Interruption of KLF5 acetylation promotes PTEN-deficient prostate cancer progression by reprogramming cancer-associated fibroblasts.

PTEN inactivation is prevalent in human prostate cancer and causes high-grade adenocarcinoma with a long latency. Cancer associated fibroblasts (CAFs) play a pivotal role in tumor progression, but it remains elusive whether and how PTEN-deficient prostate cancers reprogram CAFs to overcome the barriers for tumor progression. Herein, we report that PTEN deficiency induces KLF5 acetylation; and interruption of KLF5 acetylation orchestrates intricate interactions between cancer cells and CAFs that enhance FGFR1 signaling and promote tumor growth. Deacetylated KLF5 promotes tumor cells to secrete TNF-α, which stimulates inflammatory CAFs to release FGF9. CX3CR1 inhibition blocks FGFR1 activation triggered by FGF9 and sensitizes PTEN-deficient prostate cancer to AKT inhibitor capivasertib. This study reveals the role of KLF5 acetylation in reprogramming CAFs and provides a rational for combined therapies using inhibitors of AKT and CX3CR1.

Preparation and Support Effect of Graphdiyne Nanotubes with Abundant Cu Quantum Dots.

Graphdiyne (GDY) is considered a very attractive support for metal nanocatalysts due to its unique structure and superior properties. The metal-GDY interaction can significantly affect the performance of catalysts. Herein, GDY nanotubes abundant in in situ formed Cu quantum dots (QDs) (Cu-GDYNT) are prepared using the electrospun polyacrylonitrile nanofibers collected on the surface of electrolytic Cu foil as templates. The diameter of the Cu-GDYNT is controllable and the uniform size of the embedded Cu QDs is about 2.2 nm. And then, the uniformly dispersed and highly active supported catalysts of ruthenium nanoparticles (Rux/Cu-GDYNT) are produced using the Cu-GDYNT as the support. Among them, the Ru3/Cu-GDYNT exhibit outstanding HER performance at all pH levels. Only 17, 67 and 83 mV overpotential is required to reach a current density of 10 mA cm-2 in 1.0 M KOH, 0.5 M H2SO4 and 1.0 M neutral PBS solutions, respectively. The sample exhibits 3000 CV cycle stability and 20 h continuous electrolysis without performance degradation in an alkaline medium. This work provides a new idea for constructing the GDY-supported metal nanocatalysts.

Role of Glucose Metabolic Reprogramming in Breast Cancer Progression and Drug Resistance.

The involvement of glucose metabolic reprogramming in breast cancer progression, metastasis, and therapy resistance has been increasingly appreciated. Studies in recent years have revealed molecular mechanisms by which glucose metabolic reprogramming regulates breast cancer. To date, despite a few metabolism-based drugs being tested in or en route to clinical trials, no drugs targeting glucose metabolism pathways have yet been approved to treat breast cancer. Here, we review the roles and mechanisms of action of glucose metabolic reprogramming in breast cancer progression and drug resistance. In addition, we summarize the currently available metabolic inhibitors targeting glucose metabolism and discuss the challenges and opportunities in targeting this pathway for breast cancer treatment.

Are You Dominated by Your Affects? How and When Do Employees' Daily Affective States Impact Learning from Project Failure?

Given the enormous value that project failure brings to individuals and organizations, a large number of scholars have explored the antecedents that affect employees' learning from project failure. However, few scholars have paid attention to how individuals' affective states interact with cognition patterns to learn from failure. Based on cognitive behavioral theory, this paper explores the relationship between employees' different daily affective states and learning from project failure and incorporates the mediating role of error management strategy and the moderating role of project commitment. By using SPSS and Amos software, hierarchical regression analysis of questionnaire data collected from 774 employees in high-tech firms in China indicates that (1) positive/negative affective states positively/negatively affect learning from failure, respectively; (2) error management strategy mediates the relationship between daily affective states and learning from project failure; and (3) project commitment moderates the relationship between negative affective states and error management strategy; specifically, this relationship is weaker when project commitment is stronger. However, the moderating effect of project commitment on the relationship between positive affective states and error management strategy is not supported. The results further expand the research related to learning from failure and have practical implications for failure management in high-tech enterprises.

