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1.
Development ; 149(16)2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35899600

RESUMO

Phosphatidylinositol (PI) 4,5-bisphosphate (PIP2) is involved in many biological functions. However, the mechanisms of PIP2 in collective cell migration remain elusive. This study highlights the regulatory role of cytidine triphosphate synthase (CTPsyn) in collective border cell migration through regulating the asymmetrical distribution of PIP2. We demonstrated that border cell clusters containing mutant CTPsyn cells suppressed migration. CTPsyn was co-enriched with Actin at the leading edge of the Drosophila border cell cluster where PIP2 was enriched, and this enrichment depended on the CTPsyn activity. Genetic interactions of border cell migration were found between CTPsyn mutant and genes in PI biosynthesis. The CTPsyn reduction resulted in loss of the asymmetric activity of endocytosis recycling. Also, genetic interactions were revealed between components of the exocyst complex and CTPsyn mutant, indicating that CTPsyn activity regulates the PIP2-related asymmetrical exocytosis activity. Furthermore, CTPsyn activity is essential for RTK-polarized distribution in the border cell cluster. We propose a model in which CTPsyn activity is required for the asymmetrical generation of PIP2 to enrich RTK signaling through endocytic recycling in collective cell migration.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Carbono-Nitrogênio Ligases , Movimento Celular/genética , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo
2.
Small ; 20(6): e2304743, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37803930

RESUMO

Converting solar energy into hydrogen energy using conjugated polymers (CP) is a promising solution to the energy crisis. Improving water solubility plays one of the critical factors in enhancing the hydrogen evolution rate (HER) of CP photocatalysts. In this study, a novel concept of incorporating hydrophilic side chains to connect the backbones of CPs to improve their HER is proposed. This concept is realized through the polymerization of carbazole units bridged with octane, ethylene glycol, and penta-(ethylene glycol) to form three new side-chain-braided (SCB) CPs: PCz2S-OCt, PCz2S-EG, and PCz2S-PEG. Verified through transient absorption spectra, the enhanced capability of PCz2S-PEG for ultrafast electron transfer and reduced recombination effects has been demonstrated. Small- and wide-angle X-ray scattering (SAXS/WAXS) analyses reveal that these three SCB-CPs form cross-linking networks with different mass fractal dimensions (f) in aqueous solution. With the lowest f value of 2.64 and improved water/polymer interfaces, PCz2S-PEG demonstrates the best HER, reaching up to 126.9 µmol h-1 in pure water-based photocatalytic solution. Moreover, PCz2S-PEG exhibits comparable performance in seawater-based photocatalytic solution under natural sunlight. In situ SAXS analysis further reveals nucleation-dominated generation of hydrogen nanoclusters with a size of ≈1.5 nm in the HER of PCz2S-PEG under light illumination.

3.
Angew Chem Int Ed Engl ; : e202407702, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38751355

RESUMO

The current bottleneck in the development of efficient photocatalysts for hydrogen evolution is the limited availability of high-performance acceptor units. Over the past nine years, dibenzo[b,d]thiophene sulfone (DBS) has been the preferred choice for the acceptor unit. Despite extensive exploration of alternative structures as potential replacements for DBS, a superior substitute remains elusive. In this study, a symmetry-breaking strategy was employed on DBS to develop a novel acceptor unit, BBTT-1SO. The asymmetric structure of BBTT-1SO proved beneficial for increasing multiple moment and polarizability. BBTT-1SO-containing polymers showed higher efficiencies for hydrogen evolution than their DBS-containing counterparts by up to 166 %. PBBTT-1SO exhibited an excellent hydrogen evolution rate (HER) of 222.03 mmol g-1 h-1 and an apparent quantum yield of 27.5 % at 500 nm. Transient spectroscopic studies indicated that the BBTT-1SO-based polymers facilitated electron polaron formation, which explains their superior HERs. PBBTT-1SO also showed 14 % higher HER in natural seawater splitting than that in deionized water splitting. Molecular dynamics simulations highlighted the enhanced water-PBBTT-1SO polymer interactions in salt-containing solutions. This study presents a pioneering example of a substitute acceptor unit for DBS in the construction of high-performance photocatalysts for hydrogen evolution.

