Preparation and measurement of a sandwiched Sn atomic beam source for laser resonance ionization mass spectrometry.

Isotope analysis of Sn plays a crucial role in geochemical studies and in monitoring nuclear contamination. Nevertheless, prevalent analytical techniques for examining Sn isotopes encounter the issue of isobaric interference, markedly impacting the accuracy of the test results. Laser resonance ionization mass spectrometry (LRIMS) can effectively overcome the difficulties associated with the isobaric interference inherent in commercial mass spectrometry. In this paper, different amounts of Sn were prepared on Re filaments by electrodeposition and tested via LRIMS. The results showed that the average detection efficiency of LRIMS decreased with increasing total Sn content from 1 µg to 4 µg, and the fluctuations in the test results among the samples increased significantly. Therefore, the electrodeposition process, as well as the composition and morphology of the deposits were characterized by SEM, EDS and XPS; results showed that the degradation of the samples with increasing Sn content was attributed to the complexity of the composition, micro-structure, valence of the deposits, and the interference of various elements. To cope with the anomalies encountered above, the deposits were heat-treated at 600 °C in a hydrogen atmosphere to eliminate detrimental impurities, like Cl, and Sn was effectively reduced to an almost singular atomic state. Furthermore, a titanium layer was covered on the surface of the heat-treated deposit by magnetron sputtering. Ultimately, a highly efficient and stable Sn atomic beam source with a sandwiched structure has been successfully developed and exhibits broad application prospect.

NLRP10 promotes AGEs-induced NLRP1 and NLRP3 inflammasome activation via ROS/MAPK/NF-κB signaling in human periodontal ligament cells.

Diabetes mellitus (DM), characterized by production and accumulation of advanced glycation end products (AGEs), induces and promotes chronic inflammation in tissues, including periodontal tissue. Increasing amount of epidemiological and experimental evidence demonstrated that more extensive inflammatory reaction and bone resorption occurred in periodontal tissues in diabetic patients with periodontitis, which is speculated to be related to NLRP3 inflammasome. NLRP10 is the only NOD-like receptor protein lacking leucine-rich repeats, suggesting that NLRP10 may be a regulatory protein. The aim of this study was to investigate the regulatory role of NLRP10 on NLRP1 and NLRP3 inflammasome in human periodontal ligament cells (HPDLCs) under AGEs treatment. Expression of NLRP10 in HPDLCs stimulated with 100 ug/mL AGEs for 24 h was observed. Detection of TRIM31 is conducted, and in TRIM31-overexpressed HPDLCs, the interaction between NLRP10 with TRIM31 as well as NLRP10 with ubiquitination were explored by immunoprecipitation. Under AGEs stimulation, the activation of reactive oxidative stress (ROS) and inflammatory signaling pathway (NF-κB, MAPK pathway) was detected by biomedical microscope and western blot (WB), respectively. After stimulation with AGEs for 24 h with or without silencing NLRP10, inflammatory cytokines (IL-6 and IL-1ß), NF-κB, MAPK pathway, ROS, and components of inflammasome were assessed. In HPDLCs, we found AGEs induced NLRP10 and inhibited TRIM31. TRIM31 overexpression significantly enhanced interaction between TRIM31 and NLRP10, then induced proteasomal degradation of NLRP10. Moreover, under AGEs stimulation, NLRP10 positively regulates NLRP1, NLRP3 inflammasomes by activating NF-κB, MAPK pathway, and increasing ROS, finally promoting the expression of inflammatory cytokines. Together, we, for the first time, confirmed that NLRP10 could promote inflammatory response induced by AGEs in HPDLCs via activation of NF-κB, and MAPK pathway and increasing ROS.

Associations Between Body Composition and Sensorineural Hearing Loss Among Adults Based on the UK Biobank.