Exploring the Influence of Failure Aversion on Learning From Project Failure: A Sensemaking Perspective.

Although project failure is commonly considered a negative event, it can provide valuable resources for learning. Despite well documented research on the antecedents of learning from project failure at the individual level, individuals' attitude toward failures, a relatively proximal antecedent of learning from failure, has attracted limited attention in organizational studies. To address this paucity of research, based on the sensemaking theory, in the current study we specifically focused on individuals' failure aversion and explored how it would influence learning from failure through the process of arguing and expectation. Using a sample of 774 employees from R&D teams in China, our findings revealed that individuals' failure aversion enhanced their learning from failure through inducing a loss-focused coping, but failure aversion negatively affected learning from failure through increasing the individuals' perceived loss of self-esteem. We also found that individuals' learning goal orientation (LGO) weakened the negative relationship between the loss of self-esteem and learning from failure; however, LGO did not moderate our hypothesized relationship between loss-focused coping and learning from failure. Our study extends the literature on learning from failure in two ways. First, it explores the learning from failure process at the individual level based on the sensemaking theory and second, it sheds light on the underlying cognitive mechanisms operating between failure aversion and learning from project failure.

Shame on You! When and Why Failure-Induced Shame Impedes Employees' Learning From Failure in the Chinese Context.

The emotional experience brought about by failure, especially the important roles of negative emotions in learning behavior after failure, has received increasingly more attention from organization management scholars. Research on the impact of employees' sense of failure-induced shame is still controversial. Based on the Chinese context, according to the process model of emotion regulation theory, we have studied the influence of failure-induced shame on employees' learning from failure and the conditions that have boundary effects on this process. Through a questionnaire analysis of 776 samples from Chinese high-tech enterprises, the results show the following: (1) shame has a negative relationship with learning from failure (2) project commitment alleviates the negative relationship between shame and learning from failure, and (3) restoration orientation alleviates the negative relationship between shame and learning from failure while loss orientation cannot. Our results further enrich the research on negative emotions related to failure and provide a theoretical basis for the failure management of Chinese companies.

When Learning Goal Orientation Leads to Learning From Failure: The Roles of Negative Emotion Coping Orientation and Positive Grieving.

Considering failure is a common result in project management, how to effectively learn from failure has becoming a more and more important topic for managers. Drawing on the goal orientation theory and grief recovery theory, the purpose of this paper is to clarify the impact of learning goal orientation on learning from failure. Furthermore, this paper examines the mediating effect of two negative emotion coping orientations (restoration orientation and loss orientation) and the moderating effect of positive grieving in this relationship. The results indicated that: (1) A learning goal orientation is positively related to learning from failure; (2) As a dual-path mediation model, restoration orientation and loss orientation mediate the relationship between a learning goal orientation and learning from failure; and (3) Positive grieving negatively moderates the relationship between a loss orientation and learning from failure.

When Error Learning Orientation Leads to Learning From Project Failure: The Moderating Role of Fear of Face Loss.

As the importance of failure is widely recognized, there is increasing research interest in the antecedents of learning from failure. Basing on affective event theory, the current study cast light on individuals' cognition of error and proposed that employees with higher levels of error learning orientation tend to show more positive grieving after project failure, which in turn increases their learning from failure. Using a sample of 752 employees from 140 project teams, we found empirical evidence to support this theoretical model. Our results indicated that positive grieving mediated the relationship between error learning orientation and learning from failure. Besides, the relationship between error learning orientation and positive grieving is more positive for employees with lower levels of fear of face loss. Our findings help enrich the antecedents of learning from failure by shedding light on how and when error learning orientation matters. Theoretical and practical implications are discussed.

HIV-1 Employs Multiple Mechanisms To Resist Cas9/Single Guide RNA Targeting the Viral Primer Binding Site.

The clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein 9 (Cas9) gene-editing technology has been used to inactivate viral DNA as a new strategy to eliminate chronic viral infections, including HIV-1. This utility of CRISPR-Cas9 is challenged by the high heterogeneity of HIV-1 sequences, which requires the design of the single guide RNA (sgRNA; utilized by the CRISPR-Cas9 system to recognize the target DNA) to match a specific HIV-1 strain in an HIV patient. One solution to this challenge is to target the viral primer binding site (PBS), which HIV-1 copies from cellular tRNA3Lys in each round of reverse transcription and is thus conserved in almost all HIV-1 strains. In this study, we demonstrate that PBS-targeting sgRNA directs Cas9 to cleave the PBS DNA, which evokes deletions or insertions (indels) and strongly diminishes the production of infectious HIV-1. While HIV-1 escapes from PBS-targeting Cas9/sgRNA, unique resistance mechanisms are observed that are dependent on whether the plus or the minus strand of the PBS DNA is bound by sgRNA. Characterization of these viral escape mechanisms will inform future engineering of Cas9 variants that can more potently and persistently inhibit HIV-1 infection.IMPORTANCE The results of this study demonstrate that the gene-editing complex Cas9/sgRNA can be programmed to target and cleave HIV-1 PBS DNA, and thus, inhibit HIV-1 infection. Given that almost all HIV-1 strains have the same PBS, which is copied from the cellular tRNA3Lys during reverse transcription, PBS-targeting sgRNA can be used to inactivate HIV-1 DNA of different strains. We also discovered that HIV-1 uses different mechanisms to resist Cas9/sgRNAs, depending on whether they target the plus or the minus strand of PBS DNA. These findings allow us to predict that a Cas9 variant that uses the CCA sequence as the protospacer adjacent motif (PAM) should more strongly and persistently suppress HIV-1 replication. Together, these data have identified the PBS as the target DNA of Cas9/sgRNA and have predicted how to improve Cas9/sgRNA to achieve more efficient and sustainable suppression of HIV-1 infection, therefore improving the capacity of Cas9/sgRNA in curing HIV-1 infection.

When Project Commitment Leads to Learning from Failure: The Roles of Perceived Shame and Personal Control.

Facing a remarkably changing world, researchers have gradually shifted emphasis from successful experiences to failures. In the current study, we build a model to explore the relationship between project commitment and learning from failure, and test how emotion (i.e., perceived shame after failure) and cognition (i.e., attribution for failure) affect this process. After randomly selecting 400 firms from the list of high-tech firms reported by the Beijing Municipal Science and Technology Commission, we use a two-wave investigation of the employees, and the final sample consists of 140 teams from 58 companies in the technology industry in mainland China. The results provide evidence for the positive role of personal control attribution in the relationship between project commitment and learning from failure. However, in contrast to previous studies, perceived shame, as the negative emotion after failed events, could bring desirable outcomes during this process. Based on the results, we further expand a model to explain the behavioral responses after failure, and the implications of our findings for research and practice are discussed. The failures and reverses which await men - and one after another sadden the brow of youth - add a dignity to the prospect of human life, which no Arcadian success would do. -Henry David Thoreau.

[Quantitative experiment and analysis of gradient-induced eddy currents on magnetic resonance imaging].

Pulsed magnetic field gradients generated by gradient coils are widely used in signal location in magnetic resonance imaging (MRI). However, gradient coils can also induce eddy currents in final magnetic field in the nearby conducting structures which lead to distortion and artifact in images, misguiding clinical diagnosis. We tried in our laboratory to measure the magnetic field of gradient-induced eddy current in 1.5 T superconducting magnetic resonance imaging device; and extracted key parameters including amplitude and time constant of exponential terms according to inductance-resistance series mathematical module. These parameters of both self-induced component and crossing component are useful to design digital filters to implement pulse pre-emphasize to reshape the waveform. A measure device that is a basement equipped with phantoms and receiving coils was designed and placed in the isocenter of the magnetic field. By applying testing sequence, contrast experiments were carried out in a superconducting magnet before and after eddy current compensation. Sets of one dimension signal were obtained as raw data to calculate gradient-induced eddy currents. Curve fitting by least squares method was also done to match inductance-resistance series module. The results also illustrated that pulse pre-emphasize measurement with digital filter was correct and effective in reducing eddy current effect. Pre-emphasize waveform was developed based on system function. The usefulness of pre-emphasize measurement in reducing eddy current was confirmed and the improvement was also presented. All these are valuable for reducing artifact in magnetic resonance imaging device.