Site-Directed Electrochemical Grafting for Amplified Detection of Antibody Pharmaceuticals.

Antibody pharmaceuticals have become the most popular immunotherapeutic drugs and are often administered with low serum drug dosages. Hence, the development of a highly sensitive method for the quantitative assay of antibody levels is of great importance to individualized therapy. On the basis of the dual signal amplification by the glycan-initiated site-directed electrochemical grafting of polymer chains (glyGPC), we report herein a novel strategy for the amplified electrochemical detection of antibody pharmaceuticals. The target of interest was affinity captured by a DNA aptamer ligand, and then the glycans of antibody pharmaceuticals were decorated with the alkyl halide initiators (AHIs) via boronate cross-linking, followed by the electrochemical grafting of the ferrocenyl polymer chains from the glycans of antibody pharmaceuticals through the electrochemically controlled atom transfer radical polymerization (eATRP). As the glycans can be decorated with multiple AHIs and the grafted polymer chains are composed of tens to hundreds of electroactive tags, the glyGPC-based strategy permits the dually amplified electrochemical detection of antibody pharmaceuticals. In the presence of trastuzumab (Herceptin) as the target, the glyGPC-based strategy achieved a detection limit of 71.5 pg/mL. Moreover, the developed method is highly selective, and the results of the quantitative assay of trastuzumab levels in human serum are satisfactory. Owing to its uncomplicated operation and cost-effectiveness, the glyGPC-based strategy shows great promise in the amplified electrochemical detection of antibody pharmaceuticals.

Two-Dimensional Metal Halide Perovskites Created by Binary Conjugated Organic Cations for High-Performance Perovskite Photovoltaics.

Studies indicated that two-dimensional (2D) metal halide perovskites (MHPs) embodied with three-dimensional (3D) MHPs were a facile way to realize efficient and stable perovskite solar cells (PSCs) and perovskite photodetectors (PPDs). Here, high-performance PSCs and PPDs, which are based on 2D/3D MHPs bilayer thin films, where the 2D MHPs are created by binary conjugated organic cations, are reported. Systemically studies reveal that the above novel 2D/3D MHPs bilayer thin films possess an enlarged crystal size, balanced charge transport, reduced charge carrier recombination, smaller charge-transfer resistance, and accelerated charge-extraction process compared to the 2D/3D MHPs bilayer thin films, where the 2D MHPs are created by a single conjugated organic cation. As a result, the PSCs based on the above novel 2D/3D MHPs bilayer thin film exhibit a power conversion efficiency of 22.76%. Moreover, unencapsulated PSCs possess dramatically enhanced stability compared with those based on the 2D/3D MHPs bilayer thin films, where the 2D MHPs are created by a single conjugated organic cation. In addition, the PPDs based on the above novel 2D/3D MHPs bilayer thin film exhibit a projected detectivity of 1016 cm Hz1/2/W and a linear dynamic range of 108 dB at room temperature. Our studies indicate that the development of binary conjugated organic cation-based 2D MHPs incorporated with 3D MHPs is a simple method to realize high-performance PSCs and PPDs.

Stable and efficient perovskite solar cells via hydrogen bonding and coordination.

The instability of perovskite solar cells (PSCs) is primarily caused by the unavoidable ion migration in the perovskite layer. Ion migration and accumulation influence the properties of perovskite and functional layers, resulting in severely degraded device performance. Herein, we introduced an n-type, low optical gap-conjugated organic molecule (i.e., COTIC-4F or COTIC-4Cl) to serve as the perovskite photoactive layer in a perovskite precursor solution for broadening the near-infrared spectral response and enhancing the efficiency of PSCs. Various characterization studies have determined that COTIC-4F forms hydrogen bonds with perovskites, thereby remarkably enhancing the anchoring ability of MA+, suppressing ion migration, and reducing photocurrent hysteresis. Meanwhile, the carbonyl (CO) group of COTIC-4F and COTIC-4Cl can donate a lone electron pair to passivate the Pb trap, avoiding possible carrier recombination. The COTIC-4F- and COTIC-4Cl-treated perovskite films exhibit an optical response in the near-infrared region and an excellent morphology. Through ultraviolet photoelectron spectroscopy, it has been determined that COTIC-4F can facilitate more charge transfer than COTIC-4Cl, which results in a larger photocurrent from the PSCs. The PSCs of the COTIC-4F-treated perovskite films demonstrate a maximum power conversion efficiency of 21.72%. They exhibit a high fill factor of 82.02% and possess long-term stability under an air atmosphere.

