Genotype-phenotype analysis and functional study of three novel variants in non-syndromic oligodontia.

Introduction: Tooth agenesis (TA) is a common craniofacial malformation in humans, characterized by the absence of one or more permanent teeth. Recent studies have identified the low-density lipoprotein receptor-related protein 6 () gene as an autosomal dominant contributor to TA. Herein we aimed to identify novel variants in patients with non-syndromic oligodontia (NSO) and perform functional analyses of these variants.

EDA1 variants inhibit the odontogenic differentiation and proliferation of human dental pulp stem cells.

Background: Variants of Ectodysplasin A1 (EDA1) regulate the proliferation, migration, and odontogenic differentiation of human dental pulp stem cells (hDPSCs). Further study of these variants could reveal the mechanism by which EDA1 induces tooth development.

Methods: The following groups of hDPSCs were studied: those expressing wild-type (Wt) EDA1, those expressing EDA1 non-syndromic tooth agenesis (NSTA) variants (NSTA-A259E, NSTA-S374R), those expressing a syndrome type (STA) variant of EDA1 (STA-H252L), and those transformed with the empty vector (NC, negative control).

A novel PAX9 variant in a Chinese family with non-syndromic oligodontia and genotype-phenotype analysis of PAX9variants.

Objectives: This study aimed to identifyPAX9variants in non-syndromic tooth agenesis families of China, as well as to analyze the genotype⁃phenotype of non-syndromic tooth agenesis caused by PAX9variants, which can provide a basis for the genetic diagnosis of tooth agenesis.

Methods: We collected the data of 44 patients with non-syndromic oligodontia who underwent treatment at Stomatological Hospital of Hebei Medical University between 2018 and 2023. Whole-exome sequencing was performed on the peripheral blood of the proband and its core family members, and the variants were verified by Sanger sequencing.

Artificial intelligence, workers, and future of work skills.

Historically, the use of technology in organizations has reshaped the nature of human work. In this article, we overview how current waves of artificially intelligent (AI) technologies are following this trend, showing how its uses can both automate and complement human labor, alongside creating new forms of human work. However, AI can also generate both upsides and downsides for workers' experiences, which are dependent upon a range of factors such as how the technology is used and the support employees receive during digital transitions.

Explore public concerns about environmental protection on Sina Weibo: evidence from text mining.

The increasingly serious problem of ecological environmental pollution warns the importance of human environmental protection behavior. However, public attention to environmental protection plays an important role in solving environmental problems. Therefore, in order to explore the environmental concerns of Chinese residents, the trends in time and space, the relationship between online retweets, and the extraction of environmental concerns, this study analyzed the data of Sina Weibo users and their comments on related posts.

Novel PAX9 compound heterozygous variants in a Chinese family with non-syndromic oligodontia and genotype-phenotype analysis of PAX9 variants.

Objective: Studies have reported that >91.9% of non-syndromic tooth agenesis cases are caused by seven pathogenic genes. To report novel heterozygous PAX9 variants in a Chinese family with non-syndromic oligodontia and summarize the reported genotype-phenotype relationship of PAX9 variants.

Where there is pressure, there is motivation? The impact of challenge-hindrance stressors on employees' innovation performance.

Based on the conservation of resource theory, this manuscript explores the impact mechanism of the challenge and hindrance stressors on innovation performance, introduces emotional atmosphere as a mediation variable, and on this basis, it examines the moderating role of organizational climate on emotional atmosphere and innovation performance. A two-wave survey of 263 subordinates and 29 supervisors who come from multisource field offered support for our model. Results showed that challenge stressors have a positive effect on innovation performance, positive emotional atmosphere mediates the relationship between challenge stressors and innovation performance; hindrance stressors have a negative effect on innovation performance, and negative emotional atmosphere mediates the relationship between hindrance stressors and innovation performance.

Structural Dimension Exploration and Measurement Scale Development of Employee Involution in China's Workplace Field.

The phenomenon of workplace involution has attracted ample attention. How to make employees treat their work with the correct attitude and behavior and improve their work performance has become a realistic proposition. This study uses a combination of qualitative and quantitative research methods, with the help of grounded theory, to conduct an exploratory study on the structural dimensions of employee involution in the Chinese workplace and, on this basis, to develop and test the measurement scale.

How spiritual leadership affects team safety performance: the role of team reflexivity and work interdependence.

Frequent occurrence of workplace accidents may be caused by a lack of attention by team members to safety behaviors on the spiritual level. It is very important to investigate the incentive mechanism of spirit factor on team safety performance. Based on social cognition theory and social interaction theory, this study analyzed matching data from 717 employees across 173 teams, and verified the mechanism underlying team-level spiritual leadership on team safety performance.

Effects and Mechanisms of Five Psoralea Prenylflavonoids on Aging-Related Diseases.

During the aging process, senescent cells gradually accumulate in the organs; they secrete proinflammatory cytokines and other factors, collectively known as the senescence-associated secretory phenotype (SASP). SASP secretions contribute to "inflammaging," which is a state of chronic, systemic, sterility, low-grade inflammatory microenvironment and a key risk factor in the development of aging-related diseases. Fructus psoraleae is a traditional Chinese medical herb best known for delaying aging and treating osteoporosis.

In vitro and in vivo functional profile characterization of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3-carboxamido)morphinan (NAQ) as a low efficacy mu opioid receptor modulator.

Evidence has shown that downstream signaling by mu opioid receptor (MOR) agonists that recruit β-arrestin2 may lead to the development of tolerance. Also, it has been suggested that opioid receptor desensitization and cyclic AMP overshoot contributes to the development of tolerance and occurrence of withdrawal, respectively. Therefore, studies were conducted with 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3-carboxamido)morphinan (NAQ), a MOR selective partial agonist discovered in our laboratory, to characterize its effect on β-arrestin2 recruitment and precipitation of a cyclic AMP overshoot.

