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1.
Risk Manag Healthc Policy ; 16: 1521-1530, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37602361

RESUMO

Background: Antimicrobial agents' wastage is a huge problem, especially for pediatric patients, resulting in excessive drug expenditure and increasing the economic burden on patients' families. Moreover, the cost of disposing of antimicrobial agents' waste and the risk of environmental and occupational exposure also increased. This study aimed to explore the cost-effectiveness of the vial-sharing strategy combined with the daily-rate charge mode for pediatric inpatients to provide a strategy for reducing patients' expenditures, saving medical costs, and reducing drug proportion. Methods: This retrospective study was conducted at Pharmacy Intravenous Admixture Service (PIVAS), Shenzhen Children's Hospital, Guangdong Province, China, in 2022. Data on prescription drugs were collected from the PIVAS system. Ten antimicrobial drugs with a frequency of prescriptions no less than twice once daily were selected, and the drug costs, drug weight, and drug saved were further analyzed according to the combination of real-time vial sharing strategy and daily-rate charge mode. Traditional single vial charge mode without vial sharing was set as a control strategy. The actual expenditure of the hospital was also calculated and analyzed. Results: During 2022, ¥ 4,122,099 (34.4%) was saved for inpatients by applying a vial-sharing strategy on ten antibacterial agents, and more than 46,343,750 mg (24.6%) of drugs were totally saved. The top 5 drugs saved by the real-time vial-sharing strategy were cefoperazone-sulbactam, vancomycin, amoxicillin-sulbactam, ceftazidime, and meropenem. Taken the price into consideration, the top five payment-saved drugs were vancomycin (¥ 1,522,385), meropenem (¥ 1,311,475), cefoperazone-sulbactam (¥ 736,697), imipenem-cilastatin (¥ 406,092), and amoxicillin-sulbactam (¥ 51,394). Moreover, the account balance of the hospital was up to ¥ 426,499. Conclusion: The real-time vial sharing strategy combined with the daily-rate charge mode greatly reduces drug wastage and patients' payments. It may be useful for hospitals with PIVAS to achieve vial-sharing while protecting the best interest of inpatients.

2.
Animals (Basel) ; 13(13)2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37444009

RESUMO

Thermal infrared technology is utilized for detecting mastitis in cows owing to its non-invasive and efficient characteristics. However, the presence of surrounding regions and obstacles can impede accurate temperature measurement, thereby compromising the effectiveness of dairy mastitis detection. To address these problems, we proposed the CLE-UNet (Centroid Loss Ellipticization UNet) semantic segmentation algorithm. The algorithm consists of three main parts. Firstly, we introduced the efficient channel attention (ECA) mechanism in the feature extraction layer of UNet to improve the segmentation accuracy by focusing on more useful channel features. Secondly, we proposed a new centroid loss function to facilitate the network's output to be closer to the position of the real label during the training process. Finally, we used a cow's eye ellipse fitting operation based on the similarity between the shape of the cow's eye and the ellipse. The results indicated that the CLE-UNet model obtained a mean intersection over union (MIoU) of 89.32% and an average segmentation speed of 0.049 s per frame. Compared to somatic cell count (SCC), this method achieved an accuracy, sensitivity, and F1 value of 86.67%, 82.35%, and 87.5%, respectively, for detecting mastitis in dairy cows. In conclusion, the innovative use of the CLE-UNet algorithm has significantly improved the segmentation accuracy and has proven to be an effective tool for accurately detecting cow mastitis.

3.
J Math Biol ; 86(5): 80, 2023 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-37093296

RESUMO

In this paper, we first formulate a system of ODEs-PDE to model diseases with latency-age and differential infectivity. Then, based on the ways how latent individuals leave the latent stage, one ODE and two DDE models are derived. We only focus on the global stability of the models. All the models have some similarities in the existence of equilibria. Each model has a threshold dynamics for global stability, which is completely characterized by the basic reproduction number. The approach is the Lyapunov direct method. We propose an idea on constructing Lyapunov functionals for the two DDE and the original ODEs-PDE models. During verifying the negative (semi-)definiteness of derivatives of the Lyapunov functionals along solutions, a novel positive definite function and a new inequality are used. The idea here is also helpful in applying the Lyapunov direct method to prove the global stability of some epidemic models with age structure or delays.


