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Zoledronic acid (ZA) is one of the most important and effective class of anti-resorptive drug available among bisphosphonate (BP), which could effectively reduce the risk of skeletal-related events, and lead to a treatment paradigm for patients with skeletal involvement from advanced cancers. However, the exact molecular mechanisms of its anticancer effects have only recently been identified. In this review, we elaborate the detail mechanisms of ZA through inhibiting osteoclasts and cancer cells, which include the inhibition of differentiation of osteoclasts via suppressing receptor activator of nuclear factor κB ligand (RANKL)/receptor activator of nuclear factor κB (RANK) pathway, non-canonical Wnt/Ca2+/calmodulin dependent protein kinase II (CaMKII) pathway, and preventing of macrophage differentiation into osteoclasts, in addition, induction of apoptosis of osteoclasts through inhibiting farnesyl pyrophosphate synthase (FPPS)-mediated mevalonate pathway, and activation of reactive oxygen species (ROS)-induced pathway. Furthermore, ZA also inhibits cancer cells proliferation, viability, motility, invasion and angiogenesis; induces cancer cell apoptosis; reverts chemoresistance and stimulates immune response; and acts in synergy with other anti-cancer drugs. In addition, some new ways for delivering ZA against cancer is introduced. We hope this review will provide more information in support of future studies of ZA in the treatment of cancers and bone cancer metastasis.
Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Osteoclastos/citologia , Ácido Zoledrônico/farmacologia , Animais , Neoplasias Ósseas/metabolismo , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ácido Zoledrônico/uso terapêuticoRESUMO
Atomic engineering of the basal plane active sites in MoS2 holds great promise to boost the electrocatalytic activity for hydrogen evolution reactions (HER), yet the performance optimization and mechanism exploration are still not satisfactory. Herein, we proposed a dual-plasma engineering strategy to implant Ti and N heteroatoms into the basal plane of MoS2 supported by Ni3S2 nanorods on nickel foam (MSNF) for efficient electrocatalysis of HER. Owing to the low formation energy of Ti dopants in MoS2 and the extra charge carriers introduced by N dopants, the optimally codoped samples N1.0@Ti500-MSNF demonstrate significant morphology changes from nanorods to urchin-like nanospheres with the surface active areas increased by seven-fold, as well as enhanced electrical conductivity in comparison with the nondoped counterparts. The HER performance of N1.0@Ti500-MSNF is comparable with the Pt-based catalyst: overpotential of 26 mV at 20 mA cm-2, Tafel slope of 35.6 mV dec-1, and long-term stability over 50 h. First-principles calculation reveals that N doping accelerates the dissociation of water molecules while Ti doping activates the adjacent S sites for hydrogen adsorption by lowering the Gibbs free energy, resulting in excellent HER activity. This work thus provides an effective strategy for basal plane engineering of MoS2 heterostructures toward high-performance HER and sustainable energy supply at reasonable costs.
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A Ni/silicon microchannel plate (Ni/Si MCP) electrode modified with poly(3,4-ethylenedioxythiophene) (PEDOT) was successfully fabricated. The analytical performance of prepared electrode for the simultaneous determination of ascorbic acid (AA), dopamine (DA) and uric acid (UA) was investigated by using cyclic voltammetry and differential pulse voltammetry (DPV). The sensitivities for AA, DA and UA obtained by DPV are 5.39 A m(-2) mM(-1), 0.054 A m(-2) µM(-1) and 0.022 A m(-2) µM(-1), respectively. The calculated detection limits were 10 µM (AA), 1.5 µM (DA) and 2.7 µM (UA). The prepared electrode was successfully applied to the detection of AA, DA and UA in urine samples. The experiments illustrate that Ni/Si MCP is a good electrode material which provides a large surface-to-volume ratio and enhances the selectivity and sensitivity.
