation precisely, which provides a potential real-time online temperature compensation method and a sensor system with edge computing.

15.
Artigo em Inglês | MEDLINE | ID: mdl-36661878

RESUMO

Preexisting hard and soft tissue defects around hopeless teeth can impede the ideal esthetic and functional outcomes of implant therapy. Orthodontic extrusion has been described as a predictable nonsurgical alternative for vertical hard and soft tissue augmentation, commonly through the use of orthodontic brackets on multiple adjacent teeth. This case report describes an alternative technique via orthodontic extrusion, utilizing a digitally designed and milled fixed provisional restoration. The provisional restoration served as an anchor in the forced eruption of a maxillary lateral incisor for the development of a future implant site. Following forced eruption and a subsequent stabilization period, immediate implant placement was successfully completed with a customized healing abutment to preserve the soft tissue architecture. The use of a fixed provisional restoration as an anchor for orthodontic extrusion allows for predictable implant site development while maintaining favorable esthetics throughout the treatment.


Assuntos
Implantes Dentários para Um Único Dente , Implantes Dentários , Humanos , Implantação Dentária Endóssea/métodos , Extrusão Ortodôntica , Maxila , Estética Dentária
16.
Sci Bull (Beijing) ; 68(1): 105-116, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36621433

RESUMO

Predicting climate anomalies months in advance is of tremendous socioeconomic value. Facing both theoretical and practical constraints, this realm of "seasonal prediction" progressed slowly in recent decades. Here we devise an innovative scheme that pushes the boundary of seasonal prediction by recognizing and isolating distinct spatiotemporal footprints left by modes of climate variability that cause varying annual cycles in response to the solar forcing. The predictive power harnessed from these spatiotemporal footprints results in a prediction skill surpassing existing models for seasonal forecasts of eastern China rainfall, which is one of the most challenging seasonal prediction problems. By considering varying annual cycles explicitly, the new scheme is able to predict multi-provincial flood and/or drought occurrences seamlessly over an entire year. This novel scheme is generically applicable for improving seasonal forecasts over other monsoon regions and for critical climate variables such as surface temperature and Arctic sea-ice extent.


Assuntos
Clima , Secas , Estações do Ano , Temperatura , Inundações
17.
Chem Asian J ; 18(2): e202201132, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36479828

RESUMO

The arylcyclopropane motif as the combination of aryl and cyclopropyl ring systems can be found in an increasing amount of approved and investigational drugs. Herein, we have developed a mild, efficient nickel-catalyzed reductive cross-coupling protocol, featuring a simple Ni(II) precatalyst and a novel picolinamide NN2 pincer ligand. A variety of (hetero)aryl bromides could successfully couple with cyclopropyl bromide to furnish the valued arylcyclopropanes in good to excellent yields. This method is applicable to other alkyl bromides as well. Notably, the reaction is tolerant of a broad range of functionalities including free amines. Furthermore, the synthesis of several significant intermediates of bioactive molecules was achieved in grams, proving the practicability of this method.


Assuntos
Brometos , Níquel , Ligantes , Estrutura Molecular , Catálise
18.
Appl Microbiol Biotechnol ; 107(2-3): 853-865, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36539564

