Bacterial Community Modifies Host Genetics Effect on Early Childhood Caries.

By age 5, approximately one-fifth of children have early childhood caries (ECC). Both the oral microbiome and host genetics are thought to influence susceptibility. Whether the oral microbiome modifies genetic susceptibility to ECC has not been tested. We test whether the salivary bacteriome modifies the association of a polygenic score (PGS, a score derived from genomic data that summarizes genetic susceptibility to disease) for primary tooth decay on ECC in the Center for Oral Health Research in Appalachia 2 longitudinal birth cohort. Children were genotyped using the Illumina Multi-Ethnic Genotyping Array and underwent annual dental examinations. We constructed a PGS for primary tooth decay using weights from an independent, genome-wide association meta-analysis. Using Poisson regression, we tested for associations between the PGS (high versus low) and ECC incidence, adjusting for demographic characteristics (n = 783). An incidence-density sampled subset of the cohort (n = 138) had salivary bacteriome data at 24 mo of age. We tested for effect modification of the PGS on ECC case status by salivary bacterial community state type (CST). By 60 mo, 20.69% of children had ECC. High PGS was not associated with an increased rate of ECC (incidence rate ratio, 1.09; 95% confidence interval [CI], 0.83-1.42). However, having a cariogenic salivary bacterial CST at 24 mo was associated with ECC (odds ratio [OR], 7.48; 95% CI, 3.06-18.26), which was robust to PGS adjustment. An interaction existed between the salivary bacterial CST and the PGS on the multiplicative scale (P = 0.04). The PGS was associated with ECC (OR, 4.83; 95% CI, 1.29-18.17) only among individuals with a noncariogenic salivary bacterial CST (n = 70). Genetic causes of caries may be harder to detect when not accounting for cariogenic oral microbiomes. As certain salivary bacterial CSTs increased ECC risk across genetic risk strata, preventing colonization of cariogenic microbiomes would be universally beneficial.

[Intestinal microbiota: a new target for early warning, prognosis prediction, prevention and treatment of colorectal cancer].

As the main composition of the gut microbiota, intestinal microbiota directly or indirectly regulate epigenetic modifications, a variety of metabolisms, mucosal and even systemic immune functions of the host, and exert a great influence on the biological behavior of colorectal cancer. Although the detailed mechanism of some enterobacteria involved in the progression of colorectal cancer remains unclear, they are possible markers for early warning and prognostic prediction of colorectal cancer, as well as potential targets for treatment and prevention, which provides us with new hope for the prevention and treatment of colorectal cancer.

[Research progress of microvascular invasion in hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is a kind of highly aggressive tumor of the digestive system. Several studies have confirmed that microvascular invasion (MVI) is an independent risk factor for early recurrence and poor prognosis of HCC after surgery. Currently, pathological examination is the gold standard for diagnosing MVI. This paper summarizes concept, prognosis, preoperative prediction and treatment plan based on literature review of MVI in HCC.

Global trends of cropland phosphorus use and sustainability challenges.

To meet the growing food demand while addressing the multiple challenges of exacerbating phosphorus (P) pollution and depleting P rock reserves1-15, P use efficiency (PUE, the ratio of productive P output to P input in a defined system) in crop production needs to be improved. Although many efforts have been devoted to improving nutrient management practices on farms, few studies have examined the historical trajectories of PUE and their socioeconomic and agronomic drivers on a national scale1,2,6,7,11,16,17. Here we present a database of the P budget (the input and output of the crop production system) and PUE by country and by crop type for 1961-2019, and examine the substantial contribution of several drivers for PUE, such as economic development stages and crop portfolios. To address the P management challenges, we found that global PUE in crop production must increase to 68-81%, and recent trends indicate some meaningful progress towards this goal. However, P management challenges and opportunities in croplands vary widely among countries.

Is simple reaction time or choice reaction time an indicator of all-cause mortality or CVD mortality?

