Synergistic Lewis and Brønsted Acid Sites Promote OH* Formation and Enhance Formate Selectivity: Towards High-efficiency Glycerol Valorization.

As a sustainable valorization route, electrochemical glycerol oxidation reaction (GOR) involves in formation of key OH* and selective adsorption/cleavage of C-C(O) intermediates with multi-step electron transfer, thus suffering from high potential and poor formate selectivity for most non-noble-metal-based electrocatalysts. So, it remains challenging to understand the structure-property relationship as well as construct synergistic sites to realize high-activity and high-selectivity GOR. Herein, we successfully achieve dual-high performance with low potentials and superior formate selectivity for GOR by forming synergistic Lewis and Brønsted acid sites in Ni-alloyed Co-based spinel. The optimized NiCo oxide solid-acid electrocatalyst exhibits low reaction potential (1.219 V@10 mA/cm2) and high formate selectivity (94.0 %) toward GOR. In situ electrochemical impedance spectroscopy and pH-dependence measurements show that the Lewis acid centers could accelerate OH* production, while the Brønsted acid centers are proved to facilitate high-selectivity formation of formate. Theoretical calculations reveal that NiCo alloyed oxide shows appropriate d-band center, thus balancing adsorption/desorption of C-O intermediates. This study provides new insights into rationally designing solid-acid electrocatalysts for biomass electro-upcycling.

Major Vault Protein Prevents Atherosclerotic Plaque Destabilization by Suppressing Macrophage ASK1-JNK Signaling.

BACKGROUND: Macrophages are implicated in atherosclerotic plaque instability by inflammation and degradation of extracellular matrix. However, the regulatory mechanisms driving these macrophage-associated processes are not well understood. Here, we aimed to identify the plaque destabilization-associated cytokines and signaling pathways in macrophages. METHODS: The atherosclerotic models of myeloid-specific MVP (major vault protein) knockout mice and control mice were generated. Atherosclerotic instability, macrophage inflammatory signaling, and active cytokines released by macrophages were examined in vivo and in vitro by using cellular and molecular biological approaches. RESULTS: MVP deficiency in myeloid cells exacerbated murine plaque instability by increasing production of both MMP (matrix metallopeptidase)-9 and proinflammatory cytokines in artery wall. Mechanistically, expression of MMP-9 was mediated via ASK1 (apoptosis signal-regulating kinase 1)-MKK-4 (mitogen-activated protein kinase kinase 4)-JNK (c-Jun N-terminal kinase) signaling in macrophages. MVP and its α-helical domain could bind with ASK1 and inhibit its dimerization and phosphorylation. A 62 amino acid peptide (MVP-[686-747]) in the α-helical domain of MVP showed a crucial role in preventing macrophage MMP-9 production and plaque instability. CONCLUSIONS: MVP may act as an inhibitor for ASK1-JNK signaling-mediated MMP-9 production in macrophages and, thereby, attenuate unstable plaque formation. Our findings suggest that suppression of macrophage ASK1-JNK signaling may be a useful strategy antagonizing atherosclerotic diseases.

Co-application of chitooligosaccharides and arbuscular mycorrhiza fungi reduced greenhouse gas fluxes in saline soil by improving the rhizosphere microecology of soybean.

Soil salinization can affect the ecological environment of soil and alter greenhouse gas (GHG) emissions. Chitooligosaccharides and Arbuscular mycorrhizal fungi (AMF) reduced the GHG fluxes of salinized soil, and this reduction was attributed to an alteration in the rhizosphere microecology, including changes in the activities of ß-glucosidase, acid phosphatase, N-acetyl-ß-D-glucosidase, and Leucine aminopeptidase. Additionally, certain bacteria species such as paracoccus, ensifer, microvirga, and paracyclodium were highly correlated with GHG emissions. Another interesting finding is that foliar spraying of chitooligosaccharides could transport to the soybean root system, and improve soybean tolerance to salt stress. This is achieved by enhancing the activities of antioxidant enzymes, and the changes in amino acid metabolism, lipid metabolism, and membrane transport. Importantly, the Co-application of chitooligosaccharides and Arbuscular mycorrhiza fungi was found to have a greater effect compared to their application alone.