Natural compound bavachalcone promotes the differentiation of endothelial progenitor cells and neovascularization through the RORα-erythropoietin-AMPK axis.

In cardiovascular diseases, endothelial function is impaired and the level of circulating endothelial progenitor cells (EPCs) is low. This study investigated whether the natural bioactive component bavachalcone (BavaC) induces the differentiation of EPCs and neovascularization ; the underlying mechanisms were also examined. We observed that the treatment of rat bone marrow-derived cells with a very low dose of BavaC significantly promoted EPC differentiation.

In Vitro and In Vivo Effects of Norathyriol and Mangiferin on -Glucosidase.

Norathyriol is a metabolite of mangiferin. Mangiferin has been reported to inhibit -glucosidase. To the best of our knowledge, no study has been conducted to determine or compare those two compounds on inhibiting -glucosidase in vitro and in vivo by far.

Nanoconjugated NAP as a Potent and Periphery Selective Mu Opioid Receptor Modulator To Treat Opioid-Induced Constipation.

Opioids are the mainstay for cancer and noncancer pain management. However, their use is often associated with multiple adverse effects. Among them, the most common and persistent one is probably opioid-induced constipation (OIC).

Design, synthesis, and characterization of rhein analogs as novel inhibitors of scavenger receptor A.

Scavenger receptor A (SRA) has been known as an immunosuppressive factor and therefore therapeutic inhibition of SRA may be potentially exploited for cancer immunotherapy. Our previously work suggested that rhein may act as an inhibitor of SRA in reversing immunosuppression of SRA during T cells activation. Herein, three deconstruction analogs of rhein, compound 1, 2, and 3, were further studied as inhibitors of SRA.

Exploration of bivalent ligands targeting putative mu opioid receptor and chemokine receptor CCR5 dimerization.

Modern antiretroviral therapies have provided HIV-1 infected patients longer lifespans and better quality of life. However, several neurological complications are now being seen in these patients due to HIV-1 associated injury of neurons by infected microglia and astrocytes. In addition, these effects can be further exacerbated with opiate use and abuse.

6β-N-Heterocyclic Substituted Naltrexamine Derivative BNAP: A Peripherally Selective Mixed MOR/KOR Ligand.

The 6β-N-heterocyclic naltrexamine derivative, NAP, has been demonstrated to be a peripherally selective mu opioid receptor modulator. To further improve peripheral selectivity of this highly potent ligand, its pyridal ring was quaterinized with benzyl bromide to produce BNAP. In radioligand binding assay, the Ki of BNAP for MOR was 0.

17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(4'-pyridylcarboxamido)morphinan (NAP) Modulating the Mu Opioid Receptor in a Biased Fashion.

Mounting evidence has suggested that G protein-coupled receptors can be stabilized in multiple conformations in response to distinct ligands, which exert discrete functions through selective activation of various downstream signaling events. In accordance with this concept, we report biased signaling of one C6-heterocyclic substituted naltrexamine derivative, namely, 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(4'-pyridylcarboxamido)morphinan (NAP) at the mu opioid receptor (MOR). NAP acted as a low efficacy MOR partial agonist in the G protein-mediated [(35)S]GTPγS binding assay, whereas it did not significantly induce calcium flux or β-arrestin2 recruitment.

Exploration on natural product anibamine side chain modification toward development of novel CCR5 antagonists and potential anti-prostate cancer agents.

Prostate cancer is one of the leading causes of death among males in the world. Prostate cancer cells have been shown to express upregulated chemokine receptor CCR5, a G protein-coupled receptor (GPCR) that relates to the inflammation process. Anibamine, a natural product containing a pyridine ring and two aliphatic side chains, was shown to carry a binding affinity of 1 μM at CCR5 as an antagonist with potential anti-cancer activity.

Small molecule inhibits activity of scavenger receptor A: Lead identification and preliminary studies.

Scavenger receptor A (SRA) has been implicated in the processes of tumor invasion and acts as an immunosuppressor during therapeutic cancer vaccination. Pharmacological inhibition of SRA function thus holds a great potential to improve treatment outcome of cancer therapy. Macromolecular natural product sennoside B was recently shown to block SRA function.

Design, syntheses, and pharmacological characterization of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3'-carboxamido)morphinan analogues as opioid receptor ligands.

A series of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3'-carboxamido)morphinan (NAQ) analogues were synthesized and pharmacologically characterized to study their structure-activity relationship at the mu opioid receptor (MOR). The competition binding assay showed two-atom spacer and aromatic side chain were optimal for MOR selectivity. Meanwhile, substitutions at the 1'- and/or 4'-position of the isoquinoline ring retained or improved MOR selectivity over the kappa opioid receptor while still possessing above 20-fold MOR selectivity over the delta opioid receptor.

Investigation on vitamin D knowledge, attitude and practice of university students in Nanjing, China.

Objective: To investigate university students' knowledge, attitudes and practice (KAP) regarding vitamin D.

Design: The students were requested to answer a questionnaire related to vitamin D and sun exposure. The consumption frequency of foods rich in vitamin D was assessed.

Effects of the novel, selective and low-efficacy mu opioid receptor ligand NAQ on intracranial self-stimulation in rats.

Rationale: Low-efficacy mu opioid receptor agonists may be useful for some clinical indications, but clinically available low-efficacy mu agonists also have low selectivity for mu vs. kappa opioid receptors. NAQ (17-cyclopropylmethyl-3,14ß-dihydroxy-4,5α-epoxy-6α-[(3'-isoquinolyl)acetamido]morphinan) is a novel opioid receptor ligand with low-efficacy at mu receptors and greater mu-receptor selectivity than existing low-efficacy agonists.