Explore the vast range of titles available.

Overqualification denotes situations in which job incumbents have higher qualifications than those required for the job. Drawing on the self-regulatory perspective, we proposed that employees’ perception of overqualification positively affects their proactive behavior through the mechanism of role-breadth self-efficacy and that this indirect effect is moderated by employees’ goal orientations. We tested our hypotheses through two studies. In Study 1, we found that perceived overqualification had a positive indirect effect on employees’ proactive behavior through role-breadth self-efficacy using a sample of 323 salespeople with a cross-lagged panel design. In Study 2, the multi-wave and multi-source data from 302 teachers confirmed the indirect effect and indicated that performance goal orientation and learning goal orientation moderated the indirect relationship.

Exploring indoleacetic acid (IAA) biosynthesis pathways of plant growth promoting bacteria and their ability to synthesize IAA is crucial for understanding the promotion mechanism and for developing more efficient microbial fertilizer. In this study, 118 bacterial endophytic strains were isolated from tomato root and 68 isolates were identified as members of Bacillus and Pseudomonas genus. After screening abilities to synthesize IAA in vitro and promote plant growth for these identified Bacillus and Pseudomonas strains, 7 endophytic strains Bacillus sp. Y_21, B. paramycoides Y_29, B. albus Y_96, B. cereus Y_121, P. plecoglossicida Y_157, Bacillus sp. Y_165 and B. aryabhattai Y_170 strains showed a significant promotion role on wheat root or leaf, including 4 endophytic strains with the potential ability to utilize intermediate metabolites, such as tryptamine and indole acetamide, to produce IAA. Genomic sequencing analysis for selected representative plant growth promoting endophytes showed that IAA-producing bacteria B. cereus mr31 and P. putida Y_166 separately harbored a complete indoleacetamide (IAM) and complete tryptamine (TAM) pathway; whereas, Bacillus sp. Y_165 and B. aryabhattai Y_170, two strains producing IAA not using tryptophan but with indole-3-acetamide, had an incomplete IAM pathway. Fermentation experiments of three genome-sequenced strains using wheat or tomato root extracts as substrate, and combining with UHPLC–MS/MS analysis for wheat root extracts, demonstrated that Bacillus sp. Y_165 strain might produce IAA by using the plant-derived indole-3-acetamide. Our study first demonstrated a novel potential mechanism for the plant growth promoting endophytes to biosynthesize IAA using plant-derived intermediates. This additional mechanism has deepened our understanding of how bacterial endophytes promote plant health and resilience, offering valuable insights about how plants regulate IAA homeostasis within their internal tissues in association with bacterial endophytes.

Existing literature on creative deviance has focused exclusively on theoretical development of the construct. Empirically, very little work has been done to test the construct. The dissertation intends to fill in this gap by developing the nomological network for creative deviance. Drawing on self-determination and leadership theories, my dissertation asks the following three questions: 1) How to operationalize creative deviance at individual level? 2) What will make people engage in creative deviance? 3) How does creative deviance render people more creativity or deviance? To answer these questions, three studies were carried out to (1) develop the measurement of creative deviance, (2) build the antecedent model, and (3) develop the outcome model. In Study 1, which is designed to develop the measurement, I conducted semi-structured interviews with managers, employees, and directors of human resource management departments in two advertising firms. After distilling these qualitative insights and according to the definition of creative deviance, I developed items with a panel of three judges, including a researcher of creativity, a researcher of workplace deviance, a Design Director of the advertisement company. To gain empirical evidence on structural validity of the items that would be used in the later formal survey using the Chinese sample, I pre-tested them using 79 respondents in China. Results validated the measurement. In Study 2, which is to develop and test the antecedent model, I investigated the motivational mechanisms for creative deviance based on self-determination (SDT) and self-efficacy (SET) theories. Results from 146 matched data over a 3-month time-lagged survey supported that intrinsic motivation and creative self-efficacy toward rejected ideas mediate the effect of autonomy on creative deviance. I also tested the indirect effect of intrinsic motivation on the condition of job involvement for creative deviance in the second stage of the mediation. The results supported the hypotheses. In Study 3, which is to develop and test the outcome model, I posit that creative deviance is positively related to five leader responses: punishing, rewarding, forgiving, ignoring and manipulating. Using 226 leader-employee dyads from two advertising firms in China, I examined how leaders’ responses to creative deviance affect employees’ subsequent creative deviance and creative performance. Results demonstrated that creative deviance was positively related to five leader responses: punishing, rewarding, forgiving, ignoring and manipulating. As hypothesized, rewarding, manipulating, and punishing conveyed the effect of creative deviance on creative performance, while forgiving, ignoring and manipulating conveyed the effect of creative deviance on subsequent creative deviance. Supportive supervision for creativity moderated the relationships between creative deviance and rewarding, as well as between creative deviance and forgiving. By developing measurement at the individual level and testing the above two models for nomological network, my research sheds light on the micro-level knowledge of creative deviance and facilitates related research in the field of organizational behavior. Implications for theory and managerial practices, limitations, and directions for future research are discussed. Keywords: creative deviance, creativity, deviance, leadership, intrinsic motivation