Mycorrhizal symbiosis promotes the nutrient content accumulation and affects the root exudates in maize.

BACKGROUND: Arbuscular mycorrhizal fungi (AMF) are a group of important symbiotic microorganisms found in ecosystems. Maize is the second most produced food crop globally. To investigate the mechanisms by which mycorrhizal symbiosis improves maize yields, the effects of mycorrhizal symbiosis on root vigor, nutrient accumulation in various tissues, and root exudates were investigated. We propose the following hypothesis: The secretion of organic acids in root exudates has antagonistic or synergistic effects, which are related to the rhizosphere environment. AMF symbiosis will enhance this effect. RESULT: Rhizophagus aggreatus, Claroideoglomus etunicatum, and Funneliformis mosseae were used to inoculate maize plants separately; meanwhile, maize was inoculated with the above three fungi together for another processing. The plant tissues were sampled at five growth stages: V12 (twelve-leaf), VT (Tassel), R1 (Silking), R2 (Blister), and R4 (Dough stage). The root vigor, and nutrient content in different maize organs and organic acids in root exudates were determined in these stages. The results show that mycorrhizal symbiosis significantly improved the root vigor of maize, especially for plants inoculated with F. mosseae. AMF symbiosis significantly increased N, P, and K accumulation. Mixed inoculation with arbuscular mycorrhizal fungi significantly promoted the accumulation of N and K in maize. P accumulation was significantly promoted by C. etunicatum inoculation. Mycorrhizal symbiosis reduced the levels of protocatechuic, vanillic, citric, and ferulic acid in maize root exudates and increased the levels of p-hydroxybenzoic and caffeic acid. Except for syringic, chlorogenic and succinic acid, the levels of other organic acids in root exudates were higher in plants inoculated with F. mosseae than in other treatments. CONCLUSION: This study demonstrates that mycorrhizal symbiosis improves root vigor and promotes nutrient accumulation at various sites; in addition, mycorrhizal symbiosis affects the content of organic acids in root exudates.

The value of cardiac CT in the diagnosis of unroofed coronary sinus syndrome.

BACKGROUND: Unroofed coronary sinus syndrome (UCSS) is a rare cardiovascular malformation with nonspecific clinical manifestations that easily causes misdiagnosis and missed diagnosis. The aim of this study is to present the different features of UCSS by various CCT (cardiac CT) postprocessing techniques and evaluate the diagnostic advantages of CCT. METHODS: 9 UCSS patients who were diagnosed by imaging and undergone both CCT and transthoracic echocardiography (TTE) were included in this study, and their CCT images were reviewed. The UCSS images were classified by multiplanar reformations, maximum intensity projection, volume rendering and cinematic rendering. The size of CS roof defect was also measured. RESULTS: Only 4 of 9 CCT confirmed UCSS patients were detected by TTE (4/9, 44.4%), the sensitivity of TTE was lower compared to CCT by Fisher's exact test (P < 0.05). UCSS was classified according to the Kirklin and Barratt Boyes's method, including 1 case was classified as type I, 4 cases as type II, 1 case as type III, 2 cases as type IV, 1 case as type V (variant type), and TTE was undiagnosed in all type III-V patients. Additionally, CCT showed 12 extra malformations in these patients, only 5 of them were found by TTE (5/12, 41.7%), and TTE missed all extracardiac malformations. The mean size of CS roof defect was 3.04 ± 1.57 cm. CONCLUSIONS: CCT with various postprocessing technologies has excellent value in diagnosing and differentiating subtypes of UCSS, measuring size of coronary sinus defect, describing accompanying cardiovascular abnormalities.

