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Based on the integrated model of Super-SBM model, spatial Durbin model (SDM) and Grey neural network model, this paper analyzes the panel data of various provinces in China from multiple angles and dimensions. It was found that there were significant differences in eco-efficiency between organic rice production and conventional rice production. The response of organic rice to climate change, the spatial distribution of ecological and economic benefits and the impact on carbon emission were analyzed. The results showed that organic rice planting not only had higher economic benefits, but also showed a rising trend of ecological benefits and a positive feedback effect. This finding highlights the importance of organic rice farming in reducing carbon emissions. Organic rice farming effectively reduces greenhouse gas emissions, especially carbon dioxide and methane, by improving soil management and reducing the use of fertilizers and pesticides. This has important implications for mitigating climate change and promoting soil health and biodiversity. With the acceleration of urbanization, the increase of organic rice planting area shows the trend of organic rice gradually replacing traditional rice cultivation, further highlighting the potential of organic agriculture in emission reduction, environmental protection and sustainable agricultural production. To this end, it is recommended that the Government implement a diversified support strategy to encourage technological innovation, provide guidance and training, and raise public awareness and demand for organic products. At the same time, private sector participation is stimulated to support the development of organic rice cultivation through a public-private partnership model. Through these measures, further promote organic rice cultivation, achieve the dual goals of economic benefits and environmental benefits, and effectively promote the realization of double carbon emission reduction targets. [ABSTRACT FROM AUTHOR]

Knowledge of protein expression in mammalian brains at regional and cellular levels can facilitate understanding of protein functions and associated diseases. As the mouse brain is a typical mammalian brain considering cell type and structure, several studies have been conducted to analyze protein expression in mouse brains. However, labeling protein expression using biotechnology is costly and time-consuming. Therefore, automated models that can accurately recognize protein expression are needed. Here, we constructed machine learning models to automatically annotate the protein expression intensity and cellular location in different mouse brain regions from immunofluorescence images. The brain regions and sub-regions were segmented through learning image features using an autoencoder and then performing K-means clustering and registration to align with the anatomical references. The protein expression intensities for those segmented structures were computed on the basis of the statistics of the image pixels, and patch-based weakly supervised methods and multi-instance learning were used to classify the cellular locations. Results demonstrated that the models achieved high accuracy in the expression intensity estimation, and the F1 score of the cellular location prediction was 74.5%. This work established an automated pipeline for analyzing mouse brain images and provided a foundation for further study of protein expression and functions. [ABSTRACT FROM AUTHOR]

With rapid economic expansion, China is faced with environmental challenges like air pollution and greenhouse gas emissions. Shifting from conventional fossil fuels to renewable energy (REN) sources is critical to facilitate sustainable development in China. Compared to coal and oil, REN such as solar and wind energy emit less carbon emissions. Fostering innovation of REN technologies is thus essential for China's green transition. This study aims to analyze the impact of REN technology innovation on China's economic growth using panel data models. The results demonstrate that advancing REN technologies significantly promotes GDP increase in China. Targeted policy incentives must be implemented to accelerate REN technology progression and adoption across the country. Transitioning towards REN systems will be instrumental for China to achieve environmental sustainability while maintaining economic growth. [ABSTRACT FROM AUTHOR]

Objectives: To explore the underlying mechanism of total flavonoids of Litchi seed (TFLS) in treating prostate cancer (PCa). Methods: Cell Counting Kit-8 (CCK-8), EdU incorporation assay, trypan blue dye assay and colony formation assay were employed to evaluate the effect of TFLS on PCa in vitro. The xenograft mouse model was established to explore the anti-tumour effect of TFLS in vivo. Alterations in the metabolic profiles of the PC3 cells and mouse serum were obtained by untargeted metabolomics. Combination with metabolomics analysis and network pharmacology strategies, the potential targets were predicted and further validated by RT-qPCR. Key findings: TFLS attenuated PCa progression both in vitro and in vivo. Metabolomics results yielded from cells and serum indicated that the anti-cancer effect of TFLS was correlated with synergistic modulation of five common metabolic pathways including glycerophospholipid metabolism, arginine and proline metabolism, glycine, serine and threonine metabolism, tryptophan metabolism and steroid biosynthesis. Using in silico prediction and RT-qPCR analysis, we further revealed that TFLS exerted anti-PCa activities via regulating the expressions of nine genes, including MAOA, ACHE, ALDH2, AMD1, ARG1, PLA2G10, PLA2G1B, FDFT1 and SQLE. Conclusions: TFLS suppressed tumour proliferation in PCa, which may be associated with regulating lipid and amino acid metabolisms. [ABSTRACT FROM AUTHOR]

Although personal thermal management (PTM) materials for daily routine environments are widely investigated, the exploration of multifunctional PTM materials with excellent feasibility in complex and outdoor scenarios is still in its infancy. Herein, inspired by the temperature regulation effect of the atmosphere, a novel design for fabricating solar‐thermal gradient reduced graphene oxide (RGO) aerogel‐based bilayer phase change composite (GRGC) featuring "energy regulation" and "energy inverse compensation" is proposed for self‐adaptive PTM applications. By integrating the solar‐thermal energy conversion ability of RGO, the heat regulation of the aerogel/octadecane bilayer structure with the unique gradient RGO framework inside, and the latent‐heat compensation of octadecane, the bilayer GRGC can serve as an efficient PTM device to mitigate drastic temperature changes of human skin in harsh environments. This multifunctional PTM device can not only keep a warm skin surface microclimate in a frigid environment of −5 °C via the synergistic effect of the solar‐thermal conversion, the aerogel thermal insulation, and the phase‐change latent heat release, but also provide efficient thermal buffering to prevent hyperthermia in hot environments through its phase‐change behavior and its thermal insulation. This gradient and bilayer design opens a new avenue for fabricating self‐adaptive PTM devices for applications in harsh environments. [ABSTRACT FROM AUTHOR]

Under the current rice cropping system, excessive nitrogen application has become a major issue that needs to be changed, and nitrogen reduction has become a hot research topic in recent years. The use of optimum planting density is becoming a common agronomic management system in addition to nitrogen reduction, especially under double cropping rice systems. In this paper, changes in rice yield, nitrogen-use efficiency (NUE) and net N mineralization under dense planting with a reduced nitrogen rate (DPRN) were studied. By comparing DPRN with high-nitrogen sparse planting (SPHN), we found that the population tiller number (tiller number per unit area) increased by 9–27% under DPRN cultivation. Nitrogen accumulation under DPRN treatment of double-cropped rice was basically stable. NUE under DPRN was significantly higher by 1.3–22.7% compared to SPHN. The partial factor productivity of applied N (PFPN) was significantly higher than that of SPHN, with an increase of 4.3–22.8%. The net N mineralized of double-cropped rice under DPRN increased at different stages, and the increase in late-season rice (LSR) was greater than that of early-season rice (ESR). The highest net N mineralized in double cropping rice at different stages was found in the dense planting treatment (DP) and N2 (120 kg N h−1). In conclusion, DPRN cultivation of double-cropped rice could be accepted as a proper management strategy for reducing nitrogen input, improving NUE and promoting soil nitrogen mineralization under given conditions. [ABSTRACT FROM AUTHOR]

Nitrogen fertilization and planting density are two key factors that influence the yield of rice. Reducing nitrogen fertilizer input and increasing planting density will help to improve nitrogen use efficiency and stabilize yield. Field and 15N tracer method in plot experiments were conducted to study the trends of yield, nitrogen use efficiency (NUE) and nitrogen transfer of hybrid rice and conventional rice under dense planting with a reduced nitrogen rate (DPRN) and sparse planting with a high nitrogen rate (SPHN). Among the nitrogen in rice plants, the proportion of nitrogen from fertilizer under the DPRN was reduced by 1.8–13%. The late-season rice (LSR) had a higher rate of decrease compared with the early-season rice (ESR). The uptake efficiency of nitrogen fertilizer was significantly higher under the DPRN than that under the SPHN, with an increase of 7.7–21.9%. The accumulated nitrogen and translocated ratio under the DPRN before the heading stage were 6.1–10.8% and 2.0–9.6% higher than those under the SPHN, respectively. The yield did not change under different treatments. Those findings suggest that the DPRN could guarantee a stabilized yield while increasing the NUE and the amount of translocated nitrogen in the double-cropped rice system. [ABSTRACT FROM AUTHOR]