OBJECTIVES: Simple reaction time (SRT) and choice reaction time (CRT) have been shown to be good indicators for quantitatively assessing the level of human cognitive impairment, but these parameters have also been linked to the risk of human death. This study aimed to quantitatively assess the independent predictive value of SRT or CRT for all-cause mortality or cardiovascular disease (CVD) mortality by conducting a meta-analysis of prospective studies. STUDY DESIGN: The study design of this study is a prospective cohort study. METHODS: We conducted a meta-analysis by combining hazard ratios (HRs) and 95% confidence intervals (95% CIs) of SRT or CRT with all-cause mortality or CVD mortality in healthy community residents aged 18 and over. Heterogeneity was evaluated by using Q statistics and Cochrane's I2 statistics. RESULTS: A total of seven prospective studies that examined all-cause mortality and CVD mortality were included. The pooled HR of all-cause mortality in SRT was 1.099 (1.065-1.134, I2 = 11.9%), and an increased risk of CVD mortality was associated with lower SRT (HR = 1.186, 95% CI = 1.137-1.236; I2 = 52.4%). Similarly, the pooled HR of all-cause mortality in CRT was 1.140 (95% CI = 1.085-1.197, I2 = 33.7%). However, lower CRT was not statistically associated with an increased risk of CVD mortality. CONCLUSION: SRT may be a predictor of all-cause-mortality and CVD mortality, and CRT is significantly associated with an increased risk of all-cause mortality.

[Application of BRAF in the diagnosis and treatment of thyroid papillary carcinoma].

Thyroid cancer is the most common endocrine malignancy, and thyroid carcinoma (PTC) has the highest incidence rate, accounts for about 85%~90% of thyroid carcinoma. There are many markers of PTC, such as murine sarcoma viral oncogene homolog B1 (BRAF), telomerase reverse transcriptase, Ki-67, microRNA-146b, PDZ and LIM domain 5 (PDLIM5). Among them, BRAF plays an important role in the carcinogenesis, development and prognosis of PTC. This article summarizes the research progress of BRAF signaling pathway, its role in the carcinogenesis, development and prognosis of PTC, its clinical correlation with the clinical pathological characteristics of PTC, and its application in the diagnosis and treatment of PTC to provide the references to readers.

In Situ Oxygen Generation Enhances the SCAP Survival in Hydrogel Constructs.

Prolonged and severe hypoxia is the main cause of death of transplanted cells prior to the establishment of functional circulation. In situ generation of oxygen by oxygen-producing scaffolds-a unique solution that could produce and deliver oxygen to the adjacent cells independently of blood perfusion-has attracted considerable attention to enhance the survivability of the transplanted cells. However, the application of oxygen-generating scaffolds for facilitating cell survival in pulp-like tissue regeneration is yet to be explored. In this study, gelatin methacryloyl (GelMA)-a biocompatible scaffolding material that closely mimics the native extracellular matrix and is conducive to cell proliferation and differentiation-was used to fabricate oxygen-generating scaffolds by loading various concentrations of CaO2. The CaO2 distribution, topography, swelling, and pore size of CaO2-GelMA hydrogels were characterized in detail. The release of O2 by the scaffold and the viability, spreading, and proliferation of stem cells from apical papilla (SCAPs) encapsulated in the GelMA hydrogels with various concentrations of CaO2 under hypoxia were evaluated. In addition, cellular constructs were engineered into root canals, and cell viability within the apical, middle, and coronal portions was assessed. Our findings showed that 0.5% CaO2-GelMA was sufficient to supply in situ oxygen for maintaining the embedded SCAP viability for 1 wk. Furthermore, the 0.5% CaO2-GelMA hydrogels improved the survivability of SCAPs within the coronal portion of the engineered cellular constructs within the root canals. This work demonstrated that 0.5% CaO2-GelMA hydrogels offer a potential promising scaffold that enhances survival of the embedded SCAPs in endodontic regeneration.

Insulator-metal transition induced by electric voltage in a ruthenate Mott insulator.