4.
Small ; 19(26): e2300046, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36929623

RESUMO

The unique properties of self-healing materials hold great potential in battery systems, which can exhibit excellent deformability and return to its original shape after cycling. Herein, a Cu3 BiS3 anode material with self-healing mechanisms is proposed for use in ultrastable potassium-ion battery (PIB) and potassium-ion hybrid capacitor (PIHC). Different from the binder design, Cu3 BiS3 anode can exhibit the dual advantages of phase and morphological reversibility, further remaining original property after potassiation/depotassiation and exhibiting ultrastable cycling performance. The reversible electrochemical reconstruction during the continuous charge/discharge processes is beneficial to maintain the structure and function of the material. Furthermore, the conversion reactions during the charge and discharge process produce two advantages: i) suppressing the shuttle effect due to the formation of the heterostructure interface between Cu (111) and Bi (012); ii) Cu can avoid the agglomeration of Bi nanoparticles (NPs), further improving the electrochemical performance and long-cycle stability of the Cu3 BiS3 electrode. As a result, the Cu3 BiS3 electrode not only exhibits a long cycle life in half cells, but also 2000 cycles and 12000 cycles in PIB and PIHC full cells, respectively.

5.
Small ; 19(42): e2302682, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37322304

RESUMO

Conjugated polymers (CPs) have recently gained increasing attention as photocatalysts for sunlight-driven hydrogen evolution. However, they suffer from insufficient electron output sites and poor solubility in organic solvents, severely limiting their photocatalytic performance and applicability. Herein, solution-processable all-acceptor (A1 -A2 )-type CPs based on sulfide-oxidized ladder-type heteroarene are synthesized. A1 -A2 -type CPs showed upsurging efficiency improvements by two to three orders of magnitude, compared to their donor-acceptor -type CP counterparts. Furthermore, by seawater splitting, PBDTTTSOS exhibited an apparent quantum yield of 18.9% to 14.8% at 500 to 550 nm. More importantly, PBDTTTSOS achieved an excellent hydrogen evolution rate of 35.7 mmol h-1  g-1 and 150.7 mmol h-1  m-2 in the thin-film state, which is among the highest efficiencies in thin film polymer photocatalysts to date. This work provides a novel strategy for designing polymer photocatalysts with high efficiency and broad applicability.

6.
J Cell Sci ; 133(9)2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32184263

RESUMO

Under metabolic stress, cellular components can assemble into distinct membraneless organelles for adaptation. One such example is cytidine 5'-triphosphate synthase (CTPS, for which there are CTPS1 and CTPS2 forms in mammals), which forms filamentous structures under glutamine deprivation. We have previously demonstrated that histidine (His)-mediated methylation regulates the formation of CTPS filaments to suppress enzymatic activity and preserve the CTPS protein under glutamine deprivation, which promotes cancer cell growth after stress alleviation. However, it remains unclear where and how these enigmatic structures are assembled. Using CTPS-APEX2-mediated in vivo proximity labeling, we found that synaptosome-associated protein 29 (SNAP29) regulates the spatiotemporal filament assembly of CTPS along the cytokeratin network in a keratin 8 (KRT8)-dependent manner. Knockdown of SNAP29 interfered with assembly and relaxed the filament-induced suppression of CTPS enzymatic activity. Furthermore, APEX2 proximity labeling of keratin 18 (KRT18) revealed a spatiotemporal association of SNAP29 with cytokeratin in response to stress. Super-resolution imaging suggests that during CTPS filament formation, SNAP29 interacts with CTPS along the cytokeratin network. This study links the cytokeratin network to the regulation of metabolism by compartmentalization of metabolic enzymes during nutrient deprivation.


