LDL receptor-related protein 5 rs648438 polymorphism is associated with the risk of skeletal fluorosis.

To investigate the potential association between LRP5 rs648438 polymorphism and the risk of skeletal fluorosis (SF) was evaluated in a cross-sectional case-control study conducted in Shanxi, China, in 2019. A total of 973 individuals were enrolled in this study, in which cases and controls were 346 and 627, respectively. SF was diagnosed according to the standard WS/192-2008 (China). The LRP5 rs648438 was detected by the multiple PCR and sequencing. LRP5 rs648438 was found to follow a dominant genetic model using a web-based SNP-STATS software. Logistic regression analysis found that the TC/CC genotype of LRP5 rs648438 might be a protective factor for SF. When stratified by gender, this protective effect of TC/CC genotype in rs648438 was pronounced in males. There was an interaction between gender and rs648438 on risk of SF. Our study suggested that TC/CC genotype of rs648438 might be a protective factor for water-drinking-type skeletal fluorosis, especially in male participants.

Association between arsenic (+3 oxidation state) methyltransferase gene polymorphisms and arsenic methylation capacity in rural residents of northern China: a cross-sectional study.

Arsenic is a toxic metal-like element. The toxic reaction of the body to arsenic is related to the ability of arsenic methylation metabolism. As the rate-limiting enzyme of arsenic methylation metabolism, the genetic single nucleotide polymorphisms (SNPs) of arsenic (+ 3 oxidation state) methyltransferase (AS3MT) gene are related to capacity of arsenic methylation. In this paper, we investigated the association of five SNPs (rs7085104, rs3740390, 3740393, rs10748835, and rs1046778) in AS3MT with arsenic methylation metabolizing using the data and samples from a cross-sectional case-control study of arsenic and Type 2 diabetes mellitus conducted in Shanxi, China. A total of 340 individuals were included in the study. Urinary total arsenic (tAs, µg/L) was detected by liquid chromatography-atomic fluorescence spectrometry (LC-AFS). According to "safety guidance value of urinary arsenic for population" as specified in WS/T665-2019 (China), participants were divided into the control group (tAs ≤ 32 µg/L, n = 172) and arsenic-exposed group (tAs > 32 µg/L, n = 168). iAs%, MMA%, and DMA% are as the indicator of arsenic methylation capacity. The genotypes of AS3MT SNPs were examined by Multiple PCR combined sequencing. Linear regression analysis showed that AG + GG genotype in rs7085104 was associated with decreased iAs% and increased DMA%. Moreover, AG + AA genotype in rs10748835 and TC + CC genotype in rs1046778 were associated with decreased iAs% and MMA% and increased DMA%. The interaction between rs7085104 and arsenic is associated with iAs% and DMA%. The interaction of rs3740390 and rs10748835 with arsenic is associated with iAs%. Haplotype CTAC (rs3740393-rs3740390-rs10748835-rs1046778) was associated with lower iAs% and higher DMA%, but this association disappeared after adjusting for age, gender, drink, smoking, BMI and tAs. Haplotype GCAC was associated with decreased MMA%. Our study provides additional support for revealing the factors influencing the metabolic capacity of arsenic methylation and might be helpful to identify the population susceptible to arsenic exposure through individualized screening in the future.

SIRT1/P53 pathway is involved in the Arsenic induced aerobic glycolysis in hepatocytes L-02 cells.

Arsenic is a known human carcinogen. Low doses of arsenic can induce cell proliferation, but the mechanism remains elusive. Aerobic glycolysis, also known as the Warburg effect, is one of the characteristics of tumour cells and rapidly proliferating cells. P53 is a tumour suppressor gene that has been shown to be a negative regulator of aerobic glycolysis. SIRT1 is a deacetylase that inhibits the function of P53. In this study, we found that P53 was involved in low dose of arsenic-induced aerobic glycolysis through regulating HK2 expression in L-02 cells. Moreover, SIRT1 not only inhibited P53 expression but also decreased the acetylation level of P53-K382 in arsenic-treated L-02 cells. Meanwhile, SIRT1 influenced the expression of HK2 and LDHA, which then promoted arsenic-induced glycolysis in L-02 cells. Therefore, our study demonstrated that the SIRT1/P53 pathway is involved in arsenic-induced glycolysis, thereby promoting cell proliferation, which provides theoretical basis for enriching the mechanism of arsenic carcinogenesis.