Dual RNA and 16S ribosomal DNA sequencing reveal arbuscular mycorrhizal fungi-mediated mitigation of selenate stress in Zea mays L. and reshaping of soil microbiota.

Excessively high concentrations of selenium (Se) in soil are toxic to crop plants, and inoculation with arbuscular mycorrhizal fungi (AMF) can reverse Se stress in maize (Zea mays L.). To investigate the underlying mechanisms, maize seedlings were treated with sodium selenate (5 mg Se[VI] kg-1) and/or AMF (Funneliformis mosseae and Claroideoglomus etunicatum). Dual RNA sequencing in mycorrhiza and 16 S ribosomal DNA sequencing in soil were performed. The results showed that Se(VI) application alone decreased plant dry weight, but increased plant Se concentration, total Se content (mainly selenocysteine), and root superoxide content. Inoculation with either F. mosseae or C. etunicatum increased plant dry weight, decreased Se accumulation and selenocysteine proportion, enhanced root peroxidase activity, and alleviated oxidative stress in Se(VI)-treated plants. Inoculation also downregulated the expression of genes encoding Se transporters, assimilation enzymes, and cysteine-rich receptor-like kinases in Se(VI)-stressed plants, similar to plant-pathogen interaction and glutathione metabolism related genes. Conversely, genes encoding selenium-binding proteins and those related to phenylpropanoid biosynthesis were upregulated in inoculated plants under Se(VI) stress. Compared with Se(VI)-free plants, Se tolerance index, symbiotic feedback percentage on plant dry weight, and root colonization rate were all increased in inoculated plants under Se(VI) stress, corresponding to upregulated expression of 'key genes' in symbiosis. AMF inoculation increased bacterial diversity, decreased the relative abundances of selenobacteria related to plant Se absorption (e.g., Proteobacteria and Firmicutes), and improved bacterial network complexity in Se(VI)-stressed soils. We suggest that stress-mediated enhancement of mycorrhizal symbiosis contributed to plant Se(VI) tolerance, whereas AMF-mediated reshaping of soil bacterial community structure prevented excessive Se accumulation in maize.

Rho-GEF trio regulates osteoclast differentiation and function by Rac1/Cdc42.

Many bone diseases result from abnormal bone resorption by osteoclasts (OCs). Studying OC related regulatory genes is necessary for the development of new therapeutic strategies. Rho GTPases have been proven to regulate OC differentiation and function and only mature OCs can carry out bone resorption. Here we demonstrate that Rac1 and Cdc42 exchange factor Triple functional domain (Trio) is critical for bone resorption caused by OCs. In this study, we created LysM-Cre;Triofl/fl conditional knockout mice in which Trio was conditionally ablated in monocytes. LysM-Cre;Triofl/fl mice showed increased bone mass due to impaired bone resorption caused by OCs. Furthermore, our in vitro analysis indicated that Trio conditional deficiency significantly suppressed OC differentiation and function. At the molecular level, Trio deficiency significantly inhibited the expression of genes critical for osteoclastogenesis and OC function. Mechanistically, our researches suggested that perturbed Rac1/Cdc42-PAK1-ERK/p38 signaling could be used to explain the lower ability of bone resorption in CKO mice. Taken together, this study indicates that Trio is a regulator of OCs. Studying the role of Trio in OCs provides a potential new insight for the treatment of OC related bone diseases.

Epithelial cell -derived microvesicles: A safe delivery platform of CRISPR/Cas9 conferring synergistic anti-tumor effect with sorafenib.

