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. We conclude by outlining how AI literacy and other human-centered skills will play an increasingly important role in future workplaces.

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. At the same time, we used the text mining analysis method to analyze the social media text data, and the results are as follows. In that analysis of concern about environmental protection, women show a stronger attitude and willingness to protect the environment than men, and the public in economically developed areas is more concerned. In order to further investigate the public's environmental concerns, this study also utilized the PageRank algorithm to further study the forwarding relationships between users. The study found that celebrities and some good media organizations can attract environmental attention. Finally, we use pyLDAvis technology to visualize and analyze popular environmental themes and propose reasonable countermeasures and suggestions to enhance public environmental awareness based on the research results.

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. METHODOLOGY: We recruited 28 patients with non-syndromic oligodontia who were admitted to the Hospital of Stomatology Hebei Medical University (China) from 2018 to 2021. Peripheral blood was collected from the probands and their core family members for whole-exome sequencing (WES) and variants were verified by Sanger sequencing. Bioinformatics tools were used to predict the pathogenicity of the variants. SWISS-MODEL homology modeling was used to analyze the three-dimensional structural changes of variant proteins. We also analyzed the genotype-phenotype relationships of PAX9 variants. RESULTS: We identified novel compound heterozygous PAX9 variants (reference sequence NM_001372076.1) in a Chinese family with non-syndromic oligodontia: a new missense variant c.1010C>A (p.T337K) in exon 4 and a new frameshift variant c.330_331insGT (p.D113Afs*9) in exon 2, which was identified as the pathogenic variant in this family. This discovery expands the known variant spectrum of PAX9; then, we summarized the phenotypes of non-syndromic oligodontia with PAX9 variants. CONCLUSION: We found that PAX9 variants commonly lead to loss of the second molars.

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

Objectives. 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. Methods. 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. Results. Spiritual leadership not only helped improved a team's safety performance, but also affected it through team reflexivity. Meanwhile, work interdependence positively moderated the positive relationship between team reflexivity and team safety performance, as well as the mediating role of team reflexivity. Conclusions. The findings expanded the research scope of leadership style-safety performance at the team level, and provided guidelines for managers to promote safety and healthy development of a team in practice.

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

Abstract Studies have reported that >91.9% of non-syndromic tooth agenesis cases are caused by seven pathogenic genes. Objective To report novel heterozygous PAX9 variants in a Chinese family with non-syndromic oligodontia and summarize the reported genotype-phenotype relationship of PAX9 variants. Methodology We recruited 28 patients with non-syndromic oligodontia who were admitted to the Hospital of Stomatology Hebei Medical University (China) from 2018 to 2021. Peripheral blood was collected from the probands and their core family members for whole-exome sequencing (WES) and variants were verified by Sanger sequencing. Bioinformatics tools were used to predict the pathogenicity of the variants. SWISS-MODEL homology modeling was used to analyze the three-dimensional structural changes of variant proteins. We also analyzed the genotype-phenotype relationships of PAX9 variants. Results We identified novel compound heterozygous PAX9 variants (reference sequence NM_001372076.1) in a Chinese family with non-syndromic oligodontia: a new missense variant c.1010C>A (p.T337K) in exon 4 and a new frameshift variant c.330_331insGT (p.D113Afs*9) in exon 2, which was identified as the pathogenic variant in this family. This discovery expands the known variant spectrum of PAX9; then, we summarized the phenotypes of non-syndromic oligodontia with PAX9 variants. Conclusion We found that PAX9 variants commonly lead to loss of the second molars.

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. The research results show that employee involution is a multi-dimensional construct with rich connotations, including four dimensions: inefficient busyness, exhaustion of innovation, promotion anxiety, and internal competition. The measurement scale consists of four factors and 13 items. The factor analysis results showed that the developed scale's reliability and validity reached an ideal level. To a certain extent, this study promotes the recognition and attention of various types of organizations at all levels to involution. The research conclusions provide theoretical guidance for employees to get rid of the involution crisis and will motivate managers to formulate better intervention measures to prevent and reduce workplace involution.

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. Organizational climate strengthens the positive relationship between positive emotional atmosphere and innovation performance and weakens the negative relationship between negative emotional atmosphere and innovation performance. This study enriches the existing literature by identifying the impact of stressors on employee innovation performance and has certain practical significance for optimizing the management of enterprises and improving employee innovation 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. Prenylflavonoids from fructus psoraleae are the main bioactive compounds responsible for its pharmacological applications, such as beaching, bavachinin, bavachalcone, isobavachalcone, and neobavaisoflavone. In previous decades, there have been some promising studies on the pharmacology of fructus psoraleae. Here, we focus on the anti-inflammatory and antiaging diseases of five psoralea prenylflavonoids, such as cardiovascular protection, diabetes and obesity intervention, neuroprotection, and osteoporosis, and discuss the mechanism of these active ingredients for better understanding the material basis and drug application of fructus psoraleae in Chinese medicine.