OBJECTIVE: To explore the association between body composition and sensorineural hearing loss (SNHL). STUDY DESIGN: Cross-sectional study, prospective study and Mendelian randomization (MR) analyses. SETTING: UK Biobank. METHODS: This cross-sectional study included 147,296 adult participants with complete data on body composition and the speech-reception-threshold (SRT) test. We further conducted a prospective study with 129,905 participants without SNHL at baseline and followed up to 15 years to explore the association between body composition and new-onset SNHL. Multivariable logistic regression and Cox regression models were used. Subgroup analyses stratified by age and sex were performed. We further assessed the causal association between body composition and SNHL using two-sample MR analyses. RESULTS: Our cross-sectional study revealed that fat percentage, especially leg (odds ratio [OR] 1.46, p = .029) and arm (OR 1.43, p = .004), were significant risk factors for SNHL. However, fat-free mass, especially in the arm (OR 0.27, p < .001) and leg (OR 0.58, p < .001) showed significant protective effects against SNHL, which was substantially consistent with the results of the prospective study. In addition, we found that young women with SNHL were more susceptible to body composition indicators. However, MR analyses revealed no evidence of significant causal association. CONCLUSION: Fat percentage, especially in the leg and arm, was a significant risk factor for SNHL, whereas fat-free mass, especially in the leg and arm, had significant protective effects against SNHL, however, these associations may not be causal.

Proliferative exhausted CD8+ T cells exacerbate long-lasting anti-tumor effects in human papillomavirus-positive head and neck squamous cell carcinoma.

The survival prognosis of human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) is largely different, and little is known about the anti-tumor mechanism of tumor-infiltrated exhausted CD8+ T cells (Tex) in HNSCC. We performed cell-level multi-omics sequencing on human HNSCC samples to decipher the multi-dimensional characteristics of Tex cells. A proliferative exhausted CD8+ T cell cluster (P-Tex) which was beneficial to survival outcomes of patients with HPV-positive HNSCC was identified. Interestingly, P-Tex cells expressed CDK4 genes as high as cancer cells, which could be simultaneously inhibited by CDK4 inhibitors and might be a potential reason for the ineffectiveness of CDK4 inhibitors in treating HPV-positive HNSCC. P-Tex cells could aggregate in the antigen-presenting cell niches and activate certain signaling pathways. Together, our findings suggest a promising role for P-Tex cells in the prognosis of patients with HPV-positive HNSCC by providing modest but persistent anti-tumor effects.

The role of HPV status in patients with overlapping grey zone cancer in oral cavity and oropharynx.

PURPOSE: We aimed to explore the clinicodemographic characteristics and prognosis of grey zone squamous cell cancer (GZSCC) located in the overlapping or ambiguous area of oral cavity and oropharynx and to identify valuable factors that would improve its differential diagnosis and prognosis. METHODS: Information of GZSCC patients in the Surveillance, Epidemiology, and End Results (SEER) database were compared to patients with oral cavity (OCSCC) and oropharyngeal (OPSCC) squamous cell carcinomas with corresponding HPV status, respectively. Kaplan-Meier method with log-rank test and multivariate Cox regression analysis were applied to assess associations between clinical characteristics and overall survival (OS). A predictive model integrating age, gender, marital status, HPV status and staging variables was conducted to classify GZSCC patients into three risk groups and verified internally by tenfold cross validation. RESULTS: A total of 3318 GZSCC, 10792 OPSCC and 6656 OCSCC patients were identified. HPV-positive GZSCC patients had the best 5-year OS as HPV-positive OPSCC (81% vs. 82%). However, the 5-year OS of HPV-negative/unknown GZSCC (43%/42%) were the worst among all groups, indicating that HPV status and the overlapping nature of tumors were valuable prognostic predictors in GZSCC patients. Compared with the strategy of dividing GZSCC into two groups by HPV status, the predictive model integrating more variables could additionally identify a unique high-risk GZSCC group with the lowest OS rate. CONCLUSIONS: GZSCC patients had distinct clinical characteristics and prognosis compared with OPSCC and OCSCC, integrating HPV status and other clinical factors could help distinguish GZSCC and predict their prognosis.

A population-based cohort study for presence of ulceration among cutaneous malignant melanoma subgroups of patients.

