Two C-terminal isoforms of Aplysia tachykinin-related peptide receptors exhibit phosphorylation-dependent and phosphorylation-independent desensitization mechanisms.

Diversity, a hallmark of G protein-coupled receptor (GPCR) signaling, partly stems from alternative splicing of a single gene generating more than one isoform for a receptor. Additionally, receptor responses to ligands can be attenuated by desensitization upon prolonged or repeated ligand exposure. Both phenomena have been demonstrated and exemplified by the deuterostome tachykinin signaling system, although the role of phosphorylation in desensitization remains a subject of debate. Here, we describe the signaling system for tachykinin-related peptides (TKRPs) in a protostome, mollusk Aplysia. We cloned the Aplysia TKRP precursor, which encodes three TKRPs (apTKRP-1, apTKRP-2a, and apTKRP-2b) containing the FXGXR-amide motif. In situ hybridization and immunohistochemistry showed predominant expression of TKRP mRNA and peptide in the cerebral ganglia. TKRPs and their posttranslational modifications were observed in extracts of central nervous system ganglia using mass spectrometry. We identified two Aplysia TKRP receptors (apTKRPRs), named apTKRPR-A and apTKRPR-B. These receptors are two isoforms generated through alternative splicing of the same gene and differ only in their intracellular C termini. Structure-activity relationship analysis of apTKRP-2b revealed that both C-terminal amidation and conserved residues of the ligand are critical for receptor activation. C-terminal truncates and mutants of apTKRPRs suggested that there is a C-terminal phosphorylation-independent desensitization for both receptors. Moreover, apTKRPR-B also exhibits phosphorylation-dependent desensitization through the phosphorylation of C-terminal Ser/Thr residues. This comprehensive characterization of the Aplysia TKRP signaling system underscores the evolutionary conservation of the TKRP and TK signaling systems, while highlighting the intricacies of receptor regulation through alternative splicing and differential desensitization mechanisms.

A receptor-like protein acts as a specificity switch for the regulation of stomatal development.

Stomata are microscopic openings that allow for the exchange of gases between plants and the environment. In Arabidopsis, stomatal patterning is specified by the ERECTA family (ERf) receptor kinases (RKs), the receptor-like protein (RLP) TOO MANY MOUTHS (TMM), and EPIDERMAL PATTERNING FACTOR (EPF) peptides. Here we show that TMM and ER or ER-LIKE1 (ERL1) form constitutive complexes, which recognize EPF1 and EPF2, but the single ERfs do not. TMM interaction with ERL1 creates a binding pocket for recognition of EPF1 and EPF2, indicating that the constitutive TMM-ERf complexes function as the receptors of EPF1 and EPF2. EPFL9 competes with EPF1 and EPF2 for binding to the ERf-TMM complex. EPFL4 and EPFL6, however, are recognized by the single ERfs without the requirement of TMM. In contrast to EPF1,2, the interaction of EPFL4,6 with an ERf is greatly reduced in the presence of TMM. Taken together, our data demonstrate that TMM dictates the specificity of ERfs for the perception of different EPFs, thus functioning as a specificity switch for the regulation of the activities of ERfs.

Glucose-induced RYBP suppresses tumor cell aerobic glycolysis and migration.

RYBP (Ring 1 and YY1 binding protein) has been frequently reported to play an important role during body development, stem cell differentiation, apoptosis and tumorigenesis, but whether RYBP carries out additional functions remains mysterious. Here, we demonstrated that RYBP protein levels elevate with increasing glucose concentration in cell culture medium in human tumorigenic cell lines, but an opposite trend was observed in non-tumorigenic cells. Mechanistic exploration disclosed that glucose inhibits polyubiquitination and proteasomal degradation, leading to RYBP stabilization in tumor cells. Further study showed that RYBP inhibits the glycolysis of tumor cells, as both extracellular acidification rate (ECAR) and lactate production increase when RYBP is knocked down, and decrease when RYBP is over-expressed, and this effect is unrelated to the glucose uptake ability of tumor cells. The functional study showed that RYBP is involved in the regulation of glucose on tumor cell migration. Compared to low glucose culture and their wildtypes, high glucose significantly enhanced tumor cell migration in RYBP knockdown or knockout tumor cells. Taken together, our current study uncovered a previously unknown function of RYBP in tumor metabolism, and this finding will enhance the exploration of the interplay between RYBP and nutrients during tumor cell metabolic reprogramming.