Heavy crude oil rich in colloid and asphaltene is widely used in human life, but the collection and clean-up of its spills are difficult because of its high viscosity and low flowability. Herein, the zeolitic imidazolate framework-8/reduced graphene oxide (ZIF-8/RGO) hybrid aerogels are prepared by in situ anchoring ZIF-8 particles onto anisotropic RGO aerogel for efficient clean-up of spilled heavy crude oil. The solar-thermal ZIF-8/RGO hybrid aerogel with numerous vertical microchannels is efficient in decreasing viscosity and improving flowability of heavy crude oil because of the high solar light absorption and solar-thermal energy conversion capabilities of the RGO and the increased solar light diffuse reflection path and hydrophobicity of the aerogel by ZIF-8. Under 1-sun irradiation, the surface temperature of the aerogel reaches rapidly to 70 °C within 1 min. At the same time, the viscosity of the heavy crude oil falls quickly from 105 to 103 mPa s, and the maximum adsorption capacity of heavy crude oil reaches 112 g g−1 within 9 min. Moreover, the hybrid aerogel exhibits satisfactory adsorption and cycling ability to various organic solvents and oily media. The excellent solar-thermal energy conversion and high adsorption capacities make the anisotropic aerogel promising for efficient clean-up of spilled heavy crude oil. [Display omitted] [ABSTRACT FROM AUTHOR]

Photothermal CNT/RGO microspherical aerogels are synthesized to enhance the efficiency of heavy crude oil spill recovery. Thanks to the efficient photothermal conversion effect and the radially orientated microchannels with large specific surface area, the optimal CNT/RGO aerogels deliver an extraordinary adsorption capacity of heavy crude oil of up to 267 g g−1, significantly superior to those of other oil adsorbents reported so far. High viscosity and low fluidity of heavy crude oils usually hinder their rapid diffusion into porous adsorbents, causing a low efficiency of oil spill remediation. Photothermal effect is thus adopted to rapidly reduce the viscosity of heavy crude oil by in situ solar light heating. Photothermal carbon nanotube/reduced graphene oxide (CNT/RGO) microspherical aerogels are synthesized by fabrication of graphene oxide (GO)-based microspherical aerogels with numerous radially orientated microchannels, followed by growing CNTs inside the microchannels and high-temperature reduction of the GO components. Thanks to the efficient photothermal conversion effect and the rough and oleophilic surface of the microchannels with large surface area, such aerogels facilitate the solar light absorption and hence enhance the crude oil adsorption. Furthermore, the CNTs grown on the RGO skeleton by a chemical vapor deposition approach promote the photothermal conversion efficiency by trapping and absorbing broadband solar light. Under 1 sun irradiation, the surface temperature of the aerogel quickly rises to 83 °C in 1 min, resulting in a sharp decrease in crude oil viscosity. The optimal microspherical aerogels deliver an extraordinary adsorption capacity of heavy crude oil, up to 267 g g−1 within 10 min, superior to those of other oil adsorbents reported so far. [ABSTRACT FROM AUTHOR]

Corydalis saxicola Bunting (CS), a traditional Chinese folk medicine, has been effectively used for treating liver disease in Zhuang nationality in South China. However, the main anti-liver fibrosis ingredients in CS are incompletely understood. To elucidate the main anti-liver fibrosis ingredients in CS and its underlying mechanism. Firstly, spectrum-effect relationship (SER) strategy was applied to identify the major ingredients against liver fibrosis in CS. Subsequently, 1H NMR metabonomics and metagenomics sequencing techniques were used to clarify the intervention of palmatine (PAL) on liver fibrosis. Furthermore, the expression of tight junction proteins and the levels of liver inflammation factors were examined, the effect of PAL on microbiota was verified by FMT. The SER model revealed that PAL was the most important active ingredient in CS. 1H NMR fecal metabonomics showed that PAL could reserve the abnormal levels of gut microbial-mediated metabolites of liver fibrosis, such as isoleucine, taurine, butyrate, propionate, lactate, glucose, which mainly involved in amino acid metabolism, intestinal flora metabolism and energy metabolism. Metagenomics sequencing found that PAL could callback the abundance of s__Lactobacillus_murinus, s__Lactobacillus_reuteri, s__Lactobacillus_johnsonii, s__Lactobacillus_acidophilus and s__Faecalibaculum_rodentium to varying degree. Furthermore, the intestinal barrier function and the levels of hepatic inflammation factors were significantly ameliorated by PAL. FMT demonstrated that the therapeutic efficiency of PAL was closely associated with gut microbiota. The effects of CS on liver fibrosis were attributed in part to PAL by alleviating metabolic disorders and rebalancing gut microbiota. The SER strategy may be a useful method for the discovery of active constituents in natural plants. • SER strategy was used to identify the main active ingredients in CS. • PAL was revealed as the main component of CS against liver fibrosis. • PAL could improve CCl 4 -induced liver fibrosis by ameliorating metabolic disorder and rebalancing gut microbiota. [ABSTRACT FROM AUTHOR]

Breast cancer has been the most commonly-diagnosed cancer worldwide, and the treatment and prognosis of which are often limited by breast cancer stem cells (BCSCs). Litchi seeds have shown good anti-cancer activity in various cancers including prostate cancer, lung cancer and breast cancer. However, the activity and underlying mechanism of Litchi seeds against BCSCs remain unknown. To investigate the activity and mechanism of total flavonoids of litchi seed (TFLS) against BCSCs in vitro and in vivo. Two orthotopic xenograft mouse models were established using HCC1806 cells pretreated or untreated with TFLS to determine whether TFLS could target BCSCs in vivo. Mammosphere formation and flow cytometry assays were employed to evaluate the effect of TFLS on BCSCs in vitro. The underlying mechanism was investigated using RT-qPCR, Western blot, immunohistochemistry and immunofluorescence experiments. TFLS could significantly inhibit the viability of HCC1806, MCF-7 and HCC1937 cells in vitro and suppress the growth of HCC1806 cells in vivo. TFLS attenuated stem cell-like properties of breast cancer through reducing the percentage of CD44+CD24-/low cells, inhibiting the mammospheres formation and down-regulating the mRNA and protein levels of cancer stem cells related markers (Oct4, Nanog, Sox2) in MCF-7 and HCC1806 cells. Meanwhile, TFLS suppressed the tumor-initiating ability of BCSCs via reducing the percentage of CD44+CD24-/low cells in tumor and lowering tumor incidence rate in orthotopic xenograft mice. In addition, TFLS treatments restricted the expression and nuclear translocation of Notch3, subsequently down-regulated Hes1 and Runx2 expressions. TFLS could suppress the growth of breast cancer and eliminate breast cancer stem cells by inhibiting the Notch3 signaling pathway. [Display omitted] • TFLS inhibit breast cancer in vitro and in vivo. • TFLS attenuate breast cancer stem cells in vitro and restrict their tumorigenic ability in vivo. • TFLS decrease the expression and nuclear translocation of Notch3, subsequently down-regulate Hes1 and Runx2 expressions. [ABSTRACT FROM AUTHOR]

Diagnosis of rare skeletal diseases is based primarily on clinical phenotype and radiographic analysis. Genetic etiology of these heterogeneous diseases remains largely unknown. Here, we report the identification of two genomic mutations using exome sequencing from patients with multiple epiphyseal dysplasia (MED) of an unusual family in autosomal dominant and X-linked inheritance. A dominant mutation (c.2224G > A; p.Gly687Ser) in the known causal COL2A1 gene was identified in three patients with MED, deformed femoral heads and vertebral dysplasia. Furthermore, a hemizygous mutation (c.2830G > A; p.Ala944Thr) in the USP9X gene was identified in the fourth patient with short stature, MED, deformed femoral head, thoracic and lumbar platyspondyly, right ankle condyle dysplasia, and subchondral sclerosis. This is the first identification of an X-linked candidate causative gene in a patient with MED, suggesting a new clinical entity. Our findings shed a new light on the role of USP9X in MED-associated disorders. [ABSTRACT FROM AUTHOR]