Background: Observational studies suggest that ulceration is considered to be a negative prognostic factor for cutaneous melanoma. However, the impact of ulceration over different subgroups (e.g. AJCC Stage, thickness level) are controversial and its true causal effect on survival is lack of studies in the view of treating ulceration as an exposure. Objective: To explore the true causal effect of ulceration on melanoma's survival by adopting a combination of methods to discover proper adjustment set and confirming its correctness through a variety of means. Methods: A minimal sufficient adjustment set (MSAS) was found using directed acyclic graphs (DAG) to adjust the effect of causality. Sensitivity analysis was conducted to diagnose potential confounders in addition to MSAS. Cox models were built to analyze the causality in-depth and the model was validated using a novel method. Lastly, stratified effects of ulceration were examined to illustrate its impact within subgroups. Results: Hazard ratio (HR) of ulceration after adjustment by MSAS variables was 1.99 (95% CI=1.88-2.09). The sensitivity analysis of propensity score matching and E-value both demonstrated that variables other than MSAS do not have great influence on ulceration and MSS relationship. The HR of ulceration in AJCC Stage, thickness level, invasion level and tumor extension were all monotonically decreased from 5.76 to 1.57, 4.03 to 1.78, 2.75 to 1.78 and 2.65 to 1.71 respectively. Conclusion: Ulceration in all subgroups were shown to have a significantly negative impact on MSS and its magnitude of effect was monotonically decreased as the disease progressed. The true effect of ulceration can be adjusted by MSAS and its correctness was validated through a variety of approaches.

Gender-specific association between obstructive sleep apnea and cognitive impairment among adults.

OBJECTIVES: This study aims to explore the gender-specific association between obstructive sleep apnea (OSA) and cognitive impairment. METHODS: Participants from UK biobank who have completed at least one of the five baseline cognitive tests (visuospatial memory, prospective memory, fluid intelligence, short numeric memory and reaction time) were included, which were initially divided into two groups based on gender and were further categorized into three subgroups: (1) OSA, (2) self-reported snoring but without OSA, and (3) healthy controls (without OSA or snoring). Multivariable regression analysis was performed to examine the associations among snoring, OSA and performance of each of the five cognitive domains. RESULTS: A total of 267,889 participants (47% male, mean age: 57 years old) were included in our study. In the multivariable regression analysis, female participants in the OSA group had a higher risk of having poor prospective memory (OR: 1.24, 95% CI: 1.02～1.50, p = 0.03). Meanwhile, among female participants, OSA were inversely associated with the performances of fluid intelligence (ß: 0.29, 95% CI: 0.46～-0.13, p < 0.001) and short-numeric memory (ß: 0.14, 95% CI: 0.35～0.08, p = 0.02). Besides, age-related subgroup analyses showed that these associations were largely reserved in younger (＜65 years old) female participants rather than older (≥65 years old) female participants. In contrast, among male participants, no significant association was observed between OSA and impairment of the five cognitive domains. CONCLUSIONS: OSA was significantly associated with cognitive impairment at certain dimensions in female participants rather than in male participants, indicating that more special attention and timely interventions should be given to younger female OSA patients to prevent further cognitive impairment.

Characteristics, Prognosis, and Competing Risk Nomograms of Cutaneous Malignant Melanoma: Evidence for Pigmentary Disorders.

Purpose: Cutaneous malignant melanoma (CMM) always presents as a complex disease process with poor prognosis. The objective of the present study was to explore the influence of solitary or multiple cancers on the prognosis of patients with CMM to better understand the landscape of CMM. Methods: We reviewed the records of CMM patients between 2004 and 2015 from the Surveillance, Epidemiology, and End Results Program. The cumulative incidence function was used to represent the probabilities of death. A novel causal inference method was leveraged to explore the risk difference to death between different types of CMM, and nomograms were built based on competing risk models. Results: The analysis cohort contained 165,043 patients with CMM as the first primary malignancy. Patients with recurrent CMM and multiple primary tumors had similar overall survival status (p = 0.064), while their demographics and cause-specific death demonstrated different characteristics than those of patients with solitary CMM (p < 0.001), whose mean survival times are 75.4 and 77.3 months and 66.2 months, respectively. Causal inference was further applied to unveil the risk difference of solitary and multiple tumors in subgroups, which was significantly different from the total population (p < 0.05), and vulnerable groups with high risk of death were identified. The established competing risk nomograms had a concordance index >0.6 on predicting the probabilities of death of CMM or other cancers individually across types of CMM. Conclusion: Patients with different types of CMM had different prognostic characteristics and different risk of cause-specific death. The results of this study are of great significance in identifying the high risk of cause-specific death, enabling targeted intervention in the early period at both the population and individual levels.