Hepatocyte growth factor is protective in early stage but bone-destructive in late stage of experimental periodontitis.

BACKGROUND AND OBJECTIVE: Clinical studies found high levels of hepatocyte growth factor (HGF) expression in patients with periodontitis. Studies suggest that HGF plays an important role in periodontitis, is involved in inflammation, and modulates alveolar bone integrity in periodontitis. This study aims to investigate the effects and mechanisms of HGF in the progression of experimental periodontitis. METHODS: We used silk thread ligation to induce periodontitis in HGF-overexpressing transgenic (HGF-Tg) and wild-type C57BL/6J mice. The effects of HGF overexpression on alveolar bone destruction were assessed by microcomputed tomography imaging at baseline and on days 7, 14, 21, and 28. We analyzed the cytokines (IL-6 and TNF-α) and lymphocytes in periodontitis tissues by enzyme-linked immunosorbent assay and flow cytometry. The effects of HGF on alveolar bone destruction were further tested by quantifying the systemic bone metabolism markers CTXI and PINP and by RNA sequencing for the signaling pathways involved in bone destruction. Western blotting and immunohistochemistry were performed to further elucidate the involved signaling pathways. RESULTS: We found that experimental periodontitis increased HGF production in periodontitis tissues; however, the effects of HGF overexpression were inconsistent with disease progression. In the early stage of periodontitis, periodontal inflammation and alveolar bone destruction were significantly lower in HGF-Tg mice than in wild-type mice. In the late stage, HGF-Tg mice showed higher inflammatory responses and progressively aggravated bone destruction with continued stimulation of inflammation. We identified the IL-17/RANKL/TRAF6 pathway as a signaling pathway involved in the HGF effects on the progression of periodontitis. CONCLUSION: HGF plays divergent effects in the progression of experimental periodontitis and accelerates osteoclastic activity and bone destruction in the late stage of inflammation.

A novel strategy for improving bowel preparation based on social software-enhanced education: A prospective, multicenter, randomized controlled study.

BACKGROUND AND AIM: The compliance and timeliness of oral laxatives have always been the key factors restricting bowel preparation (BP). We have constructed a novel enhanced-educational content and process based on social software (SS) for BP to optimize these issues. METHODS: A multicenter, prospective, randomized controlled study was conducted at 13 hospitals in China from December 2019 to December 2020. A total of 1774 enrollees received standard instructions for BP and were randomly assigned (1:1) to the SS group (SSG) that received a smartphone-based enhanced-education strategy starting 4 h before colonoscopy or the control group (CG). RESULTS: A total of 3034 consecutive outpatient colonoscopy patients were assessed for eligibility, and 1774 were enrolled and randomly assigned. Ultimately, data from 1747 (SSG vs CG: 875 vs 872) enrollees were collected. The BP adequacy rate was 92.22% (95% CI: 90.46-93.98) in the SSG vs 88.05% (95% CI: 85.91-90.18) in the CG (P = 0.005), and the total Boston Bowel Preparation Scale scores (6.89 ± 1.15 vs 6.67 ± 1.15, P < 0.001) of those in the SSG were significantly higher than those in the CG. The average number of polyps detected in the SSG was considerably higher than that in the CG (0.84 ± 2.00 vs 0.53 ± 1.19, P = 0.037), and the average diameter of the polyps was significantly lower than that of the control group (4.0 ± 2.5 vs 4.9 ± 3.7, P < 0.001). CONCLUSIONS: This SS-enhanced education strategy can improve the BP adequacy rate and increase the average number of polyps detected, especially those of small diameter.

Correlations of Serum Retinol-Binding Protein and Stromal Cell-Derived Factor-1 with Renal Function in Patients with Diabetic Kidney Disease.