Assuntos
Carbono-Nitrogênio Ligases , Histidina , Animais , Citidina Trifosfato , Histidina/genética , Queratinas
7.
Sensors (Basel) ; 22(22)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36433247

RESUMO

MEMS based 3D double stacked tower pixel biosensor 10 × 10 array with integration of readout circuit for detection of saliva pH ion is demonstrated. The pixel biosensor comprised a driving electrode, sensing electrode and double stack tower pixel structure. The sensitivity of double stacked tower biosensor can be auxiliary enhanced by proposed lower-jitter low dropout regulator circuit and dual offset cancellation comparator. The double stacked tower sensor is fabricated by MEMS backend-of-line CMOS process, it is compatible with CMOS frontend readout circuits and integrated as a system-on-chip (SoC). The double stacked tower pixel by MEMS process is to obtain a larger volume ratio of charge groups in a pixel of biosensor to enhance the sensitivity and linearity for ion detection. With the double stacked tower structure in biosensor, the sensitivity is improved by 31% than that of single tower structure proved by simulation. A wide-range linearity from pH 2.0 to pH 8.3, high sensitivity of -21 ADC counts/pH (or 212 mV/pH), response time of 5 s, repetition of 98.9%, and drift over time of 0.5 mV are achieved. Furthermore, the proposed biosensor was performed to confirm the artificial saliva from healthy gingiva, chronic gingivitis and chronic periodontitis, the measured ADC counts from proposed biosensor SoC was in consistent of that measured cyclic voltametric (CV) method very well. The proposed 3D double stack tower biosensor and readout circuit can be further integrated with internet-of-thing (IoT) device and NFC for data transmission for continuous pH sensing to facilitate the chronic gingiva disease health care at home.


Assuntos
Técnicas Biossensoriais , Periodontite Crônica , Humanos , Desenho de Equipamento , Concentração de Íons de Hidrogênio , Biomarcadores
8.
Int J Comput Dent ; 25(3): 295-302, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-35072417

RESUMO

AIM: To present an image-processing measurement algorithm to evaluate the transfer accuracy of indirect bonding (IDB) trays, exemplified by a CAD/CAM-based IDB tray integrated into a digital orthodontic workflow. MATERIALS AND METHODS: Plaster casts of 24 patients with full dentition and different malocclusions were scanned with an intraoral scanner (Trios; 3Shape, Copenhagen, Denmark) to obtain digital models, which served for the virtual placement of orthodontic brackets in simulation software (OnyxCeph; Image Instruments, Chemnitz, Germany). The resulting STL files were sent to a dental laboratory (CA Digital; Hilden, Germany) for the production of INDIVIDUA IDB trays. These trays were used to transfer the brackets to the respective plaster casts. Finally, a second scan was performed to record the actual bracket positions. The transfer accuracy was then analyzed by a measurement algorithm scripted to automation, which calculated the deviations of the planned and real bracket positions with a local best-fit alignment, resulting in three linear and three angular measurements for each bracket. RESULTS: In total, 622 brackets and tubes were transferred successfully. The presented algorithm analyzed the transfer accuracy and demonstrated that the linear measurements were 98.3% within the range of the American Board of Orthodontics standard. The angular measurements were 86.7% within this range when the INDIVIDUA IDB tray was used. CONCLUSION: Scripted measurement algorithms facilitated the evaluation of present and future materials and designs for IDB trays to obtain an efficient solution for orthodontic practice. The INDIVIDUA IDB tray is a digital alternative to conventional IDB trays (Int J Comput Dent 2022;25(3):295-302; doi: 10.3290/j.ijcd.b2599775).