Assuntos
Epidemias , Modelos Biológicos , Humanos , Número Básico de Reprodução
4.
Opt Express ; 31(1): 31-43, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36606947

RESUMO

We propose a new, to the best of our knowledge, method of incoherent optical frequency selection called three-pack frequency-selective incoherent holography. Compressed holography is reconstructed using phase shift intercepts and spatial transfer function convolution in the form of separation without loss of magnification or resolution. The frequency-selective reconstruction process removes the conjugate and DC terms along with the interception of the object wave. This work attempts three-dimensional reconstruction and selected-frequency phase extraction of axial slices in submicron steps, and the experimental results show the potential of the proposed method in areas such as compressed holography, extended field of view, and slice tomography.

5.
Medicine (Baltimore) ; 101(45): e31361, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36397388

RESUMO

RATIONALE: Paxlovid has shown the potential decreasing the hospitalization rate of mild or moderate coronavirus disease 2019 (COVID-19) and death in few of clinical trials, and is expected to the most promising medicine targeting Severe Acute Respiratory Syndrome Coronavirus 2 (SRAS-COV-2). However, there are no enough evidences to show it effectiveness for all patients with SARS-COV-2, especially among elderly patients and newest Omicron variant. PATIENT CONCERNS AND DIAGNOSIS: A 79 year's old female patient was admitted to hospital because of the moderate COVID-19 caused by the Omicron variant BA2.0. He presented the initial syndromes including Xerostomia, cough and fever. Chest computed tomography (CT) scanning at admission showed the exudation lesions on lung. The laboratory examination revealed that there are increased C-reactive protein (CRP), Ferritin and erythrocytesedimentationrate (ESR) and decreased white blood cells. INTERVENTIONS: The oral Paxlovid (Nirmatrelvir/Ritonavir) was administrated on second day after admission. OUTCOMES: The syndromes of Xerostomia, cough and fever was improved on third day after use of Paxlovid. The levels of CRP, ESR and counts of white blood cells returned the normal after three days of admission. The chest CT scanned on the third and sixth day after Paxlovid used showed the absorption of lesions. The examination of SARS-COVS viral nucleic acid turned negative at fifth day of admission. LESSONS: As a result, we would consider that Paxlovid is a suitable oral drug for elderly patients with SARS-COV2 even Omicron variant, it's benefit to improve patient's symptom and signs and can prevents COVID-19 with the high-risk factors from severe disease, although it didn't shorten the time for viral nucleic acid to turn negative.


Assuntos
COVID-19 , Xerostomia , Masculino , Humanos , Feminino , Idoso , SARS-CoV-2 , Tosse/etiologia , RNA Viral , Febre/etiologia
6.
Comput Intell Neurosci ; 2022: 9728536, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35837207

