Downregulation of hepcidin by norcantharidin in macrophage.

Norcantharidin (NCTD) is a demethylated analogue of cantharidin. It was recently demonstrated that NCTD reduces iron contents in the liver and spleen of mice in vivo, indicating that NCTD can affect iron metabolism via hepcidin. Here, we investigated the effects of NCTD on expression of iron storage protein ferritin-light chain (Ft-L), transferrin receptor 1 (TfR1), divalent metal transporter 1 (DMT1), ferroportin 1 (Fpn1), hepcidin, iron regulatory protein 1 (IRP1), IL-6, p-JAK2 and p-STAT3 in lipopolysaccharides (LPS)-treated RAW264.7 cells in vitro via Real-time PCR and Western blotting analysis. We demonstrate that NCTD down-regulates Ft-L, hepcidin, IL-6, pJAK2, pSTAT3 and up-regulates TfR1, DMT1, Fpn1 and IRP1 expression in LPS treated cells, showing that NCTD can inhibit hepcidin via the IL-6/JAK2/STAT3 signalling pathway and also increase TfR1, DMT1 and Fpn1 expression via down-regulating hepcidin and up-regulating IRP1. Our findings provide further evidence in vitro for the role of NCTD in iron metabolism.

Screening of Genes Co-Associated with Sudden Infant Death Syndrome and Infectious Sudden Death in Infancy and Bioinformatics Analysis of Their Regulatory Networks.

OBJECTIVES: The common differentially expressed mRNAs in brain, heart and liver tissues of deceased sudden infant death syndrome (SIDS) and infectious sudden death in infancy (ISDI) confirmed by autopsy was screened by bioinformatics to explore the common molecular markers and pathogenesis of SIDS and ISDI. METHODS: The datasets of GSE70422 and GSE136992 were downloaded, the limma of R software was used to screen differentially expressed mRNA in different tissue samples of SIDS and ISDI decedents for overlapping analysis. The clusterProfiler of R software was used to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The protein-protein interaction (PPI) network was constructed by STRING database, while the hub gene was screened by cytoHubba plug-in. RESULTS: Compared with the control group, there were 19 significant differentially expressed genes in the tissue samples of SIDS and ISDI decedents, among which 16 in the heart tissue and 3 in the liver tissue, and the astrotactin 1 (ASTN1) gene expression difference in the heart tissue was most significant. The PPI network identified Ras homolog family member A (RHOA), integrin subunit alpha 1 (ITGA1), and H2B clustered histone 5 (H2BC5) were hub genes. The analysis of GO and KEGG showed that differentially expressed genes were enriched in the molecular pathways of actin cytoskeleton regulation, focal adhesion and response to mycophenolic acid. CONCLUSIONS: ASTN1, RHOA and ITGA1 may participate in the development of SIDS and ISDI. The enrichment of differentially expressed genes in immune and inflammatory pathways suggests a common molecular regulatory mechanism between SIDS and ISDI. These findings are expected to provide new biomarkers for molecular anatomy and forensic identification of SIDS and ISDI.

The association between blood heavy metals and gallstones: A cross-sectional study.

BACKGROUND AND AIMS: Exposure to heavy metals has been widely recognized as a risk factor for human health. However, there is limited information on the effects of blood heavy metals on gallstones. This study aims to investigate the relationship between blood heavy metals and gallstones using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: 7192 participants aged 20 years or older with complete information were included in the study. Serum concentrations of heavy metals were determined by inductively coupled plasma kinetic reaction cell mass spectrometry. Gallstones were presented by standard questionnaires. Logistic regression, nonlinear, subgroup, and sensitivity analyses were used to estimate the association between blood heavy metals and gallstones. RESULTS: Multivariate logistic regression showed that the highest quintile of blood selenium (Se) was associated with a higher risk of gallstones compared with the lowest quintile (OR = 1.66, 95% CI: 1.16-2.36), particularly in individuals who were under 65 years of age, females, non-Hispanic Whites, non-drinkers, obese, and had a college education or higher. There was no correlation between blood cadmium (Cd), mercury (Hg), lead (Pb), manganese (Mn), and gallstones in the total population. Restricted cubic spline curves showed that a negative correlation was observed between blood Cd (OR = 0.84, 95% CI: 0.710-1.00), Hg (OR = 0.87, 95% CI: 0.78-0.97) and gallstones when Cd < 0.302 µg/L and Hg < 3.160 µg/L. CONCLUSIONS: Blood Se was an independent risk factor for gallstones, particularly in individuals under 65 years old, females, non-Hispanic Whites, non-drinkers, obese, and had a college education or higher. Furthermore, blood Cd and Hg were associated with a reduced risk of gallstones within a certain range.