Marsdenia tenacissima injection (MTE), a traditional Chinese medical injection extracted from the rattan of Marsdenia tenacissima (Roxb.) Moon, has been approved for clinical use in China as an adjuvant therapeutic agent in multiple cancers, including esophageal cancer, gastric cancer, lung cancer, and liver cancer. However, the activity and mechanism of MTE on prostate cancer (PCa) remain to be defined. To investigate the activity and the underlying mechanism of MTE in the treatment of PCa. The component characterization of MTE was analyzed by HPLC-CAD-QTOF-MS/MS technology. Cell Counting Kit-8 (CCK-8) assay was used to assess PCa cell proliferation. Colony formation assay was applied to detect the clonogenic ability of the cells. MetaboAnalyst5.0 database was employed to analyze the altered metabolites of PC3 cells treated with MTE obtained by UPLC-QTOF-MS/MS. Combined with metabolomics analysis and network pharmacology, we predicted the potential targets, which further were verified by Western Blot, RT-qPCR, and Immunohistochemistry assays. Finally, SeeSAR software was applied to predict the potential active components of MTE against PCa. A total of 21 components in MTE were confirmed by HPLC-CAD-QTOF-MS/MS analysis. MTE inhibited the proliferation and colony formation of PCa cells. A total of 20 metabolites closely related to glycerophospholipid metabolism, glycolysis/gluconeogenesis, and tricarboxylic acid (TCA) cycle were significantly changed in PC3 cells treated with MTE. The network pharmacology analysis revealed that MTE suppressed the growth of PC3 cells might by regulating the ErbB2-GSK3β-HIF1α signaling axis. Furthermore, we also confirmed that stimulation of MTE significantly inhibited the phosphorylation of ErbB2 at Tyr877 and the activities of its downstream signal transducers (GSK3β and HIF1α) in PCa, as well as the mRNA levels of critical factors (IDH2, LDHA, and HIF1A) in the tricarboxylic acid (TCA) cycle. Molecular docking further suggested that Tenacissimoside E, cryptochlorogenic acid, and scopoletin might be the active ingredients of MTE for PCa treatment. This study proposed that MTE exerts a potential anti-tumor effect in PCa through inhibiting ErbB2-GSK3β-HIF1α signaling axis, which may be related to the TCA cycle. [Display omitted] • MTE inhibits the proliferation of PCa cells. • ErbB2-GSK3β-HIF1α signaling axis is involved in the activity of MTE against PCa. • MTE alters the metabolism of PC3 cells by reducing the mRNA levels of IDH2 and LDHA. [ABSTRACT FROM AUTHOR]

Study design: A retrospective case review. Introduction: To evaluate the safety and efficacy of the non-fusion technique in achieving and maintaining the proper correction for congenital spinal deformity (CSD) and allowing normal spinal growth in patients with split spinal cord malformation (SSCM). Materials and methods: Seven patients who had CSD and SSCM were adopted, with a mean age of 8 years. All the patients in this study received Halo-gravity traction (HGT) prior to expansion of the spine and instrumentation with vertical expandable titanium prosthetic rib, growing rod or their hybrid. Five of them underwent opening wedge thoracoplasty simultaneously. And the two patients with type I SSCM underwent bony spur excision in the initial surgery before corrective manipulation. Then all the patients received a lengthened operation every six months. Changes of their major curve and length of T1-S1 spine were measured, and complications, neurological status were recorded. All the patients were followed up with an average of 32.6 months. Results: Their mean major curve improved from 90.1° to 58.6° with a correction rate of 34.9 %. The T1-S1 length increased from 26.3 to 34.7 cm at final follow-up. Especially, one of the type I SSCM patients whose neurological deterioration was found preoperatively was significantly improved. Conclusion: Preoperative Halo-gravity traction followed by non-fusion and growing instrumentation may be effective and safe for young children of CSD associated with SSCM. But it is an ongoing study and additional large multicenter studies are necessary to further assess the safety and efficacy of non-fusion and growing instrumentation. [ABSTRACT FROM AUTHOR]

Abstract: A tissue-engineered scaffold with nano-silver and collagen type I was constructed and investigated for its ability to adsorb laminin and the usefulness in the repair and regeneration of damaged peripheral nerves in animals. The nano-silver scaffold displayed ideal microtubule structure under electronic microscope; even distribution of the nano-silver particles was also seen with energy spectrometry. After immersion in a laminin solution, the laminin-attached scaffolds were implanted into rabbits to repair a 10-mm injury of the sciatic nerve. At 30 days post-implantation, regeneration of the damaged nerve was evaluated by transmission electron microscopy, electrophysiological examination and fluoro-gold (FG) retrograde labelling. Compared with the control collagen-scaffold without nano-silver, the nano-silver-containing scaffold showed a higher rate of laminin adsorption, regenerated a nerve with a thicker myelin sheath and improved the nerve conduction velocity and nerve potential amplitude. FG retrograde labelled the newly grown axons in the spinal cord cortex anterior horn and the dorsal root ganglion. These results demonstrate the superior functionality of the nano-silver–collagen scaffold in the adsorption to laminin and subsequent regeneration of damaged peripheral nerves. [Copyright &y& Elsevier]

Tissue engineering has become a promising way of treating growth plate injuries. In this study, we attempted investigating the role of the autologous tissue-engineered composite in the treatment of rabbit growth plate injuries. Growth plate chondrocytes from iliac crest epiphyseal cartilage of immature New Zealand rabbits were obtained by dissection and sequential digestion with 0.2% collagenase (type II). After proliferating in monolayer culture in vitro for 3 weeks, the cells were harvested and seeded onto the demineralized bone matrix (DBM) scaffold to construct the composite. The autologous tissue-engineered composites were finally implanted into the proximal right tibia defects of the growth plate created in 12 rabbits (group A underwent the operation after obtaining chondrocytes 3 weeks beforehand), another 12 rabbits were implanted with only the DBM scaffold (group B), and the defects in group C (12 rabbits) were not implanted. The left tibias of all animals were left undone as the normal control. Two weeks after the operation, severe shortness and angulation deformity of the right tibia evaluated by X-ray were gradually observed in groups B and C. However, there were no obvious changes in group A and there were significant differences between group A and groups B and C (p < 0.05) at the 4-, 8-, and 16-weeks time points. 16 weeks after operation, histological examination revealed that the defects of the right tibias in group A had restored to almost the normal columnar structure of the growth plate. The results demonstrate that tissue-engineered composite established by combination of autologous growth plate chondrocytes and DBM can prevent the formation of a bone bridge and restore the growth of damaged growth plate. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We had reported that cajanolactone A (CLA) from Cajanus cajan dose-dependently inhibited ovariectomy-induced obesity and liver steatosis in mice, showing potential to prevent postmenopausal obesity and fatty liver. In this study, the role of CLA in the regulation of energy and lipid homeostasis was investigated. Ovariectomized mice treated with CLA or vehicle for 12 weeks were performed a 48 h monitoring for energy metabolism and food uptake. After that, hypothalami, perigonadal (pWATs), inguinal (iWATs) and brown (BATs) adipose tissues, livers, sera, and fecal and cecal contents were collected and analyzed. In CLA-treated mice, we observed reduced food uptake; increased energy expenditure; inhibited expression of orexigenic genes (ORX , ORXR2 , pMCH and Gal) in the hypothalami, of lipogenic genes (CD36 , SREBP-1c , ChREBP , PPARγ) in the livers, and of lipid storage proteins in the WATs (FSP27, MEST and caveolin-1) and livers (FSP27, Plin2 and Plin5); stimulated expression of metabolism-related proteins (pATGL and Echs1) in the adipose tissues and of thermogenic protein (UCP1) in the inguinal WATs; increased BAT content; increased mitochondria in the pWATs and livers; inhibited angiogenesis in the pWATs; and altered gut microbiome diversity with an increased abundance of Bacteroides. CLA prevents ovariectomy-induced obesity and liver steatosis via regulating energy intake and lipid synthesis/storage, promoting UCP1-dependent heat production, and protecting the mitochondrial function of hepatocytes and adipocytes. The improved gut microecology and inhibited angiogenesis may also contribute to the anti-obese activity of CLA. [Display omitted] • The stilbene cajanolactone A protects the ovariectomized mice fed a high-fat diet from obesity and fatty liver through reducing the food uptake and promoting the energy expenditure. • CLA reduces food uptake through downregulating the expression of orexigenic genes in the hypothalamus. • CLA Promotes energy expenditure through protecting the brown and beige adipose tissues and the mitochondria. • Altered gut microecology may contribute to the antiobese effect of CLA. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is a neurodegenerative disorder characterized by the presence of neurodegenerative lesions and cognitive impairment. In this study, a series of novel palmatine derivatives were designed and synthesized through the introduction of a heteroatom using carbodiimide-mediated condensation. The synthesized compounds were then screened for toxicity and potency, leading to the identification of compound 2q, which exhibited low toxicity and high potency. Our findings demonstrated that compound 2q displayed significant neuroprotective activity in vitro, emerging as a promising candidate for Alzheimer's disease treatment. [ABSTRACT FROM AUTHOR]

This study was to investigate effects of progesterone vaginal sustained-release gel and intramuscular injection of progesterone on frozen-thawed embryos transfer in 3013 patients receiving vaginal progesterone sustained-release gel and progesterone injection in artificial cycle for frozen-thawed embryo transfer. All patients were divided into two groups: group A with progesterone intramuscular injection (60 mg/d) plus dydrogesterone (10 mg tid) and group B with progesterone vaginal sustained-release gel of progesterone (90 mg/d) plus dydrogesterone (10 mg tid). There were 1988 women in group A treated with progesterone injection and 1025 women in group B with progesterone vaginal sustained-release gel. There were no statistically (P > 0.05) significant difference between the two groups in age, years of infertility, body mass index, endometrial thickness at transfer time, the average numbers of embryo transferred, cause of infertility, number of cycles, pregnancy rate and ectopic pregnancy rate. No significant (P > 0.05) differences existed in the clinical pregnancy (52.5% vs. 56.0%) and ectopic pregnancy (2.2% vs. 3.0%) rate between groups A and B. However, group B with vaginal progesterone supplementation had significantly (P < 0.05) greater implantation (37.0% vs 34.4%), delivery (45.1% vs. 41.0%) and live birth (45.0% vs. 40.8%) rate than group A with intramuscular progesterone injection, whereas group A had significantly (P < 0.05) greater early abortion rate (19.4% vs. 15.3%) than group B. This study showed that vaginal gel progesterone supplementation has good effects on frozen-thawed embryo transfer and can significantly increase the rate of implantation, delivery and live birth but decrease the abortion rate compared with intramuscular progesterone injection. [ABSTRACT FROM AUTHOR]