We report the observation of electric-voltage induced insulator-metal phase transition in a ruthenate Mott insulator Ca3(Ru0.9Ti0.1)2O7. We show that the electric field effect dominates and leads to a sharp phase transition at measurement temperatures far below the Mott transition, whereas the thermal effect becomes more significant and broadens the phase transition as the measurement temperature approaches the insulator-metal transition. The electric field induced insulator-metal transition is presumably attributed to the avalanche breakdown of the correlated insulating state when driven out of equilibrium. This work highlights the strategy of using electric voltage to control the phase transition of this system in addition to other nonthermal parameters such as magnetic field and pressure reported previously.

Dietary alanyl-glutamine improves growth performance of weaned piglets through maintaining intestinal morphology and digestion-absorption function.

Alanyl-glutamine (Ala-Gln), a highly soluble and stable glutamine dipeptide, is known to improve gut integrity and function. The aim of this study was to evaluate whether dietary Ala-Gln supplementation could improve growth performance, intestinal development and digestive-absorption function in weaned piglets. A total of 100 purebred Yorkshire piglets weaned at 21 days of age were assigned randomly to four dietary treatment groups and fed a basal diet (control group) or a basal diet containing 0.15%, 0.30% and 0.45% Ala-Gln, respectively. Compared with the control group, piglets fed the Ala-Gln diets had higher average daily gain and lower feed : gain and diarrhea rate (P < 0.05). Moreover, dietary Ala-Gln supplementation increased villous height and villous height : crypt depth ratio in duodenum and jejunum (P < 0.05), as well as the activities of maltase and lysozyme in jejunum mucosa (P < 0.05). In addition, a decrease in serum diamine oxidase activity and crypt depth in duodenum and jejunum was observed in piglets fed the Ala-Gln diets (P < 0.05). Serum cytosolic phospholipase A2 (cPLA2) concentration and gene expression of cPLA2, Na+-dependent glucose transporter 1, glucose transporter 2 and peptide transporter 1 in jejunum were increased by feeding Ala-Gln diets relative to control diet (P < 0.05). These results indicated that feeding Ala-Gln diet has beneficial effects on the growth performance of weaned piglets, which associated with maintaining intestinal morphology and digestive-absorption function.

[The curative effect of manual reduction combined with vestibular rehabilitation exercise in the treatment of benign paroxysmal positional vertigo].

Objective:To investigate the effect of vestibular rehabilitation exercise combined with manual reduction in the treatment of benign paroxysmal positional vertigo（BPPV）. Method:A total of 186 patients with benign paroxysmal positional vertigo were selected and randomly divided into experimental group and control group . The control group was treated with manual reduction, while the experimental group was treated with manual reduction combined with vestibular rehabilitation exercises. Patients with posterior semicircular canal BPPV carried out Brandt-Daroff exercises, while patients with horizontal semicircular canal BPPV carried out Cawthorne-Cooksey exercises and position restriction. To analyze the clinical curative effect, DHI score, residual dizziness and recurrence of the two groups. Result:There was no significant difference in total efficiency rate and DHI score between the two groups at the first diagnosis（P>0.05）. After 1 week, 2 weeks and 1 month of follow-up, the total efficiency rate of the experimental group were 90.3%, 91.4% and 93.5% respectively, which were significantly higher than those of the control group（P<0.05）. Synchronously, the scores of DHI in experimental group were respectively 14.33±5.71, 12.25±4.98 and 9.45±3.70, which were significantly lower than the control group（P<0.05）. For the experimental group, in the first diagnosis, 1 week, 2 weeks and 1 month after follow-up, residual dizziness patients were 29 cases, 13 cases, 8 cases and 0 cases. The mean duration of residual dizziness was （5.86±4.71） days, which was significantly lower than that in the control group（P<0.05）. One month after follow-up, the recurrence of patients in the experimental group were 5 cases, while the control group were 11 cases, significant difference between the two groups（χ²=4.704, P=0.030）. Conclusion:Manual reduction combined with vestibular rehabilitation exercise can significantly improve the therapeutic effect of BPPV, ameliorate the residual dizziness symptoms and reduce the recurrence rate, meanwhile improve the balance function and quality life of patients.