BACKGROUND: The aim is to investigate the correlations of serum retinol-binding protein (RBP) and stromal cell-derived factor-1 (SDF-1) with renal function in patients with diabetic kidney disease (DKD). METHODS: A total of 438 patients with type 2 diabetes mellitus (T2DM) treated from October 2017 to October 2020 were enrolled in this prospective study and divided into simple T2DM and DKD groups. According to urinary albumin-to-creatinine ratio (UACR), DKD patients were divided into moderate, severe, and nephrotic groups. They were assigned to one of the following categories of estimated glomerular filtration rate (eGFR): G1, G2, G3a, G3b, G4, and G5 stages. The correlations of RBP and SDF-1 with renal function were analyzed. RESULTS: The DKD group had a longer T2DM course and higher RBP, uric acid (UA), blood urea nitrogen (BUN), ß2-microglobulin (ß2-MG), serum creatinine (Scr) levels and UACR, and lower SDF-1 level and eGFR than those of simple T2DM group (p < 0.05). The areas under the receiver operating characteristic curves of RBP and SDF-1 for identifying DKD were 0.903 and 0.868, and the optimal cutoff values were 70.71 mg/L and 5.69 ng/mL, respectively. With increasing urinary albumin and clinical stage, RBP, UA, BUN, ß2-MG and Scr levels and UACR significantly rose, while SDF-1 level and eGFR declined (p < 0.05). In patients with DKD, RBP was correlated positively with UACR, UA, BUN, ß2-MG, and Scr (r = 0.764/0.787/0.693/0.577/0.801, p < 0.0001), and negatively with eGFR (r = -0.782, p < 0.0001). SDF-1 was correlated negatively with UACR, UA, BUN, ß2-MG and Scr (r = -0.744/-0.794/-0.666/-0.605/-0.820, p < 0.0001), and positively with eGFR (r = 0.767, p < 0.0001). The multiple linear regression equation was RBP = 29.852 + 0.007 x UACR + 0.101 x UA + 0.497 x BUN + 0.034 x Scr-0.083 x eGFR (p < 0.001). CONCLUSIONS: RBP and SDF-1 can identify DKD in patients with T2DM, and the degree of renal function damage is correlated positively with RBP and negatively with SDF-1. Elevated levels of UA, BUN, Scr and UACR as well as reduced eGFR are risk factors for evaluating RBP.

Biomimetic MDSCs membrane coated black phosphorus nanosheets system for photothermal therapy/photodynamic therapy synergized chemotherapy of cancer.

Photothermal therapy is favored by cancer researchers due to its advantages such as controllable initiation, direct killing and immune promotion. However, the low enrichment efficiency of photosensitizer in tumor site and the limited effect of single use limits the further development of photothermal therapy. Herein, a photo-responsive multifunctional nanosystem was designed for cancer therapy, in which myeloid-derived suppressor cell (MDSC) membrane vesicle encapsulated decitabine-loaded black phosphorous (BP) nanosheets (BP@ Decitabine @MDSCs, named BDM). The BDM demonstrated excellent biosafety and biochemical characteristics, providing a suitable microenvironment for cancer cell killing. First, the BDM achieves the ability to be highly enriched at tumor sites by inheriting the ability of MDSCs to actively target tumor microenvironment. And then, BP nanosheets achieves hyperthermia and induces mitochondrial damage by its photothermal and photodynamic properties, which enhancing anti-tumor immunity mediated by immunogenic cell death (ICD). Meanwhile, intra-tumoral release of decitabine induced G2/M cell cycle arrest, further promoting tumor cell apoptosis. In vivo, the BMD showed significant inhibition of tumor growth with down-regulation of PCNA expression and increased expression of high mobility group B1 (HMGB1), calreticulin (CRT) and caspase 3. Flow cytometry revealed significantly decreased infiltration of MDSCs and M2-macrophages along with an increased proportion of CD4+, CD8+ T cells as well as CD103+ DCs, suggesting a potentiated anti-tumor immune response. In summary, BDM realizes photothermal therapy/photodynamic therapy synergized chemotherapy for cancer.

Association between polypharmacy and chronic kidney disease among community-dwelling older people: a longitudinal study in southern China.

