A comparative study of progressive failure of granite and marble rock bridges under direct shearing.

Shear failure of rock bridges is an important process in geological phenomena, including landslides and earthquakes. However, the progressive failure of natural rock bridges has not yet been fully understood. In this work, we carried out direct shearing experiments on both granite and marble rock bridges, and applied acoustic emission (AE) monitoring throughout the experiments. With the mechanical curves and the evolution of AE activity (including AE energy rate and b value), the failure of rock bridges can be divided into three pre-failure phases and one ultimate failure phases. We analyzed the effects of normal stress and lithology on the pre-failure phases. We noted that with the increasing of normal stress, the length of stable cracking phase decreases and the length of unstable cracking phase slightly increases, except for marble rock bridges at high normal stress, which maintains a great proportion of stable cracking phase that possibly results from the great off-fault damage. Increasing normal stress also suppresses the dilation of granite rock bridges, but has a different effect on marble rock bridges, which also suggests the effect of lithology on failure modes.

Two-stage extraction by partial grinding of impacted mandibular third molar in close proximity to the inferior alveolar nerve.

BACKGROUND: Extraction of impacted third molars often leads to severe complications caused by damage to the inferior alveolar nerve (IAN). AIM: To proposes a method for the partial grinding of an impacted mandibular third molar (IMM3) near the IAN to prevent IAN injury during IMM3 extraction. METHODS: Between January 1996 and March 2022, 25 patients with IMM3 roots near the IAN were enrolled. The first stage of the operation consisted of grinding a major part of the IMM3 crown with a high-speed turbine dental drill to achieve sufficient space between the mandibular second molar and IMM3. After 6 months, when the root tips were observed to be away from the IAN on X-ray examination, the remaining part of the IMM3 was completely removed. RESULTS: All IMM3s were extracted easily without symptoms of IAN injury after extraction. CONCLUSION: Partial IMM3 grinding may be a good alternative treatment option to avoid IAN injury in high-risk cases.

Comparative complete chloroplast genome of Geum japonicum: evolution and phylogenetic analysis.

Geum japonicum (Rosaceae) has been widely used in China as a traditional herbal medicine due to its high economic and medicinal value. However, the appearance of Geum species is relatively similar, making identification difficult by conventional phenotypic methods, and the studies of genomics and species evolution are lacking. To better distinguish the medicinal varieties and fill this gap, we carried out relevant research on the chloroplast genome of G. japonicum. Results show a typical quadripartite structure of the chloroplast genome of G. japonicum with a length of 156,042 bp. There are totally 131 unique genes in the genome, including 87 protein-coding genes, 36 tRNA genes, and 8 rRNA genes, and there were also 87 SSRs identified and mostly mononucleotide Adenine-Thymine. We next compared the plastid genomes among four Geum species and obtained 14 hypervariable regions, including ndhF, psbE, trnG-UCC, ccsA, trnQ-UUG, rps16, psbK, trnL-UAA, ycf1, ndhD, atpA, petN, rps14, and trnK-UUU. Phylogenetic analysis revealed that G. japonicum is most closely related to Geum aleppicum, and possibly has some evolutionary relatedness with an ancient relic plant Taihangia rupestris. This research enriched the genome resources and provided fundamental insights for evolutionary studies and the phylogeny of Geum.

Epicardial adipose tissue in patients with chronic obstructive pulmonary disease: systematic review with meta­analysis and trial sequential analysis.