Climate and geochemistry at different altitudes influence soil fungal community aggregation patterns in alpine grasslands.

Fungi represent key ecosystem factors that affect plant growth and development and improve soil structure and fertility. Due to changes in environmental conditions, fungi show strong spatial heterogeneity along altitudinal gradients. Current knowledge of the driving mechanisms and effects of soil fungal community construction at high altitudes is very limited on a regional scale. We collected soil samples from alpine grasslands at six altitudinal gradients (2813-5228 m) in the high-altitude area of the Qinghai-Tibet Plateau. The horizontal distance of the sampling zone spanned 1500 km. Distribution patterns, key influencing factors for soil fungal diversity, and dominant mechanisms of ecological processes in the alpine grasslands were analyzed. We found that the diversity of the soil fungal communities was significantly different at different altitudes; with increasing altitude, the number of fungal species increased. Mucoromycota was better adapted to alpine grassland ecosystems at altitudes of above 4000 m. Dispersal limitation was the main ecological control process among stochastic processes. With the increase of altitude, the dominant role of dispersal limitation gradually decreased, and the proportion of other random processes such as ecological drift gradually increased. In this study, soil geochemical factors (soil organic carbon, SOC; total phosphorus, TP) mainly influenced the composition of the fungal community in the low altitude region, while climatic factors (mean annual temperature, MAT) were the key factors and main driving forces for the composition of the soil fungal community in the alpine meadow in the high altitude region. This study supplements the information on the biogeographic distribution patterns and environmental drivers of fungal communities along altitudinal gradients at high altitudes on a regional scale. Our results highlight the effects of temperature change on fungal community composition in high altitude regions of alpine grasslands. Subsurface fungal communities should be considered when predicting the function of alpine grassland ecosystems under future climate change.

Chinese herbal injections versus intrapleural cisplatin for lung cancer patients with malignant pleural effusion: A Bayesian network meta-analysis of randomized controlled trials.

Background: Malignant pleural effusion (MPE) is a common complication in patients with advanced lung cancer that can severely compromise the quality of life and limit life expectancy. Randomized controlled trials (RCTs) have shown that Chinese herbal injections (CHIs) may be beneficial in improving quality of life. This network meta-analysis (NMA) aims to explore several CHIs used for lung cancer patients with MPE. Methods: Seven databases were systematically searched for eligible RCTs from inception to November 2021. The primary outcome was the clinical effective rate. Secondary outcomes were the improvement rate of Karnofsky performance status (KPS) score and incidence of adverse events (AEs). The Cochrane risk of bias 2 tool was used to assess the quality of included studies. Data analysis was performed using STATA 16.0 and R software 4.1.0. Both pairwise meta-analysis and Bayesian NMA were conducted. Competing interventions were ranked using the surface under the cumulative ranking (SUCRA) probabilities. Evidence grading was evaluated using the Confidence in Network Meta-Analysis online software (https://cinema.ispm.unibe.ch/). Results: A total of 44 studies involving 2,573 patients were included. The combined Huachansu injection (HCS) with intrapleural cisplatin (cis-diamminedichloro-platinum, DDP) had the highest probability of improving the clinical effective rate (SUCRA, 84.33%). The Kangai injection (KA) combined with DDP had the most improvement rate of KPS score (SUCRA, 80.82%), while the Fufangkushen injection (FFKS) alone was more likely to reduce AEs including gastrointestinal reactions (SUCRA, 89.92%), leukopenia (SUCRA, 91.85%), and chest pain (SUCRA, 98.17%). FFKS combined with DDP ranked the best in reducing the incidence of fever (SUCRA, 75.45%). Conclusions: Our NMA showed that CHIs alone or combined with DDP could improve clinical effectiveness and quality of life and reduce AEs, compared to DDP alone. HSC and KA, combined with DDP, may be the most effective considering clinical effective rate and improvement of KPS score, respectively. FFKS, either used alone or in combination therapy with DDP, may be the best in reducing AEs. However, high-quality RCTs with larger sample sizes are needed to further support the evidence. Systematic review registration: PROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42021285275.

