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1.
Opt Lett ; 46(23): 5894-5897, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34851917

RESUMO

Nonlinear optical coefficients are important parameters for nonlinear optical crystals. Based on the previously disclosed BaGa4Se7 crystal coefficients, the optimum phase-matching direction with the largest effective nonlinear optical coefficient appears in the second octant (90∘<θ<180∘, 0∘<ϕ<90∘). In this study, a recalibration was performed using the second-harmonic-generation method, and it was confirmed that the optimum phase-matching direction of the BaGa4Se7 crystal is located in its XZ principal plane (ϕ=0∘). Therefore, this study will serve as a good reference for future applications of this excellent crystal.

2.
J Med Chem ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34852203

RESUMO

Metastasis is a major contributor of death in cancer patients, and there is an urgent need for effective treatments of metastatic malignancies. Herein, ketoprofen (KP) and loxoprofen (LP) platinum(IV) complexes with antiproliferative and antimetastatic properties were designed and prepared by integrating chemotherapy and immunotherapy targeting cyclooxygenase-2 (COX-2), matrix metalloproteinase-9 (MMP-9), and programmed death ligand 1 (PD-L1), besides DNA. A mono-KP platinum(IV) complex with a cisplatin core is screened out as a candidate possessing potent anti-proliferative and anti-metastasis activities both in vitro and in vivo. It induces serious DNA damage and further leads to high expression of γ-H2AX and p53. Moreover, it promotes apoptosis of tumor cells through mitochondrial apoptotic pathway Bcl-2/Bax/caspase3. Then, COX-2, MMP-9, NLRP3, and caspase1 as pivotal enzymes igniting inflammation and metastasis are obviously inhibited. Notably, it significantly improves immune response through restraining the expression of PD-L1 to increase CD3+ and CD8+ T infiltrating cells in tumor tissues.

3.
Inorg Chem ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34847322

RESUMO

Disordered crystals have attracted immense attention for the generation of ultrashort laser pulses due to their good thermomechanical characteristics and wide emission bandwidths. In this work, a Gd-based orthophosphate crystal, GdSr3(PO4)3, (GSP), and a Nd3+-doped GdSr3(PO4)3 crystal, (Nd:GSP), were obtained by the Czochralski method. The crystal structure, optical properties, electronic band structure, laser damage threshold, and hardness of the GSP crystal were comprehensively investigated. It exhibited a disordered structure due to the random distribution of Sr and Gd atoms in the same Wyckoff site, which caused inhomogeneous spectral broadening. Additionally, it exhibited a short UV absorption cutoff edge (<200 nm), a large band gap (5.81 eV), and a high laser damage threshold (∼1850 MW/cm2). The spectral properties and Judd-Ofelt calculations of the Nd:GSP crystals were analyzed. A wide absorption band at 803 nm, with a full width at half-maximum value of 20 nm, makes the Nd:GSP crystal suitable for the efficient pumping of AlGaAs laser diodes. Sub-100-fs pulses could be supported by its 25 nm emission bandwidth. Hence, the GSP crystal could be a promising disordered crystal laser matrix.

4.
Int J Biol Macromol ; 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34780896

RESUMO

Hydrogel, as a three-dimensional material with high water content, has unique physicochemical and variable mechanical properties. Natural polysaccharide-based composite hydrogels are very popular within medical industry as these viscoelastic materials are non-toxic, biodegradable, bioabsorbable, and biocompatible. This research investigates the engineering of novel composite hydrogels from natural polysaccharides salecan and curdlan without any structural modification and chemical crosslinking. The scanning electron microscopy, Fourier transform infrared spectroscopy and various rheological methods were employed to investigate the morphology, molecular interaction, and flow behavior of the samples respectively. The key rheological parameters were compared using the Power Law, Herschel-Bulkley and Arrhenius models. This is the first study reporting a novel composite hydrogel made from Salecan and Curdlan with ideal elasticity, enhanced thermostability, good injectability, self-recovery and other rheological properties that will pave the way for application in different fields.

6.
Eur J Pharm Sci ; 168: 106036, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34637896

RESUMO

In this study, the amorphous solid dispersions of cyclosporine A (CsA-ASDs) were prepared by hot melt extrusion (HME) with PVP K12 as carrier to improve the oral bioavailability of CsA. The polymers were screened by solubilization and recrystallization inhibition experiments, then the CsA-ASDs were prepared with optimized technological parameters and characterized on thermodynamics and morphology. The results showed that CsA was dispersed among PVP K12 as amorphous form in CsA-ASDs, and the infrared spectrum testified that there was possible hydrogen bond interaction between CsA and PVP K12. The in vivo pharmacokinetics of CsA formulations in rats were analyzed via LC-MS. The AUC of CsA-ASD tablets increased by 7.3 times compared to CsA bulk powder and 3.1 times in contrast to CsA-PM tablets, respectively. The experiment proved that CsA-ASD tablets significantly improved the dissolution and absorption of the drug. This study had a reference value for the bioavailability improvement of oral CsA preparations.