BACKGROUND: Limited data suggest that chronic obstructive pulmonary disease (COPD) patients have pathologic elevated epicardial adipose tissue (EAT), which is splanchnic fat tissue with anti-inflammatory properties and regulating free fatty acids functions. Therefore, there is a need for meta-analysis to explore the relationship between EAT and COPD. METHODS: Online databases were systematically searched for studies about EAT in COPD patients published up to October 5th, 2022. The EAT data of the COPD patient group and the control group were included. Trial sequential analysis (TSA) and meta-analysis were applied to assess the difference in EAT between patients with and without COPD. TSA software and Stata 12.0 were used in all statistical analyses. RESULTS: The final analysis included 5 studies (n = 596 patients). COPD patients had significantly more EAT than control subjects (SMD: 0.0.802; 95% CI: 0.231, 1.372; P = 0.006; TSA-adjusted 95% CI 1.20, 1.80; P < 0.0001). And higher CRP levels in COPD patients than non-COPD patients, whereas triglycerides and LDL were not significantly different between patients with and without COPD. CONCLUSION: EAT is abnormally elevated in COPD patients, which may be related to systemic inflammatory responses in COPD. PROSPERO NUMBER: CRD42021228273.

The osteogenesis effect of rhBMP2-loaded calcium phosphate cements in repairing dental extraction sockets.

PURPOSE: After extracting impacted mandibular third molars (IMM3), the resulting bone loss at the distal surface of the distal root of mandibular second molars (MM2) is responsible for the poor stability of MM2. This study aimed to identify the clinical osteogenesis effect of recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded calcium phosphate cements (CPCs) and rhBMP-2 delivery systems (rhBMP-2/CPCs, named CPCII) on bone loss repair at the distal surface of the MM2 distal root after IMM3 extraction. METHODS: Written informed consent was obtained from every participant whose IMM3 needed extraction. The impact of IMM3 on both sides was basically identical. From April 2014 to March 2016, extraction of IMM3 was performed in 9 patients (5 males/4 females, 26-42 years old). One side was randomly selected as the experimental group, and CPCII systems were implanted into the distal surface of the distal root in dental extraction sockets. The wounds on the other side were sutured and allowed to heal naturally (be treated as the control group). New bone formation in the alveolar fossa was detected 3 and 12 months after the operation by cone-beam computed tomography (CBCT) to measure the distance from the cementoenamel junction (CEJ) to the crest of the alveolar ridge (CAR). RESULTS: The CAR-CEJ distance on the test side was less than that on the control side (P<0.5). CONCLUSION: The quantity of new bone formation in the experimental group was greater than that in the control group. CPCII systems have osteogenic potential in the healing process of tooth extraction sockets.

Complete chloroplast genome of Gentianopsis barbata and comparative analysis with related species from Gentianaceae.

Gentianopsis barbata is an essential medicinal plant in China with high ornamental and medicinal values. Unfortunately, the study of the chloroplast genome of this plant still has a gap. This study sequenced and characterized the complete chloroplast genome of G. barbata. The complete chloroplast genome of G. barbata is a typical circular structure of 151 123 bp. It consists of a large single-copy region (82 690 bp) and a small single-copy region (17 887 bp) separated by a pair of inverted repeats (25 273 bp), which covers 78 protein-coding genes, 30 tRNAs, and 4 rRNAs. The long repeat sequence analysis showed that the P-type (palindromic) sequences were the major long repeat sequences. Thirty-seven simple sequence repeats were identified, most of which were single nucleotides. The Bayesian inference tree, maximum likelihood tree, and neighbor-joining tree suggested that G. barbata is grouped with Gentianopsis grandis and Gentianopsis paludosa. The divergence time analysis showed that G. barbata diverged at 1.243 Mya. Comparative analysis of chloroplast genomes can reveal interspecific diversity, and regions with high variation can be used to develop molecular markers applicable to various research areas. Our results provide a new insight into plastome evolution and a valuable resource for further studies on G. barbata.

Influence of natural and anthropogenic controls on runoff in the Keriya River, central Tarim Basin, China.