BACKGROUND: Polypharmacy would increase the risk of adverse drug events and the burden of renal drug excretion among older people. Nevertheless, the association between the number of medication and the risk of chronic kidney disease (CKD) remains controversial. Therefore, this study aims to investigate the association between the number of medication and the incidence of CKD in older people. METHODS: This study investigates the association between the number of medications and CKD in 2672 elderly people (≥ 65 years older) of the community health service center in southern China between 2019 and 2022. Logistic regression analysis was used to evaluate the relationship between polypharmacy and CKD. RESULTS: At baseline, the average age of the study subjects was 71.86 ± 4.60, 61.2% were females, and 53 (2.0%) suffer from polypharmacy. During an average follow-up of 3 years, new-onset CKD developed in 413 (15.5%) participants. Logistic regression analysis revealed that taking a higher number of medications was associated with increase of CKD. Compared with people who didn't take medication, a higher risk of CKD was observed in the older people who taken more than five medications (OR 3.731, 95% CI 1.988, 7.003), followed by those who take four (OR 1.621, 95% CI 1.041, 2.525), three (OR 1.696, 95% CI 1.178, 2.441), two drugs (OR 1.585, 95% CI 1.167, 2.153), or one drug (OR 1.503, 95% CI 1.097, 2.053). Furthermore, age, systolic blood pressure (SBP), white blood cell (WBC), blood urea nitrogen (BUN) and triglyceride (TG) were also independent risk factors CKD (P < 0.05). CONCLUSION: The number of medications was associated with CKD in older people. As the number of medications taken increased, the risk of CKD was increased.

AI protein structure prediction-based modeling and mutagenesis of a protostome receptor and peptide ligands reveal key residues for their interaction.

The protostome leucokinin (LK) signaling system, including LK peptides and their G protein-coupled receptors, has been characterized in several species. Despite the progress, molecular mechanisms governing LK peptide-receptor interactions remain to be elucidated. Previously, we identified a precursor protein for Aplysia leucokinin-like peptides (ALKs) that contains the greatest number of amidated peptides among LK precursors in all species identified so far. Here, we identified the first ALK receptor from Aplysia, ALKR. We used cell-based IP1 activation assays to demonstrate that two ALK peptides with the most copies, ALK1 and ALK2, activated ALKR with high potencies. Other endogenous ALK-derived peptides bearing the FXXWX-amide motif also activated ALKR to various degrees. Our examination of cross-species activity of ALKs with the Anopheles LK receptor was consistent with a critical role for the FXXWX-amide motif in receptor activity. Furthermore, we showed, through alanine substitution of ALK1, the highly conserved phenylalanine (F), tryptophan (W), and C-terminal amidation were each essential for receptor activation. Finally, we used an artificial intelligence-based protein structure prediction server (Robetta) and Autodock Vina to predict the ligand-bound conformation of ALKR. Our model predicted several interactions (i.e., hydrophobic interactions, hydrogen bonds, and amide-pi stacking) between ALK peptides and ALKR, and several of our substitution and mutagenesis experiments were consistent with the predicted model. In conclusion, our results provide important information defining possible interactions between ALK peptides and their receptors. The workflow utilized here may be useful for studying other ligand-receptor interactions for a neuropeptide signaling system, particularly in protostomes.

Construction of Graphene@Ag-MLF composite structure SERS platform and its differentiating performance for different foodborne bacterial spores.

A new surface-enhanced Raman spectroscopy (SERS) biosensor of Graphene@Ag-MLF composite structure has been fabricated by loading AgNPs on graphene films. The response of the biosensor is  based on plasmonic sensing. The results showed that the enhancement factor of three different spores reached 107 based on the Graphene@Ag-MLF substrate. In addition, the SERS performance was stable, with good reproducibility (RSD<3%). Multivariate statistical analysis and chemometrics were used to distinguish different spores. The accumulated variance contribution rate was up to 96.35% for the top three PCs, while HCA results revealed that the spectra were differentiated completely. Based on optimal principal components, chemometrics of KNN and LS-SVM were applied to construct a model for rapid qualitative identification of different spores, of which the prediction set and training set of LS-SVM achieved 100%. Finally, based on the Graphene@Ag-MLF substrate, the LOD of three different spores was lower than 102 CFU/mL. Hence, this novel Graphene@Ag-MLF SERS substrate sensor was rapid, sensitive, and stable in detecting spores, providing strong technical support for the application of SERS technology in food safety.

Effect of multidimensional lifestyle interventions on metabolic risk reduction in children: a cluster randomised controlled trial.

