Sleep Duration and Risk of Periodontitis-A Systematic Review and Meta-Analysis.

Periodontitis, with a high prevalence in the whole population, is the main cause of tooth loss. Some studies have revealed that sleep duration may be related to periodontitis, however, the opinions are not consistent. This meta-analysis was carried out to study the potential relationship between sleep duration and periodontitis. A search of relevant articles was conducted on Embase, PubMed, Cochrane Library, and Web of Science. Papers published until the end of November 2022 reporting associations between sleep duration and periodontitis were considered. The pooled odds ratio (OR) with a 95% confidence interval (CI) was calculated to assess the association. Software STATA 14.0 was employed to conduct this analysis. A total of 11 cross-sectional studies were included. Our study showed neither short sleep duration (SSD) nor long sleep duration (LSD) were associated with periodontitis (SSD: OR = 1.04, 95% CI: 0.83, 1.29; LSD: OR = 1.12, 95% CI: 0.94, 1.23), while higher prevalence was observed when sleep duration ≤5 h (OR = 1.41, 95% CI: 1.33, 1.51). In addition, both SSD and LSD were not associated with severe periodontitis (SSD: OR = 0.94, 95% CI: 0.75, 1.16; LSD: OR = 1.19, 95% CI: 0.80, 1.76). In conclusion, the present review indicated that too little sleep duration (≤5 h) significantly increased the risk of periodontitis. However, the evidence is limited due to cross-sectional design of most studies, Hence longitudinal studies should be conducted to support this finding.

Suicide Risk Screening Tools for Pediatric Patients: A Systematic Review of Test Accuracy.

CONTEXT: Health care settings have increasingly adopted universal suicide risk screening tools into nonpsychiatric pediatric care; however, a systematic review examining the accuracy of these tools does not yet exist. OBJECTIVE: Identify and review research on the test accuracy of suicide risk screening tools for pediatric patients in nonpsychiatric medical settings. DATA SOURCES: PubMed and PsycINFO were searched to identify peer-reviewed articles published before March 23, 2023. STUDY SELECTION: Articles that quantified the accuracy of a suicide risk screening tool (eg, sensitivity, specificity) in a nonpsychiatric medical setting (eg, primary care, specialty care, inpatient or surgical units, or the emergency department) were included. DATA EXTRACTION: A total of 13 studies were included in this review. Screening tool psychometric properties and study risk of bias were evaluated. RESULTS: Sensitivity among individual studies ranged from 50% to 100%, and specificity ranged from 58.8% to 96%. Methodological quality was relatively varied, and applicability concerns were low. When stratifying results by screening tool, the Ask Suicide-Screening Questions and Computerized Adaptive Screen for Suicidal Youth had the most robust evidence base. LIMITATIONS: Because of considerable study heterogeneity, a meta-analytic approach was deemed inappropriate. This prevented us from statistically testing for differences between identified screening tools. CONCLUSIONS: The Ask Suicide-Screening Questions and Computerized Adaptive Screen for Suicidal Youth exhibit satisfactory test accuracy and appear promising for integration into clinical practice. Although initial findings are promising, additional research targeted at examining the accuracy of screening tools among diverse populations is needed to ensure the equity of screening efforts.

Oxidative stress-related biomarkers in oral squamous cell carcinoma patients: a systematic review and meta-analysis.

Aim: This meta-analysis was conducted to evaluate the serum and salivary levels of oxidative stress-related biomarkers in oral squamous cell carcinoma (OSCC) patients compared with controls. Methods: A search of relevant articles that were published between 1 January 2000 and 20 March 2022, was conducted on three electronic databases (Embase, PubMed and Cochrane Library). Results: A total of 15 articles were included in the meta-analysis. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx) in serum and MDA and GSH in saliva were significantly changed in the OSCC group compared with healthy controls. Conclusion: This study suggests that some oxidative stress biomarkers may be potential biomarkers in early OSCC diagnosis.

Plumbagin Enhances the Anticancer Effects of PF Chemotherapy via Downregulation of the PI3K/AKT/mTOR/p70S6K Pathway in Human Tongue Squamous Cell Carcinoma.