Semaphorin 7A Accelerates the Inflammatory Osteolysis of Periapical Lesions.

INTRODUCTION: Semaphorin 7A (SEMA7A), the only class VII semaphorin member, has been considered as a potent immunomodulatory regulator whose function in periapical lesions remains unclear. In our previous study, we found that SEMA7A was up-regulated in human periapical periodontitis and might be involved in the immune response and tissue destruction of periapical lesions. In this research, we aimed to further explore the specifical regulatory role of SEMA7A as well as its regulatory mechanisms in the inflammatory progression of periapical lesions. METHODS: Human periodontal ligament cells (hPDLCs) were collected from intact, caries-free, and healthy third molars and stimulated with recombinant human/mouse SEMA7A (rSEMA7A). Real-time quantitative polymerase chain reaction (RT-qPCR), Western blot analysis, and enzyme-linked immunosorbent assay were used to detect the messenger RNA and protein levels of inflammatory cytokines and matrix metalloproteinases (MMPs) in hPDLCs. Twenty C57BL/6 mice were randomly divided into 4 groups: the healthy control group, pulp exposure group, pulp exposure and saline treatment group, and pulp exposure and rSEMA7A treatment group. Twenty microliters of sterile saline or 4 µg rSEMA7A were injected respectively into the buccal mucosa around the root apex at day 0, 7, and 14. Mandibular tissues were collected at day 21. Micro-computed tomographic and immunohistochemical staining were used to identify the bone destruction and inflammatory infiltration in periapical areas. Finally, an AKT inhibitor (LY294002) was used to pretreat hPDLCs before rSEMA7A stimulation to determine the role of AKT signaling activation in this process. RESULTS: After treatment with rSEMA7A, the messenger RNA and protein levels of interleukin (IL)-1ß, IL-18, cyclooxygenase-2, MMP-1, and MMP-3 were remarkably up-regulated in hPDLCs. For in vivo experiments, compared with the other 3 groups, the treatment of rSEMA7A aggravated the osteolysis of alveolar bone and promoted the infiltration of immune cells into the apex area, along with increased expression levels of IL-1ß, IL-18, MMP-1, and MMP-3. Furthermore, we found that the proinflammatory role of SEMA7A could be inhibited by the application of the AKT inhibitor (LY294002). CONCLUSIONS: SEMA7A likely aggravates the inflammatory reaction and bone destruction of existing periapical lesions. The proinflammatory role of SEMA7A in hPDLCs could partially be mediated through the AKT signaling transduction pathway.

New insights into aging-associated characteristics of female subcutaneous adipose tissue through integrative analysis of multi-omics data.

Aging could be critical in limiting the application of subcutaneous adipose tissue (SAT) in tissue repair and reconstruction. However, no systematic study on the characteristics of SAT aging has been conducted. In this study, a scanning electronic microscope was used to detect the structural and compositional changes of SAT collected from nine females in three age groups. Multi-omics data of SAT from 37 females were obtained from Gene Expression Omnibus database, and 1860 genes, 56 miRNAs, and 332 methylated genes were identified as being differentially expressed during aging among non-obese females. Using Weighted Correlation Network Analysis (WGCNA), 1754 DEGs were defined as aging-associated genes for non-obese females, distributed among ten co-expression modules. Through Gene Ontology enrichment analysis and Gene Set enrichment analysis on those aging-associated DEGs, SAT aging was observed to be characterized by variations in immune and inflammatory states, mitochondria, lipid and carbohydrate metabolism, and regulation of vascular development. SUPV3L1, OGT, and ARPC1B were identified as conserved and core SAT-aging-related genes, as verified by RT-qPCR among 18 samples in different age groups. Multi-omics regulatory networks of core aging-associated biological processes of SAT were also constructed. Based on WGCNA, we performed differential co-expression analysis to unveil the differences in aging-related co-expression patterns between obese and non-obese females and determined that obesity could be an important accelerating factor in aging processes. Our work provides a landscape of SAT aging, which could be helpful for further research in fields such as repair and reconstruction as well as aging.