Few clinical trials have investigated lifestyle intervention effect on metabolic health in children. The study aimed to examine the effect of diet and physical activity intervention on the reduction of clustered metabolic risk score (CMRS) in children and moderators and mediators of the intervention effect. A multicentre, clustered randomised controlled trial was conducted with examination conducted at baseline and after intervention over one year. 7110 children (49.7% girls) with a mean of 9.06 (95% CI: 9.03, 9.09) years were included in the analysis. In Beijing, each three schools were randomly assigned to diet-only, physical activity-only intervention and control groups. In five other urban cities, each 15 schools were randomly assigned to comprehensive intervention and control groups. CMRS was computed by summing the Z scores of % fat mass, systolic blood pressure, fasting glucose, ratio of cholesterol to high-density lipoprotein, and triglyceride. Compared with controls (n = 2808), children in the comprehensive intervention group (n = 2848) had more reduction in CMRS (multivariate-adjusted mean difference (95% CI): -0.49 (-0.85, -0.14)). The body mass index (BMI) reduction explained 7.3% (95% CI 2.8%-18.1%) of the total intervention effect. The intervention was more effective in children with higher birthweight, lower parental BMI, or complete parental data. Diet-only or physical activity-only intervention had non-significant effects on CMRS reduction. Our multidimensional comprehensive intervention resulted in significant reduction in CMRS in primary school children and this effect was modified by birthweight, parental BMI, and parental involvement. A minority of metabolic risk reduction was mediated through BMI. Clinical Trial Registry number and website: ChiCTR-PRC-09000402, URL: http://www.chictr.org.cn.

[Usage status of salt control spoon and influencing factors among students' caregivers of four cities in China in 2014].

OBJECTIVE: To analysis the usage status of salt control spoon and explore its influencing factors among student caregivers of four cities. METHODS: The data of 2014 salt knowledge, attitude, practice(KAP) survey among urban residents in China was used, which a total of 12 848 student caregivers(male 4862, female 7986) were recruited from Guangzhou, Wuhan, Chengdu and Shenyang by stratified random cluster sampling method. A self-filling questionnaire survey was used to collect information about knowledge of salt and usage of salt control spoon. Logistic regression model was used to explore influencing factors of salt control spoon usage effected by gender, education level, family income, salt related knowledge, etc. . RESULTS: The proportion of student caregivers who didn't know salt control spoon was 33. 3%, and 41. 9% of them knew salt control spoon but hadn't it. Only 24. 8% of them have heard of salt control spoon and had it at home. The proportion of having not heard salt control spoon among Wuhan, male, junior high school and below, other occupation and low family income group was higher than other groups. The proportion of having salt control spoon of groups in Guangzhou, female, high school and above, professional technical and clerical personnel, high family income was higher than other groups, and the difference was statistically significant(P<0. 01). Among the student caregivers having salt control spoon, the proportion of did not used salt control spoon, used it occasionally or used it without controlling the quantity and used it often and controlled the quantity was 10. 0%, 60. 6% and 29. 5%, respectively. The student caregivers of Shenyang, male, high family income groups used salt control spoon and controlled the quantity more often than the other groups, and the difference was statistically significant(P<0. 05). As shown in multivariate logistic regression analysis, the OR(95%CI) of high school and above, high income level, knowing the recommended intake of salt, knowing that high salt diet can cause high blood pressure on the influence of having salt control spoon was 1. 328(1. 221-1. 445), 1. 268(1. 029-1. 563), 1. 243(1. 145-1. 348)and 0. 838(0. 763-0. 921), respectively. Among the student caregivers who having salt control spoon, the OR(95%CI) of knowing the recommended intake of salt, knowing that high salt diet can cause high blood pressure, and source of salt control spoon(community/unit, friends/relatives) on the influence of using salt control spoon was 1. 473(1. 259-1. 722), 1. 249(1. 040-1. 501)and 0. 505(0. 415-0. 615)/0. 603(0. 441-0. 823), respectively. CONCLUSION: There still existed lower proportion of awareness and usage of salt control spoon.

[Salt intake knowledge and behavior among school teachers in four Chinese cities in 2014].