Assuntos
Ácido Ascórbico/análise , Compostos Bicíclicos Heterocíclicos com Pontes/química , Dopamina/análise , Níquel/química , Polímeros/química , Silício/química , Ácido Úrico/análise , Técnicas Eletroquímicas/métodos , Eletrodos , HumanosRESUMO
Drugs can be modified or degraded by the gut microbiota, which needs to be considered in personalized therapy. The clinical efficacy of the antidiabetic drug acarbose, an inhibitor of α-glucosidase, varies greatly among individuals for reasons that are largely unknown. Here we identify in the human gut acarbose-degrading bacteria, termed Klebsiella grimontii TD1, whose presence is associated with acarbose resistance in patients. Metagenomic analyses reveal that the abundance of K. grimontii TD1 is higher in patients with a weak response to acarbose and increases over time with acarbose treatment. In male diabetic mice, co-administration of K. grimontii TD1 reduces the hypoglycaemic effect of acarbose. Using induced transcriptome and protein profiling, we further identify an acarbose preferred glucosidase, Apg, in K. grimontii TD1, which can degrade acarbose into small molecules with loss of inhibitor function and is widely distributed in human intestinal microorganisms, especially in Klebsiella. Our results suggest that a comparatively large group of individuals could be at risk of acarbose resistance due to its degradation by intestinal bacteria, which may represent a clinically relevant example of non-antibiotic drug resistance.
Assuntos
Acarbose , Microbioma Gastrointestinal , Hipoglicemiantes , Hipoglicemiantes/metabolismo , Humanos , Acarbose/metabolismo , Klebsiella/genética , Klebsiella/metabolismo , Inibidores de Glicosídeo Hidrolases/metabolismo , Resistência a Medicamentos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Animais , Camundongos , Camundongos Endogâmicos C57BL , RNA-Seq , Adolescente , Adulto Jovem , Adulto , Idoso , Idoso de 80 Anos ou maisRESUMO
Inexpensive and efficient catalysts are crucial to industrial adoption of the electrochemical hydrogen evolution reaction (HER) to produce hydrogen. Although two-dimensional (2D) MoS2 materials have large specific surface areas, the catalytic efficiency is normally low. In this work, Ag and other dopants are plasma-implanted into MoS2 to tailor the surface and interface to enhance the HER activity. The HER activty increases initially and then decreases with increasing dopant concentrations and implantation of Ag is observed to produce better results than Ti, Zr, Cr, N, and C. At a current density of 400 mA cm-2 , the overpotential of Ag500-MoS2 @Ni3 S2 /NF is 150 mV and the Tafel slope is 41.7 mV dec-1 . First-principles calculation and experimental results reveal that Ag has higher hydrogen adsorption activity than the other dopants and the recovered S sites on the basal plane caused by plasma doping facilitate water splitting. In the two-electrode overall water splitting system with Ag500-MoS2 @Ni3 S2 /NF, a small cell voltage of 1.47 V yields 10 mA cm-2 and very little degradation is observed after operation for 70 hours. The results reveal a flexible and controllable strategy to optimize the surface and interface of MoS2 boding well for hydrogen production by commercial water splitting.
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Various silicon-based microchannels with different internal surface morphologies were investigated to improve the growth of carbon nanotubes on the inner surface of the pore wall. The morphology of the samples prepared under different conditions was characterized by scanning electron microscopy. Parameters such as concentration of hydrofluoric acid, potential, current density, temperature and so on were found to affect the inner surface of the pore wall. Experiments showed that certain etchant concentration, current density and temperature were important to the fabrication of samples with the regular structure and good morphology. By considering these factors, samples with the proper internal pore surface could be fabricated. Nickel was adopted as the metallic catalyst during electroless deposition onto the surface of the pore wall and bottom. The nickel/silicon microchannels were characterized and found to be suitable for the fabrication of carbon nanotubes by thermal chemical vapor deposition.