RESUMO

With the continuous development of network communication technology, the domestic network has covered the homes of ordinary people, but the indoor coverage system of the network cable network needs to be further improved. The optical fiber distribution system is a signal coverage system integrating GSM, TD-SCDMA, and other standards. It is mainly composed of system access unit, system expansion unit, and system remote unit. Wireless network is an important communication technology, which is easy to use and can be connected wirelessly over long distances. The purpose of this paper is to study an optical fiber distribution system for indoor coverage design of wireless networks, so as to achieve faster and more efficient coverage. In this paper, a wireless network signal processing algorithm is proposed, and a systematic method for designing the wireless network indoor coverage of the optical fiber distribution system is proposed, and the algorithms are compared and tested. The test results in this paper show that the signal strength obtained by the algorithm in this paper is -54.83 dB, while the traditional artificial design algorithm is only -45.97 dB. In addition, the wireless network base point of the algorithm in this paper is also 3 lower than the traditional one. Moreover, the coverage rate achieved by the algorithm in this paper is 3.17% higher than that of the network cable network base point layout given by the genetic algorithm, and the average received signal strength is 3.34 dB higher. In addition, the algorithm in this paper takes 9.1 s, 11.2 s, and 5.3 s for the three scenarios of underground parking lot, large shopping mall, and residential residential area, while the traditional manual design algorithm takes 87.9 s, 108.8 s, and 51.7 s, respectively. The algorithm in this paper is only about 1/10 of the traditional artificial design algorithm. Therefore, it can be concluded that the coverage effect of the wireless network indoor coverage system of the optical fiber distribution system designed in this paper is significantly improved.

7.
Angew Chem Int Ed Engl ; 61(38): e202210573, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-35909225

RESUMO

Sustainable processes for semi-hydrogenation of alkynes/alkadienes impurities in alkenes feedstocks are in great demand in industry as the utilization of excessive hydrogen, high temperature and unsatisfactory alkenes selectivity of the current thermo-catalytic route, however, their development is still challenging. Herein, we innovate a light-assisted semi-hydrogenation process in gas-feed fixed bed reactor, with water as hydrogen atom source by in situ photocatalysis. Using Pd/TiO2 as model catalyst, this process shows an excellent catalytic performance for the semi-hydrogenation of 1,3-butadiene, with 100 % of butenes selectivity at ≈99 % of conversion over 180 h of reaction at ambient temperature driven by 66 mW cm-2 of irradiation intensity. This light-driven, H2 -free, ambient temperature semi-hydrogenation process, with superior performance to that of thermocatalytic route, shows attractive to bring an evolution in industrial hydrogenation technology to an economical and safe way.

8.
Math Biosci Eng ; 19(7): 6489-6503, 2022 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-35730268

RESUMO

In this paper, we investigate the global dynamics of a viral infection model with defectively infected cells. The explicit expression of the basic reproduction number of virus is obtained by using the next generation matrix approach, where each term has a clear biological interpretation. We show that the basic reproduction number serves as a threshold parameter. The virus dies out if the basic reproduction number is not greater than unity, otherwise the virus persists and the viral load eventually approaches a positive number. The result is established by Lyapunov's direct method. Our novel arguments for the stability of the infection equilibrium not only simplify the analysis (compared with some traditional ones in the literature) but also demonstrate some correlation between the two Lyapunov functions for the infection-free and infection equilibria.


Assuntos
Modelos Biológicos , Viroses , Número Básico de Reprodução , Humanos , Carga Viral
9.
World J Clin Cases ; 10(8): 2474-2483, 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35434053

RESUMO

BACKGROUND: Klebsiella pneumoniae (K. pneumoniae) is an infective microorganism of worldwide concern because of its varied manifestations and life-threatening potential. Genetic analyses have revealed that subspecies of K. pneumoniae exhibit higher virulence and mortality. However, infections with Klebsiella subspecies are often misdiagnosed and underestimated in the clinic because of difficulties in distinguishing K. pneumoniae from its subspecies using routine tests. This case study reports the rapid and fatal effects of K. pneumoniae subspecies. CASE SUMMARY: A 52-year-old male patient was febrile and admitted to hospital. Examinations excluded viral and fungal causes along with mycoplasma/chlamydia and parasitic infections. Bacterial cultures revealed blood-borne K. pneumoniae sensitive to carbapenem antibiotics, although corresponding treatment failed to improve the patient's symptoms. His condition worsened and death occurred within 72 h of symptom onset from sepsis shock. Application of the PMseq-DNA Pro high throughput gene detection assay was implemented with results obtained after death showing a mixed infection of K. pneumoniae and Klebsiella variicola (K. variicola). Clinical evidence suggested that K. variicola rather than K. pneumoniae contributed to the patient's poor prognosis. CONCLUSION: This is the first case report to show patient death from Klebsiella subspecies infection within a short period of time. This case provides a timely reminder of the clinical hazards posed by Klebsiella subspecies and highlights the limitations of classical laboratory methods in guiding anti-infective therapies for complex cases. Moreover, this report serves as reference for physicians diagnosing similar diseases and provides a recommendation to employ early genetic detection to aid patient diagnosis and management.