7.
Opt Lett ; 46(18): 4454-4457, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34525020

RESUMO

In this Letter, to the best of our knowledge, we present the first thulium (Tm) single-crystal fiber (SCF) laser with free-space propagation of the laser beam only. The SCF is equipped with diffusion-bonded end caps of undoped YAG for better thermal management and enhancement of pump guiding. By utilizing mode matching and pump guiding in different SCF parts, an output power of 9.1 W is achieved at ∼2.02µm with a slope efficiency of 49.4%. This straightforward approach, which is also simple to realize and is based on combining the advantages of fiber-geometry structure and crystalline properties of Tm:YAG, is expected to be useful for 2 µm amplification stages in different time formats as well.

8.
Carbohydr Polym ; 273: 118562, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34560973

RESUMO

Amorphous solid dispersions (ASDs) are regarded as one of the most promising techniques for poorly-soluble active pharmaceutical ingredients (API). However, the thermodynamic instability of ASDs at supersaturated state makes them easy to recrystallize in aqueous media. In this study, ritonavir (RTV) was selected as a model drug for evaluating the solubility enhancement and recrystallization inhibition effect of various cellulose derivatives and the combinations of them with typical surfactants. Combination of HPMCAS-HF/SLS was filtrated for preparing ternary RTV solid dispersions (RTV SD) via solvent evaporation method. RTV SD exhibited enhanced dissolution manner, while the oral bioavailability of RTV SD was equivalent with the Reference Standard Norvir® but increased significantly compared to the ternary physical mixture. Thus, the ternary SD system might be promisingly employed as efficient drug delivery system for RTV, while the HPMCAS-HF/SLS combination could be recommended as effective excipient for fabricating steady solid dispersions loading poorly soluble API.

9.
Int J Nanomedicine ; 16: 5513-5529, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34429597

RESUMO

Background: Platinum(IV) complexes with inflammation inhibitory properties are much favored in improving antitumor activities. Nanodrug-delivery system as a preferable measure for antitumor therapy are widely explored in platinum(IV) drug delivery. Purpose: The aim for this study was to develop novel bovine serum albumin (BSA) nanoparticles (NPs) based on naproxen platinum(IV) complexes to display a synergistic antitumor mechanism targeting cyclooxygenase-2 (COX-2), metalloproteinase-9 (MMP-9) and inducible nitric oxide synthase (iNOS). Methods: Herein, we reported the preparation of two BSA NPs of naproxen platinum(IV) complexes, and their antitumor activities were investigated in vitro and in vivo. Results: Both NPs possessed relatively uniform size and good stability for 30 days in aqueous solution. They exhibited prominent antitumor activities in vitro, and showed great potential in reversing drug resistance. Furthermore, these two NPs played superior tumor growth suppression in vivo in contrast to the free compounds, which were comparable to that of cisplatin and oxaliplatin, but induced lower toxic influences than platinum(II) drugs especially to spleen and liver. Moreover, the naproxen platinum(IV) NPs could decrease tumor inflammation targeting COX-2, MMP-9 and iNOs, and decreasing NO production, which would be in favor of enhancing the antitumor competence, and reducing toxicity. Conclusion: Taken together, BSA NPs of naproxen platinum(IV) complexes demonstrated a powerful antitumor efficacy in vitro and in vivo. The platinum(IV) NPs with inflammation inhibitory competence targeting multiple enzymes reported in this work afford a new strategy for the development of antitumor therapy to overcome drawbacks of clinical platinum(II) drugs.


Assuntos
Antineoplásicos , Nanopartículas , Linhagem Celular Tumoral , Humanos , Inflamação/tratamento farmacológico , Naproxeno , Platina , Soroalbumina Bovina
10.
Opt Lett ; 46(14): 3428-3431, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34264230

RESUMO

Kerr-lens mode-locked solid-state laser operation at ∼2µm is investigated. Using a Tm3+-doped (Lu,Sc)2O3 "mixed" sesquioxide ceramic as a gain medium, pulses as short as 58 fs are generated at ∼2081nm via soft-aperture Kerr-lens mode locking. The average output power amounts to 220 mW at a pulse repetition rate of 84.8 MHz. The emitted spectrum at the long-wavelength wing extends to >2.2µm which is attributed to vibronic transitions of the Tm3+ ions. The latter is found to be essential for generating pulses with durations in the 50 fs range.