The effect of doping and strain on superconductivity of T-graphene.

As an allotrope of graphene, T-graphene was predicted to be an intrinsic two-dimensional (2D) superconductor with a superconducting critical temperature (Tc) of about 20.8 K [Gu et al., Chin. Phys. Lett. 36, 097401 (2019)]. In this work, based on first-principles calculations, hole doping and biaxial tensile strain (BTS) are considered to modulate the electron-phonon coupling (EPC) and superconductivity of T-graphene. It is found that the EPC constant of T-graphene is 0.807 and the calculated critical temperature Tc is 28.2 K at a doping level of 0.5 hole per unit cell (3.31 × 1014 cm-2) and 12% BTS. Furthermore, when 0.8 hole per unit cell (5.43 × 1014 cm-2) doping and 10% BTS are applied, the EPC constant is 0.939, and the Tc can be boosted to 35.2 K, which is higher than those of the pristine T-graphene and many other 2D carbon-based superconductors.

Particle size-resolved emission characteristics of complex polycyclic aromatic hydrocarbon (PAH) mixtures from various combustion sources.

Combustion of domestic solid fuels is a significant source of polycyclic aromatic hydrocarbons (PAHs). Some oxygenated PAHs (o-PAHs) and PAHs with molecular weight of 302 (MW302 PAHs) are more toxic than the traditional 16 priority PAHs, whereas their emissions were much less elucidated. This study characterized the size-dependent emissions of parent PAHs (p-PAHs), o-PAHs, and MW302 PAHs from various combustion sources. The estimated emission factors (eEFs) from biomass burning sources were highest for most of the PAHs (391-8928 µg/kg), much higher than that of anthracite coal combustion (43.0-145 µg/kg), both which were operated in an indoor stove. Cigarette smoking had a high eEF of o-PAHs (240 ng/g). MW302 PAHs were not found in the emissions of smoking, cooking, and vehicular exhausts. Particle-size distributions of PAHs were compound- and source-dependent, and the tendency to associate with smaller particles was observed especially in biomass burning and cigarette smoking sources. Furthermore, the inter-source differences in PAH eEFs were associated with their dominance in fine particles. PAH composition profiles also varied with the particle size, showing increasing contributions of large-molecule PAHs with decreasing sizes in most cases. The size distributions of p-PAHs are much more significantly dependent on their n-octanol/air partition coefficients and vapor pressures than those of o-PAHs, suggesting differences in mechanisms governing their distributions. Several molecular diagnostic ratios (MDRs), including two based on MW302 PAHs, specific to these combustion scenarios were identified. However, the MDRs within some sources are also strongly size-dependent, providing a new explanation for the uncertainty in their application for source identification of PAHs. This work also highlights the necessity for understanding the size-resolved atmospheric behaviors and fate of PAHs after their emission.

Accumulation and translocation of traditional and novel organophosphate esters and phthalic acid esters in plants during the whole life cycle.

Organophosphate esters (OPEs) and phthalic acid esters (PAEs) are widespread contaminants in the environment. The variations of these chemicals in plants throughout their life cycle is little known. In this study, OPEs, OPE metabolites, and PAEs in peanut and corn grown under field conditions, soil, and air were measured to understand the uptake and translocation, distributions in the plant compartments, and metabolism in the plants. The soil concentrations showed an enrichment effect of OPEs onto the rhizosphere soil but a depletion effect of PAEs on rhizosphere soils. The PAE concentrations between peanut (with a mean of 1295 ng/g dw) and corn (3339 ng/g dw) were significantly different, but the OPE concentrations were not significantly different (with means of 15.6 and 19.2 ng/g dw, respectively). OPE metabolites were also detected in the plants, with lower concentrations and detection rates. Similarities and differences in the temporal variations of the concentrations of traditional OPEs, novel OPEs, and PAEs in plants during their growth were observed. The variations were dependent on both plant species and particular tissues. The leaf compartment is the most important reservoir of OPEs and PAEs (but not OPE metabolites) for both species, highlighting the importance of an aerial uptake pathway. The chemicals have a low potential to be translocated into peanut and corn kernels, reducing their risks via food consumption. Less hydrophobic compounds have higher root concentration factors in this study. These observations differ from those of previous hydroponic experiments.