Safe and efficient intracellular delivery of CRISPR/Cas9 is a key step for effective therapeutic genome editing in a wide range of diseases. This remains challenging due to multiple drawbacks of the currently available vehicles. Here we report that epithelial cell -derived microvesicles (MVs) function as safe and natural carriers for efficient delivery of CRISPR/Cas9 to treat cancer. In our study, compared to epithelial cell -derived MVs, cancer -derived MVs were quickly absorbed intracellularly by recipient cancer cells in vitro and showed selective accumulation in tumors of HepG2 xenografts in vivo, due to their cancer cell tropism dependent targeting. Surprisingly, synergistic anti-tumor effect of sgIQ 1.1 loaded Cas9MVs/HEK293 + sorafenib was better than sgIQ 1.1 + Cas9MVs/HepG2 + sorafenib in vitro. In addition, qPCR results showed that miR-21 and miR-181a expression were upregulated in HepG2 cells treated with cancer cell -derived MVs that might support the cancer progression. Further, treatment of HepG2 xenografts with sgIQ 1.1 loaded Cas9MVs/HEK293 showed enhanced anti-cancer effect than sgIQ 1.1 + Cas9MVs/HepG2. Therefore, we conclude that normal cells -derived MVs can act as better and safe natural delivery systems for cancer therapeutics in the future.

Arbuscular mycorrhizal fungi reverse selenium stress in Zea mays seedlings by improving plant and soil characteristics.

Selenium (Se) is a beneficial trace element for certain animals including humans, while remaining controversial for plants. High Se concentration in soil is toxic to plants especially at seedling stage of the plants. Although, arbuscular mycorrhizal fungi (AMF) are important for plant stress resistance; but the mechanisms by which AMF alleviate Se stress in crop seedlings are unclear. Therefore, we investigated the potential strategies of AMF symbiosis to alleviate Se stress in maize (Zea mays) from plants and soil perspectives. Results showed that Se stress (Se application level > 5 mg kg-1) significantly inhibited leaf area, shoot dry weight, and root dry weight of maize (P < 0.05). In contrast, AM symbiosis significantly improved root morphology, increased nitrogen and phosphorus nutrition, promoted shoot growth, inhibited the transport of Se from soil/roots to shoots, and then diluted the concentration of Se in shoots (32.65-52.80%). In general, the response of maize growth to AMF was mainly observed in shoots rather than roots. In addition, AMF inoculation significantly increased the easily extractable glomalin-related soil protein and organic matter contents and decreased the availability of soil Se to the plant. Principal component analysis showed that AMF promoted growth and nutrition uptake of maize was the most dominant effect of Se stress alleviation, followed by the decrease of soil Se availability, limiting Se transport from soil/roots to shoots. Moreover, the expression of Se uptake-related ion transporter genes (ZmPht2, ZmNIP2;1, and ZmSultr1;3) in maize roots were down-regulated upon AM symbiosis which resultantly inhibited the uptake and transport of Se from soil to maize roots. Thus, AMF could impede Se stress in maize seedlings by improving plant and soil characteristics.

Major vault protein suppresses lung cancer cell proliferation by inhibiting STAT3 signaling pathway.

BACKGROUND: Major vault protein (MVP) is the major component of vault, a eukaryotic organelle involved in multiple cellular processes, and is important in multiple cellular processes and diseases including the drug resistance in cancer chemotherapies. However, the role of MVP in lung cancer remains unclear. METHODS: We examined MVP expression in 120 non-small cell lung cancer (NSCLC) tumors and matched normal tissues by immunohistochemistry. Its relationship with NSCLC prognosis was determined by investigating the patient cohort and analyzing the data from a published dataset consisting with more than 1900 lung cancer patients. We further performed shRNA-introduced knockdown of MVP in Lewis lung carcinoma (LLC) cells and examined its effects on the tumor formation in a xenograft mouse model and the tumor cell proliferation, apoptosis, and signal transduction in vitro. RESULTS: We found that MVP was up-regulated significantly in tumor tissues compared with the matched tumor-adjacent normal tissues. The increased expression of MVP in lung adenocarcinoma was associated with a better prognosis. Knockdown of MVP in LLC cells promoted xenografted lung cancer formation in mice, which was accompanied with accelerated tumor cell proliferation and suppressed cell apoptosis in vitro. Knockdown of MVP stimulated STAT3 phosphorylation, nuclear localization, and activation of JAK2 and RAF/MEK/ERK pathways in LLC cells. Administration of STAT3 inhibitor WP1066 could prevent MVP knockdown induced tumorigenesis. CONCLUSIONS: Our findings demonstrate that MVP may act as a lung tumor suppressor via inhibiting STAT3 pathway. MVP would be a potential target for novel therapies of lung adenocarcinoma.

