Recharged Catalyst with Memristive Nitrogen Reduction Activity through Learning Networks of Spiking Neurons.

Electrocatalysis from N2 to NH3 has been increasingly studied because it provides an environmentally friendly avenue to take the place of the current Haber-Bosch method. Unfortunately, the conversion of N2 to NH3 is far below the necessary level for implementation at a large scale. Inspired by signal memory in a spiking neural network, we developed rechargeable catalyst technology to activate and remember the optimal catalytic activity using manageable electrical stimulation. Herein, we designed double-faced FeReS3 Janus layers that mimic a multiple-neuron network consisting of resistive switching synapses, enabling a series of intriguing multiphase transitions to activate undiscovered catalytic activity; the activation energy barrier is clearly reduced via an active site conversion between two nonequivalent surfaces. Electrical field-stimulated FeReS3 demonstrates a Faradaic efficiency of 43% and the highest rate of 203 µg h-1 mg-1 toward NH3 synthesis. Moreover, this rechargeable catalyst displays unprecedented catalytic performance that persists for up to 216 h and can be repeatedly activated through a simple charging operation.

Disordered Eating Attitudes Among University Students: The Role of Psychological Distress.

OBJECTIVE: The aim of this study was to explore the relationship between psychological distress and disordered eating attitudes. METHODS: The study design was cross-sectional study. The 12-item General Health Questionnaire (ghq-12) and Eating Attitude Test-26 (eat-26) were used to measure psychological distress and disordered eating attitudes, respectively. The data were analyzed using spss version 20.0 Software (spss Inc, ii, Chicago, il, usa). Description statistics were used for height, weight, bmi), age, eat-26 scores and ghq-12 scores. Pearson's correlation analysis was performed to explore the relationship between the eat-26 scores and the ghq-12 scores. RESULTS: The overall prevalence of disordered eating attitudes was 4.6%. The mean ghq-12 score in subjects with disordered eating attitude was higher than that of the control group (P < .05) in both the male and female groups. CONCLUSION: Our study suggested that psychological distress is associated with disordered eating attitudes. Bmi and gender turned out to not be correlated with disordered eating attitude. The findings of this study revealed that university students who have psychological distress also have a tendency toward disordered eating attitudes.

Dual-metal-driven Selective Pathway of Nitrogen Reduction in Orderly Atomic-hybridized Re2MnS6 Ultrathin Nanosheets.

The future of sustainable fertilizers and carbon-free energy carrier demands innovative breakthroughs in the exploitation of efficient electrocatalysts for synthesizing ammonia (NH3) from nitrogen (N2) in mild conditions. Understanding and regulating the reaction intermediates that form on the catalyst surface through careful catalyst design could bypass certain limitations associated with ambiguous adsorbate evolution mechanism. Herein, we propose ternary intermetallic Re2MnS6 ultrathin nanosheets that include orderly hybridized Mn-Re dual-metal sites through strong Hubbard e-e interaction, demonstrating a promising selectivity toward reaction process from N2 to NH3. The ordered inclusion of Mn sites leads to a structural phase transition and appearance of nonbonding semimetal states, in which the rate-limiting activation energy barrier is significantly decreased through a conversion in reaction pathway. As a result, the performance of N2 reduction in Re2MnS6 is increased about 6.6 times compared to the single-metal ReS2.

Physical-Chemical Characterization of Octreotide Encapsulated in Commercial Glucose-Star PLGA Microspheres.