Cajanolactone A (CLA) is a stilbenoid discovered by us from Cajanus cajan (L.) Millsp. In our study, CLA was found to promote osteoblast differentiation in human bone marrow mesenchymal stem cells (hBMSCs), as judged by increased cellular alkaline phosphatase activity and extracellular calcium deposits, and elevated protein expression of Runx2, collagen-1, bone morphogenetic protein-2, and osteopontin. Mechanistic studies revealed that hBMSCs undergoing osteoblast differentiation expressed upregulated mRNA levels of Wnt3a, Wnt10b, LRP5/6, Frizzled 4, β-catenin, Runx2, and Osterix from the early stage of differentiation, indicating the role of activated Wnt/β-catenin signaling pathway in osteoblast differentiation. Addition of CLA to the differentiation medium further increased the mRNA level of Wnt3a, Wnt10b, Frizzled 4, LRP5, and β-catenin, inferring that CLA worked by stimulating Wnt/LRP5/β-catenin signaling. Wnt inhibitor dickkopf-1 antagonized CLA-promoted osteoblastogenesis, indicating that CLA did not target the downstream of canonical Wnt signaling pathway. Treatment with CLA caused no changes in mRNA expression level, as well as protein secretion of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL), indicating that CLA did not affect the OPG/RANKL axis. Our results showed that CLA, which promoted osteoblast differentiation in hBMSCs, through activating Wnt/LRP5/β-catenin signaling transduction, is a promising anti-osteoporotic drug candidate. [ABSTRACT FROM AUTHOR]

Objectives: Neuroprotective potential of 7‐methoxyflavanone (7MF) and its underlying mechanism was investigated. Methods: Inhibitory effects of 7MF on microglial activation and neuroinflammation were evaluated by employment of lipopolysaccharide (LPS)‐induced BV2 microglial cells. Changes in expression of genes and proteins of interest were investigated by RT‐qPCR analysis and Western blot analysis. Inhibitory effects of 7MF on microglial overactivation were verified in LPS‐treated C57BL/6J mice using ionized calcium‐binding adaptor molecule‐1 (Iba1) in the brain and interleukin‐6 (IL‐6) in serum as indicators. Key findings: In BV2 cells, pretreatment with 7MF antagonized LPS‐induced production of inflammatory factors IL‐6, tumour necrosis factor‐α (TNF‐α), cyclooxygenase‐2 (COX‐2), inducible nitric oxide synthase (iNOS), intercellular adhesion molecule‐1 (ICAM‐1) and monocyte chemoattractant protein‐1 (MCP‐1). Mechanistic studies revealed reduced expression of Toll‐like receptor 4 (TLR4), myeloid differentiation factor‐88 (MyD88), phosphorylated forms of c‐Jun N‐terminal kinase (p‐JNK) and extracellular signal‐regulated kinases 1/2 (p‐ERK) but increased nuclear accumulation of nuclear factor erythroid 2‐related factor 2 (Nrf2) and cellular expression of NAD(P)H quinone dehydrogenase‐1 (NQO‐1) by 7MF. In LPS‐treated mice, pretreatment with 7MF reduced the brain level of Iba1 and serum level of IL‐6. Conclusions: 7‐methoxyflavanone inhibited LPS‐stimulated TLR4/MyD88/MAPK signalling and activated Nrf2‐mediated transcription of antioxidant protein NQO‐1, showing antineuroinflammatory effect, so it is a potential neuroprotective agent. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Marsdenia tenacissima (Roxb.) Wight et Arn is a vine distributed in southwest area of China and used in folk medicine for treatment of tumors. Recent decades of studies on this plant reveal its synergistic effects with certain anticancer drugs in cancer therapy. In our previous study, an extract ETA which contains total aglycones made from M. tenacissima significantly enhanced antitumor activity of paclitaxel in tumor-bearing mice. However, the effective constituents in ETA and the underlying mechanisms remain unclear. Aim of the study Reveal the active components in ETA as well as the molecular mechanism in enhancing antitumor efficacy of paclitaxel. Material and methods Main constituents in ETA were purified by chemical methods. Effects of the purified constituents on metabolic activity of CYP450 enzymes were evaluated in human liver microsomes. Ability of the constituents to enhance antitumor activity of paclitaxel were investigated in nude mice bearing HeLa tumors. Pharmacokinetic study was performed in SD rats. Molecular docking was carried out for investigation of drug-protein interactions. Results Three main C 21 steroidal aglycones, 11α- O -tigloyl-12β- O -acetyl-tenacigenin B (MT1), 11α- O -2-methylbutanoyl-12β- O -tigloyl-tenacigenin B (MT2) and 11α- O -2-methylbutanoyl-12β- O -acetyl-tenacigenin B (MT3), together with tenacigenin B (MT4) was prepared from ETA. Among them, MT1 , MT2 and MT3 strongly inhibit the metabolic activity of CYP3A4. MT2 also showed inhibitory effects on CYP2C8, CYP2B6 and CYP2C19. In HeLa tumor xenografts, MT1 , MT2 and MT3 (30 mg/kg) did not affect tumor growth themselves, but significantly enhanced paclitaxel-induced growth inhibition. In addition, coadministration of MT2 with paclitaxel resulted in significant reduction of liver CYP2C8. In pharmacokinetic study, MT2 significantly increased the blood concentration of paclitaxel with increased AUC value by 2.2–5.3 folds. Molecular docking analysis suggested hydrophobic interaction modes of tenacigenin B derivatives with CYP3A4, and also the essential roles of the C-11 and C-12 ester groups for effective interaction with CYP3A4. Conclusion Our study proves that, 11α- O -tigloyl-12β- O -acetyl-tenacigenin B, 11α- O -2-methylbutanoyl-12β- O -tigloyl-tenacigenin B and 11α- O -2-methylbutanoyl-12β- O -acetyl-tenacigenin B, which are the main constituents of ETA, are active inhibitors of CYP3A4 with potential to increase therapeutic efficacy of anticancer drugs that are substrates of CYP3A4. Tenacigenin B derivatives with C-11 and C-12 ester group substitutions, or at least a large part of them, are active components in ETA and M. tenacissima to enhance in vivo antitumor efficacies of paclitaxel. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

To compare the clinical efficacy of the minimally invasive technique and the open method in the treatment of irreducible unilateral subaxial cervical facet joint dislocation (SCFD). From March 2015 to September 2018, 62 patients with unilateral SCFD were studied. The cases were divided into 2 groups based on different surgery strategies. Thirty-one patients were enrolled in the minimally invasive surgery (MIS) group, and 31 patients were enrolled in the open surgery group. The duration of prone position operation, blood loss, and total hospitalization costs were recorded. The clinical effects were evaluated using visual analogue scale scores, the Oswestry Disability Index, and Japanese Orthopedic Association scores at each follow-up. In addition, the segmental Cobb angle and intervertebral height were recorded and compared. The amount of intraoperative blood loss, prone position operation duration, and total hospital costs in the MIS group were significantly lower than in the open surgery group. The visual analogue scale, Oswestry Disability Index, and Japanese Orthopedic Association scores of the 2 groups significantly improved after the operation. A satisfactory fusion rate was obtained in both groups, and the segmental Cobb angle and intervertebral height scores in both groups improved significantly. Minimally invasive reduction had equal clinical efficacy to posterior open surgery. However, MIS was less invasive and had lower costs. Therefore, it is a potential option in the treatment of SCFD. [ABSTRACT FROM AUTHOR]

