Effects of Transition Metals on Metal-Octaaminophthalocyanine-Based 2D Metal-Organic Frameworks.

Metal-octaaminophthalocyanine (MOAPc)-based 2D conductive metal-organic frameworks (cMOFs) have shown great potential in several applications, including sensing, energy storage, and electrocatalysis, due to their bimetallic characteristics. Here, we report a detailed metal substitution study on a family of isostructural cMOFs with Co2+, Ni2+, and Cu2+ as both the metal nodes and the metal centers in the MOAPc ligands. We observed that different metal nodes had variations in the reaction kinetics, particle sizes, and crystallinities. Importantly, the electronic structure and conductivity were found to be dependent on both types of metal sites in the 2D cMOFs. Ni-NiOAPc was found to be the most conductive one among the nine possible combinations with a conductivity of 54 ± 4.8 mS/cm. DFT calculations revealed that monolayer Ni-NiOAPc has neither the smallest bandgap nor the highest charge carrier mobility. Hence its highest conductivity stems from its high crystallinity. Collectively, these results provide structure property relationships for MOAPc-based cMOFs with amino coordination units.

MET Inhibits the Proliferation of EC Cells by Increasing MPA Sensitivity.

Context: The high resistance rate and high recurrence rate of progesterone only as a treatment for endometrial cancer (EC) limit its clinical application. Metformin (MET) may have antitumor ability. Combining MET and medroxyprogesterone acetate (MPA) may strengthen their inhibitory effects on proliferation of EC cells, but MET's mechanisms remain unclear. Objective: The study intended to identify the specific molecular mechanism that MET combined with MPA uses against EC progression. Design: The research team performed a controlled animal study. Setting: The study took place at Xuzhou Medical University in Xuzhou, China. Animals: The animals were16 female non-obese diabetic-severe combined immunodeficient (NOD-SCID) nude mice, about 12 to 16 g in weight. Interventions: The research team divided randomly, the mice into four groups and induced EC in all groups, four in each group: (1) The control group which received received normal saline, (2) the MPA group, which received 100 mg/kg of MPA; (3) the MET group, which received metformin at the rate of 200 mg/kg, each gavage volume was 0.1ml; (4) the MET+MPA group, which received 100 mg/kg of MPA and 200 mg/kg of MET. Outcome measures: The research team: (1) used a CCK-8 kit, an EdU assay, and a flow-cytometry assay to measure cancer-cell proliferation, count, and viability; determine the cell cycle; and measure apoptosis; (2) performed a Western blot analysis to determine the expression of the PR, CD133, pAkt, totalAkt, p-mTOR, and totalTOR antibodies; and (3) determined the size and volume of tumors in vivo and used immunohistochemical staining to determine expression of the Ki67 protein. Results: The MET+MPA group had a significantly lower number of cancer cells than the MET or MDA groups (both P < .001). That group also had significantly more stagnated cancer cells in the G0/G1 phase and significantly fewer cancer cells in the S phase or G2/M phase control, MET, or MPA groups (all P < .01). The MET+MPA group's PCNA and Ki-67 protein expression was significantly lower than that of the MET and MPA group. The EDU assay yielded similar results. Additionally, the MET+MPA group had significantly higher PR expression than that of to MET or MPA group (both P < .001). The MET and MPA groups' expression of CD133, p-Akt, and p-mTOR were significantly lower than those of the control group, while the MET+MPA group's levels were significantly lower than those of the MET and MPA groups. In-vivo experiments revealed that the MET and MPA groups did show decreased tumor size and volume. The MET+MPA group had tumor weights that were significantly lower and tumor volumes were significantly smaller than those of the MET and MPA groups (all P < .001). Immunohistochemical analysis revealed that the MET+MPA group's levels of the Ki-67 antigen were significantly lower than those of the MET and MPA groups. Conclusions: MET inhibited the proliferation of EC cells by increasing MPA-sensitivity, which was dependent on the inhibition of the CD133 expression and the Akt/mTOR pathway. In addition, if MET acts as an effective progestin sensitizer, it certainly offers promising therapeutic prospects for patients with early-stage EC or overgrown endometrium who have fertility requirements.

Developing four cuproptosis-related lncRNAs signature to predict prognosis and immune activity in ovarian cancer.