Determination of ultra-trace level plutonium isotopes in soil samples by triple-quadrupole inductively coupled plasma-mass spectrometry with mass-shift mode combined with UTEVA chromatographic separation.

Although triple-quadrupole inductively coupled plasma-mass spectrometry (ICP-MS/MS) has become an attractive technique for the measurement of long-lived radionuclides, the abundance sensitivity, isobaric and polyatomic ions interferences seriously restrict the application. The spectral peak tailing and uranium hydrides (UH+, UH2+) from 238U have a serious influence on the accurate measurement of 239Pu and 240Pu, especially for the ultra-trace level plutonium isotopes in the higher uranium sample. A new method was developed using ICP-MS/MS measurement in mass-shift mode with collision-reaction gas combined with a chemical separation procedure. As O2 readily converted Pu+ ion to PuO2+, while disassociated the interfering diatomic ions of interfering elements (U, Pb, Hg, Tl, etc.), the interferences from these elements were completely eliminated if plutonium was detected as PuO2+ at the m/z more than 270. By the mass filter in MS/MS mode combined with O2 as reaction gas the lower peak tailing of 238U+ (<5 × 10-12) was significantly suppressed. By this way, the 238UO2H+/238UO2+ atomic ratio was reduced to 4.82 × 10-9, which is significantly lower than that of other collision-reaction gas modes. Interferences from Pb, Hg and Tl polyatomic ions were also completely eliminated. Thus, accurate measurement of ultra-trace level 239Pu in high uranium sample solutions with the 239Pu/238U concentration ratio of 10-10 was achieved by the mass-shift mode with 0.15 mL/min O2/He + 12.0 mL/min He as collision-reaction gas, and high elimination efficiency of uranium interferences up to 1014 can be obtained by combination with the chemical separation using a single UTEVA resin column. The developed method can be applied to accurately determine the fg level 239Pu in high uranium samples, such as large-size deep seawater, deep soil and sediment, uranium debris of nuclear fuel.

The level, distribution and source of artificial radionuclides in surface soil from Inner Mongolia, China.

Mid- and long-half-life artificial radioisotopes in the earth's surface environment are of great concern to the environmental radiation risk assessment. As nuclear fuel and fission products, 239Pu, 240Pu, 241Am, 90Sr and 137Cs in soils from Inner Mongolia of China were analyzed with a modified systematic separation procedure combined with ICP-MS and LSC measurements, to study the level, distribution and source of artificial radionuclides in the region. The radioactivity and inventory of 137Cs (0.26-28.3 Bq/kg, 0.5-5.4 kBq/m2), 239+240Pu (0.05-1.26 Bq/kg, 20-229 Bq/m2), 241Am (0.036-0.35 Bq/kg, 11-81 Bq/m2) and 90Sr (1.2-7.6 Bq/kg, 0.39-1.7 kBq/m2) all lie in the range of the global fallout. Vertical distributions of these radionuclides were examined for two soil core samples SC14025 and SC14038, and great differences were observed between these two sample locations. For SC14025 where little human disturbance to soil occurred, both 137Cs and 239+240Pu have a subsurface activity maximum followed by an exponential decay. Fittings base on CDE model gives a small downward migration velocity of about 0.097 cm/y for both Pu and 137Cs. Source identification for SC14025 and SC14038 soil cores with 240Pu/239Pu (average of 0.180 ± 0.017 and 0.164 ± 0.035, respectively), 137Cs/239+240Pu (average of 25.3 ± 0.6 and 25.6 ± 3.0, respectively) and 241Am/239+240Pu (average of 0.56 ± 0.08 and 0.60 ± 0.09, respectively) ratios consistently indicated that anthropogenic radionuclides in Xilingol region are mostly from the global fallout of atmospheric nuclear weapons tests in the last century. According to the geographical distribution of the radioactivity level, the high radioactivity level in the east of Inner Mongolia probably results from enhanced deposition by the blocking of the Great Khingan Range.

New Insights Into the Skin Microbial Communities and Skin Aging.