Assuntos
Colagem Dentária , Má Oclusão , Braquetes Ortodônticos , Algoritmos , Desenho Assistido por Computador , Colagem Dentária/métodos , Humanos , Modelos Dentários , Impressão Tridimensional
9.
Inorg Chem ; 59(8): 5509-5517, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32233484

RESUMO

Ba10Fe3Sb7Se24 was synthesized using a KBr flux at 850 °C (Crystal Data: orthorhombic, Cmc21, a = 9.3412(2) Å, b = 44.6666(10) Å, c = 12.5496(3) Å, V = 5236.2(2) Å3, and Z = 4). The compound adopts a new three-dimensional framework constructed by the layer to include Fe2Se6 dimers and FeSe4 tetrahedra in the linkage motifs of [Fe2SbSe10] and [FeSb6Se14], respectively. Alternatively, the all Sb-based polyhedra are assembled as a semiconducting, perovskite-like framework lacking an inversion center where these Fe-based magnetic units are trapped within the interstices. The strong antiferromagnetic interaction is revealed by a high Curie constant of -113 K, but the curvature of field-cooled and zero-field-cooled magnetic susceptibilities bifurcating at ∼19 K is observed. The critical temperature is well verified by a broad peak of χM″ signal showing a rapid increase below 19 K under an alternating current field. The Fe2Se6 dimer featuring distorted edge-sharing tetrahedra to induce the spin-canted antiferromagnetic ordering strongly dominates such magnetic ordering. Finally, a weak hysteresis loop is clearly observed at 2.0 K. This dilute magnetic selenide displays a direct bandgap at ∼1.54 eV, analyzed by the Tauc equation. Interestingly, the use of second-harmonic-generation temperature dependence shows a turning point at ∼20 ± 1 K, which precisely corresponds to the magnetic ordering temperature within the error bar, thereby demonstrating the versatility of the technique for probing magnetic phase transition.

10.
J Sports Sci Med ; 19(2): 420-428, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32390736

RESUMO

Dynamic stretching (DS) is performed to increase sports performance and is also used primarily for transiently increasing range of motion (ROM). Recently, vibration foam rolling (VFR) has emerged. Its underlying concept is that it combines foam rolling techniques with local vibration to improve ROM and muscular activation concurrently. This crossover study investigated the effects of DS or DS followed by VFR (DS + VFR) during warm-ups on flexibility, muscle stiffness, power, and agility of the lower limbs in badminton athletes. Forty badminton players performed DS or DS + VFR as warm-up exercises on two occasions in a randomized order. The target muscle groups were the bilateral shoulder, anterior and posterior thigh, posterior calf, and lower back. Main outcome measures: The primary outcome was knee range of motion (ROM), and the secondary outcomes were muscle stiffness, lower limb power (countermovement jump [CMJ]), and agility. Results indicated that the protocols improved performance. DS increased knee flexion ROM (% change = 1.92, ES = 0.3, p = 0.033), CMJ height (% change = 5.04, ES = 0.2, p = 0.004), and agility (% change = -4.97, ES = 0.4, p < 0.001) but increased quadriceps muscle stiffness (% change = 3.74, ES = 0.3, p = 0.001) and increased gastrocnemius muscle stiffness (% change = 10.39, ES = 0.5, p = 0.001). DS + VFR increased knee extension ROM (% change =2.87, ES = 0.4, p = 0.003), reduced quadriceps muscle stiffness (% change = -2.79, ES = 0.3, p = 0.017), CMJ height (% change = 2.41, ES = 0.1, p = 0.037), and agility (% change = -4.74, ES = 0.2, p < 0.001). DS + VFR was not significantly superior to DS, except for muscle stiffness reduction. Taken together, we suggest that practitioners consider DS as a first line of warm-up exercise to increase ROM, CMJ height, and agility in athletes. Moreover, the addition of VFR to DS results in a large reduction of muscle stiffness, potentially reducing the risk of sports injury. Athletes, coaches and athletic professionals may consider them when selecting effective warm-up practices to augment athletic performance.