Bone marrow mesenchymal stem cells were isolated, purified and cultured in vitro by Percoll density gradient centrifugation combined with the cell adherence method. Passages 3 5 bone marrow mesenchymal stem cells were transplanted into rats with traumatic spinal cord injury via the caudal vein. Basso-Beattie-Bresnahan scores indicate that neurological function of experimental rats was significantly improved over transplantation time （1-5 weeks）. Expressions of choline acetyltransferase, glutamic acid decarboxytase and synapsins in the damaged spinal cord of rats was significantly increased after transplantation, determined by immunofluorescence staining and laser confocal scanning microscopy. Bone marrow mesenchymal stem cells that had migrated into the damaged area of rats in the experimental group began to express choline acetyltransferase, glutamic acid decarboxylase and synapsins, 3 weeks after transplantation. The Basso-Beattie- Bresnahan scores positively correlated with expression of choline acetyltransferase and synapsins. Experimental findings indicate that intravenously transplanted bone marrow mesenchymal stem cells traverse into the damaged spinal cord of rats, promote expression of choline acetyltransferase, glutamic acid decarboxylase and synapsins, and improve nerve function in rats with spinal cord injury.

We introduce MedMNIST v2 , a large-scale MNIST-like dataset collection of standardized biomedical images, including 12 datasets for 2D and 6 datasets for 3D. All images are pre-processed into a small size of 28 × 28 (2D) or 28 × 28 × 28 (3D) with the corresponding classification labels so that no background knowledge is required for users. Covering primary data modalities in biomedical images, MedMNIST v2 is designed to perform classification on lightweight 2D and 3D images with various dataset scales (from 100 to 100,000) and diverse tasks (binary/multi-class, ordinal regression, and multi-label). The resulting dataset, consisting of 708,069 2D images and 9,998 3D images in total, could support numerous research/educational purposes in biomedical image analysis, computer vision, and machine learning. We benchmark several baseline methods on MedMNIST v2, including 2D/3D neural networks and open-source/commercial AutoML tools. The data and code are publicly available at https://medmnist.com/ . Measurement(s) supervised machine learning Technology Type(s) machine learning

Background Inactivation of the tumor suppressor p53 is critical for pathogenesis of glioma, in particular glioblastoma multiforme (GBM). MDM2, the main negative regulator of p53, binds to and forms a stable complex with p53 to regulate its activity. Hitherto, it is unclear whether the stability of the p53/MDM2 complex is affected by lncRNAs, in particular circular RNAs that are usually abundant and conserved, and frequently implicated in different oncogenic processes. Methods RIP-seq and RIP-qPCR assays were performed to determine the most enriched lncRNAs (including circular RNAs) bound by p53, followed by bioinformatic assays to estimate the relevance of their expression with p53 signaling and gliomagenesis. Subsequently, the clinical significance of CDR1as was evaluated in the largest cohort of Chinese glioma patients from CGGA ( n  = 325), and its expression in human glioma tissues was further evaluated by RNA FISH and RT-qPCR, respectively. Assays combining RNA FISH with protein immunofluorescence were performed to determine co-localization of CDR1as and p53, followed by CHIRP assays to confirm RNA-protein interaction. Immunoblot assays were carried out to evaluate protein expression, p53/MDM2 interaction and p53 ubiquitination in cells in which CDR1as expression was manipulated. After AGO2 or Dicer was knocked-down to inhibit miRNA biogenesis, effects of CDR1as on p53 expression, stability and activity were determined by immunoblot, RT-qPCR and luciferase reporter assays. Meanwhile, impacts of CDR1as on DNA damage were evaluated by flow cytometric assays and immunohistochemistry. Tumorigenicity assays were performed to determine the effects of CDR1as on colony formation, cell proliferation, the cell cycle and apoptosis (in vitro), and on tumor volume/weight and survival of nude mice xenografted with GBM cells (in vivo). Results CDR1as is found to bind to p53 protein. CDR1as expression decreases with increasing glioma grade and it is a reliable independent predictor of overall survival in glioma, particularly in GBM. Through a mechanism independent of acting as a miRNA sponge, CDR1as stabilizes p53 protein by preventing it from ubiquitination. CDR1as directly interacts with the p53 DBD domain that is essential for MDM2 binding, thus disrupting the p53/MDM2 complex formation. Induced upon DNA damage, CDR1as may preserve p53 function and protect cells from DNA damage. Significantly, CDR1as inhibits tumor growth in vitro and in vivo, but has little impact in cells where p53 is absent or mutated. Conclusions Rather than acting as a miRNA sponge, CDR1as functions as a tumor suppressor through binding directly to p53 at its DBD region to restrict MDM2 interaction. Thus, CDR1as binding disrupts the p53/MDM2 complex to prevent p53 from ubiquitination and degradation. CDR1as may also sense DNA damage signals and form a protective complex with p53 to preserve p53 function. Therefore, CDR1as depletion may play a potent role in promoting tumorigenesis through down-regulating p53 expression in glioma. Our results broaden further our understanding of the roles and mechanism of action of circular RNAs in general and CDR1as in particular, and can potentially open up novel therapeutic avenues for effective glioma treatment.