11.
Pharmaceutics ; 13(6)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34072083

RESUMO

The quality control of drug products during manufacturing processes is important, particularly the presence of different polymorphic forms in active pharmaceutical ingredients (APIs) during production, which could affect the performance of the formulated products. The objective of this study was to investigate the phase transformation of fexofenadine hydrochloride (FXD) and its influence on the quality and performance of the drug. Water addition was key controlling factor for the polymorphic conversion from Form I to Form II (hydrate) during the wet granulation process of FXD. Water-induced phase transformation of FXD was studied and quantified with XRD and thermal analysis. When FXD was mixed with water, it rapidly converted to Form II, while the conversion is retarded when FXD is formulated with excipients. In addition, the conversion was totally inhibited when the water content was <15% w/w. The relationship between phase transformation and water content was studied at the small scale, and it was also applicable for the scale-up during wet granulation. The effect of phase transition on the FXD tablet performance was investigated by evaluating granule characterization and dissolution behavior. It was shown that, during the transition, the dissolved FXD acted as a binder to improve the properties of granules, such as density and flowability. However, if the water was over added, it can lead to the incomplete release of the FXD during dissolution. In order to balance the quality attributes and the dissolution of granules, the phase transition of FXD and the water amount added should be controlled during wet granulation.

12.
Nutrition ; 89: 111286, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34090215

RESUMO

OBJECTIVE: Malnutrition is common and related to negative prognosis in patients with gastric cancer (GC). The Global Leadership Initiative on Malnutrition (GLIM), a novel consensus for the diagnosis of malnutrition, was proposed recently. However, the roles of GLIM in diagnosing malnutrition and predicting overall survival (OS) in patients with GC have been unclear. METHOD: We conducted a multicenter, observational cohort study including 877 hospitalized patients with GC 2013 through 2018. Different anthropometric measurements were compared to assess reduced muscle mass. Kaplan-Meier curves and multivariate Cox regression were used to analyze the relationship between GLIM-defined malnutrition and the OS of patients with GC. Independent prognostic variables were incorporated to develop a nomogram for individualized survival prediction. The calibration curve was used to determine the predictive accuracy and discriminatory capacity of the nomogram. In addition, 219 patients with GC were enrolled for external validation. RESULTS: A total of 464 (53%) patients with GC were diagnosed with malnutrition. Patients diagnosed with severe malnutrition based on either midarm circumference or body weight-standardized hand grip strength had a shorter median survival time (16.7 mo; interquartile range, 8.4-32.7 mo) and a higher hazard ratio (HR, 1.49; 95% CI, 1.15-1.92; P = 0.002). Severe malnutrition was an independent risk factor for OS (HR, 1.32; 95% CI, 1.02-1.71; P = 0.038). The GLIM nomogram showed good performance in predicting 3-y survival in patients with GC. CONCLUSIONS: Our findings support the effectiveness of GLIM in diagnosing malnutrition and predicting OS in patients with GC.


Assuntos
Desnutrição , Neoplasias Gástricas , Força da Mão , Humanos , Liderança , Desnutrição/diagnóstico , Músculos , Avaliação Nutricional , Neoplasias Gástricas/complicações , Neoplasias Gástricas/diagnóstico
13.
Food Funct ; 12(16): 7126-7144, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34180492

RESUMO

The co-encapsulation of multiple bioactive components in a carrier may produce synergistic effects and improve health benefits. In this study, the interactions of ß-lactoglobulin (ß-LG) with epigallocatechin-3-gallate (EGCG) and/or piceatannol (PIC)/oxyresveratrol (OXY) were investigated by multispectroscopic techniques, isothermal titration calorimetry, and molecular docking. The static quenching mechanism of ß-LG by EGCG, PIC and OXY was confirmed by fluorescence spectroscopy and UV-vis absorption difference spectroscopy. The binding sites of these three polyphenols in ß-LG were identified by site marking fluorescence experiments and molecular docking. The thermodynamic parameters of the ß-LG + EGCG/PIC/OXY binary complex and ß-LG + EGCG + PIC/OXY ternary complex were obtained from fluorescence data and used to analyze the main driving force for complex formation. The exothermic binding process was further confirmed by isothermal titration calorimetry. The α-helical content, particle size and morphology of free and ligand-bound ß-LG were determined by circular dichroism spectroscopy, dynamic light scattering and transmission electron microscopy, respectively. The effect of EGCG, PIC and OXY on the conformation of ß-LG was studied by Fourier transform infrared spectroscopy. In addition, the maximum synergistic antioxidant activity between EGCG and PIC/OXY was obtained by response surface analysis. The effects of ß-LG in the binary and ternary systems on the antioxidant activity, stability, solubility and cytotoxicity of the polyphenols were also studied. Finally, the different cytotoxicities of the complexes and nanoparticles of the binary and ternary systems were compared. The results of this study are expected to provide a theoretical basis for the development of ß-LG-based carriers co-encapsulating a variety of bioactive components.

