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This study demonstrates a universal nanocasting approach for the synthesis of novel conjugated microporous polymers (CMPs) with bicontinuous architectures.

Inflammatory bowel disease (IBD) is a chronic inflammation disease and still faces many therapeutic challenges, such as ineffective treatments, antibiotic resistance, and systematic toxicity. In order to improve the therapeutic efficacy of IBD, it is thus urgent to develop efficient, non-toxic and conveniently-administrated nanoagents to replace the currently used medicines. Casein phosphopeptide (CPP) has been found capable of chelating transition metal ions to suppress reactive oxygen species (ROS) generation, showing the potential for the treatment of IBD. However, CPP easily suffers from hydrolysis and enzymatic degradation, which limits its further clinical application. Covalent assembly of CPP to form nanoparticles (GCPP NPs) may be an efficient way to enhance the CPP stability in physiological environment and finally improve its capability of in vivo antioxidation and IBD treatment.We synthesized GCPP NPs through covalent assembly of Genipin and CPP, followed by characterizing their physicochemical properties. GCPP NPs were incubated under different physiological conditions including phosphate buffered saline, cell culture media, simulated gastrointestinal fluid for evaluation of stability. Cytotoxicity and antioxidation activities of GCPP NPs were tested in vitro under the 3T3 cell line using the ABTS and MTT assays, respectively. Finally, a DSS-induced mouse colitis model was established to assess specific accumulation and good therapeutic efficacy of GCPP NPs via an oral administration strategy.GCPP NPs are robust and stable to overcome easy degradation of CPP even under the harsh gastrointestinal environments, which are adapted for oral administration. As-prepared GCPP NPs show benign antioxidant activity to scavenge ROS. Meanwhile, nanoscale GCPP NPs can passively accumulate and maintain at inflamed sites. The body weight and colon length of DSS-induced colitis mice treated by GCPP NPs perform a rehabilitation trend. These results indicate that GCPP NPs, as peptide-based therapeutic nanoagents, have great potential in the anti-inflammatory treatment of IBD by oral administration.

Background. This study aimed to investigate the molecular mechanism of Tongfengding capsule (TFDC) in treating immune-inflammatory diseases of gouty arthritis (GA) and interleukin-1-beta (IL-1β) inhibitors by using network pharmacology, molecular docking, and cell experiments. Methods. In this study, the compounds of TFDC and the potential inflammatory targets of GA were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Online Mendelian Inheritance in Man (OMIM), and GeneCards databases. The TFDC-GA-potential targets interaction network was accomplished by the STRING database. The TFDC-active compound-potential target-GA network was constructed using Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to further explore the GA mechanism and therapeutic effects of TFDC. Quantitative real-time PCR (qPCR) was used to verify whether the TFDC inhibited IL-1β in GA. Molecular docking technology was used to analyze the optimal effective compounds from the TFDC for docking with IL-1β. Result. 133 active compounds and 242 targets were screened from the TFDC, and 25 of the targets intersected with GA inflammatory targets, which were considered as potential therapeutic targets. Network pharmacological analysis showed that the TFDC active compounds such as quercetin, stigmasterol, betavulgarin, rutaecarpine, naringenin, dihydrochelerythrine, and dihydrosanguinarine had better correlation with GA inflammatory targets such as PTGS2, PTGS1, NOS2, SLC6A3, HTR3A, PPARG, MAPK14, RELA, MMP9, and MMP2. The immune-inflammatory signaling pathways of the active compounds for treating GA are IL-17 signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway, NF-kappa B signaling pathway, Toll-like receptor signaling pathway, HIF-1 signaling pathway, etc. The TFDC reduced IL-1β mRNA expression in GA by qPCR. Molecular docking results suggested that rutaecarpine was the most appropriate natural IL-1β inhibitor. Conclusion. Our findings provide an essential role and bases for further immune-inflammatory studies on the molecular mechanisms of TFDC and IL-1β inhibitors development in GA.