Although it is well-known that human skin aging is accompanied by an alteration in the skin microbiota, we know little about how the composition of these changes during the course of aging and the effects of age-related skin microbes on aging. Using 16S ribosomal DNA and internal transcribed spacer ribosomal DNA sequencing to profile the microbiomes of 160 skin samples from two anatomical sites, the cheek and the abdomen, on 80 individuals of varying ages, we developed age-related microbiota profiles for both intrinsic skin aging and photoaging to provide an improved understanding of the age-dependent variation in skin microbial composition. According to the landscape, the microbial composition in the Children group was significantly different from that in the other age groups. Further correlation analysis with clinical parameters and functional prediction in each group revealed that high enrichment of nine microbial communities (i.e., Cyanobacteria, Staphylococcus, Cutibacterium, Lactobacillus, Corynebacterium, Streptococcus, Neisseria, Candida, and Malassezia) and 18 pathways (such as biosynthesis of antibiotics) potentially affected skin aging, implying that skin microbiomes may perform key functions in skin aging by regulating the immune response, resistance to ultraviolet light, and biosynthesis and metabolism of age-related substances. Our work re-establishes that skin microbiomes play an important regulatory role in the aging process and opens a new approach for targeted microbial therapy for skin aging.

The temporal characteristics of the lag-response relationship and related key time points between ambient temperature and hand, foot and mouth disease: A multicity study from mainland China.

BACKGROUND: Previous studies have thoroughly elucidated the exposure-response relationship between ambient temperature and hand, foot, and mouth disease (HFMD), whereas very little concern has been to the lag-response relationship and related key time points. OBJECTIVES: We aimed to clarify the temporal characteristics of the lag-response relationship between ambient temperature and HFMD and how they may vary spatially. METHODS: We retrieved the daily time series of meteorological variables and HFMD counts for 143 cities in mainland China between 2009 and 2014. We estimated the city-specific lag-response curve between ambient temperature and HFMD and related key time points by applying common distributed lag nonlinear models (DLNM) and Monte Carlo simulation methods. Then, we pooled the city-specific estimates by performing a meta-regression with the city-specific characteristics as meta-predictors to explain the potential spatial heterogeneity. RESULTS: We found a robust lag pattern between temperature and HFMD for different levels of temperatures. The temporal change of risk obtained its maximum value on the current day but dropped sharply thereafter and then rebounded to a secondary peak, which implied the presence of a harvesting effect. By contrast, the estimation of key time points showed substantial heterogeneity, especially at high temperature (the I2 statistics ranged from 47% to 80%). With one unit increase in the geographic index, the secondary peak would arrive 0.37 (0.02, 0.71) days later. With one unit increase in the economic index and climatic index, the duration time of the lag-response curve would be lengthened by 0.36 (0.1, 0.62) and 0.92 (0.54, 1.29) days, respectively. CONCLUSION: Our study examined the lag pattern and spatial heterogeneity of the lag-response relationship between temperature and HFMD. Those findings gave us new insights into the complex association and the related mechanisms between weather and HFMD and important information for weather-based disease early warning systems.

Area-specific economic status should be regarded as a vital factor affecting the occurrence, development and outcome of cervical cancer.

For patients with cervical cancer, despite the incidence and mortality rates have been declining in recent years, due to its huge population base, cervical cancer has always been a serious public health problem. Our research placed emphasis on the indices greatly associated with overall area-specific social economic status, making up for the defects of traditional research which only pay attention to the situation of some specific disease or patients' individual social status. A total of 39160 women identified cervical cancer were concluded in our study from the Surveillance, Epidemiology, and End Results (SEER) 18 Program data between 1980 and 2014. With improving the area-specific social economic factors in recent years, the occurrence and prognosis of cervical cancer showed different variation patterns respectively. Some states like California and Georgia for their better economic status and more healthcare investment by local medical institution, population there showed a lower prevalence, incidence, more timely diagnosis, effective treatment, and better prognosis. According to our study, we aimed to give a scientific interpretation on how the area-specific social economic factors affect the disease situation at the macro level and help local medical institution make advisable decisions for controlling cervical cancer.

The spatial heterogeneity of the associations between relative humidity and pediatric hand, foot and mouth disease: Evidence from a nation-wide multicity study from mainland China.