Cisplatin plus 5-fluorouracil (PF) is used as the standard neoadjuvant chemotherapy (also called preoperative chemotherapy) in the treatment of tongue squamous cell carcinoma (TSCC). Although PF chemotherapy reduces the distant metastasis of TSCC, the five-year survival rate has not significantly improved. In recent years, components considered in traditional Chinese medicine have been researched as adjuvant drugs for radiotherapy and chemotherapy. Plumbagin (PB) is a quinone component isolated from Plumbago zeylanica L. Notably, PB demonstrates numerous anticancer properties. In order to examine the chemosensitization effect of PB on PF and its associated mechanisms, in vitro experiments using TSCC Cal27 and cisplatin (CDDP)-resistant Cal27/CDDP cells were carried out in the present study, and the results were subsequently verified using nude mice xenografts. Results of the present study demonstrated that PB enhanced the anticancer effects of PF on the proliferation, migration, and invasion of Cal27 and Cal27/CDDP cells. Cell cycle assays demonstrated that both Cal27 and Cal27/CDDP cells were arrested in the S phase following the combined treatment of PF and PB. Moreover, the PF and PB combination group induced higher levels of apoptosis in Cal27 and Cal27/CDDP cells compared with the group treated with PF alone. In addition, the results of the present study demonstrated that combined PB and PF inhibited the PI3K/AKT/mTOR/p70S6K pathway in TSCC cells. Moreover, the weight and volumes of tumors in nude mice were reduced following treatment with a combination of PF and PB. Results of the present study also demonstrated that the expression levels of Ki67 were markedly reduced in the combined treatment group compared with the group treated with PF alone. In summary, the results of the present study demonstrated that PB enhanced the PF sensitivity of TSCC through induction of S-phase arrest and apoptosis via the PI3K/AKT/mTOR/p70S6K pathway.

Cryo-EM structures of recombinant human sodium-potassium pump determined in three different states.

Sodium-Potassium Pump (Na+/K+-ATPase, NKA) is an ion pump that generates an electrochemical gradient of sodium and potassium ions across the plasma membrane by hydrolyzing ATP. During each Post-Albers cycle, NKA exchanges three cytoplasmic sodium ions for two extracellular potassium ions through alternating changes between the E1 and E2 states. Hitherto, several steps remained unknown during the complete working cycle of NKA. Here, we report cryo-electron microscopy (cryo-EM) structures of recombinant human NKA (hNKA) in three distinct states at 2.7-3.2 Å resolution, representing the E1·3Na and E1·3Na·ATP states with cytosolic gates open and the basic E2·[2K] state, respectively. This work provides the insights into the cytoplasmic Na+ entrance pathway and the mechanism of cytoplasmic gate closure coupled with ATP hydrolysis, filling crucial gaps in the structural elucidation of the Post-Albers cycle of NKA.

Temporal Changes of Fish Diversity and Driver Factors in a National Nature Reserve, China.

Freshwater-fish diversity declined rapidly due to multiple anthropogenic disturbances. The loss of fish diversity often manifested itself in taxonomic homogenization over time. Knowledge of multi-faceted diversity (i.e., species, functional, and phylogenetic diversity) perspectives is important for biodiversity assessment and conservation planning. Here, we analyzed the change of the species diversity and phylogenetic diversity of fish in 2008 and 2021 as well as explored the driver factors of the biodiversity patterns in the Lushan National Nature Reserve. The results showed that the species diversity and phylogenetic diversity of fish have declined from 2008 to 2021, with five species lost over time. We found an overall homogenization trend in the fish fauna of the study area, with a 4% increase in taxonomic similarity among the rivers. Additionally, we found that community structure of fish was significantly different among the rivers, and environmental filtering was the main contributor to the phylogenetic diversity of fish in 2008 and 2021. This study provides new insight into the patterns and drivers of fish-biodiversity change in the broader Yangtze River basin and informs management efforts.

Rational exploration of fold atlas for human solute carrier proteins.