Sandostatin LAR (SLAR) is an injectable long-acting release (LAR) microsphere formulation for octreotide based on a biodegradeable glucose star copolymer of d,l-lactic and glycolic acids (PLGA-glu), which is primarily used for the treatment of patients with acromegaly. There currently is no generic SLAR approved in the United States despite expiration of patent coverage. To understand better this important formulation, SLAR was assessed for its composition and physical-chemical properties. Octreotide release kinetics was monitored under physiological conditions over 56 days together with several bioerosion parameters [mass loss, water uptake, pH of release media, polymer molecular weight (Mw), and confocal microscopy after BODIPY uptake]. A significant increase in the amount of released peptide occurred after day 14. After 1 day of incubation in PBST, octreotide was not extractable completely from SLAR during 2 h of the extraction process, but complete extraction was accomplished after 24 h, which suggested that strong and noncovalent PLGA-octreotide interactions occurred beginning in the initial release phase. Leuprolide is considered as a cationic peptide competitor for octreotide-PLGA interactions and its presence in the release medium resulted in more continuous octreotide release from SLAR, which was linearly correlated with the mass loss from the polymer (i.e., an indication of erosion-controlled release). These data strongly suggest that octreotide forms a salt with acid end groups of linear PLGA chains that are either present as impurities in, and/or produced by the degradation of, the PLGA-Glu. This salt is expected to catalyze octreotide acylation and extend peptide release beyond that driven by erosion control. The characterization studies of physicochemical properties of SLAR described here could be useful for the development and regulatory evaluation of generic octreotide microspheres as well as new polymer formulations, in which the polymer strongly interacts with encapsulated peptides.

Biomedical Applications of Metal-Encapsulated Fullerene Nanoparticles.

The carbonaceous nanomaterials known as metallofullerenes have attracted considerable attention due to their attractive properties. The robust nature of the "Trojan Horse" fullerene cage provides an important structural component, which isolates the metal cluster from the bioenvironment. The large carbon surface area is ideally suited for multiple exo-functionalization approaches to modify the hydrophobic cage for a more hydrophilic bioenvironment. Additionally, peptides and other agents are readily covalently attached to this nanoprobe for targeting applications. The recent progress in developing metallofullerenes for next-generation biomedical applications is described. Of special interest are magnetic resonance imaging (MRI) contrast agents. Several recent studies reported cumulative gadolinium deposition in the brain and bones of individuals using commercial clinical MRI contrast agents. Gadolinium-based metallofullerenes provide 2-3 orders of magnitude improvement in MRI relaxivity and potentially lower clinical levels of toxic Gd3+ ions deposited. Other potential biomedical applications are also reviewed herein.

Detecting Chronic Post-Traumatic Osteomyelitis of Mouse Tibia via an IL-13Rα2 Targeted Metallofullerene Magnetic Resonance Imaging Probe.

Differential diagnosis of chronic post-traumatic osteomyelitis (CPO) from aseptic inflammation remains challenging, since both pathological processes share similar clinical symptoms. Here we utilized a novel targeted metallofullerene nanoparticle based magnetic resonance imaging (MRI) probe IL-13-TAMRA-Gd3N@C80(OH)30(CH2CH2COOH)20 to detect CPO in mouse tibia via overexpressed IL-13Rα2 receptors. The functionalized metallofullerene was characterized by X-ray photoelectron spectroscopy. Upon lipopolysaccharide (LPS) stimulation, macrophage Raw 264.7 cells showed elevated IL-13Rα2 expression via immunofluorescence staining and increased MRI probe binding via built-in TAMRA fluorescence imaging. Trauma was induced in both tibia of mice and bacteria soaked suture was inserted into the right tibia to initiate infection. During the acute phase (1.5 weeks), luminol-bioluminescence imaging revealed much higher myeloperoxidase activity in the infected tibia compared to the sham. In the chronic phase (4 weeks), X-ray radiography illustrated bone deformation in the infected tibia compared to the sham. With T1 weighted sequences, the probe clearly exhibited hyperintensity in the infection foci at both acute and chronic phases, which was not observed in the sham tibia. Histological analysis revealed severe bone structural destruction and massive inflammatory cell infiltration in the infected tibia. Immunohistochemistry confirmed abundant expression of IL-13Rα2 in the infection site. In summary, we developed a noninvasive imaging approach to detect and differentiate CPO from aseptic inflammation using a new IL-13Rα2 targeted metallofullerene MRI probe. In addition, for the first time, IL-13Rα2 was investigated as a unique biomarker in the context of osteomyelitis. Our data established a foundation for the translational application of this MRI probe in the clinical differentiation of CPO.