Assuntos
Desempenho Atlético/fisiologia , Exercícios de Alongamento Muscular/fisiologia , Esportes com Raquete/fisiologia , Vibração , Exercício de Aquecimento/fisiologia , Adulto , Estudos Cross-Over , Elasticidade , Feminino , Humanos , Joelho/fisiologia , Extremidade Inferior/fisiologia , Masculino , Músculo Esquelético/fisiologia , Amplitude de Movimento Articular , Adulto Jovem
11.
Cancer ; 123(11): 2043-2053, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28152166

RESUMO

BACKGROUND: Few large, prospective, randomized studies have investigated the effectiveness of esophagectomy in patients with thoracic esophageal squamous cell carcinoma (TESCC) who receive definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) through modern, intensity modulated-RT (IMRT) techniques. The therapeutic effects of esophagectomy in patients with TESCC were evaluated using modern clinical staging and RT techniques and suitable RT doses. METHODS: The authors analyzed data from patients with TESCC from the Taiwan Cancer Registry database. Patients were categorized into the following groups on the basis of treatment modality to compare their outcomes: group 1 received definitive CCRT, group 2 received neoadjuvant RT followed by esophagectomy (total IMRT dose, ≥50 grays [Gy]), and group 3 receiving neoadjuvant CCRT followed by esophagectomy (total IMRT dose, ≥ 50 Gy). The median total RT dose and fraction size were 50.4 Gy and 1.8 Gy per fraction, respectively. Group 1 was used as the control arm for investigating the risk of mortality after treatment. RESULTS: In total, 3123 patients who had TESCC without distant metastasis were enrolled. Patient ages 65 years and older, Charlson comorbidity index scores ≥3, advanced clinical stages (IIA-IIIC), alcohol consumption, and cigarette smoking were identified as significant, independent poor prognostic risk factors for overall survival in multivariate Cox regression analyses. In group 3, after adjustment for confounders, the adjusted hazard ratios (95% confidence intervals [CIs]) for overall mortality were 0.62 (95% CI, 0.41-0.93) for patients with clinical stage IIA disease, 0.61 (95% CI, 0.41-0.91) for those with clinical stage IIB disease, 0.47 (95% CI, 0.38-0.55) for those with clinical stage IIIA disease, 0.47 (95% CI, 0.39-0.56) for those with clinical stage IIIB disease, and 0.46 (95% CI, 0.37-0.57) for those with clinical stage IIIC disease. CONCLUSIONS: Esophagectomy can be beneficial in patients with TESCC after definitive CCRT, especially in those who have advanced-stage disease. Cancer 2017;123:2043-2053. © 2017 American Cancer Society.


Assuntos
Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Neoplasias Esofágicas/terapia , Esofagectomia , Terapia Neoadjuvante , Radioterapia de Intensidade Modulada , Sistema de Registros , Adulto , Fatores Etários , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Terapia Combinada , Bases de Dados Factuais , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Fumar/epidemiologia , Taxa de Sobrevida , Taiwan , Adulto Jovem
12.
Cancer ; 123(20): 3904-3915, 2017 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-28608916