The potential impact of natural factors on the runoff of intermittent rivers and ephemeral streams (IRES) has been largely ignored in the Tarim Basin, China. A representative example is the Keriya River. To quantify the long-term dynamic variations in lower reach surface runoff of IRES, river length, defined as the distance between a selected fix point along the perennial river segment to its dynamic, ephemeral end, was used as an indicator. Using a total of 272 remote sensing images, we digitized and measured the distance (river length) between the center of Yutian County and the river's end point on each image, and then calculated monthly inter-annual and intra-annual variations in length of the lower Keriya River from 2000 to 2019. Hydrometeorological data were combined with descriptors of anthropogenic disturbances to assess the relative influence of natural factors and anthropogenic disturbances on lower reach river runoff. The results showed that intra-annual variations in river length fluctuated seasonally, with the minimum value occurring in June; two main peaks occurred in March and August. The minimum June value in river length was closely linked to an increase in agricultural water demand and a decrease in upper reach runoff. The August peak in river length was related to the peak values in upper reach runoff and agricultural water demand; upper reach runoff made a significant contribution because the former was about 20% more than the latter in summer. The March peak corresponded to elevated lower reach groundwater levels and to the melting of ice along river channels. Inter-annual variations in river length were due to inter-annual variations in upper reach runoff and middle reach agricultural water use which increased slightly during the study period. Inter-annual variations in frequency and amplitude of the fluctuations in river length were mainly controlled by changes in upper reach runoff. The minimum in river length in 2009 was consistent with the low in upper reach runoff of the Keriya River and other rivers in the Tarim Basin. The most significant factors controlling variations in river length are natural in origin.

Lipid kinases VPS34 and PIKfyve coordinate a phosphoinositide cascade to regulate retriever-mediated recycling on endosomes.

Cell surface receptors control how cells respond to their environment. Many cell surface receptors recycle from endosomes to the plasma membrane via a recently discovered pathway, which includes sorting-nexin SNX17, Retriever, WASH, and CCC complexes. Here, using mammalian cells, we discover that PIKfyve and its upstream PI3-kinase VPS34 positively regulate this pathway. VPS34 produces phosphatidylinositol 3-phosphate (PI3P), which is the substrate for PIKfyve to generate PI3,5P2. We show that PIKfyve controls recycling of cargoes including integrins, receptors that control cell migration. Furthermore, endogenous PIKfyve colocalizes with SNX17, Retriever, WASH, and CCC complexes on endosomes. Importantly, PIKfyve inhibition results in displacement of Retriever and CCC from endosomes. In addition, we show that recruitment of SNX17 is an early step and requires VPS34. These discoveries suggest that VPS34 and PIKfyve coordinate an ordered pathway to regulate recycling from endosomes and suggest how PIKfyve functions in cell migration.

Mechanism of crocin I on ANIT-induced intrahepatic cholestasis by combined metabolomics and transcriptomics.

Background: Intrahepatic cholestasis (IC) is a disorder of bile production, secretion, and excretion with various causes. Crocin I (CR) is effective in the treatment of IC, but its underlying mechanisms need to be further explored. We aimed to reveal the therapeutic mechanism of crocin I for IC by combining an integrated strategy of metabolomics and transcriptomics. Methods: The hepatoprotective effect of CR against cholestasis liver injury induced by α-naphthylisothiocyanate (ANIT) was evaluated in rats. The serum biochemical indices, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA), total bilirubin (TBIL), direct bilirubin (DBIL), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and interleukin 1ß (IL-1ß), as well as the liver oxidative stress indexes and the pathological characteristics of the liver were analyzed. In addition, we also performed a serum metabolomics study using UPLC-Q Exactive HF-X technology to investigate the effect of CR on the serum of rats with ANIT-induced IC and screened potential biomarkers. The enrichment analysis of differential expressed genes (DEGs) was performed by transcriptomics. Finally, the regulatory targets of CR on potential biomarkers were obtained by combined analysis, and the relevant key targets were verified by western blotting. Results: CR improved serum and liver homogenate indexes and alleviated liver histological injury. Compared with ANIT group, the CR group had 76 differential metabolites, and 10 metabolic pathways were enriched. There were 473 DEGs significantly changed after CR treatment, most of which were enriched in the retinol metabolism, calcium signaling pathway, PPAR signaling pathway, circadian rhythm, chemokine signaling pathway, arachidonic acid metabolism, bile secretion, primary bile acid biosynthesis, and other pathways. By constructing the "compound-reaction-enzyme-gene" interaction network, three potential key-target regulation biomarkers were obtained, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), ATP-binding cassette transporter G5 (ABCG5), and sulfotransferase2A1(SULT2A1), which were further verified by western blotting. Compared with the ANIT group, the CR group significantly increased the expression of ABCG5 and SULT2A1, and the expression of HMGCR significantly decreased. Conclusion: Combined metabolomic and transcriptomic analyses show that CR has a therapeutic effect on IC through regulation of the biosynthesis of bile acids and bilirubin in the bile secretion pathway and regulation of the expression of HMGCR, ABCG5, and SULT2A1.