This study is aimed at improving the accuracy of oral English recognition and proposing evaluation measures with better performance. This work is based on related theories such as deep learning, speech recognition, and oral English practice. As the literature summarized, the recurrent neural network was the calculation standard, and the oral English speech recognition indicators were the main basis on which an English speech recognition model was constructed. Then, 20 English majors and 5 sets of English sentence patterns were randomly selected as the research objects. The correction standards for English oral errors were introduced into the model to achieve further improvement. The research results showed that the average concordance rate of speech recognition reached 91% through the model test. The concordance rates of words, speech, and intonation in recognition were 89%, 91%, and 86%, respectively. The model could be used as an evaluation system for English speech recognition. Therefore, the application of the deep learning scoring model in the evaluation of oral English teaching was researched in this work, which provided an effective basis for the evaluation of intelligent English teaching.

We have investigated thermal conductivities (κ) of polycrystalline Eu1–xAxTiO3 (A = Ca, Sr, Ba, 0 ≤ x ≤ 0.8) bulk materials in the temperature range of ∼ 2 K < T < 1173 K. The EuTiO3 demonstrates anomalous glass-like κ(T) behavior at low temperatures. Partial substitutions with Sr2+ and Ba2+ do not cause a significant change in the κ(T) behavior, while a κ(T) peak, which looks like a manifestation of a typical crystalline solid, appears only in the Ca-substituted samples with an orthorhombic structure when x ≥ 0.4. After excluding the magnetic effects on κ and discussing the possible phonon scattering mechanisms in depth, together with heat capacity Cp measurements and high-resolution X-Ray diffraction characterization, we find that the unusual low κ at low temperatures is attributed to resonant scattering induced by the intrinsic disordered local structure and lattice instability in EuTiO3. Due to the different lattice dynamics of ATiO3, the lattice structure of Eu1–xCaxTiO3 can be regarded as formed by a part-soft (from EuTiO3) part-rigid (from CaTiO3) sublattice. The anomalous κ(T) behavior of Eu1–xCaxTiO3 results from the combined effect of phonon transport between the normal phononic heat transport in the rigid sublattice and the strong damping of heat conduction in the soft sublattice. published

Background Morel-lavallee injury is a kind of closed soft tissue detroculation injury. This kind of injury is caused by high energy violence (including traffic accidents and serious mechanical crushing injury). It is one of the most common clinical injuries.In recent years, such injuries caused by various reasons show an increasing trend year by year. Purpose In this paper, a case of Morel-Lavallee injury of thigh combined with open fracture of tibia and fibula was reported recently. Combined with the experience in this treatment process, it is expected to provide reference for clinical diagnosis and treatment. Case report We report a 56-year-old middle-aged and elderly male patient who was admitted to hospital due to bleeding, malformation, swelling and pain of the right calf and restriction of movement for 7 hours due to accidental injury.The patient showed signs of shock and coma before admission. After resuscitation, the patient was admitted to our department from the emergency department with "open fracture of the lower end of the right tibia".Later, it was found that the right thigh was closed and ungloved, and surgery was recommended.After obtaining the consent of the patient and his family, he was hospitalized for surgical treatment in the orthopaedic Trauma Department of the Third Affiliated Hospital of Guangzhou University of Chinese Medicine. Results Through this diagnosis and treatment, the patient's condition was controlled, the affected limb recovered well after the operation, and the function, blood circulation and sensation of the affected limb recovered well. Conclusion The combination of traditional and traditional Chinese and western medicine can promote the recovery of the affected limb better and faster, and reduce the occurrence of complications, which is beneficial to the patients.

Two-dimensional conjugated covalent organic frameworks (2D c-COFs) are emerging semiconductor materials for optoelectronic and photothermal applications. In particular, the highly tailorable, semiconducting thiophene-based 2D c-COFs have attracted considerable interest due to their nontrivial physicochemical properties such as photo-activity, broad optical absorption, tunable electronic structures, and so forth. Herein, we demonstrate a novel, crystalline 2D c-COF based on thienyl-functionalized benzodithiophene (BDT) and biphenyl (BP) via the Schiff-base polycondensation reaction. The resultant BDT-BP-COF exhibits a broad optical absorption up to ca. 600 nm and decent π-conjugation along the 2D polymer skeleton, as revealed by the optical absorption and theoretical calculations. The favorable π-conjugation and the abundant electron-rich thiophene units confer excellent photo-activity to BDT-BP-COF towards the usage of solar energy. As a proof-of-concept application, we explore BDT-BP-COF in photothermal conversion, in which it shows a fast surface-temperature increase upon light irradiation for seconds.