BACKGROUND: There has been a recent discovery of a new type of cell death produced by copper-iron ions, called Cuproptosis (copper death). The purpose of this study was to identify LncRNA signatures associated with Cuproptosis in ovarian cancer that could be used as prognostic indicators. METHODS: RNA sequencing (RNA-seq) profiles with clinicopathological data from TCGA database were used to select prognostic CRLs and then constructed prognostic risk model using multivariate regression analysis and LASSO algorithms. An independent dataset from GEO database was used to validate the prognostic performance. Combined with clinical factors, we further constructed a prognostic nomogram. In addition, tumor immune microenvironment, somatic mutation and drug sensitivity were analyzed using ssGSEA, GSVA, ESTIMATE and CIBERSORT algorithms. RESULT: A total of 129 CRLs were selected whose expression levels were significantly related to expression levels of 10 cuproptosis-related genes. The univariate Cox regression analysis showed that 12 CRLs were associated with overall survival (OS). Using LASSO algorithms and multivariate regression analysis, we constructed a four-CRLs prognostic signature in the training dataset. Patients in the training dataset could be classified into high- or low-risk subgroups with significantly different OS (log-rank p < 0.001). The prognostic performance was confirmed in TCGA-OC cohort (log-rank p < 0.001) and an independent GEO cohort (log-rank p = 0.023). Multivariate cox regression analysis proved the four-CRLs signature was an independent prognostic factor for OC. Additionally, different risk subtypes showed significantly different levels of immune cells, signal pathways, and drug response. CONCLUSION: We established a prognostic signature based on cuproptosis-related lncRNAs for OC patients, which will be of great value in predicting the prognosis patients and may provide a new perspective for research and individualized treatment.

Dynamic Changes of Phenolic Composition, Antioxidant Capacity, and Gene Expression in 'Snow White' Loquat (Eriobotrya japonica Lindl.) Fruit throughout Development and Ripening.

The newly released 'Snow White' (SW), a white-fleshed loquat (Eriobotrya japonica Lindl.) cultivar, holds promise for commercial production. However, the specifics of the phenolic composition in white-fleshed loquats, along with the antioxidant substances and their regulatory mechanisms, are not yet fully understood. In this study, we examined the dynamic changes in the phenolic compounds, enzyme activities, antioxidant capacity, and gene expression patterns of SW during the key stages of fruit development and ripening. A total of 18 phenolic compounds were identified in SW, with chlorogenic acid, neochlorogenic acid, and coniferyl alcohol being the most predominant. SW demonstrated a stronger antioxidant capacity in the early stages of development, largely due to total phenolics and flavonoids. Neochlorogenic acid may be the most significant antioxidant contributor in loquat. A decline in enzyme activities corresponded with fruit softening. Different genes within a multigene family played distinct roles in the synthesis of phenolics. C4H1, 4CL2, 4CL9, HCT, CCoAOMT5, F5H, COMT1, CAD6, and POD42 were implicated in the regulation of neochlorogenic acid synthesis and accumulation. Consequently, these findings enhance our understanding of phenolic metabolism and offer fresh perspectives on the development of germplasm resources for white-fleshed loquats.

Athermalized carrier multiplication mechanism for detectors using an amorphous silicon gain medium.

In this paper, we investigate the temperature sensitivity of gain and breakdown voltage of detectors based on cycling excitation process (CEP), an internal signal amplification mechanism found in amorphous silicon (a-Si). Changes in gain and breakdown voltage with temperature can result in pixel-to-pixel signal variation in a focal plane array and variations in photon detection efficiency for single photon detectors. We have demonstrated athermalized CEP detectors with their gain and breakdown voltage being nearly temperature independent from 200 K to 350 K, covering the temperature range for practical applications. The device appears to be more thermally stable than avalanche photodetectors (APDs) with different gain media such as Si, InP, InAlAs, etc. The excellent thermal stability of CEP detectors is attributed to the field-enhanced tunneling process for excitation of localized carriers into the mobile bands, which dominates over the phonon excitation process.

Perovskite superlattices with efficient carrier dynamics.

Compared with their three-dimensional (3D) counterparts, low-dimensional metal halide perovskites (2D and quasi-2D; B2An-1MnX3n+1, such as B = R-NH3+, A = HC(NH2)2+, Cs+; M = Pb2+, Sn2+; X = Cl-, Br-, I-) with periodic inorganic-organic structures have shown promising stability and hysteresis-free electrical performance1-6. However, their unique multiple-quantum-well structure limits the device efficiencies because of the grain boundaries and randomly oriented quantum wells in polycrystals7. In single crystals, the carrier transport through the thickness direction is hindered by the layered insulating organic spacers8. Furthermore, the strong quantum confinement from the organic spacers limits the generation and transport of free carriers9,10. Also, lead-free metal halide perovskites have been developed but their device performance is limited by their low crystallinity and structural instability11. Here we report a low-dimensional metal halide perovskite BA2MAn-1SnnI3n+1 (BA, butylammonium; MA, methylammonium; n = 1, 3, 5) superlattice by chemical epitaxy. The inorganic slabs are aligned vertical to the substrate and interconnected in a criss-cross 2D network parallel to the substrate, leading to efficient carrier transport in three dimensions. A lattice-mismatched substrate compresses the organic spacers, which weakens the quantum confinement. The performance of a superlattice solar cell has been certified under the quasi-steady state, showing a stable 12.36% photoelectric conversion efficiency. Moreover, an intraband exciton relaxation process may have yielded an unusually high open-circuit voltage (VOC).