10.
Nanomaterials (Basel) ; 12(7)2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35407251

RESUMO

The water sensitivity of metal-organic frameworks (MOFs) as a common and crucial issue has greatly hindered their practical applications. Here, we present a facile and general approach to improve the water resistance of a typical MOF, i.e., CuBTC [Cu3(BTC)2(H2O)3]n (BTC = benzene-1,3,5-tricarboxylate) using a post-modification reaction with aminopropyltriethoxylsilane (APTES) at room temperature. The afforded material is denoted as CuBTC@APTES. Various spectroscopic methods reveal that the organosilicon linkers have been successfully grafted onto CuBTC by electrostatic attraction between acid and base groups and without affecting the original coordination mode and basic structure. Compared with CuBTC, the water stability of CuBTC@APTES was significantly improved. The pristine CuBTC almost lost all its crystallinity, morphology and pore structure after 3-day treatment in water, while CuBTC@APTES is able to retain its main crystal structure and basic porosity after the same treatment. This finding can be explained by the successful introduction of the organosilicon molecular overlayer on the periphery of CuBTC to slow down the destruction of weak metal coordination bonds by water molecules, thus improving the water stability of CuBTC. The solution of water sensitivity provides more opportunities for the practical applications of CuBTC, such as aqueous phase catalysis and gas separation in humid environments. This simple approach can certainly be expanded to improve the water resistance of other carboxylate-containing ligand-based MOFs.

11.
Polymers (Basel) ; 14(3)2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35160360

RESUMO

Herein, we present two novel ferrocene-containing porous organic polymers, FPOP-1 and FPOP-2, by the Heck reactions of 1,1'-divinylferrocene with two tetrahedral silicon-centered units, i.e., tetrakis(4-bromophenyl)silane and tetrakis(4'-bromo-[1,1'-biphenyl]-4-yl)silane. The resulting materials possess high thermal stability and moderate porosity with the Brunauer-Emmer-Teller (BET) surface areas of 499 m2 g-1 (FPOP-1) and 354 m2 g-1 (FPOP-2) and total pore volumes of 0.43 cm3 g-1 (FPOP-1) and 0.49 cm3 g-1 (FPOP-2). The porosity is comparable to previously reported ferrocene-containing porous polymers. These materials possess comparable CO2 capacities of 1.16 mmol g-1 (5.10 wt%) at 273 K and 1.0 bar, and 0.54 mmol g-1 (2.38 wt%) at 298 K and 1.0 bar (FPOP-1). The found capacities are comparable to, or higher than many porous polymers having similar or higher surface areas. They have high isosteric heats of up to 32.9 kJ mol-1, proving that the affinity between the polymer network and CO2 is high, which can be explained by the presence of ferrocene units in the porous networks. These results indicate that these materials can be promisingly utilized as candidates for the storage or capture of CO2. More ferrocene-containing porous polymers can be designed and synthesized by combining ferrocene units with various aromatic monomers under this strategy and their applications could be explored.