Background: As the increasing mortality and incidence of lung cancer (LC), there is an urgent need to discover novel treatment agent. In this study, we aimed to investigate the anti-LC effects of nitidine chloride (NC), a small molecular compound extracted from Chinese herbal medicine, while detailing its underlying mechanisms. Methods: Cell viability was detected by MTT assays and five cell death inhibitors, including ferrostatin-1 (Fer-1), Z-VAD-FMK, necrostatin-1 (Nec-1), disulfiram (DSF) and IM-54 were used to explore the type of cell death induced by NC. The microscopic features of NC-induced pyroptosis were assessed by transmission electron microscopy (TEM) and the pyroptotic-related proteins such as caspase and gasdermin family, were examined by western blot. Network pharmacology was employed to predict the potential mechanisms of NC in lung cancer treatment. CETSA and DARTs were used to determine the activity of NC binding to targeted protein. Xenograft mice model was established to further investigate the inhibitory effect and mechanism of NC against LC. Results: The pyroptosis inhibitor (DSF) and apoptosis inhibitor (Z-VAD-FMK) but not IM-54, necrostatin-1, or Ferrostatin-1 rescued NC-induced cell death. Morphologically, H1688 and A549 cells treated with NC showed notably pyroptotic features, such as cell swelling and large bubbles emerging from the plasma membrane. Gasdermin E (GSDME) rather than GSDMC or GSDMD was cleaved in NC-treated H1688 and A549 cells with an increased cleavage of caspase 3. Combined with network pharmacology and molecule docking, PI3K/Akt signaling axis was predicted and was further verified by CETSA and DARTs assay. In addition, the activation of PI3K is able to rescue the pyroptosis induced by NC in vitro. In xenograft model of LC, NC significantly hindered the transduction of PI3K-AKT pathway, inducing pyroptosis of tumor. Conclusion: Our data indicated that NC is a potential therapeutic agent for the treatment of LC via triggering GSDME-dependent pyroptosis. [ABSTRACT FROM AUTHOR]

This retrospective cross-sectional study was to investigate factors affecting clinical pregnancy in patients who received gonadotropin-releasing hormone agonist luteal phase long protocol (GnRH-a long protocol) and underwent fresh in-vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) embryo transfer cycle. One thousand five hundred and twenty-five patients who received GnRH-a long protocol and underwent fresh IVF/ICSI embryo transfer cycle were enrolled. The clinical pregnancy rate (63.1 vs. 22.4%, p <.05) and live birth rate (53.8 vs. 14.5%, p <.05) were significantly higher while the miscarriage rate (12.5 vs. 35.3%, p <.05) was significantly lower in the two embryo group than those in the one embryo group. The clinical pregnancy rate (48.5 vs. 64.1%, p <.05) and live birth rate (38.4 vs. 55.0%, p <.05) were significantly lower in patients older than 33.5 years than those in younger patients. The clinical pregnancy rate (52 and 60.6 vs. 79.7%, p <.05) and live birth rate (36 and 51.4 vs. 69.6%, p <.05) of the thin and mediate groups were significantly lower than those in the thick group, whereas the ectopic pregnancy rate (11.5 and 1.9 vs. 0%, p <.05) was significantly higher in the thin group than in the mediate and thick group. Multivariate logistic regression analysis showed that age (OR = 0.956, 95% CI [0.931, 0.982], p <.05), number of embryos transferred (OR = 2.491, 95% CI [1.670, 3.715], p <.05) and endometrial thickness on the transplantation day (OR = 1.124, 95% CI [1.067, 1.185], p <.05) were independent factors significantly associated with clinical pregnancy. In conclusion, endometrial thickness (>14.69 mm) on the day of transfer, two cleavage embryos transferred, and female age (≤33.5 years) are independent factors affecting clinical pregnancy outcomes in controlled ovarian hyperstimulation with GnRH-a long protocol for assisted conception. What is already known on this subject? Fresh embryo transfer cycle with GnRH-a long protocol will result in a higher pregnancy rate in controlled ovarian hyperstimulation cycles. What do the results of this study add? Endometrial thickness on the day of transfer, number of embryos transferred, and female age were independent factors affecting clinical pregnancy outcomes. What are the implications of these findings for clinical practice and/or further research? When performing a fresh IVF/ICSI embryo transfer cycle with GnRH-a long protocol for ovulation induction, the independent affecting factors should be taken into consideration. [ABSTRACT FROM AUTHOR]

Purpose: Although there have been numerous studies aimed at determining the effects and safety of early vs. late surgical decompression for traumatic cervical spinal cord injury, controversies still exist regarding the optimal timing of surgery for this serious spinal trauma. This study was conducted to evaluate the effectiveness and safety of early vs. late surgical decompression for lower cervical spine trauma associated with spinal cord injury.Methods: A retrospective review of was performed on consecutive patients who underwent surgical decompression for lower cervical (C3-C7) spine trauma associated with spinal cord injury at six institutions across China from January 2007 to January 2012. These patients were analysed according to the timing of surgical intervention. The early group comprised patients who underwent surgery within the first 72 hours after being injured, whilst the late group comprised patients who underwent surgery after the first 72 hours. For analysis of neurologic improvement, patients who had completed a follow-up of at least six months were assessed. Other outcomes analysed were hospitalisation periods, complications and mortality.Results: A total of 595 patients were identified (456 men and 139 women at an average age of 41.4 years), with 212 in the early group and 383 in the late group. Patients in both groups had made a significant neurologic improvement in the final follow-up, but no statistically significant difference was noted between groups. Patients in the early group had a significantly shorter hospital stay (15.4 vs. 18.3 days, p <0.001) but realised no benefits in terms of intensive care unit length of stay and ventilator days. No significant differences were identified between groups with regards complications (pneumonia, pulmonary embolism, wound infection, sepsis and urinary tract infection). Compared with the late group, the early group had a significantly higher incidence of postoperative neurological deterioration (6.6 vs. 0.7 %, p <0.001) and mortality (7.1 vs. 2.1 %, p = 0.003).Conclusion: The timing of surgery for patients sustaining traumatic lower cervical spine injury with neurological involvement did not affect neurological recovery. Early surgical intervention was associated with a higher incidence of mortality and neurological deterioration compared with late surgical intervention, indicating that surgery after the first 72 hours might be relatively safe. [ABSTRACT FROM AUTHOR]

Fufang Luohanguo Qingfei granules (LQG) is a Chinese patent medicine, clinically used to treat flu-like symptoms including cough with yellow phlegm, impeded phlegm, dry throat and tongue. However, the protective activity of LQG against influenza infection is indeterminate. This study is to investigate the therapeutic effect of LQG on influenza infection and elucidate its underlying mechanism. In vivo : A viral susceptible mouse model induced by restraint stress was established to investigate LQG's beneficial effects on influenza susceptibility. MAVS knockout (Mavs −/−) mice were used to verify the potential mechanism of LQG. In vitro : Corticosteroid (CORT)-treated A549 cells were employed to identify the active ingredients in LQG. Mice morbidity and mortality were monitored daily for 21 days. Histopathologic changes and inflammatory cytokines in lung tissues were examined by H&E staining and ELISA. RNA-seq was used to explore the signaling pathway influenced by LQG and further confirmed by qPCR. Immunoblotting and immunohistochemistry (IHC) were used to determine the protein levels. CO-IP and DARTS were applied to detect protein-protein interaction and compound-protein interaction, respectively. LQG effectively attenuated the susceptibility of restrained mice to H1N1 infection. LQG significantly boosted the production of IFN-β transduced by mitochondrial antiviral-signaling protein (MAVS), while MAVS deficiency abrogated its protective effects on restrained mice infected with H1N1. Moreover, in vitro studies further revealed that mogroside Ⅱ B, amygdalin, and luteolin are potentially active components of LQG. These results suggested that LQG inhibited the mitofusin 2 (Mfn2)-mediated ubiquitination of MAVS by impeding the E3 ligase synoviolin 1 (SYVN1) recruitment, thereby enhancing IFN-β antiviral response. Overall, our work elaborates a potential regimen for influenza treatment through reduction of stress-induced susceptibility. [Display omitted] • LQG reduces influenza virus susceptibility by improving MAVS/IFN-β pathway. • LQG curbs MAVS ubiquitination degradation by disrupting Mfn2/SYVN1 recruitment. • LQG's efficacy is abolished in Mavs−/− mice. • Mogroside Ⅱ B, amygdalin, and luteolin are potentially active components of LQG. [ABSTRACT FROM AUTHOR]

Abstract: In the work, two novel conceptions of “capacity quality” (CQ) and “capacity quality coefficient” (λ) were defined to evaluate cycling power capabilities of Ni–MH rechargeable batteries when considering the effect of the kinetic limitation. For convenient comparison, the capacity quality coefficient (λ) and the efficiency of charge/discharge (η) were in parallel applied to characterize cycling capabilities based on the data from BYD H-3/4AAA800Ni–MH batteries at 1C–3.5C. The results show that there is an obvious difference between λ and η which served as evaluation indexes for rechargeable batteries, and that the secondary battery with good capacity quality also has a good cycling capability and rate capability, especially at high rate. The introduced capacity quality not only subtly covered kinetic information of the rechargeable batteries but also factually reflected stability of the electrode materials. [Copyright &y& Elsevier]