Five-Flavor Sophora flavescens Enteric-Coated Capsules for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Ulcerative colitis (UC), a chronic inflammatory bowel disease, is characterized by abdominal pain, diarrhea, and mucopurulent bloody stool. In recent years, the incidence and prevalence of UC have been increasing consistently. Five-flavor Sophora falvescens enteric-coated capsule (FSEC), a licensed Chinese patent medicine, was specifically used to treat UC. This review was aimed to assess the effectiveness and safety of FSEC for the treatment of UC. METHODS: Six electronic databases were searched from inception to March 2021. Randomized clinical trials (RCTs) comparing FSEC or FSEC plus conventional Western medicine with conventional Western medicine in participants with UC were included. Two authors screened all references, assessed the risk of bias, and extracted data independently. Binary data were presented as risk ratios (RRs) with 95% confidence intervals (CIs) and metric data as mean difference (MD) with 95% CI. The overall certainty of the evidence was assessed by GRADE. RESULTS: We included 15 RCTs (1194 participants, 763 in the FSEC group and 431 in the control group). The treatment duration ranged from 42 to 64 days. Twelve trials compared FSEC with conventional Western medicine, and two trials compared FSEC plus conventional medicine with conventional medicine. Another trial compared FSEC plus mesalazine with compound glutamine enteric capsules plus mesalazine. FSEC showed a higher clinical effective rate (improved clinical symptoms, colonoscopy results, and stools) (RR 1.12, 95% CI 1.05 to 1.20; 729 participants; 8 trials; low-quality evidence) as well as the effective rate of traditional Chinese medicine (TCM) syndromes (RR 1.10, 95% CI 1.01 to 1.20; 452 participants; 5 trials; low-quality evidence) compared to mesalazine. There was no significant difference in the adverse events between FSEC and control groups. CONCLUSIONS: FSEC may show effectiveness in UC treatment compared to conventional medicine, and the use of FSEC may not increase the risk of adverse events. Due to the limited number of clinical trials and low methodological quality of the included trials, our findings must be interpreted with discretion.

An evidence mapping of systematic reviews and meta-analysis on traditional Chinese medicine for ulcerative colitis.

BACKGROUND: Traditional Chinese Medicine (TCM) has been a proposed treatment option for ulcerative colitis (UC), however it has been difficult to understand the breadth and depth of evidence as various Chinese medicine therapies may produce effects differently. The aim of this evidence mapping is to visually understand the available evidence in the use of TCM in the treatment of UC, and to identify gaps in evidence to inform priorities of future research. METHODS: A systematic electronic literature search of six databases were performed to identify systematic reviews (SRs) on different Chinese medicine therapies in the treatment in UC. Methodological quality of the included SRs was assessed using AMSTAR 2. RESULTS: The mapping was based on 73 SRs, which included nine interventions that met eligibility criteria. The quality of the included SRs was very low. The diseases stages of patients with UC varied greatly, from active to remission, to non-acute outbreak, to not reported. The results mostly favored the method of intervention. Oral administration combined with enema was the most widely used route of administration in secondary research. CONCLUSION: Based on the current evidence, the treatment of UC with TCM can only be recommended cautiously. A majority of included SRs did not report the location of the disease, the disease classification, and the route of administration of the intervention. Further research is needed on the effectiveness of Chinese medicine alone in the treatment of UC. The effectiveness of combined Chinese and conventional medicine combined with different routes of administration cannot be confirmed. Attention should be paid to the methodological quality of the systematic review. Unifies the outcome indicators used in the evaluation of effectiveness.