The solute carrier (SLC) superfamily is the largest group of proteins responsible for the transmembrane transport of substances in human cells. It includes more than 400 members that are organized into 65 families according to their physiological function and sequence similarity. Different families of SLCs can adopt the same or different folds that determine the mechanism and reflect the evolutionary relationship between SLC members. Analysis of structural data in the literature before this work showed 13 different folds in the SLC superfamily covering 40 families and 343 members. To further study their mechanism, we systematically explored the SLC superfamily to look for more folds. Based on our results, at least three new folds are found for the SLC superfamily, one of which is in the choline-like transporter family (SLC44) and has been experimentally verified. Our work has laid a foundation and provided important insights for the systematic and comprehensive study of the structure and function of SLC.

Dihydroartemisinin Induces ER Stress-Mediated Apoptosis in Human Tongue Squamous Carcinoma by Regulating ROS Production.

BACKGROUND: Tongue squamous cell carcinoma is a fatal disease characterized by high invasion and early metastasis. Dihydroartemisinin, an antimalarial drug with multiple biological activities, is reported to be a potential anti-cancer agent. OBJECTIVE: This study aimed to evaluate the antitumor effect of Dihydroartemisinin on tongue squamous cell carcinoma cells, and to identify the underlying mechanisms of Dihydroartemisinin-induced cell apoptosis. METHODS: Here, Cell Counting Kit 8 assay and colony formation assay were conducted to study cell proliferation. Annexin V-FITC/propidium iodide staining and western blot analysis were performed to analyze cell apoptosis. DCFHDA probe was used to measure the generation of cellular reactive oxygen species. Endoplasmic reticulum stress activation was also determined via western blot analysis. RESULTS: The results showed that Dihydroartemisinin substantially inhibited cell proliferation and induced cell apoptosis in vivo. Moreover, reactive oxygen species production and endoplasmic reticulum stress activation were both observed after stimulation with Dihydroartemisinin. However, the reactive oxygen species inhibitor N-acetylcysteine significantly alleviated Dihydroartemisinin-induced endoplasmic reticulum stress and apoptosis. CONCLUSION: These results imply that Dihydroartemisinin induced cell apoptosis by triggering reactive oxygen speciesmediated endoplasmic reticulum stress in CAL27 cells. In addition, Dihydroartemisinin might be an effective drug for tongue squamous cell carcinoma therapy.

Cryo-EM structure of human Wntless in complex with Wnt3a.

Wntless (WLS), an evolutionarily conserved multi-pass transmembrane protein, is essential for secretion of Wnt proteins. Wnt-triggered signaling pathways control many crucial life events, whereas aberrant Wnt signaling is tightly associated with many human diseases including cancers. Here, we report the cryo-EM structure of human WLS in complex with Wnt3a, the most widely studied Wnt, at 2.2 Å resolution. The transmembrane domain of WLS bears a GPCR fold, with a conserved core cavity and a lateral opening. Wnt3a interacts with WLS at multiple interfaces, with the lipid moiety on Wnt3a traversing a hydrophobic tunnel of WLS transmembrane domain and inserting into membrane. A ß-hairpin of Wnt3a containing the conserved palmitoleoylation site interacts with WLS extensively, which is crucial for WLS-mediated Wnt secretion. The flexibility of the Wnt3a loop/hairpin regions involved in the multiple binding sites indicates induced fit might happen when Wnts are bound to different binding partners. Our findings provide important insights into the molecular mechanism of Wnt palmitoleoylation, secretion and signaling.

BDNF Activates Postsynaptic TrkB Receptors to Induce Endocannabinoid Release and Inhibit Presynaptic Calcium Influx at a Calyx-Type Synapse.