As ultralight and superelastic aerogels are quite desirable for pressure sensing and energy storage applications, superelastic and ultralight carbon nanofiber (CNF)/transition metal carbides and carbonitrides (MXenes) hybrid aerogels with anisotropic microchannels are thus fabricated by liquid nitrogen-assisted unidirectional-freezing followed by freeze-drying. The CNFs with high aspect ratios entangle and assemble into the interconnected scaffolds, while the MXene sheets enhance structural stability of the framework of CNFs and endow the aerogels with satisfactory electronic conductivities. Benefiting from the stable architecture with orientated microchannels, the CNF/MXene aerogel (CNF/MX) with an ultralow density of 4.87 mg cm−3 exhibits superb compressible resilience at the strain of 50% for at least 5000 cycles and a high strain of 95% for 500 cycles. Importantly, the outstanding strain- or pressure-responses endow the CNF/MX aerogel sensor with high sensitivity (65 kPa−1), ultralow detection limit (<5 Pa), rapid response (26 ms), large workable strain range (0–95%), and superb response stability. Furthermore, the presence of MXene with excellent electrochemical activity makes the binder-free CNF/MX electrode exhibit a high rate performance with 80% capacitance retention when the current density increases by 100 times and a high cycling stability with capacitance retention of 90% after 20,000 cycles at 5 A g−1. [ABSTRACT FROM AUTHOR]

An optimized Enhanced Recovery After Surgery (ERAS) program is lacking for adolescent idiopathic scoliosis (AIS). The aim of the present study was to evaluate the impact and feasibility of an optimized ERAS pathway in patients with surgically treated AIS. In total, 79 patients with AIS who underwent corrective surgery without 3-column osteotomy were recruited from Xijing Hospital of the Fourth Military Medical University between 2012 and 2018. Forty-four patients were treated according to a traditional protocol and 35 were managed using an optimized ERAS pathway, which was designed and implemented by a multidisciplinary team. The following data were collected and retrospectively analyzed, demographic characteristics, Cobb angle, curve type (Lenke), surgical duration, fusion level, correction rate, estimated blood loss, postoperative hemoglobin level, postoperative pain score, pain relief time, hemovac drainage, drainage removal time, first ambulation time, length of hospital stay, and postoperative complications. There was no significant difference between the traditional and ERAS groups with respect to demographic characteristics, Cobb angle, curve type (Lenke), fusion level, and correction rate. However, the ERAS group had a shorter surgical duration, less blood loss and hemovac drainage, a higher postoperative hemoglobin level, and earlier pain relief, ambulation, and discharge. The rates of postoperative nausea and vomiting were lower in the ERAS group than in the traditional group. The ERAS pathway is capable of improving the perioperative status of patients with AIS by offering stronger analgesia, faster ambulation, and earlier discharge. [ABSTRACT FROM AUTHOR]

Chronic stress‐evoked depression has been implied to associate with the decline of adult hippocampal neurogenesis. Caffeine has been known to combat stress‐evoked depression. Herein, we aim to investigate whether the protective effect of caffeine on depression is related with improving adult hippocampus neurogenesis and explore the mechanisms. Mouse chronic water immersion restraint stress (CWIRS) model, corticosterone (CORT)‐established cell stress model, a coculture system containing CORT‐treated BV‐2 cells and hippocampal neural stem cells (NSCs) were utilized. Results showed that CWIRS caused obvious depressive‐like disorders, abnormal 5‐HT signaling, and elevated‐plasma CORT levels. Notably, microglia activation‐evoked brain inflammation and inhibited neurogenesis were also observed in the hippocampus of stressed mice. In comparison, intragastric administration of caffeine (10 and 20 mg/kg, 28 days) significantly reverted CWIRS‐induced depressive behaviors, neurogenesis recession and microglia activation in the hippocampus. Further evidences from both in vivo and in vitro mechanistic experiments demonstrated that caffeine treatment significantly suppressed microglia activation via the A2AR/MEK/ERK/NF‐κB signaling pathway. The results suggested that CORT‐induced microglia activation contributes to stress‐mediated neurogenesis recession. The antidepression effect of caffeine was associated with unlocking microglia activation‐induced neurogenesis inhibition. [ABSTRACT FROM AUTHOR]

3A on p. 8312 showing the results from ALP staining and Alizarin Red S staining experiments, two pairs of apparently overlapping data panels were identified in the Dex 10 SP 6 sp M / TMP 50 M, 100 M and 200 M data panels. 2A on p. 8311, portraying the results of immunostaining experiments for osterix, the "GIOP" and "GIOP+TMP (20)" data panels contained overlapping data, such that these images were derived from apparently the same original source, where they were intended to show the results from differently performed experiments. Mol Med Rep 16: 8307-8314, 2017; DOI: 10.3892/mmr.2017.7610 Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. [Extracted from the article]

Herpes simplex virus type 1 (HSV-1) is the most common virus, with an estimated infection rate of 60–95% among the adult population. Once infected, HSV-1 can remain latent in the host for a lifetime and be reactivated in patients with a compromised immune system. Reactivation of latent HSV-1 can also be achieved by other stimuli. Though acyclovir (ACV) is a classic drug for HSV-1 infection, ACV-resistant strains have been found in immune-compromised patients and drug toxicity has also been commonly reported. Therefore, there is an urge to search for new anti-HSV-1 agents. Natural products with potential anti-HSV-1 activity have the advantages of minimal side effects, reduced toxicity, and they exert their effect by various mechanisms. This paper will not only provide a reference for the safe dose of these agents if they are to be used in humans, referring to the interrelated data obtained from in vitro experiments, but also introduce the main pharmacodynamic mechanisms of traditional Chinese medicine (TCM) against HSV-1. Taken together, TCM functions as a potential source for HSV-1 therapy by direct (blocking viral attachment/absorption/penetration/replication) or indirect (reducing the susceptibility to HSV-1 or regulating autophagy) antiviral activities. The potential of these active components in the development of anti-HSV-1 drugs will also be described. [ABSTRACT FROM AUTHOR]

Longitudinally oriented microstructures are essential for a nerve scaffold to promote the significant regeneration of injured peripheral axons across nerve gaps. In the current study, we present a novel nerve-guiding collagen-chitosan (CCH) scaffold that facilitated the repair of 30 mm-long sciatic nerve defects in beagles. The CCH scaffolds were observed with a scanning electron microscope. Eighteen beagles were equally divided into CCH group, autograft group and non-graft group. The posture and gait of each dog was recorded at 12 and 24 weeks after surgery. Electrophysiological tests, Fluoro-Gold retrograde tracing test, Histological assessment of gastrocnemius and immunofluorescent staining of nerve regeneration were performed. Our investigation of regenerated sciatic nerves indicated that a CCH scaffold strongly supported directed axon regeneration in a manner similar to that achieved by autologous nerve transplantation. In vivo animal experiments showed that the CCH scaffold achieved nerve regeneration and functional recovery equivalent to that achieved by an autograft but without requiring the exogenous delivery of regenerative agents or cell transplantation. We conclude that CCH nerve guides show great promise as a method for repairing peripheral nerve defects. [ABSTRACT FROM AUTHOR]

Small-cell lung cancer (SCLC) is a highly metastatic and recalcitrant malignancy. Metastasis is the major cause of death in patients with SCLC but its mechanism remains poorly understood. An imbalance of hyaluronan catabolism in the extracellular matrix accelerates malignant progression in solid cancers due to the accumulation of low-molecular-weight HA. We previously found that CEMIP, a novel hyaluronidase, may act as a metastatic trigger in SCLC. In the present study, we found that both CEMIP and HA levels were higher in SCLC tissues than in paracancerous tissues from patient specimens and in vivo orthotopic models. Additionally, high expression of CEMIP was associated with lymphatic metastasis in patients with SCLC, and in vitro results showed that CEMIP expression was elevated in SCLC cells relative to human bronchial epithelial cells. Mechanistically, CEMIP facilitates the breakdown of HA and accumulation of LMW-HA. LMW-HA activates its receptor TLR2, and subsequently recruits c-Src to activate ERK1/2 signalling, thereby promoting F-actin rearrangement as well as migration and invasion of SCLC cells. In addition, the in vivo results verified that depletion of CEMIP attenuated HA levels and the expressions of TLR2, c-Src, and phosphorylation of ERK1/2, as well as liver and brain metastasis in SCLC xenografts. Furthermore, the application of the actin filament inhibitor latrunculin A significantly inhibited the liver and brain metastasis of SCLC in vivo. Collectively, our findings reveal the critical role of CEMIP-mediated HA degradation in SCLC metastasis and suggest its translational potential as an attractive target and a novel strategy for SCLC therapy. • Firstly revealing that CEMIP generates LMW-HA, leading to the accumulation of LMW-HA in SCLC ECM. • Indicating LMW-HA is an extracellular signal for promoting metastasis in SCLC. • Binding of LMW-HA and TLR2 induces F-actin rearrangement by activating c-Src/ERK1/2 axis. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