RESUMO

BACKGROUND: Few large, prospective, randomized studies have investigated the value and optimal application of neoadjuvant chemoradiotherapy followed by surgery (trimodality therapy) or definitive concurrent chemoradiotherapy (CCRT) for patients with thoracic esophageal squamous cell carcinoma (TESCC). METHODS: The authors analyzed data from patients with TESCC in the Taiwan Cancer Registry database. To compare their outcomes, patients with TESCC were enrolled and categorized into the following groups according to treatment modality: group 1, those who underwent surgery alone; group 2, those who received trimodality therapy; and group 3, those who received definitive CCRT. Group 1 was used as the control arm for investigating the risk of mortality after treatment. RESULTS: In total, 3522 patients who had TESCC without distant metastasis were enrolled. Multivariate Cox regression analysis indicated that a Charlson comorbidity index score ≥3, American Joint Committee on Cancer stage ≥IIA, earlier year of diagnosis, alcohol consumption, cigarette smoking, and definitive CCRT were significant, independent predictors of a poor prognosis. After adjustment for confounders, adjusted hazard ratios and 95% confidence intervals (CIs) for overall mortality in patients with clinical stage I, IIA, IIB, IIIA, IIIB, and IIIC TESCC were 2.01 (95% CI, 0.44-6.18), 1.65 (95% CI, 0.99-2.70), 1.48 (95% CI, 0.91-2.42), 0.66 (95% CI, 1.08-1.14), 0.39 (95% CI, 0.26-0.57), and 0.44 (95% CI, 0.24-0.83), respectively, in group 2; and 2.06 (95% CI, 1.18-3.59), 2.65 (95% CI, 1.76-4.00), 2.25 (95% CI, 1.49-3.39), 1.34 (95% CI, 0.79-2.28), 0.82 (95% CI, 0.57-1.17), and 0.93 (95% CI, 0.51-1.71), respectively, in group 3. CONCLUSIONS: Trimodality therapy may be beneficial for the survival of patients with advanced-stage (IIIA-IIIC) TESCC, and CCRT might be an alternative to surgery alone in these patients. Cancer 2017;123:3904-15. © 2017 American Cancer Society.


Assuntos
Carcinoma de Células Escamosas/terapia , Procedimentos Cirúrgicos do Sistema Digestório , Neoplasias Esofágicas/terapia , Esôfago/cirurgia , Terapia Neoadjuvante , Sistema de Registros , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/epidemiologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Terapia Combinada , Bases de Dados Factuais , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Fumar/epidemiologia , Taiwan , Adulto Jovem
13.
J Cell Sci ; 128(19): 3550-5, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26303200

RESUMO

Cytidine triphosphate synthase (CTPS) and inosine monophosphate dehydrogenase (IMPDH) (both of which have two isoforms) can form fiber-like subcellular structures termed 'cytoophidia' under certain circumstances in mammalian cells. Although it has been shown that filamentation of CTPS downregulates its activity by disturbing conformational changes, the activity of IMPDH within cytoophidia is still unclear. Most previous IMPDH cytoophidium studies were performed under conditions involving inhibitors that impair GTP synthesis. Here, we show that IMPDH forms cytoophidia without inhibition of GTP synthesis. First, we find that an elevated intracellular CTP concentration or treatment with 3'-deazauridine, a CTPS inhibitor, promotes IMPDH cytoophidium formation and increases the intracellular GTP pool size. Moreover, restriction of cell growth triggers the disassembly of IMPDH cytoophidia, implying that their presence is correlated with active cell metabolism. Finally, we show that the presence of IMPDH cytoophidia in mouse pancreatic islet cells might correlate with nutrient uptake in the animal. Collectively, our findings reveal that formation of IMPDH cytoophidia reflects upregulation of purine nucleotide synthesis, suggesting that the IMPDH cytoophidium plays a role distinct from that of the CTPS cytoophidium in controlling intracellular nucleotide homeostasis.


Assuntos
IMP Desidrogenase/genética , Regulação para Cima , Animais , Carbono-Nitrogênio Ligases/metabolismo , Linhagem Celular Tumoral , Citoplasma/metabolismo , Imunofluorescência , Humanos , IMP Desidrogenase/metabolismo , Camundongos , Nucleotídeos/metabolismo
14.
Int J Mol Sci ; 18(1)2016 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-28035994