A New Interleukin-13 Amino-Coated Gadolinium Metallofullerene Nanoparticle for Targeted MRI Detection of Glioblastoma Tumor Cells.

The development of new nanoparticles as next-generation diagnostic and therapeutic ("theranostic") drug platforms is an active area of both chemistry and cancer research. Although numerous gadolinium (Gd) containing metallofullerenes as diagnostic magnetic resonance imaging (MRI) contrast agents have been reported, the metallofullerene cage surface, in most cases, consists of negatively charged carboxyl or hydroxyl groups that limit attractive forces with the cellular surface. It has been reported that nanoparticles with a positive charge will bind more efficiently to negatively charged phospholipid bilayer cellular surfaces, and will more readily undergo endocytosis. In this paper, we report the preparation of a new functionalized trimetallic nitride template endohedral metallofullerene (TNT EMF), Gd3N@C80(OH)x(NH2)y, with a cage surface bearing positively charged amino groups (-NH3(+)) and directly compare it with a similar carboxyl and hydroxyl functionalized derivative. This new nanoparticle was characterized by X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), and infrared spectroscopy. It exhibits excellent (1)H MR relaxivity. Previous studies have clearly demonstrated that the cytokine interleukin-13 (IL-13) effectively targets glioblastoma multiforme (GBM) cells, which are known to overexpress IL-13Rα2. We also report that this amino-coated Gd-nanoplatform, when subsequently conjugated with interleukin-13 peptide IL-13-Gd3N@C80(OH)x(NH2)y, exhibits enhanced targeting of U-251 GBM cell lines and can be effectively delivered intravenously in an orthotopic GBM mouse model.

Liposomal hypocrellin B as a potential photosensitizer for age-related macular degeneration: pharmacokinetics, photodynamic efficacy, and skin phototoxicity in vivo.

Photodynamic therapy (PDT) has been successfully implemented as a treatment for wet age-related macular degeneration (AMD), but very few photosensitizers have been developed for clinical use. Herein, we describe a novel formulation of liposomal hypocrellin B (LHB) that was prepared by high-pressure homogenization. The encapsulation efficiency and PDT efficacy in vitro of this new preparation were found to remain nearly constant over 1 year. Moreover, LHB is rapidly cleared from the blood, with a half-life of 2.319 ± 0.462 h and a very low serum concentration at 24 h after injection. Testing in a rat model of choroidal neovascularization (CNV) showed that leakage of blood vessels in CNV lesions was significantly reduced when LHB PDT was given at a dose of 1 mg kg(-1) along with yellow laser irradiation; the damage to the collateral retina and the retinal pigment epithelium was minimal. Skin phototoxicity assays showed that only two of the 200 mice given a 4 mg per kg dose of LHB experienced an inflammatory reaction in the auricle irradiated at 24 h after dosing. These data collectively indicate that LHB may be a safe and effective photosensitizer for vascular-targeted PDT of AMD.

Gd3N@C84(OH)x: a new egg-shaped metallofullerene magnetic resonance imaging contrast agent.

Water-soluble derivatives of gadolinium-containing metallofullerenes have been considered to be excellent candidates for new magnetic resonance imaging (MRI) contrast agents because of their high relaxivity and characteristic encapsulation of the lanthanide ions (Gd(3+)), preventing their release into the bioenvironment. The trimetallic nitride template endohedral metallofullerenes (TNT EMFs) have further advantages of high stability, high relative yield, and encapsulation of three Gd(3+) ions per molecule as illustrated by the previously reported nearly spherical, Gd3N@I(h)-C80. In this study, we report the preparation and functionalization of a lower-symmetry EMF, Gd3N@C(s)-C84, with a pentalene (fused pentagons) motif and an egg-shaped structure. The Gd3N@C84 derivative exhibits a higher (1)H MR relaxivity compared to that of the Gd3N@C80 derivative synthesized the same way, at low (0.47 T), medium (1.4 T), and high (9.4 T) magnetic fields. The Gd3N@C(s)-C84 derivative exhibits a higher hydroxyl content and aggregate size, as confirmed by X-ray photoelectron spectroscopy (XPS) and dynamic light scattering (DLS) experiments, which could be the main reasons for the higher relaxivity.