Summary Pigging technology is the most common and cost-effective method for wax deposition remediation, but the inability to accurately predict the pigging parameters during the field pigging process causes pipe plugging incidents to occur from time to time. This study developed a theoretical model that incorporates the rheomalaxis elastoviscoplasticity (REVP) of the wax deposit. The concepts of dynamic and static yield stresses were introduced to determine the maximum shear stress in two shear states. The proposed model can accurately estimate the wax breaking force (WBF) and the wax removal efficiency (WRE) under various pigging conditions, according to the experimental results and published data. In addition, the indoor pigging experiments revealed for the first time that a higher pigging speed could increase the WBF while reducing the WRE of the disk pig. The model interpreted these experimental results as a consequence of the rheological behavior of the wax deposit (i.e., the increase in the ramp rate of the shear rate leads to higher dynamic yield stress).

Wood properties are crucial for the development and application of poplar clones. Here, the effects of clone and age on anatomical and chemical properties were analyzed in eight poplar clones (50, Zhonglin46, 108, 36, N179, Danhong, Sangju, and Nanyang) from Henan province, China. The results show that the effects of clone and age are both significant for these wood properties. The eight clones were grouped into three clusters according to their annual ring width, fiber quality, and chemical properties. For some properties, including annual ring width, fiber length, and microfibril angle, all clones displayed the same radial variation trends; however, for other properties, such as holocellulose content, the radial variation trends were different depending on the clones. The culmination of the mean annual increment corresponded to the turning ages of wood properties such as annual ring width in the eight clones, and holocellulose content in the partial clones except for fiber length, microfibril angle, and vessel length. The recommended rotation age of these poplar clones is 8–9 years based on the fiber quality and chemical components. These results indicate strong genetic and age control of the wood properties and highlight the rich source of variation for poplar clone selection.

This work focuses on the genetic variation of Chinese fir clones in the radial direction. Four 20-year-old Chinese fir clones were selected in Kaihua Forest Farm, Zhejiang, China, and the differences and genetic characteristics were studied. Clonal repeatability, genotype coefficient of variable, and phenotypical coefficient of variable were calculated to light on the genetic variation on the radial direction. Results showed significant differences (P

Background Diet, as a modifiable factor, plays an important role in cognitive function. However, the association between adherence to the 2015–2020 Dietary Guidelines for Americans (DGA), measured by Healthy Eating Index (HEI)-2015, and cognitive function remains unclear. This study aims to explore whether HEI-2015 is associated with various cognitive domains and whether such association is modified by age, gender, or ethnicity in the US adults aged 60 years or older using data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014. Methods HEI-2015 scores were calculated from 24-h dietary recall interviews. Cognitive function was evaluated by Digit Symbol Substitution Test (DSST, a measure of processing speed), Animal Fluency Test (AFT, a measure of executive function), a subtest from Consortium to Establish a Registry for Alzheimer’s disease (CERAD, a measure of memory), and a composite-z score calculated by summing z scores of individual tests. The associations between HEI-2015 scores and cognitive performance were explored using multiple linear regression models. Results A total of 2450 participants aged 60 years or older were included. Participants with higher HEI-2015 scores were more likely to have higher DSST, AFT as well as composite-z scores (PPinteractionP Conclusion Higher adherence to DGA is associated with better cognitive performance, especially regarding processing speed and executive function among the US adults aged 60 years or older.

Diet plays an important role in the development of age-related chronic diseases. However, the association between diet quality assessed by Healthy Eating Index (HEI)-2015, the latest version of HEI, and physical frailty among the general United States (US) elderly adults remains unclear. The present study aims to explore the association between HEI-2015 and physical frailty in elderly adults using data from National Health and Nutrition Examination Survey (NHANES) 2011–2014. HEI-2015 scores were calculated from 2 days 24-h recall interviews. Physical frailty status was assessed by four criteria developed by Fried et al.: exhaustion, weakness, low body mass, and low physical activity, and then categorized into robust (0 criteria), pre-frail (1–2 criteria), or frail (3–4 criteria). The binary and multinomial logistic regressions were used to examine the odds of frailty status. A total of 2345 participants aged 60 years or older were included. According to the 4-items frailty criteria, 51.1% participants were robust, 42.1% were pre-frail, and 6.8% were frail. Compared to the lowest HEI-2015 quartile, the elderly adults in the higher quartile had a lower odds of physical frailty (P

Although the past decade has witnessed tremendous progress in the development of covalent organic frameworks (COFs), three-dimensional (3D) COFs fabrications and characterizations are still much le...