Pax2 is essential for proliferation and osteogenic differentiation of mouse mesenchymal stem cells via Runx2.

Mesenchymal stem cells (MSCs) have been widely studied in the field of regenerative medicine with the potential to solve osteoporosis. Paired box 2 (Pax2), as a transcription factor, is the master regulator of embryogenesis and oncogenesis. However, the function of Pax2 in osteogenesis is unknown. Here, we reported for the first time that the expression of Pax2 gradually increased during osteogenic differentiation of mouse MSCs, and osteoprogenitor cells. However, detected in osteoblastic cells of mouse tibia, the expression of Pax2 in the embryonic stage was higher than that in adulthood. In C3H/10/T1/2 cells and compact bone-derived mouse MSCs (mMSCs), Pax2 knock-down inhibited the proliferation of these cells, down-regulated the expression of osteogenic marker genes, as well as repressed the ALP activity and mineralization. In addition, Pax2 enhanced the transcriptional activity of Runx2, and activated the MAPK pathway genes (ERK, JNK and p38). Furthermore, knock-down of Pax2 repressed the mMSCs-mediated bone regeneration in an ectopic bone formation model. In conclusion, Pax2 promotes osteogenesis of mouse MSCs, suggesting that Pax2 has a role in the pathophysiology of bone related diseases, and has potential application in bone tissue regeneration.

The role of Rho-GEF Trio in regulating tooth root development through the p38 MAPK pathway.

Trio, the Rho guanine nucleotide exchange factor (Rho-GEF), plays diverse roles in cell migration, cell axon guidance and cytoskeleton reorganization. Conserved during evolution, Trio encodes two guanine nucleotide exchange factor domains (GEFs) and activates small GTPases. The Rho-family small GTPases RhoA and Rac1, which are target molecules of Trio, have been described to engage in craniofacial development and tooth formation. However, the exact role of Trio in tooth development remains elusive. In this study, we generated Wnt1-cre;Triofl/fl mice to address the potential function of Trio in tooth development. Wnt1-cre;Triofl/fl mice showed short root deformity as well as decreased expression of odontogenic makers such as RUNX2, OSX, OCN, and OPN. In vitro, Trio was silenced in human stem cells of dental papilla (SCAPs). Compared with the control group, the proliferation and migration ability in the experimental group was disrupted. After knocking down Trio in SCAPs, the cells showed phenotypes of poor odontogenic differentiation and weak mineralized nodules. To study the underlying mechanism, we investigated the p38 MAPK pathway and found that loss of Trio blocked the cascade transduction of p38 MAPK signaling. In conclusion, we identified Trio as a novel coordinator in regulating root development and clarified its relevant molecular events.

Transcriptomic and proteomic response of Manihot esculenta to Tetranychus urticae infestation at different densities.