Screening ssDNA Aptamers Against Human Vascular Endothelial Factor 165 via Semirational Design.

As a valid tumor marker, vascular endothelial growth factor 165 (VEGF165) is an effective therapeutic target for anticancer treatments. Aptamers hold great promise for the development of anti-VEGF strategies. In this study, anti-VEGF165 ssDNA aptamers were screened using a semirational design and a multilevel screening strategy. Recombinant human VEGF165 protein was used as a target for the construction of an ssDNA virtual aptamer library with ssDNA that had one sole secondary structure. After silicon-assisted prescreening, circular dichroism and isothermal titration calorimetry were used to further screen for candidates. Three aptamers (nos. 524, 529, and 64) with one sole secondary and tertiary structure, showing a high affinity for VEGF165, were identified. The KD values obtained using surface plasmon resonance analysis were 36.3, 288, and 79.3 nM for aptamers 524, 529, and 64, respectively. Cytological tests revealed that the three aptamers inhibit rhVEGF165-induced proliferation of HUVECs. Specifically, aptamer 529 had the strongest inhibitory effect (nearly 100% inhibition). The screening strategy used in our study showed improved screening efficiency relative to other methods and resulted in aptamers with one sole conformation. The aptamers had an advantage in ensuring the uniqueness of aptamer targeting. This semirational design and multilevel screening strategy provide a reference for the screening of other aptamers.

Intraportal infusion of ghrelin could inhibit glucose-stimulated GLP-1 secretion by enteric neural net in Wistar rat.

As a regulator of food intake and energy metabolism, the role of ghrelin in glucose metabolism is still not fully understood. In this study, we determined the in vivo effect of ghrelin on incretin effect. We demonstrated that ghrelin inhibited the glucose-stimulated release of glucagon-like peptide-1 (GLP-1) when infused into the portal vein of Wistar rat. Hepatic vagotomy diminished the inhibitory effect of ghrelin on glucose-stimulated GLP-1 secretion. In addition, phentolamine, a nonselective α receptor antagonist, could recover the decrease of GLP-1 release induced by ghrelin infusion. Pralmorelin (an artificial growth hormone release peptide) infusion into the portal vein could also inhibit the glucose-stimulated release of GLP-1. And growth hormone secretagogue receptor antagonist, [D-lys3]-GHRP-6, infusion showed comparable increases of glucose stimulated GLP-1 release compared to ghrelin infusion into the portal vein. The data showed that intraportal infusion of ghrelin exerted an inhibitory effect on GLP-1 secretion through growth hormone secretagogue receptor 1α (GHS1α receptor), which indicated that the downregulation of ghrelin secretion after food intake was necessary for incretin effect. Furthermore, our results suggested that the enteric neural net involved hepatic vagal nerve and sympathetic nerve mediated inhibition effect of ghrelin on incretin effect.

Diabetes education improves depressive state in newly diagnosed patients with type 2 diabetes.

OBJECTIVES: The prevalence of depression is relatively high in individuals with diabetes. However, screening and monitoring of depressive state in patients with diabetes is still neglected in developing countries and the treatment of diabetes-related depression is rarely performed in these countries. In this study, our aim was to study the role of diabetes education in the improvement of depressive state in newly diagnosed patients with type 2 diabetes. METHODS: The Dutch version of the center for epidemiological studies depression scale (CES-D scale) and the problem areas in diabetes (PAID) questionnaire were used to assess depression and diabetes-specific emotional distress in 1200 newly diagnosed male adult patients with type 2 diabetes before and after a two-week diabetes education by professionally trained nurses. Pearson correlation and regression analysis were used to analyze the factors related to depression in patients with type 2 diabetes. RESULTS: The incidence of depression in newly diagnosed patients with type 2 diabetes was 28%, and the rate of diabetes-specific emotional distress was 65.5%. High education levels, low income were correlated to depression in individuals with diabetes. After two weeks of diabetes education, the incidence of depression and diabetes-specific emotional distress decreased significantly to 20.5% (P < 0.05) and 11% (P < 0.001), respectively. CONCLUSIONS: The incidence of depression, especially diabetes-specific emotional distress, was relatively high in newly diagnosed patients with type 2 diabetes. The depression state could be improved by diabetes education.