Effects of medicine food Fructus Gardeniae on liver and kidney functions after oral administration to rats for 12 weeks.

Fructus Gardeniae (FG) is medicine food widely used for the treatment and prevention of various diseases. However, in recent years, research has suggested that high doses of FG can cause hepatotoxicity and nephrotoxicity. To assess this potential toxicity in more depth, this study investigated the effects of decocted FG and two of its bioactive constituents (geniposide and genipin) on liver and kidney function in rats. Rats were intragastrically administered FG (330 mg/kg body weight), geniposide (50 mg/kg body weight), or genipin (50 mg/kg body weight) for 12 weeks. Changes in body weight, liver and kidney indices, biochemical indices, and inflammatory factors were monitored. In addition, pathological sections were assessed and the expression of caspase-3, NF-κBp65, COX-2, and iNOS was detected by immunohistochemistry and Western blot. It was found that the levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine, and urea nitrogen increased following administration of FG, geniposide, and genipin. Furthermore, the activities of superoxide dismutase and reduced glutathione decreased following treatment, while malondialdehyde levels increased. Pathological and immunohistochemical evaluations further confirmed that FG and its constituents may cause damage to the liver and kidneys. The mechanism study revealed that the protein level of inflammatory pathway increased and further promoted apoptosis, suggesting that it should not be taken orally for extended periods of time. PRACTICAL APPLICATIONS: Chinese medicine and food safety have always been public health concerns. Fructus Gardeniae (FG) is a plant with a dual-purpose as it is used as both a medicine and food. Medicinally, it has the effects of heat-clearing and detoxification. However, its adverse effects and related mechanisms are not clear, and this has potential safety implications. In this study, rats were treated with FG for 12 weeks and found that the long-term administration of FG or high dosing can lead to damage to liver and kidney function. Therefore, close attention must be paid to the dosage of FG in order to achieve a therapeutic effect and avoid adverse reactions. Thus, this study lays a foundation for the safety evaluation and clinical application of FG.

A New Shear Strength Criterion for Rock Masses with Non-Persistent Discontinuities Considering the Nonlinear Progressive Failure Process.

The shear strength characteristics of rock masses containing non-persistent discontinuities are strongly affected by discontinuities and rock bridges. The linear Jennings criterion cannot reflect the nonlinear mechanical behavior during progressive failure of rock masses with non-persistent discontinuities. In this study, a new nonlinear shear strength criterion was developed. First of all, a series of shear test data about artificial rock mass samples were collected on the basis of the published literatures, and five types of samples were differentiated according to the positions of discontinuities. After that, a new nonlinear shear strength criterion was proposed by introducing two correction coefficients A and B into the basic form of the Jennings criterion, which could correct the weight of the cohesion and the internal friction coefficient of rock bridges respectively. Then, the new criterion was determined by fitting the basic form of the Jennings criterion with the laboratory data. It was found that the parameters A and B had a nonlinear exponential and negative exponential relation with the connectivity rate respectively. It indicated that both the cohesion and the internal friction coefficient estimated by the new criterion were superior to those estimated by the Jennings criterion. Compared with the linear Jennings criterion, the new nonlinear shear strength criterion had a better applicability.

Screening of the Hepatotoxic Components in Fructus Gardeniae and Their Effects on Rat Liver BRL-3A Cells.