Circular RNA_LARP4 is lower expressed and serves as a potential biomarker of ovarian cancer prognosis.

OBJECTIVE: Circular RNAs (circRNAs) have been identified as important regulators in regulating cancer progression. The study aims to investigate the expression of circular RNA_LARP4 (circ LARP4) and clinical significance in ovarian cancer (OC). PATIENTS AND METHODS: The expression of circ LARP4 was detected in a total of 78 paired ovarian cancer tissue and adjacent normal tissue samples using quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) analyses. The chi-square test was used to assess the association between expression of circLARP4 and clinical-pathological parameters. Survival plot was evaluated using the Kaplan-Meier method. The multivariate Cox analysis model was used for tumor prognosis analysis. RESULTS: We identified that circLARP4 expression was significantly down-regulated in ovarian cancer tissues compared with corresponding controls. Furthermore, we found that circLARP4 expression was significantly associated with International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastases. Lower circLARP4 expression was associated with poor prognosis of OC patients. Moreover, multivariate Cox analysis showed that lower circLARP4 was an independent risk for OC prognosis. CONCLUSIONS: These results indicated that circLARP4 expression was lower and highlighted that circLARP4 was identified as a potential biomarker of ovarian cancer prognosis.

The LEPR K109R and Q223R Might Contribute to the Risk of NAFLD: A Meta-Analysis.

BACKGROUND: Leptin and insulin resistance have been pointed out to play a role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Increasing genes were shown to be associated with the risk of NAFLD. OBJECTIVE: The study aimed to investigate the genetic association between two leptin receptor (LEPR) polymorphisms (Q223R and K109R) and the NAFLD risk. METHODS: Studies were retrieved and included by using PubMed, Web of Science, the Cochrane Library databases, Chinese National Knowledge Infrastructure (CNKI) and EMBASE database. Genetic associations were assessed with pooled odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Five case-control studies with 1711 NAFLD patients and 1732 healthy controls were included in this meta-analysis. The K109R was significantly associated with NAFLD in allelic model in Southeast Asian subgroup (p=0.01, OR=0.59, 95% CI [0.39- 0.90]), but not in Chinese subgroup (p=0.24, OR=1.10, 95% CI [0.94-1.29]). The Q223R was significantly associated with NAFLD in both allelic and recessive models (allelic model: p<0.001, OR=0.57, 95% CI [0.50-0.65]; recessive model: p=0.001, OR=0.67, 95% CI [0.52-0.85]). However, subgroup analysis showed that the significant association between Q223R and NAFLD in allelic model cannot be found in Southeast Asians subgroup (p=0.07, OR=0.67, 95% CI [0.52-0.85]). CONCLUSION: LEPR K109R might be a susceptible factor for NAFLD in Southeast Asian population. And LEPR Q223R might be a susceptible factor for NAFLD in Chinese population.

Thickness evolution of transport properties in exfoliated Fe1+y Te nanoflakes.

We report the evolution of transport properties in exfoliated Fe1+y Te (y = 0.04) nanoflakes of various thickness. In contrast to the sharp semiconducting-to-metallic phase transition observed in both bulk and thicker flakes, this transition becomes broadened for flakes with an intermediate thickness followed by the appearance of a superconducting-like feature upon further cooling. With the thickness further decreased, the flakes exhibit insulating transport behavior with significantly enhanced positive magnetoresistance, which can be explained using a variable range hopping mechanism, suggesting the nature of a highly disordered 2D system.

Field-induced magnetic phase transitions and memory effect in bilayer ruthenate Ca3Ru2O7 with Fe substitution.