Chinese Patent Medicine as Adjuvant for Mild-to-Moderate Active Ulcerative Colitis: A Network Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To evaluate the effectiveness and safety of Chinese patent medicine for mild-to-moderate active ulcerative colitis (UC) using network meta-analysis (NMA). METHODS: We systematically searched PubMed, Cochrane library, Embase, Sino-Med, China National Knowledge Infrastructure (CNKI), Wanfang, and Chinese Scientific Journal Database (VIP) databases to October, 2020. We included randomized controlled trials (RCTs) on Chinese patent medicine for mild-to-moderate active UC. The main analysis was complemented by network subanalyses and standard pairwise comparisons. Statistical heterogeneity, inconsistencies, and ranking probability were also evaluated. RESULTS: The databases search identified 3222 citations, of which 33 RCTs involving 2971 patients met the inclusion criteria. A total of 15 Chinese patent medicines were analyzed. The overall quality of the included studies was low. Pairwise meta-analysis showed that Chinese patent medicine was superior to Mesalazine in improving disappearances of clinical symptoms, recurrence rate, and Mayo score. Based on decreases in adverse events, results from NMA showed that Xilei powder plus Mesalazine was more effective than other drugs. Other NMA results indicated that Danshen freeze-dried powder plus Mesalazine (RR: 0.13; 95% CI, 0.02-0.78) and Kangfuxin lotion plus Mesalazine (RR: 0.24; 95% CI, 0.07-0.57) were superior to Mesalazine in decreasing recurrence rate. Another NMA result indicated that Kangfuxin lotion plus Mesalazine (RR: 0.00; 95% CI, 0.00-0.02) and Zhi Kang capsule plus Mesalazine (RR: 0.00; 95% CI, 0.00-0.02) were superior to Mesalazine in increasing the disappearance of tenesmus. CONCLUSION: In the probability sorting, Xilei powder combined with Mesalazine ranked first for having the fewest adverse events, Maintaining Intestines Antidiarrheal Pills combined with Mesalazine ranked first for having the lowest recurrence rate, Xilei powder combined with Mesalazine ranked first for improving disappearance rate of mucopurulent bloody stool/abdominal pain, and Kangfuxin lotion combined with Mesalazine ranked first for improving the disappearance rate of diarrhea/tenesmus. However, there is a lack of direct comparisons among Chinese patent medicines for UC. More multiarm RCTs are needed in the future to provide direct comparative evidence.

[Effect of Erxian Decoction on proteomics and PI3K signaling pathway of osteoblasts stimulated by H2O2].

The present study aimed to explore the effect of Erxian Decoction on proteomics of osteoblasts stimulated by hydrogen peroxide(H_2O_2) and its protective mechanism with the H_2O_2-induced cell model of oxidative stress. The primary osteoblasts were cultured from the skulls of newborn rats(within 24 hours) and divided into a control group, a model group, a Fosamax group, and an Erxian Decoction group. Blank serum was added in the control group and model group, and the drug-containing serum was added correspondingly to the remaining two groups. After 45 hours, H_2O_(2 )stimulation was conducted for three hours except for the control group, followed by protein extraction. Nano-LC-LTQ-Orbitrap system was used for protein detection, Protein Discovery for protein identification, and SIEVE for quantitative and qualitative analysis. Furthermore, following the blocking of PI3 K signaling pathway by LY294002(10 µmol·L~(-1)), a control group, a model group, an LY294002 group, an Erxian Decoction group, and an Erxian Decoction + LY294002 group were set up to observe the effect of Erxian Decoction on cell proliferation, alkaline phosphatase(ALP) activity, and the relative expression of BMP-2, OPG, p-Akt, p-FoxO1 of osteoblasts stimulated by H_2O_2 under LY294002 intervention. The results revealed that 78 differential proteins were discovered between the Erxian Decoction group and model group, which were involved in the regulation of PI3 K/Akt, glucagon, estrogen, insulin, and other signaling pathways. LY294002 blunted the promoting effect of Erxian Decoction on osteoblast proliferation and significantly down-regulated the expression of OPG and p-FoxO1, whereas its down-regulation on the expression of BMP-2 and p-Akt was not significant. Both LY294002 and Erxian Decoction increased the ALP activity of osteoblasts, which may be related to the cell state and the cell differentiation. The above results suggest that Erxian Decoction can protect osteoblasts stimulated by H_2O_2, with the PI3 K/Akt signaling pathway as one of the internal mechanisms.