The memory effect of micro/nano-structures activating osteogenic differentiation of BMSCs.

Degradable bioceramics such as hydroxyapatite (HA) are usually used as bone grafts due to their excellent osteoconductive ability. Recent studies have proved that decorated micro/nano-structures on HA could enhance its osteogenic capacity by directly activating osteogenic differentiation of bone marrow-derived stem cells (BMSCs) or by indirectly activating the osteoimmune microenvironment. However, it is still unclear whether the degradation process of HA affects the activation effect of micro/nano-structures. In this study, we first demonstrate that the enhanced osteogenic properties activated by micro/nano-structures could be memorized and continue to play a role even after the removal of micro/nano-structures. More interestingly, this topography-triggered osteogenic memory effect (TTOME) could be regulated through the stimulation time, indicating the importance of the rational maintenance of micro/nano-structures as well as the degradation process of bioceramics. These findings provide a perspective of the design of bone implants with a biodegradable surface topography.

Subjective and Objective Evaluation of Speech in Adult Patients With Repaired Cleft Palate.

OBJECTIVE: To explore the speech outcomes of adult patients with repaired cleft palate through subjective perception evaluation and objective acoustic analysis, and to compare the differences in pronunciation characteristics between speakers with complete velopharyngeal closure (VPC) and velopharyngeal insufficiency (VPI) patients. PARTICIPANTS AND INTERVENTION: Subjective evaluation indicators included speech intelligibility, nasality and consonant missing rate, for objective acoustic analysis, we used speech sample normalization and objective acoustic parameters included normalized vowel formants, voice onset time and the analysis of 3-dimensional spectrogram and spectrum, were carried out on speech samples produced by 3 groups of speakers: (a) speakers with velopharyngeal competence after palatorrhaphy (n=38); (b) speakers with velopharyngeal incompetence after palatorrhaphy (n=70), (c) adult patients with cleft palate (n=65) and (d) typical speakers (n=30). RESULTS: There was a highly negative correlation between VPC grade and speech intelligibility (ρ=-0.933), and a highly positive correlation between VPC and nasality (ρ=0.813). In subjective evaluation, the speech level of VPI patients was significantly lower than that of VPC patients and normal adults. Although the nasality and consonant loss rate of VPC patients were significantly higher than that of normal adults, the speech intelligibility of VPC patients was not significantly different from that of normal adults. In acoustic analysis, patients with VPI still performed poorly compared with patients with VPC. CONCLUSIONS: The speech function of adult cleft palate patients is affected by abnormal palatal structure and bad pronunciation habits. In subjective evaluation, there was no significant difference in speech level between VPC patients and normal adults, whereas there was significant difference between VPI patients and normal adults. The acoustic parameters were different between the 2 groups after cleft palate repair. The condition of palatopharyngeal closure after cleft palate can affect the patient's speech.

Field recommended concentrations of pyraclostrobin exposure disturb the development and immune response of worker bees (Apis mellifera L.) larvae and pupae.

The strobilurin fungicide pyraclostrobin is widely used to prevent and control the fungal diseases of various nectar and pollen plants. Honeybees also directly or indirectly contact this fungicide with a long-term exposure period. However, the effects of pyraclostrobin on the development and physiology of Apis mellifera larvae and pupae during continuous exposure have been rarely known. To investigate the effects of field-realistic concentrations of pyraclostrobin on honeybee survival and development, the 2-day-old larvae were continuously fed with different pyraclostrobin solutions (100 mg/L and 83.3 mg/L), and the expression of development-, nutrient-, and immune-related genes in larvae and pupae were examined. The results showed that two field-realistic concentrations of pyraclostrobin (100 and 83.3 mg/L) significantly decreased the survival and capped rate of larvae, the weight of pupae and newly emerged adults, and such decrease was a positive correlation to the treatment concentrations. qPCR results showed that pyraclostrobin could induce the expression of Usp, ILP2, Vg, Defensin1, and Hymenoptaecin, decrease the expression of Hex100, Apidaecin, and Abaecin in larvae, could increase the expression of Ecr, Usp, Hex70b, Vg, Apidaecin, and Hymenoptaecin, and decreased the expression of ILP1, Hex100 and Defensin1in pupae. These results reflect pyraclostrobin could decrease nutrient metabolism, immune competence and seriously affect the development of honeybees. It should be used cautiously in agricultural practices, especially in the process of bee pollination.