The prognosis for patients with colorectal cancer (CRC) remains worse than expected due to metastasis, recurrence, and resistance to chemotherapy. Colorectal cancer stem cells (CRCSCs) play a vital role in tumor metastasis, recurrence, and chemotherapy resistance. However, there are currently no prognostic markers based on CRCSCs-related genes available for clinical use. In this study, single-cell transcriptome sequencing was employed to distinguish cancer stem cells (CSCs) in the CRC microenvironment and analyze their properties at the single-cell level. Subsequently, data from TCGA and GEO databases were utilized to develop a prognostic risk model for CRCSCs-related genes and validate its diagnostic performance. Additionally, functional enrichment, immune response, and chemotherapeutic drug sensitivity of the relevant genes in the risk model were investigated. Lastly, the key gene RPS17 in the risk model was identified as a potential prognostic marker and therapeutic target for further comprehensive studies. Our findings provide new insights into the prognostic treatment of CRC and offer novel perspectives for a systematic and comprehensive understanding of CRC development.

Tumor immune microenvironment exerts a profound effect on the population of infiltrating immune cells. Tissue inhibitor of matrix metalloproteinase 1 (TIMP1) is frequently overexpressed in a variety of cells, particularly during inflammation and tissue injury. However, its function in cancer and immunity remains enigmatic. In this study, we find that TIMP1 is substantially up-regulated during tumorigenesis through analyzing cancer bioinformatics databases, which is further confirmed by IHC tissue microarrays of clinical samples. The TIMP1 level is significantly increased in lymphocytes infiltrating the tumors and correlated with cancer progression, particularly in GBM. Notably, we find that the transcriptional factor Sp1 binds to the promoter of TIMP1 and triggers its expression in GBM. Together, our findings suggest that the Sp1-TIMP1 axis can be a potent biomarker for evaluating immune cell infiltration at the tumor sites and therefore, the malignant progression of GBM.

Despite advancements in antiretroviral therapy (ART) suppressing HIV-1 replication, existing antiviral drugs pose limitations, including lifelong medication, frequent administration, side effects and viral resistance, necessitating novel HIV-1 treatment approaches. CD4, pivotal for HIV-1 entry, poses challenges for drug development due to neutralization and cytotoxicity concerns. Nevertheless, Ibalizumab, the sole approved CD4-specific antibody for HIV-1 treatment, reignites interest in exploring alternative anti-HIV targets, emphasizing CD4’s potential value for effective drug development. Here, we explore anti-CD4 nanobodies, particularly Nb457 from a CD4-immunized alpaca. Nb457 displays high potency and broad-spectrum activity against HIV-1, surpassing Ibalizumab’s efficacy. Strikingly, engineered trimeric Nb457 nanobodies achieve complete inhibition against live HIV-1, outperforming Ibalizumab and parental Nb457. Structural analysis unveils Nb457-induced CD4 conformational changes impeding viral entry. Notably, Nb457 demonstrates therapeutic efficacy in humanized female mouse models. Our findings highlight anti-CD4 nanobodies as promising HIV-1 therapeutics, with potential implications for advancing clinical treatment against this global health challenge. In this study, Zhu et al. report Nb457, an alpaca-derived nanobody with broad-spectrum anti-HIV1 activity and show that Nb457 induces conformational changes in CD4, blocking viral entry and completely inhibiting HIV-1 in its trimeric form.