Tetranychus urticae (Acari: Tetranychidae) is an extremely serious cassava (Manihot esculenta) pest. Building a genomic resource to investigate the molecular mechanisms of cassava responses to T. urticae is vital for characterizing cassava resistance to mites. Based on the tolerance of cassava varieties to mite infestation (focusing on mite development rate, fecundity and physiology), cassava variety SC8 was selected to analyze transcriptomic and proteomic changes after 5 days of T. urticae feeding. Transcriptomic analysis revealed 698 and 2140 genes with significant expression changes under low and high mite infestation, respectively. More defense-related genes were found in the enrichment pathways at high mite density than at low density. In addition, iTRAQ-labeled proteomic analysis revealed 191 proteins with significant expression changes under low mite infestation. Differentially expressed genes and proteins were mainly found in the following defense-related pathways: flavonoid biosynthesis, phenylpropanoid biosynthesis, and glutathione metabolism under low-density mite feeding and plant hormone signal transduction and plant-pathogen interaction pathways under high-density mite feeding. The plant hormone signal transduction network, involving ethylene, jasmonic acid, and salicylic acid transduction pathways, was explored in relation to the M. esculenta response to T. urticae. Correlation analysis of the transcriptome and proteome generated a Pearson correlation coefficients of R = 0.2953 (P < 0.01), which might have been due to post-transcriptional or post-translational regulation resulting in many genes being inconsistently expressed at both the transcript and protein levels. In summary, the M. esculenta transcriptome and proteome changed in response to T. urticae, providing insight into the general activation of plant defense pathways in response to mite infestation.

A Review on Comparison of Tooth Size Discrepancies among Angle's Class I, II, and III Malocclusion: Is There a Significance?

AIM: The contemporary article aims to review and compare various literatures concerning different conclusions regarding the correlation between tooth size discrepancy (TSD) and Angle's malocclusion groups. BACKGROUND: Acquiring the ideal occlusion plays one of the major roles while designing the treatment plan for an orthodontic patient, any alterations in the individual tooth sizes are called TSD and will hinder this prime requirement. By determining the correct tooth size ratio, it further helps in acquiring the accurate interdigitation, balanced occlusion, and also predicting the orthodontic treatment results. Various investigations were carried out to know the correlation between tooth size discrepancies and different malocclusion groups, of which, a few reported a statistically significant difference whereas others reported no significant difference. REVIEW RESULTS: A computerized database quest was operated utilizing the Medline database (Pubmed/Medline) for original research and review articles. Publications between 1946 and 2018 were included. Four hundred twenty-one articles were recovered from database search and, among them, 66 articles were selected to review the full-article. CONCLUSION: Although a comparison was done between the tooth-size ratios and malocclusion groups (classes I, II, and III), many investigators noted no significant difference but there is an inadequacy in the data particularly related to subgroups of Angle's classification of malocclusion among these investigations; therefore, further studies are required to interpret this correlation. CLINICAL SIGNIFICANCE: As there is high incidence of tooth size discrepancies noted in the previous literature orthodontist, Bolton's analysis regardless of malocclusion group, sex, and ethnicity is highly recommended.

Gold nanoparticles in injectable calcium phosphate cement enhance osteogenic differentiation of human dental pulp stem cells.

In this study, a novel calcium phosphate cement containing gold nanoparticles (GNP-CPC) was developed. Its osteogenic induction ability on human dental pulp stem cells (hDPSCs) was investigated for the first time. The incorporation of GNPs improved hDPSCs behavior on CPC, including better cell adhesion (about 2-fold increase in cell spreading) and proliferation, and enhanced osteogenic differentiation (about 2-3-fold increase at 14 days). GNPs endow CPC with micro-nano-structure, thus improving surface properties for cell adhesion and subsequent behaviors. In addition, GNPs released from GNP-CPC were internalized by hDPSCs, as verified by transmission electron microscopy (TEM), thus enhancing cell functions. The culture media containing GNPs enhanced the cellular activities of hDPSCs. This result was consistent with and supported the osteogenic induction results of GNP-CPC. In conclusion, GNP-CPC significantly enhanced the osteogenic functions of hDPSCs. GNPs are promising to modify CPC with nanotopography and work as bioactive additives thus enhance bone regeneration.

Cbfß deletion in mice recapitulates cleidocranial dysplasia and reveals multiple functions of Cbfß required for skeletal development.