Malignant growth of arsenic-transformed cells depends on activated Akt induced by reactive oxygen species.

Arsenic is an identified carcinogen for humans.In this study, chronic exposure of human hepatocyte L-02 to low-doses of inorganic arsenic caused cell malignant proliferation. Meanwhile, compared with normal L-02 cells, arsenic-transformed malignant cells, L-02-As displayed more ROS and significantly higher Cyclin D1 expression as well as aerobic glycolysis. Moreover, Akt activation is followed by the upregulation of Cyclin D1 and HK2 expression in L-02-As cells, since inhibition of Akt activity by Ly294002 attenuated the colony formation in soft agar and decreased the levels of Cyclin D1 and HK2. In addition, scavenging of ROS by NAC resulted in a decreased expression of phospho-Akt, HK2 and Cyclin D1, and attenuates the ability of anchorage-independent growth ofL-02-As cells, suggested that ROS mediated the Akt activation in L-02-As cells. In summary, our results demonstrated that ROS contributes to the malignant phenotype of arsenic-transformed human hepatocyte L-02-As via the activation of Akt pathway.

Low-dose arsenic trioxide enhances membrane-GLUT1 expression and glucose uptake via AKT activation to support L-02 cell aberrant proliferation.

Long term low dose exposure of arsenic has been reported to lead various cells proliferation and malignant transformation. GLUT1, as the key transporter of glucose, has been reported to have association with rapid proliferation of various cells or tumor cells. In our study, we found that low dose exposure to arsenic trioxide (0.1µmol/L As2O3) could induce an increase in glucose uptake and promote cell viability and DNA synthesis. And, 2-DG, a non-metabolized glucose analog, significantly decreased the glucose uptake and cell proliferation of 0.1µmol/L As2O3 treated L-02 cells. However, 4 mmol/L 2-DG was co-utilized with equal dose glucose had no significant effect on the cell proliferation of 0.1µmol/L As2O3 treated L-02 cells. Further studies showed that exposure to 0.1µmol/L As2O3 could promote the expression of GLUT1 on plasma membrane. Inhibition of GLUT1 expression by 5µmol/L BAY-876 significantly decreased the abilities of glucose uptake and cell proliferation in As2O3-treated L-02 cells. Moreover, 0.1µmol/L As2O3 induced the AKT activation indicated by increased the phospho-AKT (Ser473 and Thr308). Knockdown AKT by shRNA or inhibited AKT activation by LY294002 was followed by significantly decreased glucose uptake, GLUT1 plasma membrane expression and cell proliferation in As2O3-treated L-02 cells. All in all, these results demonstrated that arsenic trioxide-induced AKT activation contributed to the cells proliferation through upregulating expression of GLUT1 on plasma membrane that enhanced glucose uptake.

Arsenic exposure elevated ROS promotes energy metabolic reprogramming with enhanced AKT-dependent HK2 expression.

Exposure to inorganic or organic arsenic compounds continues to pose substantial public health concerns for hundreds of millions of people around the globe. Highly exposed individuals are susceptible to various illnesses, including impairments and cancers of the lung, liver, skin and bladder. Long-term exposure to low-dose arsenic has been identified to induce aerobic glycolysis, which contributes to cells aberrant proliferation. However, the mechanism underlying arsenic-induced aerobic glycolysis is still unclear. Here, mtDNA copy number is enhanced in arsenic-exposed populations and a positive correlation between serum HK2 and urinary total arsenic was observed in the individuals with high urine arsenic (≥ 0.032 mg/L). In a rat model of trivalent arsenic (iAs3+) exposure, the levels of HK2, NDUFA9 and NDUFB8 were increased in the rats treated with iAs3+ daily by gavage for 12 weeks than those in the control rats. Subsequently, in a low-dose arsenic exposure cell model we found that 0.2 µmol/L iAs3+ induced aerobic glycolysis to promote L-02 cells proliferation and inhibit apoptosis, in which HK2 played an important role. Further studies showed accumulated ROS determined the metabolic reprogramming via activating AKT and then increasing HK2 expression. On the one hand, activated AKT induced aerobic glycolysis by increasing HK2 to promote L-02 cells viability and DNA synthesis; on the other hand, phosphorylated AKT induced HK2 mitochondrial outer-membrane location with VDAC1 to inhibit apoptosis. Taken together, our results indicated that ROS induced by low-dose arsenic exposure determined energy metabolic reprogramming and acted a critical regulator for AKT-dependent HK2 expression and aerobic glycolysis.