[Display omitted] Small cell lung cancer (SCLC) is the most malignant lung cancer with rapid growth and early metastasis, but still lacks effective targeted therapies to improve the prognosis. Here, we demonstrated that a novel oncogenic protein, cell migration inducing hyaluronic binding protein (CEMIP), was robustly overexpressed in SCLC tissues than that in noncancerous tissues and high expression of CEMIP predicted poor outcomes in clinical specimens and in large sample size cohorts from public databases (GEPIA 2 and CPTAC). Liquid chromatography mass spectrometry (LC-MS) and in vitro/in vivo functional assays indicated that CEMIP contributed to the proliferation by increasing glutamine consumption and their metabolites (glutamate and glutathione) levels in SCLC cells. Moreover, the addition of a GLS1 inhibitor CB-839 dramatically reduced CEMIP-induced SCLC cell proliferation. Mechanistically, beyond as a scaffold protein, CEMIP facilitates glutamine-dependent cell proliferation through inhibiting c-Myc ubiquitination and increasing c-Myc stabilization and nuclear accumulation via hindering the interaction between FBXW7 (a E3 ubiquitin ligase) and its target substrate c-Myc. Taken together, our findings reveal a novel oncogenic role of CEMIP in sustaining SCLC growth via FBXW7/c-Myc-dependent axis, and provide new evidence that inhibition of CEMIP might be a potential therapeutic strategy for the treatment of SCLC. [ABSTRACT FROM AUTHOR]

ABSTRACT The molecular mechanisms of intervertebral disc degeneration (IDD) remain elusive. We found that miR-155 is down-regulated in degenerative nucleus pulposus (NP), and more severe degeneration is correlated with higher matrix metallopeptidase 16 (MMP-16) expression. MMP-16 also degraded matrix aggrecan. Here, we addressed the in vivo miR-155-mediated pathological impact on IDD using a classic puncture mouse model. Lentiviral upregulated-miR-155 or downregulated-miR-155 was transduced into the discs of C57 mice, which was validated by real-time polymerase chain reaction (real-time PCR) and in situ hybridization. Immunohistochemistry and western blotting revealed that up-regulation of miR-155 resulted in down-regulation of MMP-16 and an increase in aggrecan and collagen type II in mouse NP; whereas, down-regulation of miR-155 resulted in up-regulation of MMP-16 and a decrease in aggrecan in mouse NP. Radiographic and histological analysis showed that the up-regulation of miR-155 attenuated IDD, while down-regulation of miR-155 resulted in the deterioration of IDD. These findings indicate that decreased miR-155 contributed to the up-regulation of MMP-16 in vivo, and MMP-16 further degraded aggrecan and collagen type II, leading to the dehydration and degeneration of discs. Our findings revealed a therapeutic role for miR-155 in IDD. © 2017 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 35:1323-1334, 2017. [ABSTRACT FROM AUTHOR]

Objective: Symptomatic cervical disc disease (SCDD) is a common degenerative disease, and Discover artificial cervical disc, a new-generation nonconstrained artificial disk, has been developed and performed gradually to treat it. We performed this meta-analysis to compare the efficacy and safety between Discover cervical disc arthroplasty (DCDA) and anterior cervical discectomy and fusion (ACDF) for SCDD. Methods: An exhaustive literature search of PubMed, EMBASE, and the Cochrane Library was conducted to identify randomized controlled trials that compared DCDA with ACDF for patients suffering SCDD. A random-effect model was used. Results were reported as standardized mean difference or risk ratio with 95% confidence interval. Results: Of 33 articles identified, six studies were included. Compared with ACDF, DCDA demonstrated shorter operation time (P < 0.0001), and better range of motion (ROM) at the operative level (P < 0.00001). But no significant differences were observed in blood loss, neck disability index (NDI) scores, neck and arm pain scores, Japanese orthopaedic association (JOA) scores, secondary surgery procedures and adverse events (P > 0.05). Subgroup analyses did not demonstrated significant differences. Conclusion: In conclusion, DCDA presented shorter operation time, and better ROM at the operative level. However, no significant differences were observed in blood loss, NDI scores, neck and arm pain scores, JOA scores, secondary surgery procedures and adverse events between the two groups. Additionally, more studies of high quality with mid- to long-term follow-up are required in future. [ABSTRACT FROM AUTHOR]

Glucocorticoid-induced osteoporosis (GIOP) is a widespread clinical complication due to the common use of glucocorticoids. Excess glucocorticoids induce apoptosis of bone marrow-derived mesenchymal stem cells (BMSCs), which have been shown to play an increasingly important role in the pathogenesis and therapy of osteoporosis. Tetramethylpyrazine (TMP), an extract from one of the most recognized herbs in traditional Chinese medicine (Chuanxiong), has been reported to have antiapoptotic properties. In this study, we tested whether TMP protects rat BMSCs following exposure to glucocorticoids in vitro and in vivo. We treated BMSCs with different concentrations of TMP (50, 100, or 200 μM) and exposed them to 10−6 M dexamethasone (Dex) for 48 h in vitro. Our data showed that TMP inhibited Dex-induced cytotoxicity and protected BMSCs from apoptosis. Interestingly, further results demonstrated that TMP prevented apoptosis in BMSCs by promoting autophagy in an AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) pathway-dependent manner. In addition, calcein fluorescence double labeling and microcomputed tomography scanning indicated that 12 weeks of TMP administration augmented bone formation and protected trabecular bone mass in GIOP rats. We also discovered that first-passage BMSCs isolated from the TMP treatment group had a lower rate of apoptosis and a higher light chain 3 (LC3)-II/LC3-I ratio than the GIOP group. Our findings demonstrate for the first time that TMP can protect BMSCs from exposure to excess glucocorticoids by promoting autophagy through AMPK/mTOR pathway and might be an effective agent for the prevention and treatment of GIOP. [ABSTRACT FROM AUTHOR]

Element doping is a promising strategy to improve the photo-response and photocatalytic activity of semiconductor photocatalyst with a wide band gap. To reduce the band gap of LiInO 2 that is considered as a novel photocatalyst, nitrogen-doped LiInO 2 (N-LiInO 2 ) is successfully fabricated by treating LiInO 2 and urea at 200 °C. It is found that interstitial instead of substitutional configurations are formed in the crystal structure of N-LiInO 2 due to the low-treating temperature and rich-oxygen conditions. The interstitial N-doping forms a doping state with 0.6 eV above the valence band maximum and a defect state with 0.1 eV below the conduction band minimum, reducing the band gap of LiInO 2 from 3.5 to 2.8 eV. N-LiInO 2 exhibits higher photocatalytic activity towards methylene blue (MB) degradation under 380 nm light irradiation, which is 1.4 times that of pure LiInO 2 . The enhanced photocatalytic activity of N-LiInO 2 is attributed to the extended light absorption and the improved charge carrier separation, which result in more reactive species participating in the photcatalytic process. This work provides a further understanding on tuning the band structure of semiconductor photocatalyst by N-doping strategies. [ABSTRACT FROM AUTHOR]

This work reported the synthesis of submicrometric TaB 2 powders by reduction of Ta 2 O 5 using B 4 C in vacuum. The starting mixture with a molar ratio of B 4 C/Ta 2 O 5 =1.57 completely converted to a mixture of TaB 2 and B 2 O 3 at 1100 °C, whereas that converted to a mixture of TaB 2 , Ta 3 B 4 and minor TaB at 1550 °C due to the boron loss resulting from the formation of gaseous boron-rich oxides. Microstructure observation showed the TaB 2 and Ta 3 B 4 particles had small equiaxed and large plate-like shapes, respectively. Excess B 4 C should be added to compensate for the boron loss. Phase-pure TaB 2 powders with equiaxed shape were synthesized at 1550 °C with a molar ratio of B 4 C/Ta 2 O 5 =1.90. The particle size and oxygen content of TaB 2 powders were ~0.7 µm and ~0.80 wt%, respectively. [ABSTRACT FROM AUTHOR]