OBJECTIVE: To learn the knowledge level on "salt and health", and analyze the influence on related behavior among school teachers in four Chinese cities. METHODS: The data of 2014 salt KAP among urban residents in China was used, with stratified random cluster sampling, a total of 2518(male 708, female 1810) school teachers were selected from four cities of China, including Shenyang, Wuhan, Chengdu and Guangzhou city. Self-filled questionnaire was used to collect the information on the salt intake knowledge and behavior. The statistical software package SAS version 9. 4 was used for data analysis. RESULTS: Among the teachers in four Chinese cities, about 50. 9% of them knew the recommendation of salt intake, about 66. 6% of them knew sodium in the salt may influence health. Approximately 85. 3% of them knew eating long-term salty food may cause hypertension. The proportions of knowing salt intake among female, 40 years and older, below the undergraduate, higher family income teachers were higher than their counterparts(P<0. 05). The proportions of knowing the health influence of sodium among female, higher family income teachers were higher than their counterparts(P<0. 05). The proportions of knowing that eating long-term salty food may cause hypertension among female, undergraduate and above, higher family income teachers were higher than their counterparts(P<0. 05). About 80. 1% of them knew the nutrition labeling on the package food, about 19. 7% of them knew the nutrition labeling contents. Teachers utilized nutrition labeling differently owing to their knowledge on the labeling contents(P<0. 05). In the past three months, about 21. 4% of the teachers always use low-sodium salt when cooking, only 4. 2% of them always control their family's salt intake by using salt control spoon, about 25. 4% of them always choose low-sodium food when purchasing, only 15. 1% of the teachers requested the meals cooked lightly when eating out. The proportions of teachers who used low-sodium salt among female, higher family income, knowing salt intake recommended, knowing the health influence of sodium, knowing that long-term salty food may cause hypertension, active learning related knowledge, family members suffering from hypertension were higher than their counterparts(P<0. 05). The proportions of using salt control spoon among teachers under Bachelor's degree, active learning related knowledge were higher than their counterparts(P<0. 05). The proportions of teachers purchasing low-sodium food among 40 years and older, under Bachelor's degree, higher family income, knowing salt intake recommended, knowing the health influence of sodium, knowing that long-term salty food may cause hypertension, family members not suffering from hypertension, active learning related knowledge were higher than their counterparts(P<0. 05). The proportions of teachers requesting the meals cooked slightly when eating-out among 40 years and older, under Bachelor's degree, not knowing salt intake recommended, not knowing that long-term salty food may cause hypertension, not knowing if their family members suffered from hypertension, active learning related knowledge were higher than their counterparts(P<0. 05). The teachers consumed soy sauce, bean paste, fried bread stick differently owing to their knowledge about this(P<0. 05). CONCLUSION: The teachers in the four cities have grasped some knowledge on salt and health, but their related behaviors should be improved to reduce the salt intake.

Prevalence of body dissatisfaction and its effects on health-related quality of life among primary school students in Guangzhou, China.

BACKGROUND: The relationship between body dissatisfaction (BD) and health-related quality of life (HRQoL) has been well documented in adolescents and adults but is less clear in children, particularly in China. The aims of this study were to describe body image perception and dissatisfaction and to examine their effects on HRQoL among primary school students in Guangzhou, China. METHODS: A total of 5734 children aged 8-12 years from 29 schools completed self-report questionnaires, which included the Paediatric Quality of Life Inventory 4.0 for measuring HRQoL and Ma figural stimuli for measuring BD. Based on their level of BD, the children were divided into three groups: no dissatisfaction, mild dissatisfaction and moderate or high dissatisfaction. Based on the children's perceptions of their own body image, the groups were also categorized into just right, too fat and too thin groups. Height and weight were objectively measured using standardized methods, and a BMI z-score was derived using the age- and sex-specific WHO references from 2007 for children aged 5-19 years. Weight status was classified as underweight, healthy weight, overweight or obese. RESULTS: A total of 78.10% of children aged 8-12 years in Guangzhou had different levels of BD; boys had slightly higher levels BD than girls (p < 0.01), and obese children demonstrated the highest degree of BD (p < 0.01). However, BD levels did not differ significantly according to age (p = 0.194). Gender differences in body image perceptions were only found in children with a healthy weight (p < 0.01), but age differences in body image perception were present in both children with a healthy weight (p < 0.05) and underweight children (p < 0.05). Of the children with a healthy weight who were dissatisfied with their body image, 65.54% of the boys wanted to be heavier, whereas 52.95% of the girls wanted to be thinner (p < 0.01), and older children were more inclined to perceive themselves as too fat (p < 0.01). After controlling for the influence of confounding factors, significant trends for lower HRQoL scores with increasing BD levels persisted in all domains (p < 0.01). CONCLUSIONS: BD is as common in children as in adolescents and adults and might be independently associated with HRQoL impairment. The present findings suggest that the current epidemic of BD is a threat to the health of primary school children in China, and prevention programmes for this population should be implemented in the future.

The anticaries effects of pit and fissure sealant in the first permanent molars of school-age children from Guangzhou: a population-based cohort study.