Research for type 2 diabetes mellitus in endemic arsenism areas in central China: role of low level of arsenic exposure and KEAP1 rs11545829 polymorphism.

Type 2 diabetes mellitus (T2DM) is one of the major public health problems worldwide; both genetic and environmental factors are its risk factors. Arsenic, an environmental pollutant, might be a risk factor for T2DM, but the association of low-to-moderate level arsenic exposure with the risk of T2DM is still inconsistent. Single nucleotide polymorphisms (SNPs) can affect the development of T2DM, but the study on KEAP1 rs11545829 (G>A) SNP is few. In this paper, we explored the effect of KEAP1 rs11545829 (G>A) SNP and low-to-moderate level arsenic exposure on risk of T2DM in a cross-sectional case-control study conducted in Shanxi, China. Total of 938 participants, including 318 T2DM cases and 618 controls, were enrolled. Blood glycosylated haemoglobin (HbA1c) was detected by Automatic Biochemical Analyzer, and participants with HbA1c≧6.5% were diagnosed as T2DM. Urinary total arsenic (tAs, mg/L), as the indicator of arsenic exposure, was detected by liquid chromatography-atomic fluorescence spectrometry (LC-AFS). Genomic DNA was extracted and the genotypes of KEAP1 rs11545829 SNP were examined by multiplex polymerase chain reaction (PCR). The urinary tAs concentration in recruited participants was 0.075 (0.03-0.15) mg/L, and was associated with an increased risk of T2DM (OR = 8.45, 95% CI 2.63-27.17); rs11545829 mutation homozygote AA genotype had a protective effect on risk of T2DM (OR = 0.42, 95 % CI 0.25-0.73). Although this protective effect of AA genotype was found in participants with higher urinary tAs level (>0.032 mg/L) (OR = 0.48, 95% CI 0.26-0.86), there was no interaction effect for arsenic exposure and rs11545829 SNP on risk of T2DM. In addition, BMI modified the association between rs11545829 SNP and the risk of T2DM (RERI = -1.11, 95% CI -2.18-0.04). The present study suggest that low-to-moderate level arsenic exposure may be a risk factor, while KEAP1 rs11545829 SNP mutation homozygote AA genotype may be a protective factor for risk of T2DM, especially for T2DM patients with urinary tAs level>0.032 mg/L.

Subjective and Objective Evaluation of Speech in Adult Patients with Unrepaired Cleft Palate.

OBJECTIVE: To explore the speech outcomes of adult patients through subjective perception evaluation and objective acoustic analysis, and to compare the differences in pronunciation characteristics between speakers with adult patients with unrepaired cleft palate and their non-cleft peers. PARTICIPANTS AND INTERVENTION: Subjective evaluation indicators included speech intelligibility, nasality, and consonant missing rate, whereas objective acoustic parameters included normalized vowel formants, voice onset time, and the analysis of three-dimensional spectrogram and spectrum, were carried out on speech samples produced by 2 groups of speakers: (a) speakers with unrepaired cleft palate ( n = 65, mean age = 25.1 years) and (b) typical speakers ( n = 30, mean age = 23.7 years). RESULTS: Compared with typical speakers, individuals with unrepaired cleft palate exhibited a lower speech intelligibility with higher nasality and consonant missing rate, the missing rate is highest for the 6 consonants syllables The acoustic parameters are mainly manifested as differences in vowel formants and voice onset time. CONCLUSIONS: The results revealed important acoustical differences between adult patients with unrepaired cleft palate and typical speakers. The trend of spectral deviation may have contributed to the difficulty in producing pressure vowels and aspirated consonants in individuals with speech disorders related to cleft palate.

Association between Bone Morphogenetic Protein 2 Gene Polymorphisms and Skeletal Fluorosis of The Brick-tea Type Fluorosis in Tibetans and Kazakhs, China.