RESUMO

The goal of bacterial engineering is to rewire metabolic pathways to generate high-value molecules for various applications. However, the production of recombinant proteins is constrained by the complexity of the connections between cellular physiology and recombinant protein synthesis. Here, we used a rational and highly efficient approach to improve bacterial engineering. Based on the complete genome and annotation information of the Escherichia coli ER2566 strain, we compared the transcriptomic profiles of the strain under leaky expression and low temperature-induced stress. Combining the gene ontology (GO) enrichment terms and differentially expressed genes (DEGs) with higher expression, we selected and knocked out 36 genes to determine the potential impact of these genes on protein production. Deletion of bluF, cydA, mngR, and udp led to a significant decrease in soluble recombinant protein production. Moreover, at low-temperature induction, 4 DEGs (gntK, flgH, flgK, flgL) were associated with enhanced expression of the recombinant protein. Knocking out several motility-related DEGs (ER2666-ΔflgH-ΔflgL-ΔflgK) simultaneously improved the protein yield by 1.5-fold at 24 °C induction, and the recombinant strain had the potential to be applied in the expression studies of different exogenous proteins, aiming to improve the yields of soluble form to varying degrees in comparison to the ER2566 strain. Totally, this study focused on the anabolic and stress-responsive hub genes of the adaptation of E. coli to recombinant protein overexpression on the transcriptome level and constructs a series of engineering strains increasing the soluble protein yield of recombinant proteins which lays a solid foundation for the engineering of bacterial strains for recombinant technological advances. KEY POINTS: • Comparative transcriptome analysis shows host responses with altered induction stress. • Deletion of bluF, cydA, mngR, and udp genes was identified to significantly decrease the soluble recombinant protein productions. • Synchronal knockout of flagellar genes in E. coli can enhance recombinant protein yield up to ~ 1.5-fold at 24 °C induction. • Non-model bacterial strains can be re-engineered for recombinant protein expression.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas Recombinantes/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Transcriptoma , Difosfato de Uridina/metabolismo , Engenharia Metabólica
19.
Brief Bioinform ; 23(1)2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-34581409

RESUMO

Long non-coding RNAs (lncRNAs) that emanate from enhancer regions (defined as enhancer-associated lncRNAs, or elncRNAs) are emerging as critical regulators in disease progression. However, their biological characteristics and clinical relevance have not been fully portrayed. Here, based on the traditional expression quantitative loci (eQTL) and our optimized residual eQTL method, we comprehensively described the genetic effect on elncRNA expression in more than 300 lymphoblastoid cell lines. Meanwhile, a chromatin atlas of elncRNAs relative to the genetic regulation state was depicted. By applying the maximum likelihood estimate method, we successfully identified causal elncRNAs for protein-coding gene expression reprogramming and showed their associated single nucleotide polymorphisms (SNPs) favor binding of transcription factors. Further epigenome analysis revealed two immune-associated elncRNAs AL662844.4 and LINC01215 possess high levels of H3K27ac and H3K4me1 in human cancer. Besides, pan-cancer analysis of 3D genome, transcriptome, and regulatome data showed they potentially regulate tumor-immune cell interaction through affecting MHC class I genes and CD47, respectively. Moreover, our study showed there exist associations between elncRNA and patient survival. Finally, we made a user-friendly web interface available for exploring the regulatory relationship of SNP-elncRNA-protein-coding gene triplets (http://bio-bigdata.hrbmu.edu.cn/elncVarReg). Our study provides critical mechanistic insights for elncRNA function and illustrates their implications in human cancer.


Assuntos
Neoplasias , RNA Longo não Codificante , Cromatina/genética , Regulação da Expressão Gênica , Humanos , Funções Verossimilhança , Neoplasias/genética , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética
20.
Biochem Biophys Res Commun ; 639: 46-53, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36463760

RESUMO

Long noncoding RNAs (lncRNAs) are emerging as critical regulators in the biological development of breast cancer. In this study, we aimed to determine the roles and mechanisms of the lncRNA COX10 divergent transcript (COX10-DT) in breast cancer progression. The relative expression level of COX10-DT was calculated in matched breast cancer tissues and adjacent normal tissues using quantitative real-time PCR. Gain-of-function and loss-of-function approaches further revealed the functions and mechanisms of COX10-DT in breast cancer cells. Clinically, we found that the lncRNA COX10-DT was commonly overexpressed in breast cancer tissues compared to paired peritumoural tissues. Functionally, the lncRNA COX10-DT might promote the proliferation and migration of breast cancer cells. Mechanistically, the lncRNA COX10-DT did not play a role by regulating the expression of its divergent gene COX10 but acted as a competitive endogenous RNA (ceRNA) by directly sponging miR-206, which further regulated the expression of brain-derived neurotrophic factor (BDNF). Taken together, our results proved that the lncRNA COX10-DT could function via the COX10-DT/miR-206/BDNF axis, thereby promoting the development of breast cancer. These findings indicated that the lncRNA COX10-DT might be a potential biomarker and therapeutic target for breast cancer.

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