Acupuncture for ulcerative colitis: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Ulcerative colitis, characterized by diarrhea, bloody stools and abdominal pain, is a chronic, idiopathic inflammatory disease of the colonic mucosa. In recent years, the incidence of ulcerative colitis presents an increasing trend year by year. Acupuncture, as a potential effective treatment for ulcerative colitis, is widely used in clinical practice. METHODS: We searched PubMed, the Cochrane Library, Chinese CBM Database, China National Knowledge Infrastructure, Chinese VIP Information, and Wanfang Database from the date of the establishment of each database up to March, 2019. We included randomized controlled clinical trials (RCT) comparing acupuncture versus conventional conventional medicine or comparing acupuncture combined with conventional medicine versus conventional medicine in participants with ulcerative colitis. Two authors screened all references, assessed the risk of bias and extracted data independently. We summarized data using risk ratios (RR) with 95% confidence intervals (CI) for binary outcomes. We performed meta-analyses using random effects model. We assessed overall quality of evidence using GRADE. RESULTS: We included 13 RCTs (1030 participants, 515 in the acupuncture group and 515 in the control group). Only one study tested head acupuncture, and the other 12 tested body acupuncture. The treatment duration ranged from 14 to 60 days. Seven trials compared acupuncture alone versus conventional medicine, and six compared acupuncture combined with conventional medicine versus conventional medicine. Acupuncture combined with mesalazine showed better clinical effect (improved clinical symptoms, colonoscopy results and stool examination results) (RR 1.25, 95% CI 1.19 to 1.41; 232 participants; 4 trials; low quality evidence) and better colonoscopy curative effect (RR 1.33, 95% CI 1.04 to 1.71; 108 participants; 2 trials; moderate quality evidence) compared to mesalazine. Acupuncture showed better clinical effect compared to the combination of metronidazole and sulfasalazine (RR 1.21, 95%CI 1.10, 1.34; 318 participants; 3 trials; moderate quality evidence). There was no significant difference in the incidence of adverse events between groups. CONCLUSIONS: Both acupuncture alone and acupuncture combined with conventional medicine may be effective in treating ulcerative colitis compared to conventional medicine. Our findings must be interpreted with caution due to high or unclear risk of bias of the included trials.

Endoscopic full-thickness resection to treat active Dieulafoy's disease: A case report.

BACKGROUND: At present, minimally invasive endoscopic treatment is mostly used for patients with actively bleeding Dieulafoy's lesions, , as it has the advantages of minimal trauma, short operation time and good hemostatic effect, although bleeding can easily recur postoperatively. Recently, extensive gastric cuneiform resection has been advocated for use in these patients because the constant-diameter artery follows a long path to the gastric mucosa. CASE SUMMARY: A 47-year-old man was admitted to the hospital for repeated hematemesis and black stool, and he was diagnosed with Dieulafoy's disease. We chose a method that not only simulates surgical gastric cuneiform resection but also reduces trauma. We performed enlarged local endoscopic full-thickness resection of the gastric wall and abdominal constant-diameter artery and sutured the gastric wall. Postoperative follow-up showed that the constant-diameter artery had been resected from the gastric wall, which was confirmed to have no blood flow signals by endoscopic ultrasonography. CONCLUSION: Endoscopic full-thickness resection of the gastric wall and abdominal constant-diameter artery with suturing of the gastric wall has demonstrated potential as a new treatment for Dieulafoy's disease.

Bioactive PLGA/tricalcium phosphate scaffolds incorporating phytomolecule icaritin developed for calvarial defect repair in rat model.