Bilayer ruthenate Ca3(Ru1-x Fe x )2O7 (x = 0.05) exhibits an incommensurate magnetic soliton lattice driven by the Dzyaloshinskii-Moriya interaction. Here we report complex field-induced magnetic phase transitions and memory effect in this system via single-crystal neutron diffraction and magnetotransport measurements. We observe first-order incommensurate-to-commensurate magnetic transitions upon applying the magnetic field both along and perpendicular to the propagation axis of the incommensurate spin structure. Furthermore, we find that the metastable states formed upon decreasing the magnetic field depend on the temperature and the applied field orientation. We suggest that the observed field-induced metastability may be ascribable to the quenched kinetics at low temperature.

Inhibition of TGF-ß Signaling in SHED Enhances Endothelial Differentiation.

Low efficiency of deriving endothelial cells (ECs) from adult stem cells hampers their utilization in tissue engineering studies. The purpose of this study was to investigate whether suppression of transforming growth factor beta (TGF-ß) signaling could enhance the differentiation efficiency of dental pulp-derived stem cells into ECs. We initially used vascular endothelial growth factor A (VEGF-A) to stimulate 2 dental pulp-derived stem cells (dental pulp stem cells and stem cells from human exfoliated deciduous teeth [SHED]) and compared their differentiation capacity into ECs. We further evaluated whether the vascular endothelial growth factor receptor I (VEGF-RI)-specific ligand placental growth factor-1 (PlGF-1) could mediate endothelial differentiation. Finally, we investigated whether the TGF-ß signaling inhibitor SB-431542 could enhance the inductive effect of VEGF-A on endothelial differentiation, as well as the underlying mechanisms involved. ECs differentiated from dental pulp-derived stem cells exhibited the typical phenotypes of primary ECs, with SHED possessing a higher endothelial differentiation potential than dental pulp stem cells. VEGFR1-specific ligand-PLGF exerted a negligible effect on SHED-ECs differentiation. Compared with VEGF-A alone, the combination of VEGF-A and SB-431542 significantly enhanced the endothelial differentiation of SHED. The presence of SB-431542 inhibited the phosphorylation of Suppressor of Mothers Against Decapentaplegic 2/3 (SMAD2/3), allowing for VEGF-A-dependent phosphorylation and upregulation of VEGFR2. Our results indicate that the combination of VEGF-A and SB-431542 could enhance the differentiation of dental pulp-derived stem cells into endothelial cells, and this process is mediated through enhancement of VEGF-A-VEGFR2 signaling and concomitant inhibition of TGF-ß-SMAD2/3 signaling.

Unusual interlayer quantum transport behavior caused by the zeroth Landau level in YbMnBi2.

Relativistic fermions in topological quantum materials are characterized by linear energy-momentum dispersion near band crossing points. Under magnetic fields, relativistic fermions acquire Berry phase of π in cyclotron motion, leading to a zeroth Landau level (LL) at the crossing point, a signature unique to relativistic fermions. Here we report the unusual interlayer quantum transport behavior resulting from the zeroth LL mode observed in the time reversal symmetry breaking type II Weyl semimetal YbMnBi2. The interlayer magnetoresistivity and Hall conductivity of this material are found to exhibit surprising angular dependences under high fields, which can be well fitted by a model, which considers the interlayer quantum tunneling transport of the zeroth LL's Weyl fermions. Our results shed light on the unusual role of zeroth LLl mode in transport.The transport behavior of the carriers residing in the lowest Landau level is hard to observe in most topological materials. Here, Liu et al. report a surprising angular dependence of the interlayer magnetoresistivity and Hall conductivity arising from the lowest Landau level under high magnetic field in type II Weyl semimetal YbMnBi2.

[Prognostic value of modified lung ultrasound aeration loss score in shock patient in intensive care unit].