Enhanced in situ H2O2 electrosynthesis and leachate concentrate degradation through side-aeration and modified cathode in an electro-Fenton system.

The active graphite felt (GF) catalytic layer was effectively synthesized through a wet ultrasonic impregnation-calcination method, modified with CB and PTFE, and implemented in a pioneering side-aeration electrochemical in-situ H2O2 reactor. The optimal mass ratio (CB: PTFE 1:4) for the modified cathode catalytic layer was determined using a single-factor method. Operating under optimum conditions of initial pH 5, 0.5 L/min air flow, and a current density of 9 mA/cm2, the system achieved a remarkable maximum H2O2 accumulation of 560 mg/L, with the H2O2 production capacity consistently exceeding 95 % over 6 usage cycles. The refined mesoporous structure and improved three-phase interface notably amplified oxygen transfer, utilization, and H2O2 yield. Side aeration led to an oxygen concentration near the cathode reaching 20 mg/L, representing a five-fold increase compared to the 3.95 mg/L achieved with conventional bottom aeration. In the final application, the reaction system exhibited efficacy in the degradation of landfill leachate concentrate. After a 60-minute reaction, complete removal of chroma was attained, and the TOC degradation rate surpassed 60 %, marking a sixfold improvement over the conventional system. These results underscore the substantial potential of the system in H2O2 synthesis and environmental remediation.

Bioinformatics approach to identify the hub gene associated with COVID-19 and idiopathic pulmonary fibrosis.

The coronavirus disease 2019 (COVID-19) has developed into a global health crisis. Pulmonary fibrosis, as one of the complications of SARS-CoV-2 infection, deserves attention. As COVID-19 is a new clinical entity that is constantly evolving, and many aspects of disease are remain unknown. The datasets of COVID-19 and idiopathic pulmonary fibrosis were obtained from the Gene Expression Omnibus. The hub genes were screened out using the Random Forest (RF) algorithm depending on the severity of patients with COVID-19. A risk prediction model was developed to assess the prognosis of patients infected with SARS-CoV-2, which was evaluated by another dataset. Six genes (named NELL2, GPR183, S100A8, ALPL, CD177, and IL1R2) may be associated with the development of PF in patients with severe SARS-CoV-2 infection. S100A8 is thought to be an important target gene that is closely associated with COVID-19 and pulmonary fibrosis. Construction of a neural network model was successfully predicted the prognosis of patients with COVID-19. With the increasing availability of COVID-19 datasets, bioinformatic methods can provide possible predictive targets for the diagnosis, treatment, and prognosis of the disease and show intervention directions for the development of clinical drugs and vaccines.

Has enterprise digital transformation improved the efficiency of enterprise technological innovation? A case study on Chinese listed companies.

Digital transformation is a new driving force of enterprise efficiency reform. Enterprises' digital transformation can effectively improve their technological innovation efficiency, thereby promoting their high-quality development. Using the panel data of 930 Chinese A-share listed companies from 2015 to 2020, we have studied the impact and heterogeneity of digital transformation on enterprise technological innovation efficiency with a panel data model. Further, a mediating effect model and a moderating effect model were constructed to study the mechanism of digital transformation affecting the efficiency of enterprise technological innovation. The conclusions are as follows. First, enterprise digital transformation significantly improves the efficiency of enterprise technological innovation. Second, the impact of digital transformation on the efficiency of enterprise technological innovation is heterogeneous, which is reflected in two aspects: the factor intensity and the nature of ownership. Third, financing constraints and equity concentration play a mediating and a moderating role, respectively, in the impact of digital transformation on the efficiency of enterprise technological innovation.

Can the Digital Economy Facilitate Carbon Emissions Decoupling? An Empirical Study Based on Provincial Data in China.