12.
Lab Invest ; 101(10): 1371-1381, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34239033

RESUMO

Sepsis is an acute inflammatory reaction and a cause of acute respiratory distress syndrome (ARDS). In the present study, we explored the roles and underlying mechanism of the lncRNA Nuclear enriched abundant transcript 1 (NEAT1) in ARDS. The expression levels of genes, proteins and pro-inflammatory cytokines in patients with ARDS, LPS-stimulated cells and septic mouse models were quantified using qPCR, western blotting and ELISA assays, respectively. The molecular targeting relationship was validated by conducting a dual-luciferase reporter assay. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8) assay. The cell cycle phase was determined by flow cytometry assay. The expression levels of NEAT1 and pro-inflammatory cytokines were higher in patients with ARDS and septic models than in controls. Knockdown of NEAT1 significantly increased cell proliferation and cycle progression and prolonged mouse survival in vitro and in vivo. Mechanistically, miR-27a was identified as a downstream target of NEAT1 and directly inhibited PTEN expression. Further rescue experiments revealed that inhibition of miR-27a impeded the promoting effects of NEAT1 silence on cell proliferation and cycle progression, whereas inhibition of PTEN markedly weakened the inhibitory effects of NEAT1 overexpression on cell proliferation and cycle progression. Altogether, our study revealed that NEAT1 plays a promoting role in the progression of ARDS via the NEAT1/miR-27a/PTEN regulatory network, providing new insight into the pathologic mechanism behind ARDS.


Assuntos
MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , RNA Longo não Codificante , Síndrome do Desconforto Respiratório/metabolismo , Sepse/metabolismo , Adulto , Animais , Linhagem Celular , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genética
13.
World J Clin Cases ; 9(6): 1394-1401, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33644207

RESUMO

BACKGROUND: A disease caused by a novel coronavirus virus, named coronavirus disease 2019 (COVID-19), broke out in Wuhan, China in December 2019, and spread around the word. As of March 4, 2020, 93090 confirmed cases and 2984 deaths have been reported in more than 80 countries and territories. It has triggered global public health security. However, the features and prognosis of COVID-19 are incompletely understood. CASE SUMMARY: We here report that the erythrocyte sedimentation rate (ESR) increased in a confirmed COVID patient. The high level of ESR sustained for a long time even after the patient recovered from COVID-19, while all results related to tumor, tuberculosis, rheumatic diseases, anemia, etc. cannot explain the abnormal elevation of ESR presented in this case. CONCLUSION: Although the increased ESR cannot be explained by all existing evidence, it possibly links the abnormal pathologic change in some COVID-19 patients and negative prognosis, and provides the clue to dissect the mechanism of illness progressing in COVID-19 and its prognosis.

14.
J Biol Dyn ; 15(1): 19-34, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33357087

RESUMO

In this paper, a deterministic model characterizing the within-host infection of Hepatitis C virus (HCV) in intrahepatic and extrahepatic tissues is presented. In addition, the model also includes the effect of the cytotoxic T lymphocyte (CTL) immunity described by a linear activation rate by infected cells. Firstly, the non-negativity and boundedness of solutions of the model are established. Secondly, the basic reproduction number R01 and immune reproduction number R02 are calculated, respectively. Three equilibria, namely, infection-free, CTL immune response-free and infected equilibrium with CTL immune response are discussed in terms of these two thresholds. Thirdly, the stability of these three equilibria is investigated theoretically as well as numerically. The results show that when R01<1 , the virus will be cleared out eventually and the CTL immune response will also disappear; when R02<11 , both of the virus and the CTL immune response persist within the host. Finally, a brief discussion will be given.


Assuntos
Hepacivirus , Hepatite C , Humanos , Imunidade , Modelos Biológicos , Linfócitos T Citotóxicos
15.
Opt Express ; 28(4): 5179-5188, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32121743

RESUMO

In this paper, pure silk protein was extracted from Bombyx mori silks and fabricated into a new kind of disordered bio-microfiber structure using electrospinning technology. Coherent random lasing emission with low threshold was achieved in the silk fibroin fibers. The random lasing emission wavelength can be tuned in the range of 33 nm by controlling the pump location with different scattering strengths. Therefore, the bio-microfiber random lasers can be a wide spectral light source when the system is doped with a gain or energy transfer medium with a large fluorescence emission band. Application of the random lasers of the bio-microfibers as a low-coherence light source in speckle-free imaging had also been studied.