Brain-derived neurotropic factor (BDNF) has been shown to play critical roles in neural development, plasticity, and neurodegenerative diseases. The main function of BDNF in the brain is widely accepted to be synaptic regulation. However, how BDNF modulates synaptic transmission, especially the underlying signaling cascades between presynaptic and postsynaptic neurons, remains controversial. In the present study, we investigated the actions of BDNF at rat calyx-type synapses of either sex by measuring the excitatory postsynaptic current (EPSC) and presynaptic calcium current and capacitance changes. We found that BDNF inhibits the EPSC, presynaptic calcium influx, and exocytosis/endocytosis via activation of the presynaptic cannabinoid Type 1 receptors (CB1Rs). Inhibition of the CB1Rs abolished the BDNF-induced presynaptic inhibition, whereas CB1R agonist mimicked the effect of BDNF. Exploring the underlying signaling cascade, we found that BDNF specifically activates the postsynaptic TrkB receptors, inducing the release of endocannabinoids via the PLCγ/DGL pathway and retrogradely activating presynaptic CB1Rs. We also reported the involvement of AC/PKA in modulating vesicle endocytosis, which may account for the BDNF-induced calcium-dependent and -independent regulation of endocytosis. Thus, our study provides new insights into the BDNF/endocannabinoid-associated modulation of neurotransmission in physiological and pathologic processes.SIGNIFICANCE STATEMENT BDNF plays critical roles in the modulation of synaptic strength. However, how BDNF regulates synaptic transmission and its underlying signaling cascade(s) remains elusive. By measuring EPSC and the presynaptic calcium current and capacitance changes at rat calyces, we found that BDNF inhibits synaptic transmission via BDNF-TrkB-eCB signaling pathway. Activation of postsynaptic TrkB receptors induces endocannabinoid release via the PLCγ/DGL pathway, retrogradely activating the presynaptic CB1Rs, inhibiting the AC/PKA, and suppressing calcium influx. Our findings provide a comprehensive understanding of BDNF/endocannabinoid-associated modulation of neuronal activities.

Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma.

Cisplatin is widely used in the treatment of tongue squamous cell carcinoma (TSCC), but its clinical efficacy is limited by drug resistance and toxic side effects. Hence, a novel compound capable of enhancing the anticancer effect of cisplatin while reducing the side effects is urgently needed. We have previously shown that plumbagin (PLB), an anticancer phytochemical, is able to inhibit the growth of TSCC in vitro and in vivo. The objective of this study was to investigate the effect of PLB in reversing the resistance of TSCC to cisplatin as well as its molecular mechanisms. Here, we found that PLB enhances cisplatin-induced cytotoxicity, apoptosis, and autophagy in CAL27 and cisplatin-resistant CAL27/CDDP cells. PLB could inhibit the viability and growth of TSCC cells by increasing the production of intracellular reactive oxygen species (ROS). In addition, the combination treatment of PLB and cisplatin resulted in a synergistic inhibition of TSCC viability, apoptosis, and autophagy by increasing intracellular ROS, which may be achieved by activating JNK and inhibiting AKT/mTOR signaling pathways. Finally, the synergistic treatment was also demonstrated in vivo. Therefore, PLB combined with cisplatin is a potential therapeutic strategy against therapy TSCC cisplatin resistance.

Coordinated evolution of co-expressed gene clusters in the Drosophila transcriptome.

BACKGROUND: Co-expression of genes that physically cluster together is a common characteristic of eukaryotic transcriptomes. This organization of transcriptomes suggests that coordinated evolution of gene expression for clustered genes may also be common. Clusters where expression evolution of each gene is not independent of their neighbors are important units for understanding transcriptome evolution. RESULTS: We used a common microarray platform to measure gene expression in seven closely related species in the Drosophila melanogaster subgroup, accounting for confounding effects of sequence divergence. To summarize the correlation structure among genes in a chromosomal region, we analyzed the fraction of variation along the first principal component of the correlation matrix. We analyzed the correlation for blocks of consecutive genes to assess patterns of correlation that may be manifest at different scales of coordinated expression. We find that expression of physically clustered genes does evolve in a coordinated manner in many locations throughout the genome. Our analysis shows that relatively few of these clusters are near heterochromatin regions and that these clusters tend to be over-dispersed relative to the rest of the genome. This suggests that these clusters are not the byproduct of local gene clustering. We also analyzed the pattern of co-expression among neighboring genes within a single Drosophila species: D. simulans. For the co-expression clusters identified within this species, we find an under-representation of genes displaying a signature of recurrent adaptive amino acid evolution consistent with previous findings. However, clusters displaying co-evolution of expression among species are enriched for adaptively evolving genes. This finding points to a tie between adaptive sequence evolution and evolution of the transcriptome. CONCLUSION: Our results demonstrate that co-evolution of expression in gene clusters is relatively common among species in the D. melanogaster subgroup. We consider the possibility that local regulation of expression in gene clusters may drive the connection between adaptive sequence and coordinated gene expression evolution.