The digital economy plays a dual role in the process of global carbon emissions decoupling; for this reason, its overall impact direction and mechanism are worth discussing. This paper attempts to answer the question of the role of the digital economy, based on a review of the existing literature. By constructing a panel smooth transition regression (PSTR) model, this paper empirically tests the effect of the digital economy on carbon emissions decoupling, based on panel data from 30 provinces in China from 2010 to 2019. In order to study the impact mechanism of the digital economy on carbon emissions decoupling, the mediating effect of industrial structure optimization is analyzed through a mediating effect model; the moderating effect is also explored by analyzing the network centrality characteristics of the digital economy. The core-periphery analysis method is adopted to group the samples to test the impact heterogeneity of the digital economy on carbon emissions decoupling. Based on this empirical analysis, the following conclusions are drawn. First, the digital economy has a promoting effect on carbon emissions decoupling, but this effect gradually weakens with the development of the digital economy. Second, the digital economy can promote carbon emissions decoupling through industrial structure optimization, and network centrality has a positive moderating effect on this mechanism. Third, heterogeneity exists in the promoting effect of the digital economy on carbon emissions decoupling, which is reflected in the different intensities of the promotion effect between the core nodes and the peripheral nodes in the network; the attenuation range of the promotion effect is also different when the regime switches.

Aptamer-siRNA chimera and gold nanoparticle modified collagen membrane for the treatment of malignant pleural effusion.

Malignant pleural effusion is one of the most common complications of advanced lung cancer and there is no effective clinical treatment at present. Here, we constructed an aptamer-siRNA chimeras/PEI/PEG/gold nanoparticle (AuNP)/collagen membrane that can progressively activate T cells by layer by layer assembly. Electron microscope showed this collagen membrane could be divided into 10 layers with a total thickness of 50-80µm, and AuNPs could be observed. Aptamer-siRNA chimeras could bind specifically to OX40+ cells and silencing programmed death receptor-1 (PD-1) gene. In vitro experiments demonstrated that chimeras/PEI/PEG/AuNPs gradually activated T cells to continuously kill lung adenocarcinoma cells in malignant pleural effusion. Animal experiments showed that chimeras/PEI/PEG/AuNP/collagen membrane effectively treated malignant pleural effusion. Compared with PD-1 inhibitor group, the number of cancer cells, ki-67 proliferation index and CD44 expression in the pleural effusion was significantly decreased and the lymphocyte/cancer cell ratio was significantly increased in the chimeras/AuNP-CM group. Flow cytometry showed that compared with PD-1 inhibitor group, T cell number in the chimeras/AuNP-CM group was significantly increased, while the proportion of PD-1+ T cells was markedly decreased. In conclusion, we constructed an chimeras/PEI/PEG/AuNP/collagen membrane, which was more effective in the treatment of malignant pleural effusion, and had less side effects than PD-1 inhibitors.

Terahertz wave modulation properties of graphene with different excitation laser power.

The terahertz wave modulation properties of graphene were investigated using an external 975 nm continuous wave laser with different power. Upon excitation laser, the transmission and modulation depth was measured using terahertz time-domain spectroscopy. The experimental results showed that the modulation depth of monolayer graphene and 3-layer graphene was 16% and 32% under the 1495 mW excitation power. Further, we analyzed the graphene modulation mechanism based on the Drude model and the thin-film approximation. Both theoretical analysis and calculation results showed that the terahertz wave could be modulated using graphene with different excitation laser power.

Glucose substrate in the hydrogen breath test for gut microbiota determination: A recommended noninvasive test.

Intestinal dysbiosis and small intestinal bacterial overgrowth (SIBO) are common in patients with liver cirrhosis. Existing studies have not explored the association between gut dysbiosis and SIBO. We propose some suggestions for the authors' experimental methods and concepts, and we hope these suggestions can be adopted. The hydrogen breath test is worthy of recommendation due to its high accuracy and convenient operation. We suggest changing the substrate of the hydrogen breath test from lactulose to glucose to improve the accuracy of each parameter. SIBO is a small subset of gut dysbiosis, and we propose clarifying the concept of both. SIBO may be caused by liver cirrhosis or one of the pathogeneses of gastrointestinal diseases. Therefore, interference from other gastrointestinal diseases should be excluded from this study.