The pathogenesis of cleidocranial dysplasia (CCD) as well as the specific role of core binding factor ß (Cbfß) and the Runt-related transcription factor (RUNX)/Cbfß complex in postnatal skeletogenesis remain unclear. We demonstrate that Cbfß ablation in osteoblast precursors, differentiating chondrocytes, osteoblasts, and odontoblasts via Osterix-Cre, results in severe craniofacial dysplasia, skeletal dysplasia, abnormal teeth, and a phenotype recapitulating the clinical features of CCD. Cbfß(f/f)Osterix-Cre mice have fewer proliferative and hypertrophic chondrocytes, fewer osteoblasts, and almost absent trabecular bone, indicating that Cbfß may maintain trabecular bone formation through its function in hypertrophic chondrocytes and osteoblasts. Cbfß(f/f)Collagen, type 1, alpha 1 (Col1α1)-Cre mice show decreased bone mineralization and skeletal deformities, but no radical deformities in teeth, mandibles, or cartilage, indicating that osteoblast lineage-specific ablation of Cbfß results in milder bone defects and less resemblance to CCD. Activating transcription factor 4 (Atf4) and Osterix protein levels in both mutant mice are dramatically reduced. ChIP assays show that Cbfß directly associates with the promoter regions of Atf4 and Osterix. Our data further demonstrate that Cbfß highly up-regulates the expression of Atf4 at the transcriptional regulation level. Overall, our genetic dissection approach revealed that Cbfß plays an indispensable role in postnatal skeletal development and homeostasis in various skeletal cell types, at least partially by up-regulating the expression of Atf4 and Osterix. It also revealed that CCD may result from functional defects of the Runx2/Cbfß heterodimeric complex in various skeletal cells. These insights into the role of Cbfß in postnatal skeletogenesis and CCD pathogenesis may assist in the development of new therapies for CCD and osteoporosis.

TPM1 polymorphisms and nonsyndromic orofacial clefts susceptibility in a Chinese Han population.

Located at 15q22 a susceptibility region for nonsyndromic orofacial clefts (NSOC), TPM1 encodes a group of highly conserved ubiquitous actin-binding proteins involved in the muscle contraction and cytoskeleton organization. Considering the multiple functions of TPM1 gene, we investigated the potential relationship between TPM1 polymorphisms and risk of NSOC in a Chinese Han population. Four tag single nucleotide polymorphisms (tSNPs) of TPM1 (rs11071720, rs3803499, rs12148828, and rs1972041) were selected to conduct a case-control study with 673 NSOC patients and 705 unrelated healthy controls from a Chinese Han population. The SNPs were genotyped by the IPLEX Sequenom MassARRAY platform. SNP rs1972041GA showed a decreased risk of NSOC in heterozygotes (P = 0.038, OR = 0.77, 95%CI = [0.61, 0.99]). Further stratified analysis revealed an enhanced protective effect of the minor allele G at rs197204 on lip with cleft palate (CLP) and cleft lip with or without cleft palate (CL/P) groups under a codominant or dominant model. No association was observed between the remaining three markers (rs11071720, rs3803499, and rs12148828) and NSOC as well as its subgroups. TPM1 polymorphisms might contribute to the etiology of NSOC, and more emphasis should be placed on TPM1 during craniofacial development.

Association of IL-6 G-174C polymorphism with bone mineral density.