Assuntos
Fibroínas/química , Lasers , Luz , Animais , Bombyx , Fibroínas/ultraestrutura , Processamento de Imagem Assistida por Computador , Dispositivos Ópticos
16.
Polymers (Basel) ; 12(3)2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32192198

RESUMO

Silicon-containing hyperbranched polymers (Si-HBPs) have drawn much attention due to their promising applications. However, the construction of Si-HBPs, especially those containing functional aromatic units in the branched backbones by the simple and efficient Piers-Rubinsztajn (P-R) reaction, has been rarely developed. Herein, a series of novel hyperbranched polycarbosiloxanes were prepared by the P-R reactions of methyl-, or phenyl-triethoxylsilane and three Si-H containing aromatic monomers, including 1,4-bis(dimethylsilyl)benzene, 4,4'-bis(dimethylsilyl)-1,1'-biphenyl and 1,1'-bis(dimethylsilyl)ferrocene, using B(C6F5)3 as the catalyst for 0.5 h at room temperature. Their structures were fully characterized by Fourier transform infrared spectroscopy, 1H NMR, 13C NMR, and 29Si NMR. The molecular weights were determined by gel permeation chromatography. The degrees of branching of these polymers were 0.69-0.89, which were calculated based on the quantitative 29Si NMR spectroscopy. For applications, the ferrocene-linked Si-HBP can be used as precursors to produce functional ceramics with good magnetizability after pyrolysis at elevated temperature.

17.
Polymers (Basel) ; 11(10)2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31658618

RESUMO

The most common self-assembly structure for A2B copolymer is the micellar structure with B/A segments being the core/corona, which greatly limits its application range. Following the principle of structure deciding the properties, a reformation in the molecular structure of A2B copolymer is made by appending three segments of a third component C with the same length to the three arms, resulting (AC)2CB 3-miktoarm star terpolymer. A reverse micellar structure in self-assembly is expected by regulating the C length and the pairwise repulsive strength of C to A/B, aiming to enrich its application range. Keeping both A and B lengths unchanged, when the repulsion strength of C to A is much stronger than C to B, from the results of mesoscopic simulations we found, with a progressive increase in C length, (AC)2CB terpolymer undergoes a transition in self-assembled structures, from a cylindrical structure with B component as the core, then to a deformed lamellar structure, and finally to a cylindrical structure with A component as the core. This reverse micellar structure is formed with the assistance of appended C segments, whose length is longer than half of B length, enhancing the flexibility of three arms, and further facilitating the aggregation of A component into the core. These results prove that the addition of a third component is a rational molecular design, in conjunction with some relevant parameters, enables the manufacturing of the desired self-assembly structure while avoiding excessive changes in the involved factors.

18.
J Biol Chem ; 294(42): 15544-15556, 2019 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-31492755

RESUMO

The Escherichia coli cAMP receptor protein, CRP, is a homodimeric global transcription activator that employs multiple mechanisms to modulate the expression of hundreds of genes. These mechanisms require different interfacial interactions among CRP, RNA, and DNA of varying sequences. The involvement of such a multiplicity of interfaces requires a tight control to ensure the desired phenotype. CRP-dependent promoters can be grouped into three classes. For decades scientists in the field have been puzzled over the differences in mechanisms between class I and II promoters. Using a new crystal structure, IR spectroscopy, and computational analysis, we defined the energy landscapes of WT and 14 mutated CRPs to determine how a homodimeric protein can distinguish nonpalindromic DNA sequences and facilitate communication between residues located in three different activation regions (AR) in CRP that are ∼30 Šapart. We showed that each mutation imparts differential effects on stability among the subunits and domains in CRP. Consequently, the energetic landscapes of subunits and domains are different, and CRP is asymmetric. Hence, the same mutation can exert different effects on ARs in class I or II promoters. The effect of a mutation is transmitted through a network by long-distance communication not necessarily relying on physical contacts between adjacent residues. The mechanism is simply the sum of the consequences of modulating the synchrony of dynamic motions of residues at a distance, leading to differential effects on ARs in different subunits. The computational analysis is applicable to any system and potentially with predictive capability.