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We propose a stacked dual-band quantum well infrared photodetector (QWIP) integrated with a double-layer gold disk. Two 10-period quantum wells (QW) operating at different wavelengths are stacked together, and gold nano-disks are integrated on their respective surfaces. Numerical calculations by finite difference time domain (FDTD) showed that the best enhancement can be achieved at 13.2 and 11.0 µm. By integrating two metal disks, two plasmon microcavity structures can be formed with the substrate to excite localized surface plasmons (LSP) so that the vertically incident infrared light can be converted into electric field components perpendicular to the growth direction of the quantum well (EZ). The EZ electric field component can be enhanced up to 20 times compared to the incident light, and it is four times that of the traditional two-dimensional hole array (2DHA) grating. We calculated the enhancement factor and coupling efficiency of the device in the active region of the quantum well. The enhancement factor of the active region of the quantum well on the top layer remains above 25 at the wavelength of 13.2 µm, and the enhancement factor can reach a maximum of 45. Under this condition, the coupling efficiency of the device reaches 2800%. At the wavelength of 11.0 µm, the enhancement factor of the active region of the quantum well at the bottom is maintained above 6, and the maximum can reach about 16, and the coupling efficiency of the device reaches 800%. We also optimized the structural parameters and explored the influence of structural changes on the coupling efficiency. When the radius (r1, r2) of the two metal disks increases, the maximum coupling efficiency will be red-shifted as the wavelength increases. The double-layer gold disk structure we designed greatly enhances the infrared coupling of the two quantum well layers working at different wavelengths in the dual-band quantum well infrared photodetector. The structure we designed can be used in stacked dual-band quantum well infrared photodetectors, and the active regions of quantum wells working at two wavelengths can enhance the photoelectric coupling, and the enhancement effect is significant. Compared with the traditional optical coupling structure, the structure we proposed is simpler in process and has a more significant enhancement effect, which can meet the requirements of working in complex environments such as firefighting, night vision, and medical treatment.
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Flexible rechargeable Zn//Ni batteries are attractive owing to their high energy density, good safety, inexpensive cost, and simple manufacturing process. However, the effects of metal doping on the properties of Ni3S2 cathodes in Zn/Ni batteries are not well understood. Herein, a binder-free Ni3S2 electrode is doped with Zn and Co and the nanocomposite structures are prepared on nickel foam (named ZCNS/NF) by a simple two-step hydrothermal technique. The ZCNS/NF//Zn battery delivers excellent electrochemical performance such as a working voltage window can be as high as 2.05 V, a capacity of 2.3 mAh cm-2 at 12 mA cm-2, and 82% retention going through 2000 cycles at 20 mA cm-2. The battery has a maximum output area energy density of 1.8 mWh cm-2 (462 Wh kg-1) and a power density of 36.8 mW cm-2 (9.2 kW kg-1). In addition, the flexible battery remains operational while being bent at a large angle and even punctured. The high performance and robustness of the composite cathode suggest that the design principle and materials have large commercial potential in Ni//Zn batteries.
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BACKGROUND: Brunner's gland adenoma is a rare benign tumor arising from Brunner's glands. It is mostly small in size, and patients with this tumor are asymptomatic. CASE PRESENTATION: We report the case of a 63-year-old woman with upper gastrointestinal obstruction for almost 10 years, who was pathologically diagnosed with large Brunner's gland adenoma of the duodenum. Postoperatively, no sign of recurrence has been noted until now. CONCLUSION: This study may help clinicians to understand and provide a more accurate diagnosis of Brunner's gland adenoma.
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RATIONALE: Pleomorphic liposarcoma (PLS), is a rare subtype of liposarcoma, and is considered to be of the highest malignancy grade. PATIENT CONCERNS: We aimed to analyze the clinical features, diagnosis, treatment, and recurrence of the 6 cases of PLS. DIAGNOSES: Six cases with confirmed pathological PLS presented at out hospital from January 2003 to January 2017. The postoperative pathology of 5 cases confirmed PLS, and the other was confirmed as PLS with well-differentiated liposarcoma. INTERVENTIONS: All 6 patients underwent complete tumor resection at the time of the first definite diagnosis, and one of them had underwent 3 cycles of chemotherapy treatment. OUTCOMES: There were 4 cases with local recurrence and surgery was repeated after the first radical excision. One case was not recurrent after 27 months post-operation, and the other was lost. The shortest recurrence time of all of these cases was 4 months, and the longest was 29 months after the first radical surgery. LESSONS: PLS is a rare and high-grade malignancy with high recurrence, poor prognosis, and its treatment is still highly controversial. More studies are required to determine the appropriate treatment and therapeutic strategies to improve the survival rate of patients with PLS, as the disease is associated with frequent relapse.