BACKGROUND: Analyses of the effects of pit and fissure sealant have been based on small samples and lack large-scale field evaluation data in China. The aim of this study was to understand the effect of pit and fissure sealant in preventing caries in the first permanent molars (FPMs) of children in Guangzhou. METHODS: We conducted a population-based cohort study using the database of the pit and fissure sealant program of Guangzhou. The carious status and sealant retention of the FPMs were assessed in 4,822 school children who received pit and fissure sealant 3 years prior to the study. The control group included 4,396 children who had indications for receiving pit and fissure sealant but were not treated and were matched according to sex, age and school. RESULTS: In the sealant group, the rate of sealant retention in the FPMs was 72.2%. Children in the sealant group had a 37% decreased risk of dental caries compared with the control group (adjusted HR = 0.63 [95% confidence interval (CI), 0.57-0.69], P < 0.001). Compared to no sealant use, the use of pit and fissure sealants reduced the risk of developing dental caries by 44% after 3 years in the FPMs of children from rural areas, reflecting a greater reduction than that among urban children (35%) during the same period (urban: adjusted hazard ratio (HR) = 0.65 [95% CI, 0.58-0.72]; rural: adjusted HR = 0.56 [95% CI, 0.45-0.70], P < 0.001). The mean number of decayed, missing, or filled permanent teeth (DMFT) in the control group was higher than that in the sealant group, and the difference was statistically significant regardless of sex. CONCLUSIONS: Pit and fissure sealant has a significant preventive effect against dental caries in the FPMs, especially for children in rural areas; thus, this sealant represents an effective technique for preventing and controlling dental caries.

Lysyl Hydroxylase Inhibition by Minoxidil Blocks Collagen Deposition and Prevents Pulmonary Fibrosis via TGF-ß1/Smad3 Signaling Pathway.

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a deadly disease characterized by excessive collagen in the extracellular matrix (ECM) of the lungs. Collagen is the primary protein component of the ECM. However, the exact mechanisms underlying the formation and deposition of collagen in the ECM under normal and pathological conditions remain unclear. Previous studies showed that lysyl hydroxylase (LH) plays a crucial role in the formation of collagen. Minoxidil is an FDA-approved anti-hypertensive agent that inhibits LH that reduces fibrosis. In this study, we investigated the functional roles of LHs (LH1, LH2, and LH3) in pulmonary fibrosis and the anti-fibrotic effects of minoxidil. MATERIAL AND METHODS Patient serum samples were examined for their expression of procollagen-lysine, 2-oxoglutarate 5-dioxygenases (PLOD) 1-3, the genes encoding LH 1-3. Mice with bleomycin (BLM 2.5 mg/kg)-induced pulmonary fibrosis were administered a minoxidil solution (30 mg/kg) by oral gavage. RESULTS The PLOD mRNA levels were significantly higher in the IPF patients than in the healthy control subjects. Minoxidil suppressed the BLM-induced pulmonary fibrosis in vivo. These effects were associated with blocking TGF-ß1/Smad3 signal transduction and attenuating the expression and activity of LHs, resulting in decreased collagen formation, thus reducing the pulmonary fibrosis. The anti-fibrotic effects of minoxidil may be mediated through competitive inhibition of LHs activity, resulting in decreased pyridine cross-link formation and collagen production and deposition. CONCLUSIONS The results of this study suggest that LH represents a target to prevent or treat pulmonary fibrosis, and minoxidil may provide an effective agent to inhibit LHs.

Prevalence of adiposity and its association with sleep duration, quality, and timing among 9-12-year-old children in Guangzhou, China.