Assuntos
Proteína Receptora de AMP Cíclico/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Regiões Promotoras Genéticas , Sítios de Ligação , Proteína Receptora de AMP Cíclico/química , Proteína Receptora de AMP Cíclico/genética , Dimerização , Escherichia coli/química , Escherichia coli/genética , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Domínios Proteicos , Subunidades Proteicas/química , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo
19.
Cell Div ; 14: 5, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249607

RESUMO

BACKGROUND: Drugs such as taxanes, epothilones, and vinca alkaloids are widely used in the treatment of breast, ovarian, and lung cancers but come with major side effects such as neuropathy and loss of neutrophils and as single agents have a lack of efficacy. M2I-1 (MAD2 inhibitor-1) has been shown to disrupt the CDC20-MAD2 interaction, and consequently, the assembly of the mitotic checkpoint complex (MCC). RESULTS: We report here that M2I-1 can significantly increase the sensitivity of several cancer cell lines to anti-mitotic drugs, with cell death occurring after a prolonged mitotic arrest. In the presence of nocodazole or taxol combined with M2I-1 cell death is triggered by the premature degradation of Cyclin B1, the perturbation of the microtubule network, and an increase in the level of the pro-apoptotic protein MCL-1s combined with a marginal increase in the level of NOXA. The elevated level of MCL-1s and the marginally increased NOXA antagonized the increased level of MCL-1, a pro-survival protein of the Bcl-2 family. CONCLUSION: Our results provide some important molecular mechanisms for understanding the relationship between the mitotic checkpoint and programmed cell death and demonstrate that M2I-1 exhibits antitumor activity in the presence of current anti-mitotic drugs such as taxol and nocodazole and has the potential to be developed as an anticancer agent.

20.
Polymers (Basel) ; 11(2)2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30960246

RESUMO

The self-assembly of an amphiphilic Y-shaped copolymer consisting of two hydrophilic branches and one hydrophobic branch in a thin film is investigated under different conditions by virtue of mesoscopic computer modelling, accompanied by doping with a single solvent, doping with a binary solvent, and those solvent environments together with the introduction of confinement defined by various acting distances and influencing regions. A cylindrical micellar structure is maintained, as it is in the thin film with the doping of either 10% hydrophobic solvent or 10% hydrophilic solvent, whose structure consists of the hydrophobic core and hydrophilic shell. Attributed to the hydrophobicity/hydrophilia nature of the solvents, different solvents play an obvious role on the self-assembled structure, i.e., the hydrophobic solvent presents as a swelling effect, conversely, the hydrophilic solvent presents as a shrinking effect. Further, the synergistic effect of the binary solvents on the self-assembly produces the lowest values in both the average volumetric size and free energy density when the quantity of hydrophobic solvent and hydrophilic solvent is equivalent. Interestingly, the solvent effect becomes more pronounced under the existent of a confinement. When a lateral-oriented confinement is introduced, a periodically fluctuating change in the cylindrical size occurs in two near-wall regions, but the further addition of either hydrophobic or hydrophilic solvent can effectively eliminate such resulting hierarchical-sized cylinders and generate uniform small-sized cylinders. However, with the introduction of a horizontal-orientated confinement, the copolymers self-assemble into the spherical micellar structure. Moreover, the further addition of hydrophobic solvent leads to a decrease in the average size of micelles via coalescence mechanism, in contrast, the further addition of hydrophilic solvent causes an increase in the average size of micelles via splitting mechanism. These findings enrich our knowledge of the potential for the solvent effect on the self-assembly of amphiphilic copolymer system, and then provide theoretical supports on improving and regulating the mesoscopic structure of nanomaterials.

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