In vitro and in vivo functional profile characterization of 17-cyclopropylmethyl-3,14ß-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 ß-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-3,14ß-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3-carboxamido)morphinan (NAQ), a MOR selective partial agonist discovered in our laboratory, to characterize its effect on ß-arrestin2 recruitment and precipitation of a cyclic AMP overshoot. DAMGO, a MOR full agonist dose-dependently increased ß-arrestin2 association with the MOR, whereas NAQ did not. Moreover, NAQ displayed significant, concentration-dependent antagonism of DAMGO-induced ß-arrestin2 recruitment. After prolonged morphine treatment of mMOR-CHO cells, there was a significant overshoot of cAMP upon exposure to naloxone, but not NAQ. Moreover, prolonged incubation of mMOR-CHO cells with NAQ did not result in desensitization nor downregulation of the MOR. In functional studies comparing NAQ with nalbuphine in the cAMP inhibition, Ca2+ flux and [35S]GTPγS binding assays, NAQ did not show agonism in the Ca2+ flux assay but showed partial agonism in the cAMP and [35S]GTPγS assays. Also, NAQ significantly antagonized DAMGO-induced intracellular Ca2+ increase. In conclusion, NAQ is a low efficacy MOR modulator that lacks ß-arrestin2 recruitment function and does not induce cellular hallmarks of MOR adaptation and fails to precipitate a cellular manifestation of withdrawal in cells pretreated with morphine. These characteristics are desirable if NAQ is pursued for opioid abuse treatment development.

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 in vivo; 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 our hindlimb ischemia models, low-dose BavaC administered orally for 14 days stimulated the recovery of ischemic hindlimb blood flow, increased circulating EPCs, and promoted capillary angiogenesis. The BavaC treatment of rat bone marrow cells for 24 h initiated the AMP-activated protein kinase (AMPK) activity required for the differentiation of EPCs. Further testing revealed that BavaC and CGP52608, a retinoic acid receptor-related orphan receptor α (RORα) activator, enhanced the activity of RORα1 and EPO luciferase reporter gene. BavaC treatment also elevated EPO mRNA and protein expression in vitro and in vivo and the circulating EPO levels in rats. By contrast, the RORα antagonist VPR66 inhibited BavaC-induced EPO reporter activity, and differentiation of bone marrow cells into endothelial progenitor cells. Overall, this study revealed that BavaC promotes EPC differentiation and neovascularization through a RORα-EPO-AMPK axis. BavaC can be used as a promising angiogenesis agent for enhancing angiogenesis and tissue repair.

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

Norathyriol is a metabolite of mangiferin. Mangiferin has been reported to inhibit α-glucosidase. To the best of our knowledge, no study has been conducted to determine or compare those two compounds on inhibiting α-glucosidase in vitro and in vivo by far. In this study, we determined the inhibitory activity of norathyriol and mangiferin on α-glucosidase in vitro and evaluated their antidiabetic effect in diabetic mice. The results showed that norathyriol inhibited α-glucosidase in a noncompetitive manner with an IC50 value of 3.12 µM, which is more potent than mangiferin (IC50 = 358.54 µM) and positive drug acarbose (IC50 = 479.2 µM) in the zymological experiment. Both of norathyriol and mangiferin caused significant (p < 0.05) reduction in fasting blood glucose and the blood glucose levels at two hours after carbohydrate loading and it was interesting that mangiferin and norathyriol can make the decline of the blood glucose earlier than other groups ever including normal group in the starch tolerance test. However, norathyriol and mangiferin did not significantly influence carbohydrate absorption in the glucose tolerance test. Therefore, the antidiabetic effects of norathyriol and mangiferin might be associated with α-glucosidase, and norathyriol was more potent than mangiferin.

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). Periphery selective opioid antagonists may alleviate the symptoms of OIC without compromising the analgesic effects of opioids. Recently our laboratories have identified one novel lead compound, 17-cyclopropylmethyl-3,14ß-dihydroxy-4,5α-epoxy-6ß-[(4'-pyridyl)acetamido]morphinan (NAP), as a peripherally selective mu opioid receptor ligand carrying subnanomolar affinity to the mu opioid receptor and over 100-folds of selectivity over both the delta and kappa opioid receptors, with reasonable oral availability and half-life, and potential to treat OIC. Nanoparticle-based drug delivery systems are now widely considered due to their technological advantages such as good stability, high carrier capacity, low therapeutic side effects, etc. Herein we report nanoparticle supported NAP as a potential candidate for OIC treatment with improved peripheral selectivity over the original lead compound NAP.

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. These three compounds, particularly compound 1, also known as a natural product danthron, enhanced T cells activation, indicated by increased transcriptional activation of interleukin 2 (Il2) gene, production of IL-2 protein, and proliferation of T cells. Additionally, the interaction between these compounds and SRA was studied by molecular modeling. Compound 1 showed a favorable binding mode with the cysteine rich domain of SRA protein compared to compound 2 and 3. Collectively, those results would provide insight for future design and development of next generation rhein derivatives as SRA inhibitors.