Fructus Gardeniae (FG) is a common Chinese medicine and food. However, the toxicity of FG has drawn increasing concern, especially its hepatotoxicity. The purpose of this study was to screen the hepatotoxic components of FG and evaluate their effects on rat liver BRL-3A cells. The chemical composition of FG was determined by HPLC-ESI-MS. CCK-8 assay was used to evaluate the cytotoxicity of ten chemical components from FG, and then the toxic components with significant inhibitory activity were selected for further study. The results showed that geniposide, genipin, genipin-1-gentiobioside, gardenoside, and shanzhiside all suppress cells viability. Apoptosis assays further indicated that geniposide and its metabolite genipin are the main hepatotoxic components of FG. Pretreatment of cells with geniposide or genipin increased the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). The activities of superoxide dismutase (SOD) and glutathione (GSH) were decreased, while the malondialdehyde (MDA) level was increased. The cell contents of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) were also increased. Molecular docking simulations were used to investigate the mechanism of FG-induced hepatotoxicity, revealing that geniposide and genipin bind strongly to the pro-inflammatory factor TNFR1 receptor of the NF-κB and MAPK signaling pathways. The obtained results strongly indicate that the hepatotoxicity of FG is caused by iridoids compounds. Genipin had the most significant hepatotoxic effect. These toxic substances destroy the cell antioxidant defense system, increasing inflammatory injury to the liver cells and leading to apoptosis and even necrosis. Thus, this study lays a foundation for toxicology research into FG and its rational application.

[Research on XOD captured components in Lagotis brevituba based on UPLC-Q-TOF-MS and molecular docking technology].

Potential xanthine oxidase (XOD) inhibitors in Lagotis brevituba were captured by using affinity and ultrafiltration. The structures of the captured components were identified by ultra-performance liquid chromatography coupled with Q-TOF mass spectrometry (UPLC-Q-TOF-MS). The binding intensity and binding mechanism between the captured components and XOD were analyzed by using molecular docking software Autodock 4.2. A total of 17 compounds were identified, including 9 flavonoids, 5 phenolic acids and 3 triterpenes. Molecular docking results showed that all the captured components could be spontaneously bound with XOD mainly via hydrogen bond, Van der Waals' force and hydrophobic interaction. From the perspective of binding energy and scoring function, the collected fractions all had potential prospects for XOD inhibitors, and the flavonoid luteolin-3',7 glucuronide had the best effect. The results also showed that affinity and ultrafiltration, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and molecular docking technology can provide a powerful tool for the analysis of XOD inhibitor components in natural products.

Self-reported reasons for treatment non-adherence in Chinese asthma patients: A 24-week prospective telephone follow-up study.

BACKGROUND: Treatment non-adherence is a challenge to achieve asthma control. However, few prospective studies were done for exploring asthma patient adherence in real world. OBJECTIVES: To evaluate treatment adherence and causes of non-adherence in a large asthma Chinese population. To analyze newly-diagnosed patients' adherence first time. METHODS: About 1582 asthma patients' data were collected from 12 study centers in China from February, 2012 to October, 2012. Disease and treatment information of subjects were collected were at first clinic visit, at 4, 12, and 24 weeks after that, follow-up phone calls were carried out for recording subjects' treatment adherence based on their self-reports. Subjects who reported non-adherence were additionally asked to choose the primary non-adherence cause from a list of nine potential causes. RESULTS: Treatment adherence rate of all subjects markedly decreased from 83.3% at week 4 to 42.0% at week 24 after the first clinic visit. Significantly, at week 24, good treatment adherence rate in newly-diagnosed patients was lower than those patients with asthma history (22.9% vs. 63.9%, P < .001). Newly-diagnosed patients were three times more likely to become non-adherence than those patients with asthma history. Female patients had lower treatment adherence rate than male patients (38.3% vs. 45.6%, P = .006). Subjects in 30-39 year age group had the worst treatment adherence (27.3%). The most commonly chosen cause for non-adherence was "relief of symptoms after short-term controller medication use" (43.8%). CONCLUSIONS: Asthma patients' treatment adherence could be improved by improving patient education, doctor/patient partnership, and level of medical service in Chinese population.