To investigate the potential association between BMP2 single nucleotide polymorphisms (SNPs) and brick-tea-type skeletal fluorosis risk in cross-sectional case-control study conducted in Sinkiang and Qinghai, China, a total of 598 individuals, including 308 Tibetans and 290 Kazakhs, were enrolled. Using the standard WS/192-2008 (China), 221 skeletal fluorosis cases were diagnosed, including 123 Tibetans and 98 Kazakhs. Logistic regressions 2 analysis did not find the association between SNPs (Rs235764, Rs235739 and Rs996544) and skeletal fluorosis. Genetic models, linkage disequilibrium (LD) and haplotype analysis were not found to be associated with risk of skeletal fluorosis after adjustment by age and sex (P>0.05).Our data suggested that Rs 235764, Rs 235739 and Rs 996544 were not linked susceptibility for skeletal fluorosis in our cross-sectional case-control study.

miR-21-5p and canonical Wnt signaling pathway promote osteoblast function through a feed-forward loop induced by fluoride.

Long-term excessive exposure to fluoride from environmental sources can cause serious public health problems such as dental fluorosis and skeletal fluorosis. The aberrant activation of osteoblasts in the early stage is one of the critical steps during the pathogenesis of skeletal fluorosis and canonical Wnt signaling pathway participate in the progress. However, the specific mechanism that how canonical Wnt signaling pathway was mediated is not yet clear. In this study, we found that miR-21-5p induced the activation of canonical Wnt signaling pathway via targeting PTEN and DKK2 during fluoride induced osteoblasts activation and firstly demonstrated the forward loop between canonical Wnt signaling and miR-21-5p in the process. These findings suggested an important regulatory role of miR-21-5p on canonical Wnt signaling pathway during skeletal fluorosis and miR-21-5p might be a potential therapeutic target for skeletal fluorosis.

Association between fluoride exposure and kidney function in adults: A cross-sectional study based on endemic fluorosis area in China.

BACKGROUND: The kidney toxicity of fluoride exposure has been demonstrated in animal studies, and a few studies have reported kidney function injury in children with fluoride exposure. However, epidemiological information for the effects of long-term fluoride exposure on adult kidney function remains limited. METHODS: We conducted a cross-sectional investigation in Wenshui County, Shanxi Province to examine the association between fluoride exposure and kidney function in adults, and a total of 1070 adults were included in our study. Urinary fluoride concentrations were measured using the national standardized ion selective electrode method. And markers of kidney function injury (urinary NAG, serum RBP, serum Urea, serum C3, serum UA and serum αl-MG) were measured using automatic biochemical analyzer. Multivariate linear regression analysis and binary logistic regression model were used to assess the relationship between urinary fluoride and markers of kidney function injury. RESULTS: Urinary fluoride was positively correlated with urinary NAG and serum Urea, negatively correlated with serum C3. In multivariate linear regression models, every 1 mg/L increment of urinary fluoride was associated with 1.583 U/L increase in urinary NAG, 0.199 mmol/L increase in serum Urea, 0.037 g/L decrease in serum C3 after adjusting for potential confounding factors. In the binary logistic regression model, higher levels of urinary fluoride were associated with an increased risk of kidney function injury. Determination of kidney function based on urinary NAG, every 1 mg/L increment in the urinary fluoride concentrations was associated with significant increases of 22.8% in the risk of kidney function injury after adjusting for potential confounding factors. Sensitivity analysis for the association between urinary fluoride concentrations and markers of kidney function (urinary NAG, serum Urea, and serum C3) by adjusting for the covariates, it is consistent with the primary analysis. CONCLUSIONS: Our study suggests that long-term fluoride exposure is associated with kidney function in adults, and urinary NAG is a sensitive and robust marker of kidney dysfunction caused by fluoride exposure, which could be considered for the identification of early kidney injury in endemic fluorosis areas.

An Observational Study to Evaluate Association Between Velopharyngeal Anatomy and Speech Outcomes in Adult Patients With Severe Velopharyngeal Insufficiency.