Background Mesenchymal stem cells (MSCs) are promising targets for therapeutic use in regenerative medicine and tissue engineering. In the previous study, we have found that MSCs could be reverted to a primitive stem cell population after in vitro induction of osteogenic and de-osteogenic differentiation (de-osteogenic differentiated MSCs, De-Os-MSCs). De-Os-MSCs showed improved cell survival and osteogenic potential. However, the underlying mechanism and its potential effect on fracture healing has not been explored. Methods MSCs were isolated from the rat bone marrow. MicroRNAs were cloned into lentiviral vectors and transduced into MSCs to observe the effects on osteogenesis. The expression levels of marker genes were evaluated by quantitative RT-PCR. Ectopic bone formation model was used to evaluate the bone regeneration ability of mir-92b transduced MSCs in vivo. An open femur fracture model was established, and MSCs or De-Os-MSCs were administrated to the fracture sites. Histological, biomechanical and microCT analysis were used to evaluate the quality of bone. Results In the present study, we found that mir-92b was significantly increased in the secretions of De-Os-MSCs. And mir-92b could promote the osteogenic differentiation potential of MSCs by activating pERK and JNK signaling pathways. The ectopic bone formation assay showed that MSCs overexpressing mir-92b formed more bone like tissues in vivo. Most importantly, we found local administration of De-Os-MSCs could accelerate fracture healing using an open femur fracture model in rats. The quality of bone property was much better as shown by microCT and biomechanical testing. Conclusion Taken together, our study demonstrated that mir-92b promoted osteogenesis of MSCs, which was partially accounted for the enhanced osteogenic differentiation potential of De-Os-MSCs. And De-Os-MSCs had shown better regenerative capacity in accelerating fracture healing when they were locally given. The translational potential of this article De-Os-MSCs could be used to accelerate fracture healing, and reduce the occurrence of delayed unions and non-unions.

Mechanical testing, microscopic image analysis, and X-ray diffraction were used to study the mechanical properties and their correlation with microstructure in three 20-year-old Chinese fir clones (Kailin 24, Kaihua 13, and Kaihua 3). The Chinese fir clones featured a modulus of rupture (MOR) of 52–59 MPa, a modulus of elasticity (MOE) of 10–11 GPa, and a compressive strength parallel to the grain of 31–34 MPa. Kaihua 13 and Kailin 24 had similar mechanical properties and were superior to Kaihua 3 among the tree clones. Radial variation indicated that their outerwood (rings 9–18) had better mechanical properties than their corewood (rings 3–7). Kaihua 13 with better mechanical properties had a larger ratio of cell wall to lumen than Kaihua 3 and Kailin 24. Outerwood with better mechanical properties also had a larger ratio of cell wall to lumen and a smaller microfibril angle compared to corewood with poor mechanical properties. Linear regression analysis also shows that for various clones and different radial positions in the same clone, anatomical structure parameters such as average cell wall thickness and the ratio of cell wall to lumen were positively correlated to their mechanical properties, while the microfibril angle was negatively correlated to mechanical properties. The two factors synergistically influence the mechanical properties of wood.

Rutaevin is one of the major bioactive constituents isolated from Evodia rutaecarpa, a well-known herbal medicine that has been widely prescribed for the treatment of gastrointestinal disorders in China. However, oral administration of rutaevin has been shown to cause hepatotoxicity in mice. Bioactivation was suggested to be involved in rutaevin-induced hepatotoxicity. The aim of this study was to investigate the bioactivation of rutaevin in rat and human liver microsomes fortified with NADPH. Rutaevin was metabolized into the reactive intermediate cis-butene-1,4-dial (BDA) that was dependent on NADPH. The rutaevin-derived BDA intermediate was trapped by nucleophiles such as glutathione (GSH), N-acetyl-lysine (NAL), and methoxylamine (MOA) in the microsomal incubation system. A total of 10 conjugates resulting from the conjugation of the intermediate with GSH, NAL, or MOA were detected and structurally characterized by liquid chromatography combined with high-resolution tandem mass spectrometry. M1, structurally confirmed by NMR spectroscopic analysis, was identified as a cyclic mono(GSH) conjugate of the BDA intermediate, which was also found in the biliary samples of rutaevin-treated rats. Further inhibitory experiments suggested that ketoconazole showed strong inhibitory effect on the formation of the rutaevin-derived BDA intermediate. CYP3A4 was demonstrated to be the major enzyme responsible for rutaevin bioactivation by using cDNA-expressed human recombinant cytochrome P450 enzymes. Additionally, it was found that rutaevin was a mechanism-based inactivator of CYP3A4, with inactivation parameters of KI = 15.98 μM, kinact = 0.032 min-1, and t1/2 inact = 21.65 min. In summary, these findings are of great significance in understanding the bioactivation mechanism of rutaevin, the potential mechanism of rutaevin-caused hepatotoxicity, and the drug-drug interactions associated with rutaevin mainly via CYP3A4 inactivation.