Study of the osteogenesis effect of icariside II and icaritin on canine bone marrow mesenchymal stem cells.

This study aimed to identify the osteogenesis effect of icariside II (ICSII) and icaritin (ICT) in vitro. Bone marrow mesenchymal stem cells (BMSCs) were treated with ICSII and ICT in order to detect the proliferation and differentiation of BMSCs, the expression of the osteogenesis-related proteins with or without osteogenic medium (OM) and genes, Runt-related transcription factor 2 (Runx-2), osteocalcin (OCN), osteopontin (OPN), osterix, and basic fibroblast growth factor (bFGF), and the phosphorylation levels of mitogen-activated protein kinase (MAPK). We found that the optical density increased and alkaline phosphatase decreased after the BMSCs were treated with different concentrations of ICSII; however, ICT showed an opposing effect. The formation of calcium nodules was observed after the BMSCs were treated with ICSII and ICT. The expression level of osteogenesis-related proteins was enhanced following treatment with both ICSII or ICT, while the expression level of the osteogenesis-related genes Runx-2, OCN, OPN, osterix, and bFGF significantly increased with ICSII treatment (P < 0.05), and only Runx-2 and bFGF significantly increased (P < 0.01) with ICT. The expression of osteogenic differentiation-related proteins (except OPN) following treatment with ICSII + OM or ICT + OM was not notably increased. Both ICSII and ICT elevated the phosphorylation levels of MAPK/ERK, which was attenuated by GDC-0994 (an inhibitor of MAPK/ERK). Collectively, these data indicate that ICSII and ICT facilitate orientation osteogenic differentiation of BMSCs, which is most likely via the MAPK/ERK pathway. OM did not synergistically enhance the osteogenesis effect of ICSII and ICT.

[Study on commercial specification of Gardenia jasminoides].

Collecting different commodity grade Gardenia jasminoides of wild and cultivated varieties all over the country, obtaining color information from each batch of G. jasminoides by the standard D65 light source and image acquisition system, quantifing the gardenia plumpness information by the digital display vernier caliper, determinating 6 kinds of effective components of G. jasminoides by HPLC, classifing from ten indicators by two step clustering analysis and correspondence analysis method of statistics, clearing the importance of the traditional identification indexes, establishing multiple corresponding relation between the skin color and commercial specification of G. jasminoides,exploring the correlation of the skin color and chemical composition, to provide the reference for the reasonable division of commercial specifications and grades of G. jasminoides. Medicine is divided into two classes and has obvious distinguish meaning, The importance of the skin color is greater than the plumpness in traditional identification characteristics, it can accurately distinguish the specifications of G. jasminoides. We improve and rebuild the standard of commodity specifications and grades of Gardenia jasminoides Ellis and establish the rapid evaluation method by the study, it provide a new way and idea for the comprehensive evaluation of G. jasminoides quality.

[Fast identification of constituents of Lagotis brevituba by using UPLC-Q-TOF-MS/MS method].

The chemical constituents of Lagotis brevituba were rapidly determined and analyzed by using ultra performance liquid chromatography tandem quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) method, providing material basis for the clinical application of L. brevituba. The separation was performed on UPLC YMC-Triart C18 (2.1 mm×100 mm, 1.9 µm) column, with acetonitrile-water containing 0.2% formic acid as mobile phase for gradient elution. The flow rate was 0.4 mL•min-1 gradient elution and column temperature was 40 ℃, the injection volume was 2 µL. ESI ion source was used to ensure the data collected in a negative ion mode. The chemical components of L. brevituba were identified through retention time, exact relative molecular mass, cleavage fragments of MS/MS and reported data. The results showed that a total of 22 compounds were identified, including 11 flavones, 6 phenylethanoid glycosides, 1 iridoid glucosides, and 4 organic acid. The UPLC-Q-TOF-MS/MS method could fast identify the chemical components of L. brevituba, providing valuable information about L. brevituba for its clinical application.