Electrochemical flow injection analysis of the interaction between pyrroloquinoline quinone (PQQ) and α-synuclein peptides related to Parkinson's disease.

α-Synuclein (α-syn) is a hallmark protein of Parkinson's disease (PD). The aggregation process of α-syn has been heavily associated with the pathogenesis of PD. With the exponentially growing number of potential therapeutic compounds that can inhibit the aggregation of α-syn, there is now a significant demand for a high-throughput analysis system. Herein, a novel flow injection analysis system with an electrochemical biosensor as the detector was developed to study the interaction of a well-described antioxidant and amyloid inhibitor, pyrroloquinoline quinone (PQQ) with α-synuclein peptides. Screen-printed gold electrodes (SPEs) were modified using heptapeptides from α-syn wild-type (WT) and mutants such as lysine knock-out (ETEE) and E46K. Affinity binding events between these peptides and PQQ were analyzed by electrochemical impedance spectroscopy (EIS) and further confirmed by high-performance liquid chromatography (HPLC), liquid chromatography/mass spectrometry (LC/MS), and nuclear magnetic resonance (NMR) spectroscopy. HPLC and LC/MS results revealed that PQQ formed a stable complex with α-syn. NMR results confirmed that the α-syn-PQQ complex was formed via a Schiff base formation-like process. In addition, results showed that lysine residues influenced the binding event, in which the presence of an extra lysine stabilized the α-syn-PQQ complex, and the absence of a lysine significantly decreased the interaction of α-syn with PQQ. Therefore, we concluded that EIS is a promising technique for the evaluation of the interaction between PQQ-based amyloid inhibitors and α-syn. The electrochemical flow injection analysis assembly provided a rapid and low-cost drug discovery platform for the evaluation of small molecule-protein interactions.

Graphene Oxide Nanoribbons in Chitosan for Simultaneous Electrochemical Detection of Guanine, Adenine, Thymine and Cytosine.

Herein, graphene oxide nanoribbons (GONRs) were obtained from the oxidative unzipping of multi-walled carbon nanotubes. Covalent coupling reaction of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxy succinimide (NHS) with amine functional groups (-NH2) of the chitosan natural polymer (CH) was used for entrapping GONRs on the activated glassy carbon electrode (GCE/GONRs-CH). The nanocomposite was characterized by high-resolution transmission electron microscopy (HRTEM), and field-emission scanning electron microscopy (FESEM). In addition, the modification steps were monitored using FTIR. The nanocomposite-modified electrode was used for the simultaneous electrochemical determination of four DNA bases; guanine (G), adenine (A), thymine (T) and cytosine (C). The nanocomposite-modified GCE displayed a strong, stable and continuous four oxidation peaks during electrochemistry detection at potentials 0.63, 0.89, 1.13 and 1.27 V for G, A, T and C, respectively. The calibration curves were linear up to 256, 172, 855 and 342 µM with detection limits of 0.002, 0.023, 1.330 and 0.641 µM for G, A, T and C, respectively. The analytical performance of the GCE/GONRs-CH has been used for the determination of G, A, T and C in real samples and obtained a recovery percentage from 91.1%-104.7%. Our preliminary results demonstrated that GCE/GONRs-CH provided a promising platform to detect all four DNA bases for future studies on DNA damage and mutations.

Reversal of multidrug resistance in leukemia cells using a transferrin-modified nanomicelle encapsulating both doxorubicin and psoralen.