Transient receptor potential vanillic acid 2 (TRPV2) are well recognized for their contributions to neuronal development, cardiac function, immunity and cancer. However, the precise roles for this thermo TRPchannels in neurological disorder remain unknown. In this study, we employed the CRISPR/Cas9 system to generate genetic mutations of TRPV2. Genetic mutation of TRPV2 resulted in autistic-like phenotypes in mice accompanied with the disordered electrical signals recorded by multi-channels in vivo. To determine possible molecular mechanisms, western blotting was further used to assess the possible involvement of several autism-related proteins. The significantly decreased expression of the R2 subunit of the GABA-B receptor in the hippocampus was observed. Together, our findings suggest that genetic mutation of TRPV2 induces autism-like behavior, results in decreased expression of the R2 subunit of the GABA-B receptor.

Autism spectrum disorder (ASD) is a complex neurological disease characterized by impaired social communication and interaction skills, rigid behavior, decreased interest, and repetitive activities. The disease has a high degree of genetic heterogeneity, and the genetic cause of ASD in many autistic individuals is currently unclear. In this study, we report a patient with ASD whose clinical features included social interaction disorder, communication disorder, and repetitive behavior. We examined the patient’s genetic variation using whole-exome sequencing technology and found new de novo mutations. After analysis and evaluation, ARRB2 was identified as a candidate gene. To study the potential contribution of the ARRB2 gene to the human brain development and function, we first evaluated the expression profile of this gene in different brain regions and developmental stages. Then, we used weighted gene coexpression network analysis to analyze the associations between ARRB2 and ASD risk genes. Additionally, the spatial conformation and stability of the ARRB2 wild type and mutant proteins were examined by simulations. Then, we further established a mouse model of ASD. The results showed abnormal ARRB2 expression in the mouse ASD model. Our study showed that ARRB2 may be a risk gene for ASD, but the contribution of de novo ARRB2 mutations to ASD is unclear. This information will provide references for the etiology of ASD and aid in the mechanism-based drug development and treatment.

The abnormal function of the voltage-gated potassium channel Kv10.2 can induce epilepsy. However, the physiological function of Kv10.2 in the central nervous system remains unclear. In this study, we found that Kv10.2 knockout (KO) increased the complexity of neurons in the CA3 subarea of hippocampus. Kv10.2 KO led to enlarged somata, elongated dendritic length, and increased the number of dendritic tips in cultured rat hippocampus neurons. Kv10.2 KO also increased Synapsin I and PSD95 protein density in cultured rat hippocampal neurons. Whole cell patch-clamp recordings of brain slices in the CA3 subarea of hippocampus revealed that Kv10.2 KO increased the amplitude of spontaneous excitatory postsynaptic currents (sEPSC) and miniature excitatory postsynaptic currents (mEPSC), depolarized the resting membrane potential and increased the action potential firing, reduced the rheobase and increased the input resistance, which results in enhanced neuronal excitability. Furthermore, we made electroencephalogram (EEG) recordings of brain activity in freely moving rats before and after inducing seizures by pentylenetetrazole (PTZ) injection. Kv10.2 KO rats dramatically increased the EEG amplitude during epilepsy. Behavioral observation after seizure induction revealed that Kv10.2 KO rats demonstrated shortened onset latency, prolonged duration, and increased seizure severity when compared with wild type rats. Therefore, this study provides a new link between Kv10.2 and neuronal morphology and higher intrinsic excitability.