Efficient aqueous remote loading of peptides in poly(lactic-co-glycolic acid).

Poly(lactic-co-glycolic acid) (PLGA) long-acting release depots are effective for extending the duration of action of peptide drugs. We describe efficient organic-solvent-free remote encapsulation based on the capacity of common uncapped PLGA to bind and absorb into the polymer phase net positively charged peptides from aqueous solution after short exposure at modest temperature. Leuprolide encapsulated by this approach in low-molecular-weight PLGA 75/25 microspheres slowly and continuously released peptide for over 56 days in vitro and suppressed testosterone production in rats in an equivalent manner as the 1-month Lupron Depot®. The technique is generalizable to encapsulate a number of net cationic peptides of various size, including octreotide, with competitive loading and encapsulation efficiencies to traditional methods. In certain cases, in vitro and in vivo performance of remote-loaded PLGA microspheres exceeded that relative to marketed products. Remote absorption encapsulation further removes the need for a critical organic solvent removal step after encapsulation, allowing for simple and cost-effective sterilization of the drug-free microspheres before encapsulation of the peptide.

Development and characterization of composition-equivalent formulations to the Sandostatin LAR® by the solvent evaporation method.

Sandostatin long-acting release® (SLAR) is a long-acting injectable somatostatin analogue formulation composed of octreotide encapsulated in glucose-initiated poly(lactic-co-glycolic acid) (PLGA) microspheres. Despite the end of patent protection, SLAR remains resistant to generic competition likely due to complexity of production process, the uniqueness of the glucose star polymer, and the instability of octreotide in the formulation. Here, we describe development of glucose-PLGA-based composition-equivalent to SLAR formulations prepared by double emulsion-solvent evaporation method and the effect of variations in encapsulation variables on release kinetics and other formulation characteristics. The following encapsulation variables were adjusted at constant theoretical loading of 7.0% peptide: PLGA concentration, pH of inner water phase, and stirring rate. After final drying, the microspheres were examined with and without annealing at 50 °C under vacuum for 3 days. The loading and encapsulation efficiency (EE) of octreotide acetate, manufacturing yield, and in vitro drug release kinetics in PBStc (10 mM phosphate-buffered saline (PBS) with 1% triethyl citrate and 0.02% sodium azide at pH 7.4) were determined by UPLC. The in vitro release and acylation kinetics of octreotide for the solvent evaporation formulations prepared were similar to SLAR although the initial burst was slightly higher. Key formulation steps identified to maximize microsphere yield and minimize residual solvent and initial burst release included (a) addition of acetic acid to the peptide before preparation and (b) annealing the microspheres under vacuum after drying. Controlled release octreotide formulations prepared and investigated in this study could provide a better understanding of the effect of production variables on release performance and supply information useful for making progress in manufacturing of SLAR generic equivalents.

Does Environmental Policy Affect Green Total Factor Productivity? Quasi-Natural Experiment Based on China's Air Pollution Control and Prevention Action Plan.

It is the scientific way to promote the transformation and optimization of an industrial structure to promote the improvement of its green total factor productivity (GTFP) by formulating environmental regulation policies. Based on the GTFP panel data of 30 provinces in China from 2004 to 2017, this paper takes the "Air Pollution Control and Prevention Action Plan" (APCP Action Plan) as the proxy dummy variable of environmental regulation, and uses the difference-in-differences (DID) model to explore the impact of the implementation of the APCP Action Plan on GTFP. In addition, by constructing the industrial structure optimization index, this paper analyzes how the APCP Action Plan policy affects GTFP through the transformation and optimization of industrial structure. The following basic conclusions are obtained: First, environmental regulation policies like the APCP Action Plan can improve GTFP. Second, the APCP Action Plan has regional heterogeneity in promoting GTFP in different regions. The policy only significantly affects the GTFP in the Pearl River Delta region in southern China. Third, the "quantity" and "quality" of the optimization of industrial structure will weaken the promoting effect of the APCP Action Plan on GTFP. In contrast, the rationalization of industrial structure will aggravate this promoting effect.