Heterojunction can not only offer a wide range of solar light absorption but also facilitate the separation of photoinduced charge carriers, and thereby lead to enhanced photoelectrochemical efficiency. Herein, we report the heterostructured g -C 3 N 4 /ZnO nanorod arrays (NRAs) for enhanced photoelectrocatalytic performance. The g -C 3 N 4 shell layer of about 20–30 nm was coated on the surface of ZnO nanorod uniformly through thermal annealing the melamine precursor. Compared to the pristine ZnO and g -C 3 N 4 , the as-prepared g -C 3 N 4 /ZnO NRAs exhibit enhanced photoelectrocatalytic activity for methylene blue (MB) decolorization under visible light illumination. This enhancement of photoelectrocatalytic performance may be mainly attributed to improved separation efficiency of charge carriers from photoexcited g -C 3 N 4 to ZnO across the g -C 3 N 4 /ZnO interfaces. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective case series.Objective: To investigate the safety and efficacy of spine-shortening osteotomy for congenital scoliosis with tethered cord.Summary Of Background Data: Conventional surgery for congenital scoliosis associated with tethered cord risks the complications of detethering. Spine-shortening osteotomy holds the potential to correct scoliosis and decrease spinal cord tension simultaneously without an extra detethering procedure, but no data on this issue is available.Methods: 21 patients (14 females and 7 males, average age 15.4 yr) underwent spine-shortening osteotomy without detethering. All of the patients had tethered cord. Patients with main curve more than 90° underwent vertebral column resection (VCR), whereas the others had pedicle subtraction osteotomy (PSO) performed. The average postoperative follow-up period was 45.2 months.Results: The mean operation time was 544.5 min with average blood loss of 2769.1 ml. The deformity correction was 61.3% in the coronal plane and 43.9° in the sagittal plane. 10 patients had neurological deficits preoperatively. At the final follow-up, the deficits in 8 (80%) patients were significantly improved, whereas 2 (20%) remained unchanged. At final follow-up, 71.4% (5/7) patients reported improvement in motor function, 100% (3/3) had improved pain scores, and 75% (3/4) reported better sensory function after the spine-shortening osteotomy. Urinary dysfunction and bowel incontinence present preoperatively in 3 patients all recovered by final follow-up. 5 (23.8%) patients incurred complications including temporary neurological deterioration in 1 patient, urinary tract infection in 2 patients, cerebrospinal fluid leakage in 1 patient, and blood loss more than 5000 ml in 1 patient.Conclusion: Spine-shortening osteotomy is a safe and effective procedure for congenital scoliosis associated with tethered cord. Spine-shortening osteotomy at the thoracic apical vertebrae level not only corrects the spine deformity but also simultaneously releases the tension of the tethered cord, resulting in improved neurologic function. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective clinical study.Objective: To retrospectively evaluate the safety and efficacy of one-stage spinal osteotomy in the treatment of severe and progressive congenital scoliosis (CS) associated with split spinal cord malformation (SSCM).Summary Of Background Data: For severe and rigid spinal deformity, spinal osteotomies are often advocated for correcting the deformity. However, the safety and efficacy of one-stage spinal osteotomy in the treatment of severe and rigid CS with SSCM have been unclear thus far.Methods: Patients were treated by one-stage spinal osteotomy between September 2007 and June 2011 in our hospital. The clinical records were reviewed for demographic and radiographical data, operative time, intraoperative blood loss, blood transfusion, perioperative complications, and functional outcomes.Results: There were 18 females and 11 males with an average age of 15.5 ± 3.6 years (range, 12-28 yr). Spinal cord was longitudinally split by a bony spur in 11 patients (type I SSCM) and by a fibrous band in 18 patients (type II SSCM). Patients were observed for a minimum of 24 months after initial surgical treatment with an average follow-up of 43.0 ± 17.1 months (range 24-68 mo) from September 2007 to June 2013. The mean operative time and average blood loss of type ISSCM was significantly greater than those of type II SSCM (P < 0.05). The major curve was corrected from an average of 97.2°± 17.8° to 35.7°± 15.9°, a mean correction rate of 64.3% ± 11.0%. The average loss of correction at final follow-up was 2.9% for major curves. The overall complication rate was 24.1%, including transient neurological deterioration in 3 patients, cerebrospinal fluid leakage in 2 patients, urinary tract infection in 1 patient and pleural rupture in 1 patient.Conclusion: Relative to multistage corrective surgery, one-stage spinal osteotomy is effective for the correction of severe CS and SSCM without increasing the rate of surgical complications. However, surgical treatment of type I SSCM does require more operating time and blood loss.Level Of Evidence: 4. [ABSTRACT FROM AUTHOR]

Although silica aerogels with ultralow thermal conductivity are competitive for thermal insulation, their deficiencies in mechanical properties and single function affect their wide applications. Herein, we demonstrate a "soft fiber-stiff sheet" synergistic strategy for fabricating superelastic and responsive anisotropic silica nanofiber/polyvinylpyrrolidone/MXene hybrid aerogels by electrospinning, calcination, and directional-freezing. The anisotropic hybrid aerogel exhibits satisfactory thermal insulation performances at both high and low temperatures, delivering a low thermal conductivity of 21 mW m−1 K−1. The top surface temperature of the hybrid aerogel maintains at ∼74 °C after its standing on a hot plate of 300 °C. By putting the hybrid aerogel on a cold plate of −30 °C, its surface temperature is only 7.2 °C lower than the ambient temperature. Interestingly, the oxidation of MXene at high temperatures could transform the hybrid aerogel from electrically conductive to insulating, leading to sharp changes in electrical signals to trigger overheating alarm. Furthermore, the hybrid aerogel exhibits high compressibility and fatigue resistance with a high stress retention rate of 97.3% after 100 cycles under the compressive strain of 50%. Such compressive and thermally insulating aerogels are promising thermal management materials for smart alarms, and heat and cold protection of electronic devices. [Display omitted] [ABSTRACT FROM AUTHOR]

The aim of this study was to synthesis drug-loaded fibrous membrane scaffolds for potential applications as wound dressing. Polyvinylidene fluoride (PVDF) fibrous membranes were loaded with enrofloxacin (Enro) drugs by using an electrospinning process, and their mechanical strength, drug release profile and anti-bacterial properties were evaluated. Enro drug-loaded PVDF membranes exhibited good elasticity, flexibility and excellent mechanical strength. The electrospinning Enro/PVDF membranes showed a burst drug release in the initial 12 h, followed by sustained release for the next 3 days, which was an essential property for antibiotic drugs applied for wound healing. The drug-loaded PVDF fibrous membranes displayed excellent anti-bacterial activity toward Escherichia coli and Staphylococcus aureus. The results suggest that electrospinning PVDF membrane scaffolds loaded with drugs can be used as wound dressing. [ABSTRACT FROM AUTHOR]

Increased levels of reactive oxygen species (ROS) are a crucial pathogenic factor of osteoporosis. Gastrodin, isolated from the traditional Chinese herbal agent Gastrodia elata , is a potent antioxidant. We hypothesized that gastrodin demonstrates protective effects against osteoporosis by partially reducing reactive oxygen species in human bone marrow mesenchymal stem cells (hBMMSCs) and a macrophage cell line (RAW264.7 cells). We investigated gastrodin on osteogenic and adipogenic differentiation under oxidative stress in hBMMSCs. We also tested gastrodin on osteoclastic differentiation in RAW264.7 cells. Hydrogen peroxide (H 2 O 2 ) was used to establish an oxidative cell injury model. Our results showed that gastrodin significantly promoted the proliferation of hBMMSCs, improved some osteogenic markers, reduced lipid generation and inhibited the mRNA expression of several adipogenic genes in hBMMSCs. Moreover, gastrodin reduced the number of osteoclasts, TRAP activity and the expression of osteoclast-specific genes in RAW264.7 cells. Gastrodin suppressed the production of reactive oxygen species in both hBMMSCs and RAW264.7 cells. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Our data revealed that gastrodin treatment reduced the activity of serum bone degradation markers, such as CTX-1 and TRAP. Importantly, it ameliorated the micro-architecture of trabecular bones. Gastrodin decreased osteoclast numbers in vivo by TRAP staining. To conclude, these results indicated that gastrodin shows protective effects against osteoporosis linking to a reduction in reactive oxygen species, suggesting that gastrodin may be useful in the prevention and treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

Apoptosis of bone marrow-derived mesenchymal stem cells (BMMSCs) is an essential pathogenic factor of osteoporosis. Ginsenoside-Rb2 (Rb2), a 20(S)-protopanaxadiol glycoside extracted from ginseng, is a potent treatment for bone loss, which raises interest regarding the bone metabolism area. In the present study, we found that dose-response Rb2 inhibited high dosage of dexamethasone (Dex)-induced apoptosis in primary murine BMMSCs. Interestingly, Rb2 promoted GPR120 induction, which is the unsaturated long-chain fatty acid receptor. We further confirmed that GPR120-specific ShRNA reversed the inhibition of Rb2 on Dex-induced apoptosis by activating caspase-3 and reducing cell viability. In addition, Rb2 notably increased phosphorylated ERK1/2 levels and Ras kinase activity dependently through the GPR120. The ERK1/2 activity-specific inhibitor U0126 remarkably blocked the Rb2-induced antiapoptotic effect in response to Dex-induced apoptosis. Together, dose-response Rb2 protected BMMSCs against Dex-induced apoptosis dependently by inducing GPR120 promoted Ras-ERK1/2 signaling pathway. Therefore, in the prevalence of the abuse of Dex in the clinic, our findings suggest for the first time that Rb2 is not only a key to understand the link between Chinese medicine and the pathology of osteoporosis but also an underlying target for the treatment of bone complications in the foreseeable future. [ABSTRACT FROM AUTHOR]