BACKGROUND: Short sleep duration has been reported to be associated with obesity in children, but findings are not consistent. Since few studies have examined the relationship between more complex sleep characteristics and obesity, we examined the association between adiposity and self-reported sleep duration, bedtime, and sleep quality in 9-12-year-old Chinese children using multilevel mixed models. METHODS: 5518 children aged 9-12 years were recruited from 29 randomly selected primary schools in Guangzhou, China in 2014. Standardized questionnaires were used to obtain data to estimate sleep duration on typical weekdays and weekends. Sleep quality data were collected using the Children's Sleep Habits Questionnaire (CSHQ). Trained researchers undertook measurements of weight, height, and waist circumference (WC) for all participating children. Body mass index (BMI) z-scores were derived using the World Health Organization (WHO) child growth reference, and children were classified as overweight or obese using +1 and +2 SD as cut-offs, respectively. Percentage body fat (BF%) was calculated using bioelectrical impedance. RESULTS: Longer sleep duration was inversely associated with BMI z-score (ß = -0.16, p < 0.05), WC (ß = -1.11, p < 0.05) and later bedtime was associated with higher BMI z-score (ß = 0.03, p < 0.05), WC (ß = 1.72, p < 0.001), and BF% (ß = 0.15, p < 0.05) in multivariable multilevel mixed models, after adjustment for age, gender, physical activity, parental education level, and average monthly income. No association was seen between sleep quality and adiposity. CONCLUSION: Shorter sleep duration and later bedtime are associated with higher adiposity indices in early adolescents from southern China.

Dimethyl sulfide emission behavior from landfill site with air and water control.

Municipal solid waste landfills are responsible for odors affecting the environment and human health. Dimethyl sulfide (DMS) is one of the major odorous compounds known for its low odor threshold and wide distribution. This study examined the generation, migration and emission of DMS in four artificial landfill-simulating reactors: Reactor 1 and Reactor 2, running under anaerobic and semi-aerobic conditions, respectively, without leachate recirculation; and Reactor 3 and Reactor 4, running under anaerobic and semi-aerobic conditions, respectively, with leachate recirculation. From the odor control perspective, aeration can efficiently inhibit maximum DMS headspace concentration by 31.7-93.7%, especially with the functioning of leachate recirculation. However, leachate recirculation in anaerobic conditions may double the DMS emission concentration but may also shorten the period over which DMS is effective because of the upward migration of liquid DMS in the recirculated leachate. The DMS generation was active in the acidification and methane fermentation phase of the simulated landfill and was possibly affected by the volatile fatty acid concentration, chemical oxygen demand, total organic carbon concentration and pH of the leachate, as well as total organic carbon in the refuse. Most significantly, DMS emission can be effectually dealt with by aeration along with leachate recirculation.

A Novel Inhibitor of the Obesity-Related Protein FTO.

Fe(II) and α-ketoglutarate-dependent fat mass and obesity associated protein (FTO)-dependent demethylation of m6A is important for regulation of mRNA splicing and adipogenesis. Developing FTO-specific inhibitors can help probe the biology of FTO and unravel novel therapeutic targets for treatment of obesity or obesity-associated diseases. In the present paper, we have identified that 4-chloro-6-(6'-chloro-7'-hydroxy-2',4',4'-trimethyl-chroman-2'-yl)benzene-1,3-diol (CHTB) is an inhibitor of FTO. The crystal structure of CHTB complexed with human FTO reveals that the novel small molecule binds to FTO in a specific manner. The identification of the novel small molecule offers opportunities for further development of more selective and potent FTO inhibitors.

Evaluation of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Identification of Mycobacterium abscessus Subspecies According to Whole-Genome Sequencing.

This study was undertaken to evaluate the utility of matrix-assisted laser desorption ionization-time of flight mass spectrometry with the Vitek MS Plus system for identifying Mycobacterium abscessus subspecies in order to facilitate more rapid and appropriate therapy. A total of 175 clinical M. abscessus strains were identified by whole-genome sequencing analysis: 139 Mycobacterium abscessus subsp. abscessus and 36 Mycobacterium abscessus subsp. massiliense The research-use-only (RUO) Saramis Knowledge Base database v.4.12 was modified accordingly by adding 40 M. abscessus subsp. abscessus and 19 M. abscessus subsp. massiliense reference spectra to construct subspecies SuperSpectra. A blind test, used to validate the remaining 116 isolates, yielded 99.1% (n = 115) reliability and only 0.9% (n = 1) error for subspecies identification. Among the two subspecies SuperSpectra, two specific peaks were found for M. abscessus subsp. abscessus and four specific peaks were found for M. abscessus subsp. massiliense Our study is the first to report differential peaks 3,354.4 m/z and 6,711.1 m/z, which were specific for M. abscessus subsp. massiliense Our research demonstrates the capacity of the Vitek MS RUO Saramis Knowledge Base database to identify M. abscessus at the subspecies level. Moreover, it validates the potential ease and accuracy with which it can be incorporated into the IVD system for the identification of M. abscessus subspecies.