OBJECTIVE: By measuring velopharyngeal structure and evaluating speech intelligibility, to explore and observe the association between velopharyngeal anatomy and speech outcomes in these patients. METHODS: Thirty-one adult patients with velopharyngeal insufficiency after the primary palatoplasty aged 18 to 35 years (mean 22.03 years) were enrolled as the study group. The patients had significant hypernasality and audible nasal emission. The degree of velopharyngeal closure assessed by electronic nasopharyngeal fiberoptic endoscopy was grade III. Cephalometric analysis was performed on lateral cephalograms to measure velopharyngeal structure, including hard palate length (ANS-PNS), velar length (PNS-U), pharyngeal depth (PNS-PPW), and oropharyngeal airway space (U-MPW). Their speech intelligibility was evaluated through the Mandarin Chinese speech intelligibility test, and each speech sample was examined by 2 speech and language pathologists. The results were assessed with the SPSS 23.0 software package, and regression analysis was used to examine the relationship between velopharyngeal structure and speech outcomes. RESULTS: A significant negative correlation was confirmed between speech intelligibility and pharyngeal depth. Pharyngeal depth also showed a linear relationship with speech intelligibility, and there was no significant correlation between speech intelligibility and other measures (hard palate length, velar length, oropharyngeal airway space). CONCLUSIONS: In the velopharyngeal anatomy, only pharyngeal depth was associated with speech intelligibility in adult patients with severe velopharyngeal insufficiency, this is consistent with our clinical observation. It suggests that appropriate reduction of pharyngeal depth during palatopharyngoplasty may have a good effect on the speech recovery in patients with cleft palate and patients with velopharyngeal insufficiency after palatorrhaphy.

NO2 Gas Sensing Performance of a VO2(B) Ultrathin Vertical Nanosheet Array: Experimental and DFT Investigation.

A VO2(B) ultrathin vertical nanosheet array was prepared by the hydrothermal method. The influence of the concentration of oxalic acid on the crystal structure and room-temperature NO2 sensing performance was studied. The morphology and crystal structure of the nanosheets were characterized by scanning electron microscopy, transmission electron microscopy, and X-ray diffraction. Room-temperature gas sensing measurements of this structure to NO2 with a concentration span from 0.5 to 5 ppm were carried out. The experimental results showed that the thickness of the vertical VO2(B) nanosheet was lower than 20 nm and close to the 2 times Debye length of VO2(B). The response of the sensor based on this structure to 5 ppm NO2 was up to 2.03, and the detection limit was 20 ppb. Its high response performance was due to the fact that the target gas could completely control the entire conductive path by forming depletion layers on the surface of VO2(B) nanosheets. Density functional theory was used to analyze the adsorption of NO2 on the VO2(B) surface. It is found that the band gap of VO2(B) becomes narrower and the Fermi level moves to the valence band after NO2 adsorption, and the density of states near the Fermi level increases significantly. This ultrathin vertical nanosheet array structure can make VO2(B) detect NO2 with high sensitivity at room temperature and therefore has potential applications in the field of low-power-consumption gas sensors.

Research progress of plant cytogenetics in Jiangsu province.

Cytogenetics was established based on the "Chromosome theory of inheritance", proposed by Boveri and Sutton and evidenced by Morgan's lab in early stage of the 20 th centrary. With rapid development of related research areas, especially molecular genetics, cytogenetics developed from traditional into a new era, molecular cytogenetics in late 1960s. Featured by an established technique named DNA in situ hybridization (ISH), molecular cytogenetics has been applied in various research areas. ISH provids vivid and straightforward figures showing the virtual presence of DNA, RNA or proteins. In combination with genomics and cell biology tools, ISH and derived techniques have been widely used in studies of the origin, evolution, domestication of human, animal and plant, as well as wide hybridization and chromosome engineering. The physical location and order of DNA sequences revealed by ISH enables the detection of chromosomal re-arrangments among related species and gaps of assembled genome sequences. In addition, ISH using RNA or protein probes can reveal the location and quantification of transcripted RNA or translated protein. Since the 1970s, scientists from universities or institutes belonging to the Jiangsu Society of Genetics have initiated cytogenetics researches using various plant species. In recent years, research platforms for molecular cytogenetics have also been well established in Nanjing Agricultural University, Yangzhou University, Nanjing Forestry University, Jiangsu Xuhuai Academy of Agricultural Sciences, and Jiangsu Normal University. The application of molecular cytogenetics in plant evolution, wide hybridization, chromosome engineering, chromosome biology, genomics has been successful. Significant progresses have been achieved, both in basic and applied researches. In this paper, we will review main research progresses of plant cytogenetics in Jiangsu province, and discuss the potential development of this research area.