Functional polymorphisms in the promoter region of interleukin-6 (IL-6) are known to be involved in bone mineral density (BMD) and the development of osteoporosis, but the reported results have been inconsistent. Using the meta-analysis approach, the present study is designed to provide a relatively comprehensive picture of the relationship between bone mineral density (BMD) or osteoporosis and polymorphisms in the promoter region of IL-6 (rs1800795 and rs1800796). The difference of bone mineral density (BMD) values between genotypes was examined by mean difference and 95 % confidence intervals (CIs). Association between IL-6 polymorphism and clinical osteoporosis was evaluated by pooled odds ratios (ORs) and 95 % CIs. A total of 13 articles with 11,499 subjects were included in the present study. For -174 (rs1800795), we found that individuals with the G/G genotype had a significantly lower BMD value than those with C/C genotype at femoral neck (0.02 g/cm(2), 95 % CI 0.00-0.03) (p = 0.04) and distal radius (0.01 g/cm(2), 95 %CI 0.01-0.01) (p < 0.0001). However, we did not find a statistically significant difference of BMD at the spine. When analysis was limited to postmenopausal women, similar results were obtained. We further found that the C/C genotype was associated with a reduced risk of osteoporosis compared to G/G genotype, and the pooled OR was 0.72 (95 % CI 0.54-0.95, p = 0.02). In addition, a significant relationship was found between G-634C (rs1800796) polymorphism and distal radius BMD (CC vs. GG: 0.02 g/cm(2), 95 % CI 0.01-0.03; GC vs. GG: 0.02 g/cm(2), 95 % CI 0.00-0.03) in the Asian population. These findings suggest that the CC genotype of IL-6 G-174C polymorphism may be associated with high BMD at femoral neck and distal radius and decreased risk of osteoporosis in the Caucasian population whereas G-634C polymorphism was associated with distal radius BMD in Asians.

The axis inhibition protein 2 polymorphisms and non-syndromic orofacial clefts susceptibility in a Chinese Han population.

BACKGROUND: The axis inhibition protein 2 (AXIN2) is an important regulator of ß-catenin degradation in the Wnt pathway, which plays a key role in craniofacial morphogenesis. The goal of this study was to investigate the potential relationship between AXIN2 polymorphisms and the risks of non-syndromic orofacial clefts (NSOC) in a Chinese Han population. METHODS: Four polymorphisms of AXIN2 (rs2240307, rs11867417, rs2240308, and rs7591) were selected to perform a case-control study with 599 NSOC cases and 602 healthy individuals from a Chinese Han population. The single nucleotide polymorphisms (SNPs) were genotyped on basis of double ligation and multiplex fluorescence PCR. RESULTS: Weak associations were found between these four SNPs and the risk of NSOC. Further stratified analysis showed that the overall genotype frequencies of rs2240307 were different between the cleft palate only (CPO) group and the control group (P = 0.048), and GG genotype markedly contributed to the susceptibility to CPO (OR = 3.22, 95% CI = 1.13-9.18). The similar effect was also observed on GA/AA genotype compared with GG homozygote (OR = 0.30, 95% CI = 0.11-0.84). The results of LD analysis between each pair of SNPs revealed that two SNPs (rs11867417 and rs7591) were in a LD block (r(2) > 0.8). But no statistically significant was found between cases and controls from haplotype analysis in these two loci. CONCLUSIONS: The borderline results gave us a hint that rs2240307 contributed to the susceptibility to CPO in a Chinese Han population, which was conductive to improving our awareness of the causes of NSOC.

Effect of 3 vertical facial patterns on alveolar bone quality at selected miniscrew implant sites.

OBJECTIVE: To evaluate dental alveolar bone quality among young healthy Chinese adults having 3 different vertical patterns. MATERIALS AND METHODS: Three-dimensional cone-beam computed tomography images of 101 subjects (15 low-angle, 48 average-angle, and 38 high-angle) were reconstructed. Facial alveolar cortical bone thicknesses and cortical and cancellous bone densities at 4 selected miniscrew implant sites in both arches, together with cancellous bone densities of third cervical vertebrae, were measured. Bone qualities were compared among the 3 vertical pattern groups. RESULTS: The cortical bone thicknesses at mandibular 5-6 and 6-7 and the cortical and cancellous bone densities at maxillary and mandibular 5-6 and 6-7 were generally greater in the low-angle than in the other 2 groups. There was no similar consistent vertical pattern apparent for bone quality at the 1-1 and 1-2 sites. No significant differences in bone densities for third cervical vertebrae were found among the 3 groups. CONCLUSION: Careful selection of suitable implantation sites and sizes of the miniscrews used should be made to reduce the possible occurrence of implant loosening in patients with average-angle and high-angle vertical facial patterns in particular.