BACKGROUND: Hand, foot, and mouth disease (HFMD) remains a serious health threat to young children in East and Southeast Asia. The humidity is crucial for the survival of enterovirus, but the evidence of the humidity-HFMD association is inconsistent. In this study we investigated the spatial heterogeneity of humidity-HFMD associations and related effect modifiers. METHODS: We retrieved the daily surveillance data of childhood HFMD counts and meteorological variables from 143 cities in mainland China between 2009 and 2014 and then adopted a three-stage time series analysis. We first fitted a common distributed lag nonlinear model (DLNM) for each of the 143 cities separately to obtain the city-specific estimates of humidity-HFMD association. Then, we pooled the city-specific estimates through multivariate meta-regression with city-level characteristics as potential effect modifiers to study the reasons for heterogeneity. Finally, we applied a region-specific analysis to verify our findings and to better visualize our results. RESULTS: We found that the overall pooled humidity-HFMD relationship was shown as an approximately U-shaped curve with substantial spatial heterogeneity (I2 = 77.8%). Taking the reference relative humidity as 70%, the minimum relative risk (RR) was obtained at 45% with a value of 0.83 (0.79, 0.87), while the maximum RR was found to be at both 20% and over 85% separately with a value of 1.10 (1.05, 1.15). The spatial heterogeneity can be well explained by the climatic, social characteristics and terrains among cities. The modification effects can be roughly classified into two types, including change in the overall slope and the shape of the curve. CONCLUSIONS: Due to substantial spatial heterogeneity, caution should be taken when interpreting the weather-HFMD association in a single-site study and to avoid generalizing its findings to another site. Our study also implied the existence of interactions among meteorological factors given that climatic factors can modify the weather-HFMD association.

The effect of NLRP inflammasome on the regulation of AGEs-induced inflammatory response in human periodontal ligament cells.

BACKGROUND AND OBJECTIVE: Diabetes influences the frequency and development of periodontitis. Inflammation of human periodontal ligament cells (HPDLCs) participates in this pathologic process. Hence, this study aims to explore whether advanced glycation end products (AGEs), by-products of diabetes, could exaggerate inflammation induced by muramyl dipeptide (MDP) in HPDLCs, and whether nucleotide-binding oligomerization domain-like receptors (NLRs) signaling pathway was involved. MATERIAL AND METHODS: Human periodontal ligament cells were pre-treated with 100 µg/mL AGEs for 24 hours and stimulated with 10 µg/mL MDP for 24 hours. IL-6, IL-1ß, and RAGE were detected, and the activation of NF-κB signaling pathway was observed. The expression of NLRs was evaluated with or without silencing RAGE or blocking NF-κB pathway under AGEs stimulation. Statistical analyses were performed by using independent sample t test. RESULTS: Advanced glycation end products induced significant increase of inflammatory cytokines in HPDLCs (P < 0.05). Results of western blot (WB) showed that after 45 minutes stimulation of AGEs, p-p65/p65 ratio peaked; AGEs promoted the expression of NLRP1, NLRP3, and apoptosis-associated speck-like protein containing a CARD (ASC). After silencing RAGE or blocking NF-κB pathway, the up-regulation of NLRs protein caused by AGEs was attenuated. Additionally, AGEs pre-treatment could enhance the inflammatory response of MDP and the expression of NLRs, which were demonstrated by more expression of IL-6, IL-1ß, NOD2, NLRP1, NLRP3, and ASC. CONCLUSION: Advanced glycation end products induced inflammatory response in HPDLCs via NLRP1-inflammasome and NLRP3-inflammasome activation in which NF-κB signal pathway was involved. Besides, AGEs promoted the inflammatory response of MDP via NOD2, NLRP1-inflammasome, and NLRP3-inflammasome.

EDTA Enhances Stromal Cell-derived Factor 1α-induced Migration of Dental Pulp Cells by Up-regulating Chemokine Receptor 4 Expression.