BACKGROUND/OBJECTIVES: For treatment of large bone defects challenging in orthopaedic clinics, bone graft substitutes are commonly used for the majority of surgeons. It would be proposed in the current study that our bioactive scaffolds could additionally serve as a local delivery system for therapeutic small molecule agents capable of providing support to enhance biological bone repair. METHODS: In this study, composite scaffolds made of poly (lactic-co-glycolic acid) (PLGA) and tricalcium phosphate (TCP) named by P/T was fabricated by a low-temperature rapid prototyping technique. For optimizing the scaffolds, the phytomolecule icaritin (ICT) was incorporated into P/T scaffolds called P/T/ICT. The osteogenic efficacies of the two groups of scaffolds were compared in a successfully established calvarial defect model in rats. Bone regeneration was evaluated by X-ray, micro-computerised tomography (micro-CT), and histology at weeks 4 and/or 8 post-implantation. In vitro induction of osteogenesis and osteoclastogenesis was established for identification of differentiation potentials evoked by icaritin in primary cultured precursor cells. RESULTS: The results of radiographies and decalcified histology demonstrated more area and volume fractions of newly formed bone within bone defect sites implanted with P/T/ICT scaffold than that with P/T scaffold. Undecalcified histological results presented more osteoid and mineralized bone tissues, and also more active bone remodeling in P/T/ICT group than that in P/T group. The results of histological staining in osteoclast-like cells and newly formed vessels indicated favorable biocompatibility, rapid bioresorption and more new vessel growth in P/T/ICT scaffolds in contrast to P/T scaffolds. Based on in vitro induction, the results presented that icaritin could significantly facilitate osteogenic differentiation, while suppressed adipogenic differentiation. Meanwhile, icaritin demonstrated remarkable inhibition of osteoclastogenic differentiation. CONCLUSION: The finding that P/T/ICT composite scaffold can enhance bone regeneration in calvarial bone defects through facilitating effective bone formation and restraining excessive bone resorption. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The osteogenic bioactivity of icaritin facilitated PLGA/TCP/icartin composite scaffold to exert significant bone regeneration in calvarial defects in rat model. It might form an optimized foundation for potential clinical validation in bone defects application.

Combining Pro-peptide Engineering and Multisite Saturation Mutagenesis To Improve the Catalytic Potential of Keratinase.

Keratinases are becoming biotechnologically important since they have shown potential in hydrolysis of recalcitrant keratins with highly rigid and strongly cross-linked structures. However, the large-scale application of keratinases has been limited by the inefficient expression level and low enzyme activity. In this work, we employed pro-peptide engineering and saturation mutagenesis to construct excellent keratinase variants with improved activities. It turned out that amino acid substitutions at the pro-peptide cleavage site (P1) could accelerate the release of active mature enzymes, resulting in a 3-fold activity increase. Eighteen sites of the pro-peptide area were targeted for codon mutagenesis, and a multisite saturation mutagenesis library of the six potential sites was generated, achieving a significant improvement of keratinase activity from 179 to 1114 units/mL. Also, the mutants exhibited alterant catalytic properties. Finally, fermentation for keratinase production in a 15 L fermenter was carried out, and the enzyme activity reached up to over 3000 units/mL. Our results demonstrated that pro-peptide engineering played a crucial role in high expression and engineering of proteases. This study provides a universal route toward improvement of industrial enzymes that were first synthesized as precursors in the form of pre-pro-protein.

Sorption and desorption of phenanthrene on biodegradable poly(butylene adipate co-terephtalate) microplastics.

Biodegradable plastics, as alternatives to conventional plastics, are increasingly used, but their interactions with organic pollutants are still unknown. In this study, the sorption and desorption behaviors on a type of biodegradable plastic-poly(butylene adipate co-terephtalate) (PBAT) were investigated, and at the same time two types of conventional plastics-polyethylene (PEc and PEv) and polystyrene (PS) were used for comparison. Phenanthrene (PHEN) was chosen as one of representative organic pollutants. Results indicated that the sorption and desorption capacities of PBAT were not only higher than those of the other types of microplastics, but also higher than those of carbonaceous geosorbents. The surface area normalized results illustrated that sorption and desorption of the microplastics were positively correlated with their abundance of rubbery subfraction. The sorption kinetic results showed that the sorption rates of PBAT and PEc were higher than PEv and PS. The effects of water chemistry factors including salinity, dissolved organic matter and Cu2+ ion on the sorption process displayed the same trend, but the degrees of influence on the four microplastics differed. The degrees of influence were mainly dependent on the abundance of rubbery subfraction for microplastics. These findings indicate that the biodegradable poly(butylene adipate co-terephtalate) microplastics are actually stronger vectors than the conventional microplastics, and crystallization characteristics of the microplastics have great influences on the vector effect.