Assuntos
Lipossarcoma/patologia , Neoplasias Pélvicas/patologia , Neoplasias Retroperitoneais/patologia , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Lipossarcoma/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Pélvicas/cirurgia , Neoplasias Retroperitoneais/cirurgia , Neoplasias Cutâneas/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Liposarcoma, which develops in adipose tissue, is one of the most common soft tissue sarcomas. It appears mostly in the lower limbs, particularly in the thigh and limb girdles, followed by the upper extremities, thoracoabdominal wall, and the internal trunk and retroperitoneum. Pleomorphic liposarcoma (PLS), a rare subtype of liposarcoma is considered a highgrade malignancy. CASE PRESENTATION: We present a case of primary PLS in the left fallopian tube of a 47-year-old female. Ten months previously, she was diagnosed with PLS of the left fallopian tube in another hospital and had a wide excision of left fallopian tube mass, including total abdominal hysterectomy and bilateral salpingo-oophorectomy for left fallopian tube PLS. Presently, she has developed a recurrence and metastasis of PLS in the pelvic and abdominal cavities. CONCLUSION: This may be the first case of primary fallopian tube PLS, wherein the prognosis of this patient was poor due to the high-grade malignancy of PLS.
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Nano energetic materials have attracted great attention recently owing to their potential applications for both civilian and military purposes. By introducing silicon microchannel plates (Si-MCPs) three-dimensional (3D)-ordered structures, monocrystalline MnMoO4 with a size of tens of micrometres and polycrystalline MnMoO4 nanoflakes are produced on the surface and sidewall of nickel-coated Si-MCP, respectively. The MnMoO4 crystals ripen controllably forming polycrystalline nanoflakes with lattice fringes of 0.542 nm corresponding to the [Formula: see text] plane on the sidewall. And these MnMoO4 nanoflakes show apparent thermite performance which is rarely reported and represents MnMoO4 becoming a new category of energetic materials after nanocrystallization. Additionally, the nanocrystallization mechanism is interpreted by ionic diffusion caused by 3D structure. The results indicate that the Si-MCP is a promising substrate for nanocrystallization of energetic materials such as MnMoO4.
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An activated RDX-Fe2O3 xerogel in a Si-microchannel plate (MCP) has been successfully prepared by a novel propylene epoxide-mediated sol-gel method. A decrease of nearly 40 °C in decomposition temperature has been observed compared with the original cyclotrimethylene trinitramine (RDX). The RDX-Fe2O3 xerogel can release gas and solid matter simultaneously, and the ratio of gas to solid can be tailored easily by changing the initial proportions of RDX and FeCl3·6H2O, which significantly enhances the explosive and propulsion effects and is of great benefit to the applications. The approach, which is simple, safe, and fully compatible with MEMS technology, opens a new route to the introduction of organic energetic materials to a silicon substrate.
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A silicon microchannel plate (MCP) array electrode modified with over-oxidized polypyrrole (OPPy) has been fabricated to detect glucose. The morphology and structure of the electrode are characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The OPPy modified silicon MCP array electrode exhibits high electrocatalytic activity as well as excellent selectivity to the electrochemical oxidation of glucose. At a potential of +0.08 V, good sensitivity of 0.37 mA mM(-1) cm(-2) and detection limit of 2.06 µM are attained. The linear range is up to 24 mM with a linear correlation coefficient of 0.997. Furthermore, the electrode is highly resistant to interfering substances because the effects of common coexisting substances can be effectively eliminated by the OPPy film and the response in the current to interferences on the electrode surface is almost negligible. This novel electrode has high potential in nonenzymatic detection of glucose.