RESUMO

Colorectal cancer is the third most common cancer worldwide. Aberrant overexpression of antiapoptotic BCL-2 (B-cell lymphoma 2) family proteins is closely linked to tumorigenesis and poor prognosis in colorectal cancer. Obatoclax is an inhibitor targeting all antiapoptotic BCL-2 proteins. A previous study has described the antiproliferative action of obatoclax in one human colorectal cancer cell line without elucidating the underlying mechanisms. We herein reported that, in a panel of human colorectal cancer cell lines, obatoclax inhibits cell proliferation, suppresses clonogenicity, and induces G1-phase cell cycle arrest, along with cyclin D1 downregulation. Notably, ectopic cyclin D1 overexpression abrogated clonogenicity suppression but also G1-phase arrest elicited by obatoclax. Mechanistically, pre-treatment with the proteasome inhibitor MG-132 restored cyclin D1 levels in all obatoclax-treated cell lines. Cycloheximide chase analyses further revealed an evident reduction in the half-life of cyclin D1 protein by obatoclax, confirming that obatoclax downregulates cyclin D1 through induction of cyclin D1 proteasomal degradation. Lastly, threonine 286 phosphorylation of cyclin D1, which is essential for initiating cyclin D1 proteasomal degradation, was induced by obatoclax in one cell line but not others. Collectively, we reveal a novel anticancer mechanism of obatoclax by validating that obatoclax targets cyclin D1 for proteasomal degradation to downregulate cyclin D1 for inducing antiproliferation.


Assuntos
Carcinoma/metabolismo , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Ciclina D1/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Pirróis/farmacologia , Regulação para Baixo , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Células HCT116 , Células HT29 , Humanos , Indóis , Proteólise , Pirróis/toxicidade
15.
Org Biomol Chem ; 13(46): 11376-81, 2015 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-26442709

RESUMO

A procedure has been developed for the regioselective, high yielding synthesis of 2H-indazoles that involves direct alkylation of indazoles with various allyl and benzyl bromides, and α-bromocarbonyl compounds.

17.
Appl Opt ; 54(29): 8738-41, 2015 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-26479812

RESUMO

In this work, the photonic band gap (PBG) structure in a one-dimensional ferroelectric photonic crystal (PC) is theoretically investigated. We consider a PC, air/(AB)N/air, in which layer A is a dielectric of MgO and layer B is taken to be a ferroelectric of Ba0.55Sr0.45TiO3 (BSTO). With an extremely high value in the dielectric constant in BSTO, the calculated photonic band structure at microwave frequencies exhibits some interesting features that are significantly different from those in a usual dielectric-dielectric PC. First, the photonic transmission band consists of multiple and nearly discrete transmission peaks. Second, the calculated bandwidth of the PBG is nearly unchanged as the angle of incidence varies in the TE wave. The bandwidth will slightly reduce for the TM mode. Thus, a wide omnidirectional PBG can be obtained. Additionally, the effect of the thickness of the ferroelectric layer on the PBG is much more pronounced compared to the dielectric layer thickness. That is, the increase of ferroelectric thickness can significantly decrease the PBG bandwidth.

18.
Antimicrob Agents Chemother ; 58(9): 5181-90, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24957827

RESUMO

Polymyxins, which are increasingly being used to treat infections caused by multidrug-resistant bacteria, perform poorly against Serratia marcescens. To investigate the underlying mechanisms, Tn5 mutagenesis was performed and two mutants exhibiting increased polymyxin B (PB) susceptibility were isolated. The mutants were found to have Tn5 inserted into the arnB and arnC genes. In other bacteria, arnB and arnC belong to the seven-gene arn operon, which is involved in lipopolysaccharide (LPS) modification. LPSs of arn mutants had greater PB-binding abilities than that of wild-type LPS. Further, we identified PhoP, a bacterial two-component response regulator, as a regulator of PB susceptibility in S. marcescens. By the reporter assay, we found PB- and low-Mg2+-induced expression of phoP and arn in the wild-type strain but not in the phoP mutant. Complementation of the phoP mutant with the full-length phoP gene restored the PB MIC and induction by PB and low Mg2+ levels, as in the wild type. An electrophoretic mobility shift assay (EMSA) further demonstrated that PhoP bound directly to the arn promoter. The PB challenge test confirmed that pretreatment with PB and low Mg2+ levels protected S. marcescens from a PB challenge in the wild-type strain but not in the phoP mutant. Real-time reverse transcriptase-PCR also indicated that PB serves as a signal to regulate expression of ugd, a gene required for LPS modification, in S. marcescens through a PhoP-dependent pathway. Finally, we found that PB-resistant clinical isolates displayed greater expression of arnA upon exposure to PB than did susceptible isolates. This is the first report to describe the role of S. marcescens arn in PB resistance and its modulation by PB and Mg2+ through the PhoP protein.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Polimixina B/farmacologia , Serratia marcescens/efeitos dos fármacos , Proteínas de Bactérias/fisiologia , Farmacorresistência Bacteriana/genética , Ensaio de Desvio de Mobilidade Eletroforética , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/genética , Técnicas de Inativação de Genes , Genes Bacterianos/genética , Loci Gênicos/genética , Testes de Sensibilidade Microbiana , Óperon/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Serratia marcescens/genética
19.
Electrophoresis ; 35(11): 1751-5, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24535662