To ameliorate multidrug resistance (MDR) observed in leukemia cells, nanomicelles modified by transferrin (Tf-M-DOX/PSO), coencapsulating doxorubicin (DOX) and psoralen (PSO), were designed, synthesized and tested in K562 and doxorubicin-resistant K562 (K562/DOX) cells. In vitro drug release kinetics for constructed nanomicelles were measured using high-performance liquid chromatography. Characterization of the produced nanomicelles was completed using transmission electron microscopy and dynamic light scattering. Uptake of the nanomicelles in K562 cells was investigated using both confocal microscopy and flow cytometry. Apoptosis levels as well as the expression of glycoprotein (P-gp) were analyzing by western blotting and flow cytometry. Cellular cytotoxicity resulting from the exposure of nanomicelles was evaluated using MTT assays. The nanomicelles all showed mild release of DOX in PBS solution. In K562/DOX cells, Tf-M-Dox/PSO exhibited higher uptake compared to the other nanomicelles observed. Furthermore, cellular cytotoxicity when exposed to Tf-M-Dox/PSO was 2.8 and 1.6-fold greater than observed in the unmodified DOX and Tf-nanomicelles loaded with DOX alone, respectively. Tf-M-Dox/PSO strongly increased apoptosis of K562/DOX cells. Finally, the reversal of the drug resistance when cells are exposed to Tf-M-DOX/PSO was associated with P-gp expression inhibition. The Tf-M-Dox/PSO nanomicelle showed a reversal of MDR, with enhanced cellular uptake and delivery release.

Frequency- and Power-Dependent Photoresponse of a Perovskite Photodetector Down to the Single-Photon Level.

Organometallic halide perovskites attract strong interests for their high photoresponsivity and solar cell efficiency. However, there was no systematic study of their power- and frequency-dependent photoresponsivity. We identified two different power-dependent photoresponse types in methylammonium lead iodide perovskite (MAPbI3) photodetectors. In the first type, the photoresponse remains constant from 5 Hz to 800 MHz. In the second type, absorption of a single photon can generate a persistent photoconductivity of 30 pA under an applied electric field of 2.5 × 104 V/cm. Additional absorbed photons, up to 8, linearly increase the persistent photoconductivity, which saturates with the absorption of more than 10 photons. This is different than single-photon avalanche detectors (SPADs) because the single-photon response is persistent as long as the device is under bias, providing unique opportunities for novel electronic and photonic devices such as analogue memories for neuromorphic computing. We propose an avalanche-like process for iodine ions and estimate that absorption of a single 0.38 aJ photon triggers the motion of 108-9 ions, resulting in accumulations of ions and charged vacancies at the MAPbI3/electrode interfaces to cause the band bending and change of electric material properties. We have made the first observation that single-digit photon absorption can alter the macroscopic electric and optoelectronic properties of a perovskite thin film.

Room-temperature long-wave infrared detector with thin double layers of amorphous germanium and amorphous silicon.

A longwave-infrared photodetector made of double layers of 100nm amorphous germanium (a-Ge) and 25nm amorphous silicon (a-Si) have been demonstrated. Under room temperature, the device shows the responsivity of 1.7 A/W, detectivity of 6×108 Jones, and noise equivalent power (NEP) of 5pW/√Hz under 5V bias and at 20kHz operation. Studies of frequency dependent characteristics and device modeling indicate that, above 100Hz or beyond the bandwidth of thermal response, the device operates as a quantum detector having the photoelectrons produced by optical excitation from the bandtail states to the mobile states of a-Ge. The superior device performance may be attributed to the combination of two amplification mechanisms: photoconductive gain in a-Ge and cycling excitation process (CEP) in a-Si, with the latter being the dominant factor. Besides its attractive performance, the device has a simple structure and is easy to fabricate at low cost, thus holding promise for night vision, sensing, autonomous driving, and many other applications.

Leptin, hs-CRP, IL-18 and urinary protein before and after treatment of children with nephrotic syndrome.

We aimed to analyze the changes in plasma leptin, serum inflammatory factors and urinary protein in children with nephrotic syndrome before and after treatment and their clinical significance. A total of 28 children treated and diagnosed with nephrotic syndrome between November 2015 and October 2016 were selected as treatment group, while 25 healthy children were selected as control group. There were no statistically significant differences in age, sex, body mass index (BMI), serum albumin and other general data between treatment group and control group (P>0.05). There was a positive correlation between serum high-sensitivity C-reactive protein (hs-CRP) level and 24 h urinary protein level in children with nephrotic syndrome before treatment (r=0.408, P=0.005). Twenty-four hours urinary protein, urea nitrogen (BUN) and serum creatinine (SCr) levels in children with nephrotic syndrome before treatment were significantly higher than those in normal children, and these indexes were significantly decreased after treatment. The levels of plasma leptin and serum inflammatory factors (hs-CRP and IL-18) in children with nephrotic syndrome before treatment were obviously higher than those in normal children, and these indexes were obviously decreased after treatment. In conclusion, the detection of changes in plasma leptin, serum inflammatory factors (hs-CRP and IL-18) and urinary protein in children with nephrotic syndrome before and after treatment has important reference value for reflecting the severity of disease and evaluating the prognosis of children with nephrotic syndrome.