High Iodine Induces the Proliferation of Papillary and Anaplastic Thyroid Cancer Cells via AKT/Wee1/CDK1 Axis.

High iodine can alter the proliferative activity of thyroid cancer cells, but the underlying mechanism has not been fully elucidated. Here, the role of high iodine in the proliferation of thyroid cancer cells was studied. In this study, we demonstrated that high iodine induced the proliferation of BCPAP and 8305C cells via accelerating cell cycle progression. The transcriptome analysis showed that there were 295 differentially expressed genes (DEGs) in BCPAP and 8305C cells induced by high iodine, among which CDK1 expression associated with the proliferation of thyroid cancer cells induced by high iodine. Moreover, the western blot analysis revealed that cells exposed to high iodine enhanced the phosphorylation activation of AKT and the expression of phospho-Wee1 (Ser642), while decreasing the expression of phospho-CDK1 (Tyr15). Importantly, the inhibition of AKT phosphorylation revered the expression of CDK1 induced by high iodine and arrested the cell cycle in the G1 phase, decreasing the proliferation of thyroid cancer cells induced by high iodine. Taken together, these findings suggested that high iodine induced the proliferation of thyroid cancer cells through AKT-mediated Wee1/CDK1 axis, which provided new insights into the regulation of proliferation of thyroid cancer cells by iodine.

Speech Outcomes Comparison Between Adult Velopharyngeal Insufficiency and Patients With Unrepaired Cleft Palate.

OBJECTIVE: This study compared the speech outcomes of adult velopharyngeal insufficiency patients and adult cleft palate (ACP) patients, and explored whether there was any difference in the phonological level of these 2 types of patients. METHODS: Perceptual evaluation was used to assess speech intelligibility, hypernasality and compensatory articulation in 89 adult patients with velopharyngeal insufficiency and 35 adult patients with unrepaired cleft palate. Each group was divided into complete cleft palate and incomplete cleft palate (including submucous cleft palate). The phonological differences were compared between the 2 groups of patients and 2 types of cleft palate. RESULTS: The mean speech intelligibility was 43.04% in velopharyngeal insufficiency group and 32.87% in ACP group. There was a significant difference in speech intelligibility between the 2 groups by T test, t = 2.916 (P < 0.01), speech intelligibility between 2 types of cleft palate was no significant difference. Also, there was a significant difference between the 2 groups in the constitution of hypernasality degree by Chi-Square test, x2 = 31.650 (P < 0.01), compensatory articulation were present in 74.3% ACP patients (26/35) and 47.2% velopharyngeal insufficiency patients (42/89), x2 = 7.446 (P < 0.01), there was a significant difference in incidence of compensatory articulation between the 2 groups. CONCLUSIONS: Adult patients with unpaired cleft palate present an even worse speech intelligibility and hypernasality degree than velopharyngeal insufficiency patients after cleft palate repair, regardless of the cleft type. Additionally, patients in ACP group have a higher incidence of compensatory articulation than that in incomplete cleft palate group. In sequenced treatments of cleft lip and palate, evaluation and treatment of speech disorders cannot be ignored.

Association between ALOX15 gene polymorphism and brick-tea type skeletal fluorosis in Tibetans, Kazaks and Han, China.

To evaluate the association between ALOX15 gene polymorphism and skeletal fluorosis (SF), a case-control study was conducted. A total of 1023 individuals, including 308 Tibetans, 290 Kazaks and 425 Han, were enrolled in this study, in which cases and controls were 278 and 745, respectively. SF was diagnosed by X-ray absorptiometry. SNPs were genotyped using the Sequenom Mass ARRAY system. The genotypes of ALOX15 rs7220870, rs2664593 and rs1107852 were not associated with the risk of SF. After reconstructing the haplotype of rs7220870 and rs11078528, the risk effect of haplotype CA was found in Han participants aged ≤45 years or with moderate fluoride intake. Diplotype of CC/CC had a protective effect on SF risk in Han participants; whereas, CA/CC diplotype showed a risk effect on SF risk in participants aged ≥65; Our results provide the first evidence of an association between ALOX15 gene polymorphism and SF risk in Han participants.Abbreviation: SF: Skeletal fluorosis; SNP: Single Nucleotide polymorphism.