15.
Nat Chem Biol ; 17(10): 1065-1074, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34168367

RESUMO

The clinical benefits of pan-mTOR active-site inhibitors are limited by toxicity and relief of feedback inhibition of receptor expression. To address these limitations, we designed a series of compounds that selectively inhibit mTORC1 and not mTORC2. These 'bi-steric inhibitors' comprise a rapamycin-like core moiety covalently linked to an mTOR active-site inhibitor. Structural modification of these components modulated their affinities for their binding sites on mTOR and the selectivity of the bi-steric compound. mTORC1-selective compounds potently inhibited 4EBP1 phosphorylation and caused regressions of breast cancer xenografts. Inhibition of 4EBP1 phosphorylation was sufficient to block cancer cell growth and was necessary for maximal antitumor activity. At mTORC1-selective doses, these compounds do not alter glucose tolerance, nor do they relieve AKT-dependent feedback inhibition of HER3. Thus, in preclinical models, selective inhibitors of mTORC1 potently inhibit tumor growth while causing less toxicity and receptor reactivation as compared to pan-mTOR inhibitors.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Desenho de Fármacos , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Relação Estrutura-Atividade
16.
Med Ultrason ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33793697

RESUMO

AIMS: In the present study, a meta-analysis was performed to evaluate the diagnostic value of endobronchial ultrasound (EBUS) elastography for differentiating benign and malignant hilar and mediastinal lymph nodes (LNs). MATERIAL AND METHODS: A comprehensive literature search was carried out through PubMed, Embase, and Cochrane Library. Two authors screened the papers and extracted the data independently and any discrepancies were resolved by discussion. The methodolog-ical quality of each included study was assessed by the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and area under the curve were calculated to evaluate the value of EBUS elastography for hilar and mediastinal LNs. RESULTS: Seventeen studies with the number of 2307 LNs were included. There was significant heterogeneity across the included studies. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio for the diagnosis of hilar and mediastinal LNs by EBUS elastography were 0.90 (95% confidence interval [CI], 0.84-0.94), 0.78 (95% CI, 0.74-0.81), 4.1 (95% CI, 3.4-4.9), 0.12 (95% CI, 0.07-0.21) and 33 (95% CI, 17-64), respectively. Furthermore, area under the curve was calculated to be 0.86 (95% CI, 0.82-0.88). CONCLUSION: EBUS elastography is a valuable technology in the differentiation of benign and malignant hilar and mediastinal LNs and could provide supplementary diagnostic information during endobronchial ultrasound-guided transbronchial needle aspiration. The combination of EBUS elastography and B-mode EBUS could improve the diagnostic accuracy for hilar and mediastinal LNs.

17.
Angew Chem Int Ed Engl ; 60(20): 11326-11334, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33626224

RESUMO

Two-dimensional (2D) nanomaterials are attracting much attention due to their excellent electronic and optical properties. Here, we report the first experimental preparation of two free-standing mercurated graphyne nanosheets via the interface-assisted bottom-up method, which integrates both the advantages of metal center and graphyne. The continuous large-area nanosheets derived from the chemical growth show the layered molecular structural arrangement, controllable thickness and enhanced π-conjugation, which result in their stable and outstanding broadband nonlinear saturable absorption (SA) properties (at both 532 and 1064 nm). The passively Q-switched (PQS) performances of these two nanosheets as the saturable absorbers are comparable to or higher than those of the state-of-the-art 2D nanomaterials (such as graphene, black phosphorus, MoS2 , γ-graphyne, etc.). Our results illustrate that the two metallated graphynes could act not only as a new class of 2D carbon-rich materials, but also as inexpensive and easily available optoelectronic materials for device fabrication.