Icariside II promotes the osteogenic differentiation of canine bone marrow mesenchymal stem cells via the PI3K/AKT/mTOR/S6K1 signaling pathways.

The aim of the present study was to investigate the osteogenic effects of icariside II (ICSII) on canine bone marrow mesenchymal stem cells (BMSCs) and the pathways by which these effects were induced. BMSCs were cultured and expanded to the fourth passage. The proliferative effects of ICSII were assessed using the cell counting kit-8 (CCK-8) assay. The osteogenic response to ICSII in BMSCs in vitro was examined by alkaline phosphatase (ALP) activity assays and Alizarin red staining. Using Western blot assays and real-time PCR (RT-PCR), we examined the expression of osteogenetic proteins/genes. We also evaluated changes in Akt and S6K1 phosphorylation levels, along with changes in the expression of osteogenesis proteins/genes after pretreatment with wortmannin (an inhibitor of phosphatidylinositol 3-kinase; PI3K) or rapamycin [a specific inhibitor of mammalian target of rapamycin (mTOR)] in the presence or absence of ICSII. Our results show that ICSII promotes the proliferation of BMSCs, while inhibiting ALP activity. We also found that calcium nodules form after BMSCs are treated with ICSII and osteogenetic medium for 21 days. ICSII significantly increased the expression of osteogenesis proteins/genes and elevated the phosphorylation levels of Akt and S6K1. Treatment with wortmannin or rapamycin attenuated the expression of p-Akt, p-S6K1, and osteogenesis proteins/genes. These results suggest that ICSII promotes the osteogenic differentiation of canine BMSCs via the PI3K/AKT/mTOR/S6K1 signaling pathways.

rhBMP2-loaded calcium phosphate cements combined with allogenic bone marrow mesenchymal stem cells for bone formation.

OBJECTIVE: The osteogenesis effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) and osteogenic differentiation potential of bone marrow mesenchymal stem cells (BMSCs) has been generally acknowledged. However, human bone formation effect of rhBMP-2 loaded calcium phosphate cememts (CPC) combined with allogenic BMSCs is still undefined. This study aimed to investigate how composite osteogenic bone marrow mesenchymal stem cells (BMSCs) and osteoinductive bone morphogenetic protein-2 (BMP-2) influenced the process of bone formation. METHODS: We chose calcium phosphate cements (cancellous bone granules; cancellous bone granules contained rhBMP-2) to facilitate osteogenesis. The composites of CPC+BMSC and CPC/rhBMP-2+BMSC were implanted respectively into nude mice via subcutaneous implantation and the tooth socket after maxillary canine teeth extraction. MAR analysis, Micro-CT analysis and immunohistochemistry assay were performed in this study to observe and compare by the schedule. RESULTS: It was showed that combined with CPC+BMSC or CPC/rhBMP-2+BMSC induced stronger ability of the proliferation of allogenic BMSCs observed by scanning electron microscopy (SEM). Picric acid-fuchsin staining and immunohistochemical analysis illustrated the stronger new bone forming ability of CPC+BMSC group and CPC/rhBMP-2+BMSC group than those of controlled group. CONCLUSION: The combinations of rhBMP2-loaded CPC with allogeneic BMSCs promote new bone tissue formation.

Synthesis and Evaluation of 5-(o-Tolyl)-1H-tetrazole Derivatives as Potent Anticonvulsant Agents.

A series of 5-(o-tolyl)-1H-tetrazole derivatives were synthesized and evaluated for their anticonvulsant activities. 1-(2-Methylbenzyl)-5-(o-tolyl)-1H-tetrazole (3h) showed important anticonvulsant activity against the MES-induced seizures, as well as lower neurotoxicity with an ED50 value of 12.7 mg/kg and a TD50 value of over 500 mg/kg after intraperitoneal injection into mice, providing 3h with a high protective index (TD50 /ED50 ) of over 39.4. The achieved results prove that the distinctive compounds could be valuable as a model for future development, adaptation, and investigation to construct more active analogues.