Comparing the osteoconductive potential between tubular and cylindrical beta-tricalcium phosphate scaffolds: An experimental study in rats.

Beta-tricalcium phosphate (ß-TCP) has been widely used for bone regeneration for many years. However, there are few studies on the osteoconduction ability of different shaped ß-TCP scaffolds. In this study, we compared the osteoconductive potential between the tubular and cylindrical ß-TCP scaffolds in long bone defect animal model. The results showed that more regenerated bone and a better healing property were observed in tubular group than that in cylindrical group. By hematoxylin-eosin staining, the central part of the callus was more compacted in tubular group. And moreover, the increased osteocalcin and osterix expression were found in tubular group, suggesting more vigorous regeneration of bone defect. These results demonstrated that tubular ß-TCP scaffold would be more benefit to promote bone regeneration, indicating that tubular ß-TCP scaffold has a good potential for long bone defect repair in clinical practice. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1934-1940, 2018.

MicroRNA-144-3p inhibits bone formation in distraction osteogenesis through targeting Connexin 43.

Distraction osteogenesis (DO), one of effective therapies for bone regeneration, has been received more attention in recent years. However, the underlying mechanism remains elusive. Recently, microRNAs (miRNAs) have been reported to play important roles in regulating osteogenesis and bone formation. We therefore provided the hypothesis that miRNAs could involve in the DO-mediated bone regeneration. After successfully established the DO model of rats, a miRNA microarray was performed to find the differently expressed miRNAs in DO and control groups in this study. As one of the most downregulated miRNAs, miR-144-3p was found to be decreased during osteogenic differentiation in mesenchymal stem cells of rats (rBMSCs) and DO model. And miR-144-3p overexpression suppressed the osteogenesis while its inhibitor promoted osteogenesis. Furthermore, Connexin-43, an essential regulator for osteogenesis, was validated to be a novel target for miR-144-3p. Finally, miR-144-3p inhibitor modified MSCs promoted mineralization of distracted bone in rat DO model. In conclusion, miR-144-3p was found to regulate osteogenesis and inhibition of miR-144-3p resulted in acceleration of mineralization of DO, which not only give clues to understanding the mechanism of DO but also provide a potential therapeutic target in clinical practice.

Organophosphorus flame retardants in mangrove sediments from the Pearl River Estuary, South China.

Forty-eight surface sediments were collected from three mangrove wetlands in the Pearl River Estuary (PRE) of South China to investigate the distribution of organophosphorus flame retardants (OPFRs) and the relationship between OPFRs and microbial community structure determined by phospholipid fatty acid. Concentrations of ΣOPFRs in mangrove sediments of the PRE ranged from 13.2 to 377.1 ng g-1 dry weight. Levels of ΣOPFRs in mangrove sediments from Shenzhen and Guangzhou were significantly higher than those from Zhuhai, indicating that OPFRs were linked to industrialization and urbanization. Tris(chloropropyl)phosphate was the predominant profile of OPFRs in mangrove sediments from Shenzhen (38.9%) and Guangzhou (35.0%), while the composition profile of OPFRs in mangrove sediments from Zhuhai was dominated by tris(2-chloroethyl) phosphate (25.5%). The mass inventories of OPFRs in the mangrove sediments of Guangzhou, Zhuhai and Shenzhen were 439.5, 133.5 and 662.3 ng cm-2, respectively. Redundancy analysis revealed that OPFRs induced a shift in the structure of mangrove sediment microbial community and the variations were significantly correlated with tris(1,3-dichloro-2-propyl)phosphate and tris(2-butoxyethyl) phosphate.