INTRODUCTION: In regenerative endodontics, irrigation is an important step to ensure the success of treatment. EDTA as a common irrigant has been recommended in the American Associations of Endodontists guidelines. It has been suggested that EDTA-treated dentin slices could increase the attachment, differentiation, and migration of dental pulp stem cells. However, no information is available about the effect of EDTA on the migration of dental pulp cells (DPCs). The aim of this study was to explore how EDTA affects the migration of DPCs. METHODS: Cells were obtained from human premolars or third molars, and cell counting kit-8 was used to evaluate the influence of EDTA on cell proliferation at various concentrations and time points. Real-time polymerase chain reaction was used to detect the messenger RNA expression levels of transforming growth factor beta (TGF-ß) and chemokine receptor 4 (CXCR4). Protein expression was tested by the enzyme-linked immunosorbent assay and Western blot, respectively. In addition, the transwell migration assay was performed to investigate the role of EDTA pretreatment in stromal cell-derived factor 1α (SDF-1α)-induced DPC migration. RESULTS: Stimulation with 12% EDTA enhanced SDF-1α-induced migration of DPCs. Both expressions of TGF-ß1 and CXCR4 were increased by 12% EDTA in a time-dependent manner. After silencing CXCR4, EDTA-enhanced migration was decreased. Furthermore, the transcriptional regulation of CXCR4 by EDTA was found to be mediated by TGF-ß1/ERK1/2 and TGF-ß1/Smad2/3 signal pathways. CONCLUSIONS: Our results showed that 12% EDTA could promote SDF-1α-induced migration of DPCs by up-regulating CXCR4 expression in which TGF-ß1 signal pathways were involved.

Jumonji domain-containing protein 3 regulates the early inflammatory response epigenetically in human periodontal ligament cells.

OBJECTIVE: To investigate the role of the histone 3 lysine 27 trimethylation (H3K27me3) demethylase Jumonji domain-containing protein 3 (Jmjd3) in the epigenetic regulation of the inflammatory response in human periodontal ligament cells (HPDLs). DESIGN: HPDLs were stimulated with lipopolysaccharide from E. coli. The expression of Jmjd3 in HPDLs was examined by quantitative real-time polymerase chain reaction (Q-PCR), Western Blot and immunofluorescent staining. Potential target genes were selected by silencing Jmjd3 and were confirmed by Chromatin Immunoprecipitation (ChIP). RESULTS: Q-PCR, Western Blot and immunofluorescent staining revealed that the expression of Jmjd3 was increased in inflamed HPDLs. Knockdown of Jmjd3 led to the suppression of inflammation-induced up-regulation of interleukin-6 and interleukin-12. Moreover, ChIP assays demonstrated that Jmjd3 was recruited to the promoters of interleukin-6 and interleukin-12b and this recruitment was associated with decreased levels of trimethylated histone 3 lysine 27 (H3K27). CONCLUSIONS: It was concluded that Jmjd3 regulated the activation of interleukin-6 and interleukin-12b in the early inflammatory response of HPDLs via demethylation of H3K27me3 at promoters. This molecular event may play an important role in the regulation of the inflammatory response in HPDLs.

Polymorphisms in four microRNAs and risk of oral squamous cell cancer: a meta-analysis.

OBJECTIVES: Single nucleotide polymorphisms in microRNAs (microRNA-196a2 rs11614913, microRNA-146a rs2910164, microRNA-149 rs2292832 and microRNA-499 rs3746444) have been inconsistently associated with risk for oral squamous cell cancer (OSCC). This meta-analysis aimed to assess the correlation between microRNA polymorphisms and susceptibility to OSCC. MATERIALS AND METHODS: Free words were used to search for the relevant studies without language limitations in electronic databases including PubMed, Embase, Web of Science and SCOPUS through June 15, 2017. Odds ratios (ORs) were calculated to investigate the effects of microRNA polymorphisms on oral cancer risk. RESULTS: Eleven studies were included. Analysis under the recessive model of microRNA-146a (CC vs GG+CG) showed significant differences (ORs = 0.874, P = 0.041). The G allele and the GG genotype of microRNA-499 were associated with OSCC risk (ORs >1, P < 0.05). MicroRNA-196a2 rs11614913 and microRNA-149 polymorphisms appeared to have no relationship with OSCC risk (P > 0.05). In the sensitivity analysis, there was a significant association between the TT genotype of microRNA-196a2 and OSCC risk (TT vs TC + CC, ORs < 1, P < 0.05). CONCLUSIONS: There may be no significant relationship between microRNA-149 polymorphisms and OSCC risk, and the CC genotype of microRNA-146a may have protective effects against oral cancer. However, the G allele and the GG genotype of microRNA-499 may increase OSCC risk.