RESUMO

In this study, detection of 20 FITC-derivatized amino acids using an MEEKC-LIF was demonstrated. In order to achieve good separation for hydrophobic amino acids, the MEEKC method was employed and detection limits were obtained in the range of 0.32-2.2 nM, which is comparable to previous reports on amino acid analyses. Furthermore, a significant reduction in the reaction time from 1 h for conventional derivatization to 3 min for the microwave-assisted derivatization was observed and achieved, as opposed to the traditional pretreatment of real sample due to its complexity prior to the analysis of amino acid content. Finally, this microwave-assisted derivatization MEEKC-LIF method successfully determined amino acids in beverage, food, and biological samples (rat brain) with good recovery.


Assuntos
Aminoácidos/análise , Bebidas/análise , Química Encefálica , Cromatografia Capilar Eletrocinética Micelar/métodos , Animais , Emulsões/química , Fluoresceína-5-Isotiocianato/análise , Fluorescência , Lasers , Limite de Detecção , Masculino , Micro-Ondas , Ratos , Espectrometria de Fluorescência
20.
World J Emerg Surg ; 19(1): 25, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926694

RESUMO

BACKGROUND: Monitoring Intraabdominal Pressure (IAP) is essential in critical care, as elevated IAP can lead to severe complications, including Abdominal Compartment Syndrome (ACS). Advances in technology, such as digital capsules, have opened new avenues for measuring IAP non-invasively. This study assesses the feasibility and effectiveness of using a capsular device for IAP measurement in an animal model. METHOD: In our controlled experiment, we anesthetized pigs and simulated elevated IAP conditions by infusing CO2 into the peritoneal cavity. We compared IAP measurements obtained from three different methods: an intravesical catheter (IAPivp), a capsular device (IAPdot), and a direct peritoneal catheter (IAPdir). The data from these methods were analyzed to evaluate agreement and accuracy. RESULTS: The capsular sensor (IAPdot) provided continuous and accurate detection of IAP over 144 h, with a total of 53,065,487 measurement triplets recorded. The correlation coefficient (R²) between IAPdot and IAPdir was excellent at 0.9241, demonstrating high agreement. Similarly, IAPivp and IAPdir showed strong correlation with an R² of 0.9168. CONCLUSION: The use of capsular sensors for continuous and accurate assessment of IAP marks a significant advancement in the field of critical care monitoring. The high correlation between measurements from different locations and methods underscores the potential of capsular devices to transform clinical practices by providing reliable, non-invasive IAP monitoring.


Assuntos
Estudos de Viabilidade , Hipertensão Intra-Abdominal , Animais , Suínos , Hipertensão Intra-Abdominal/diagnóstico , Hipertensão Intra-Abdominal/fisiopatologia , Monitorização Fisiológica/métodos , Monitorização Fisiológica/instrumentação , Pressão , Cavidade Abdominal/fisiologia , Cavidade Abdominal/fisiopatologia , Reprodutibilidade dos Testes , Modelos Animais de Doenças
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