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. One possible mechanism for such potentiation effects of opiates is the interaction of the mu opioid receptor (MOR) with the chemokine receptor CCR5 (CCR5), a known HIV-1 co-receptor, to form MOR-CCR5 heterodimer. In an attempt to understand this putative interaction and its relevance to neuroAIDS, we designed and synthesized a series of bivalent ligands targeting the putative CCR5-MOR heterodimer. To understand how these bivalent ligands may interact with the heterodimer, biological studies including calcium mobilization inhibition, binding affinity, HIV-1 invasion, and cell fusion assays were applied. In particular, HIV-1 infection assays using human peripheral blood mononuclear cells, macrophages, and astrocytes revealed a notable synergy in activity for one particular bivalent ligand. Further, a molecular model of the putative CCR5-MOR heterodimer was constructed, docked with the bivalent ligand, and molecular dynamics simulations of the complex was performed in a membrane-water system to help understand the biological observation.

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

The 6ß-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 0.76 ± 0.09 nM and was >900-fold more selective for MOR than DOR. The Ki for KOR was 3.46 ± 0.05 nM. In [(35)S]GTPγS ligand stimulated assay, BNAP showed low agonist efficacy with 14.6% of the maximum response of DAMGO with an EC50 of 4.84 ± 0.6 nM. However, unlike its parent compound NAP, BNAP displayed partial agonist activity at KOR with % maximum response at 45.9 ± 1.7% of U50,488H. BNAP did not reverse morphine-induced antinociception when administered subcutaneously but did antagonize when administered intracerebroventricularly. BNAP antagonized morphine-induced contractions of the circular muscle in mice colon. BNAP inhibition of field-stimulated contractions in longitudinal muscle strips for the guinea-pig ileum were also blocked by nor-BNI, a kappa opioid receptor antagonist. BNAP induced inhibition of acetic acid induced abdominal stretching in chronic morphine treated mice. These findings suggest that BNAP is a dual MOR antagonist/KOR agonist and may have functional use in irritable bowel patients.

17-Cyclopropylmethyl-3,14ß-dihydroxy-4,5α-epoxy-6ß-(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-3,14ß-dihydroxy-4,5α-epoxy-6ß-(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 ß-arrestin2 recruitment. In contrast, it potently blocked MOR full agonist-induced ß-arrestin2 recruitment and translocation. Additionally, NAP dose-dependently antagonized MOR full agonist-induced intracellular calcium flux and ß-arrestin2 recruitment. Further results in an isolated organ bath preparation confirmed that NAP reversed the morphine-induced reduction in colon motility. Ligand docking and dynamics simulation studies of NAP at the MOR provided more supporting evidence for biased signaling of NAP at an atomic level. Due to the fact that NAP is MOR selective and preferentially distributed peripherally upon systemic administration while ß-arrestin2 is reportedly required for impairment of intestinal motility by morphine, biased antagonism of ß-arrestin2 recruitment by NAP further supports its utility as a treatment for opioid-induced constipation.

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. Additionally, the intake of vitamin D-containing supplements was recorded. SETTING: A medical university in Nanjing, China. SUBJECTS: Five hundred and fifteen medical students were included. RESULTS: The highest rate of correct responses for the quiz was 68·0 %, while the lowest was 9·6 %. Most students lacked sun exposure because they did not want to get tanned; 82·7 % of students used some sun protection and sunscreen use was more popular in the female group. The consumption frequency of foods rich in vitamin D was low and 5·6 % of the students used vitamin D supplements. The students' knowledge on vitamin D was derived mainly from the media and health professionals. Most of the students were interested to know more about vitamin D. CONCLUSIONS: The present study suggested that medical students had little knowledge and unfavourable behaviours. They should get more health education through the media and health professionals. It is advisable to increase their consumption of foods rich in vitamin D.

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. However, it is not drug-like according to the Lipinski's rule of five mainly due to its two long aliphatic side chains. In our effort to improve its drug-like property, a series of anibamine derivatives were designed and synthesized by placement of aromatic side chains through an amide linkage to the pyridine ring. The newly synthesized compounds were tested for their CCR5 affinity and antagonism, and potential anti-proliferation activity against prostate cancer cell lines. Basal cytotoxicity was finally studied for compounds showing potent anti-proliferation activity. It was found that compounds with hydrophobic substitutions on the aromatic systems seemed to carry more promising CCR5 binding and prostate cancer cell proliferation inhibition activities.

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. Here we report the identification and characterization of a small molecule SRA inhibitor rhein. Rhein, a deconstructed analog of sennoside B, reversed the suppressive activity of SRA in dendritic cell-primed T cell activation, indicated by transcription activation of il2 gene and production of IL-2. Rhein also inhibited SRA ligand polyinosinic:polycytidylic acid (poly(I:C)) induced activation of transcriptional factors, including interferon regulatory factor 3 (IRF3) and signal transducer and activator of transcription 1 (STAT1). Additionally, this newly identified lead compound was docked into the homology models of the SRA cysteine rich domain to gain insights into its interaction with the receptor. It was then found that rhein can favorably interact with SRA cysteine rich domain. Collectively, rhein, being the first identified small molecule inhibitors for SRA, warrants further structure-activity relationship studies, which may lead to development of novel pharmacological intervention for cancer therapy.