18.
Med Ultrason ; 23(2): 203-212, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-33220035

RESUMO

AIMS: Foot and ankle injuries are a common presenting complaint in the emergency department. The diagnosis of foot and ankle fractures is conventionally accomplished through X-rays. Whether ultrasound (US) can be considered as a primary scanning modality is still a controversial issue; therefore, we did a meta-analysis to synthesize the diagnostic performance ofultrasound for foot and ankle fractures. MATERIAL AND METHODS: A comprehensive search was carried out to identify studies in which patients with clinically suspected foot and ankle fractures were assessed by US. Two investigators independently screened the literature and extracted the data. Any discrepancies were resolved via discussion. Study quality was assessed by the Quality Assessment of Diagnostic Accuracy Studies 2 tool, and pooled sensitivity and specificity of various US findings were determined. RESULTS: Ten studies with a total of 1065 patients were included. There was significant heterogeneity across the included studies. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for the diagnosis of foot and ankle fractures by US were 0.96 (95% confidence interval [CI], 0.90-0.99), 0.94 (95% CI, 0.88-0.97), 15.0 (95% CI, 7.9-28.6), 0.04 (95% CI, 0.02-0.11), and 367 (95% CI, 101-1338), respectively. Furthermore, the summary receiver operating characteristic area under the curve was calculated to be 0.99. CONCLUSIONS: Ultrasound has an excellent diagnostic performance for foot and ankle fractures and should be considered as a primary and radiation-free scanning modality in the diagnosis of foot and ankle fractures.


Assuntos
Fraturas do Tornozelo , Traumatismos do Tornozelo , Fraturas do Tornozelo/diagnóstico por imagem , Traumatismos do Tornozelo/diagnóstico por imagem , Humanos , Radiografia , Sensibilidade e Especificidade , Ultrassonografia
19.
J Cancer ; 12(24): 7436-7444, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35003363

RESUMO

Background: Changes in platelet count (PLT) are strongly associated with patient survival and may be clinically indicative of certain underlying diseases. However, there were few studies on the prognosis of patients with cancer cachexia. Objective: The purpose of this study was to investigate the relationship between PLT and 1-year survival in patients with cancer cachexia. Methods: We performed a nested case-control study of data from a multicenter clinical study of cancer. There were 252 patients with cancer cachexia whose survival time was less than or equal to 1 year and 252 patients with cancer cachexia whose survival time was more than 1 year meeting the inclusion criteria. The mortality risk and the adjusted risk were estimated by logistic regression and displayed as odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: PLT was negatively correlated with 1-year overall survival (OS) of patients with cancer cachexia (increased per standard deviation (SD): OR = 1.29; 95% CI: 1.05-1.60; P = 0.018). The higher the PLT, the lower the OS of patients. When classified by dichotomy (D1 < 296×109/L, D2 ≥ 296×109/L), OS of patients in the D2 group was worse (OR = 2.18; 95% CI: 1.38-3.47; P = 0.001). When classified by quartile (Q1- Q3 < 305×109/L, Q4 ≥ 305×109/L), OS of patients in the Q4 group was poorer (OR = 1.82; 95% CI: 1.14-2.94; P = 0.013). In addition, patients with a low PLT (< 296×109/L) and either a high total bilirubin (TBIL) (≥ 17.1 µmol/L) or a smoking history had poor 1-year survival. Based on our primary cohort study, we conducted a survival analysis of 3130 patients with cancer cachexia and found that OS was better in patients with low PLT (< 296×109/L). Conclusion: PLT was negatively correlated with 1-year overall survival of patients with cancer cachexia.

20.
Biomed Res Int ; 2020: 1971324, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33313311

RESUMO

Objective: To optimize the allocation of nursing resources, we investigate an alternative strategy for indwelling catheter cleaning. Methods: The present study involved a total of 117 male patients and 54 female patients, who were catheterized after urinary surgery from Aug 2018 to Feb 2019. The samples of indwelling catheter cleaning solutions were divided by two parts for microbiological culture and microbiome analysis. Results: No pathogenic bacteria were observed in the microbiological culture of the indwelling catheter cleaning samples from 24 h-uncleaned group and 48 h-uncleaned group. The microbiome analysis also showed no significant difference in bacterial diversity and quantity of the indwelling catheter cleaning solutions between the two groups. Conclusion: The indwelling catheter cleaning for male after urinary surgery can be prolonged to 48 h. The result of this study provided reliable basis for optimizing the allocation of clinical nursing resources.


Assuntos
Infecções Relacionadas a Cateter/prevenção & controle , Cateterismo/métodos , Cateteres de Demora/efeitos adversos , Infecções Urinárias/terapia , Adulto , Idoso , Biofilmes , Feminino , Hospitalização , Humanos , Masculino , Microbiota , Pessoa de Meia-Idade , Período Pós-Operatório , RNA Ribossômico 16S/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
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