Objective: To investigate the prognostic value of modified lung ultrasound aeration loss score(mLUS) in shock patients in intensive care unit(ICU). Methods: This was a prospective study.Shock patients who were admitted to ICU from April 2016 to August 2016 were eligible; 90 consecutive shock patients were enrolled.Chest ultrasound examination were done within the first 6 hours after included. The mLUS and other ultrasound variables were recorded as well as the clinical data and the outcome. Data has been analyzed, and a bivariate logistic regression model was established to identify the correlation between mLUS on admission and the ICU mortality. Results: The mean APACHE Ⅱ score, lactate, mLUS were significantly increased in non-survivors while the PaO(2)/FiO(2) was decreased in these patients(P=0.048, 0.000, 0.048, 0.000, 0.004). The univariate analysis revealed that the above variables were significantly related to ICU mortality.The multivariate analysis demonstrated that mLUS are the independent risk factors of ICU mortality as well as the lactate(P=0.045, 0.006; AUC=0.733, 0.793, respectively). Conclusion: Modified lung ultrasound aeration loss score can predict the outcome of shock patients in ICU.

Isoindoline nitroxide-labeled porphyrins as potential fluorescence-suppressed spin probes.

A series of isoindoline nitroxide-labeled porphyrins were synthesized by the reaction of 5-phenyldipyrromethane and 5-(4'-carboethoxy-methyleneoxyphenyl)dipyrromethane with 5-formyl-1,1,3,3-tetramethylisoindolin-2-yloxyl (FTMIO) using the Lindsey method. The corresponding water-soluble spin-labeled porphyrins were also prepared. Subsequently, these compounds were characterized and their in vitro properties were evaluated. The electrochemical assay demonstrated that these isoindoline nitroxide-labeled porphyrins had similar electrochemical and redox properties to 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO). The electron paramagnetic resonance test showed that these porphyrins exhibited hyperfine splittings and characteristic spectra of CTMIO with typical nitroxide g-values and nitrogen isotropic hyperfine coupling constants. The in vitro cytotoxicity assay indicated that these porphyrins possessed low cytotoxicity to human renal tubular epithelial 293T cells (normal cells) and human hepatoma HepG2 cells (tumor cells). Fluorescence spectroscopy revealed that free base isoindoline nitroxide-labeled porphyrins exhibited fluorescence suppression characteristic of nitroxide-fluorophore systems. In vitro fluorescene imaging demonstrated that the reduced isoindoline nitroxide-labeled porphyrins eliminated fluorescence suppression and displayed strong red fluorescence imaging in HepG2 cells. Thus these isoindoline nitroxide-labeled porphyrins may be considered potentially as biological spin probes for fluorescence imaging and EPR spectroscopy.

Mitochondrial biogenesis is decreased in skeletal muscle of pig fetuses exposed to maternal high-energy diets.

Mitochondria plays an important role in the regulation of energy homeostasis. Moreover, mitochondrial biogenesis accompanies skeletal myogenesis, and we previously reported that maternal high-energy diet repressed skeletal myogenesis in pig fetuses. Therefore, the aim of this study was to evaluate the effects of moderately increased maternal energy intake on skeletal muscle mitochondrial biogenesis and function of the pig fetuses. Primiparous purebred Large White sows were allocated to a normal energy intake group (NE) as recommended by the National Research Council (NRC) and a high energy intake group (HE, 110% of NRC recommendations). On day 90 of gestation, fetal umbilical vein blood and longissimus (LM) muscle were collected. Results showed that the weight gain of sows fed HE diet was higher than NE sows on day 90 of gestation (P<0.05). Maternal HE diet increased fetal umbilical vein serum triglyceride and insulin concentrations (P<0.05), and tended to increase the homeostasis model assessment index (P=0.08). Furthermore, HE fetuses exhibited increased malondialdehyde concentration (P<0.05), and decreased activities of antioxidative enzymes (P<0.05) and intracellular NAD+ level (P<0.05) in LM muscle. These alterations in metabolic traits of HE fetuses were accompanied by reduced mitochondrial DNA amount (P<0.05) and down-regulated messenger RNA expression levels of genes responsible for mitochondrial biogenesis and function (P<0.05). Our results suggest that moderately increased energy supply during gestation decreases mitochondrial biogenesis, function and antioxidative capacity in skeletal muscle of pig fetuses.