Bulk heterojunction solar cells using thieno[3,4-c]pyrrole-4,6-dione and dithieno[3,2-b:2',3'-d]silole copolymer with a power conversion efficiency of 7.3%.

A new alternating copolymer of dithienosilole and thienopyrrole-4,6-dione (PDTSTPD) possesses both a low optical bandgap (1.73 eV) and a deep highest occupied molecular orbital energy level (5.57 eV). The introduction of branched alkyl chains to the dithienosilole unit was found to be critical for the improvement of the polymer solubility. When blended with PC(71)BM, PDTSTPD exhibited a power conversion efficiency of 7.3% on the photovoltaic devices with an active area of 1 cm(2).

[Diagnostic value of muscle, sural nerve and skin biopsies in childhood neuromuscular disorders].

OBJECTIVE: To elicit the usefulness of muscle, sural nerve and skin biopsies in neuromuscular disease, including its diagnostic value and indications for biopsy. METHOD: The authors retrospectively evaluated the clinical data of every patient who underwent muscle, sural nerve and/or skin biopsy in the department between January 1999 and December 2004. RESULT: One hundred and two patients with the suspected neuromuscular diseases were included. Muscle disease or hereditary metabolic/degenerative diseases with muscular injury were suspected in 82 patients, specific or typical histological findings confirmed diagnosis in 33 of these patients. The diagnosis included muscular dystrophies in 13 patients; inflammatory myopathies in 4 patients; congenital centronuclear myopathies in 2 patients; vacuole myopathy in 1 patient; mitochondrial myopathies in 8 patients; lipid storage myopathy in 1 patient; glycogenosis in 1 patient; spinal muscular atrophy in 3 patients. Nonspecific changes were seen in 25 patients, and in 24 patients nothing abnormal was revealed. Neuropathy or hereditary metabolic/degenerative diseases with peripheral nerve injury were suspected in 23 patients, specific or typical histological findings confirmed diagnosis in 10 of these patients, including hereditary motor and sensory neuropathy in 9 patients and metachromatic leukodystrophy with peripheral nerve abnormality in 1 patient. Nonspecific changes were seen in 11 patients and 2 patients had normal sural nerve. Skin biopsies were performed in 8 patients, specific or typical histological findings confirmed diagnosis in 4 of these patients. The diagnosis included neuronal ceroid lipofuscinosis in 2 patients, infantile axonal dystrophy in 1 patient, vacuole lysosomal disease in 1 patient, and 4 patients had normal skin biopsy. CONCLUSION: Muscle, sural nerve and skin biopsies play an important role in diagnosis of childhood neuromuscular disease, and should be done only in carefully selected cases after thorough clinical work-up. Muscle biopsy is essential for diagnosis of congenital and metabolic myopathies. Typical pathologic alterations of sural nerve have diagnostic value for hereditary neuropathies. Skin biopsy should be performed to verify neuronal ceroid lipofuscinosis.

Preparation of magnetic microspheres from water-in-oil emulsion stabilized by block copolymer dispersant.

A new method for the preparation of magnetic microspheres is reported. The preparation involved first the dispersion of an aqueous phase, containing magnetite nanoparticles and a water-soluble homopolymer, into droplets in an organic medium using an amphiphilic block copolymer as the dispersant. This was followed by water distillation at a raised temperature from the aqueous droplets to yield polymer/magnetite particles. The structure of the particles was then locked in by a reagent being added to cross-link the water-soluble copolymer block and homopolymer. Since the hydrophobic block of the copolymer consisted of a protected polyester, the removal of the protective moieties from the coronal chains yielded poly(acrylic acid) or other functional polymers to render water dispersibility to the spheres and to enable biomolecule immobilization.

End coupling of block copolymer nanotubes to nanospheres.

Triblock copolymer nanotubes bearing end-exposed poly(acrylic acid) or PAA core chains were prepared. The exposed PAA chains were reacted by amidization with a large excess of polystyrene spacer chains possessing amino end groups or amino-containing end blocks to graft the spacer chains. The amino groups at the other end of the spacer chains were then reacted with nanospheres bearing surface carboxyl groups to connect the nanotubes to nanospheres. The products from such a coupling reaction ranged from multiarm adduct to surfactant- and dumbbell-like objects. Product control using different strategies was explored. The products may have interesting properties and applications.