The NAE1-mediated neddylation operates as an essential post-translational modification checkpoint for effector CD8 T cells.

Optimal activation of CD8+ T cells is crucial for immunity-mediated destruction of cancer, requiring a substantial amount of proteins involved in metabolism, proliferation, and effector function. Despite extensive studies emphasizing the role of transcriptional regulation in this process, paired transcriptomic and proteomic analyses reveal that the RNA profile is poorly correlated with protein levels. This discrepancy underscores the importance of post-translational modifications (PTMs) in controlling protein abundance during activation.

Metabolically active neutrophils represent a permissive niche for Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb)-infected neutrophils are often found in the airways of patients with active tuberculosis (TB), and excessive recruitment of neutrophils to the lung is linked to increased bacterial burden and aggravated pathology in TB. The basis for the permissiveness of neutrophils for Mtb and the ability to be pathogenic in TB has been elusive. Here, we identified metabolic and functional features of neutrophils that contribute to their permissiveness in Mtb infection.

Neutrophil extracellular traps induced by chemotherapy inhibit tumor growth in murine models of colorectal cancer.

Neutrophil extracellular traps (NETs), a web-like structure of cytosolic and granule proteins assembled on decondensed chromatin, kill pathogens and cause tissue damage in diseases. Whether NETs can kill cancer cells is unexplored. Here, we report that a combination of glutaminase inhibitor CB-839 and 5-FU inhibited the growth of PIK3CA-mutant colorectal cancers (CRCs) in xenograft, syngeneic, and genetically engineered mouse models in part through NETs.

Why Do Employees Show Pro-Environmental Behaviors? A Perspective of Environment Social Responsibility.

This research uses social identity theory to propose that environmental social responsibility perceptions influence green commitment, and then influence pro-environmental behaviors, which are moderated by institutional pressure. Data were collected from 100 employees of technology firms in Taiwan, and the results support all hypotheses. This research chose technology firms as empirical data because Taiwan's technological level is known to the world, which can reduce sampling errors caused by the lack of environmental knowledge.

The glycolysis/HIF-1α axis defines the inflammatory role of IL-4-primed macrophages.

T helper type 2 (Th2) cytokine-activated M2 macrophages contribute to inflammation resolution and wound healing. This study shows that IL-4-primed macrophages exhibit a stronger response to lipopolysaccharide stimulation while maintaining M2 signature gene expression. Metabolic divergence between canonical M2 and non-canonical proinflammatory-prone M2 (M2) macrophages occurs after the IL-4Rα/Stat6 axis.

How the Unfolded Protein Response Is a Boon for Tumors and a Bane for the Immune System.

The correct folding of proteins is essential for appropriate cell function and is tightly regulated within the endoplasmic reticulum (ER). Environmental challenges and cellular conditions disrupt ER homeostasis and induce ER stress, which adversely affect protein folding and activate the unfolded protein response (UPR). It is now becoming recognized that cancer cells can overcome survival challenges posed within the tumor microenvironment by activating the UPR.

Control of immune cell function by the unfolded protein response.

Initiating and maintaining optimal immune responses requires high levels of protein synthesis, folding, modification and trafficking in leukocytes, which are processes orchestrated by the endoplasmic reticulum. Importantly, diverse extracellular and intracellular conditions can compromise the protein-handling capacity of this organelle, inducing a state of 'endoplasmic reticulum stress' that activates the unfolded protein response (UPR). Emerging evidence shows that physiological or pathological activation of the UPR can have effects on immune cell survival, metabolism, function and fate.

To help others or not: A moderated mediation model of emotional dissonance.

This article proposes a moderated mediation model of emotional dissonance. In the model, emotional leadership negatively affects emotional dissonance, which, in turn, negatively affects helping behavior. Furthermore, the negative effect of emotional dissonance is assumed to be moderated by work-family conflict.

Breathe In, Breathe Out: Metabolic Regulation of Lung Macrophages in Host Defense Against Bacterial Infection.

Lung macrophages are substantially distinct from other tissue-resident macrophages. They act as frontier sentinels of the alveolar-blood interface and are constantly exposed to various pathogens. Additionally, they precisely regulate immune responses under homeostatic and pathological conditions to curtail tissue damage while containing respiratory infections.

The aryl hydrocarbon receptor instructs the immunomodulatory profile of a subset of Clec4a4 eosinophils unique to the small intestine.

C-type lectin domain family 4, member a4 (Clec4a4) is a C-type lectin inhibitory receptor specific for glycans thought to be exclusively expressed on murine CD8α− conventional dendritic cells. Using newly generated Clec4a4-mCherry knock-in mice, we identify a subset of Clec4a4-expressing eosinophils uniquely localized in the small intestine lamina propria. Clec4a4+ eosinophils evinced an immunomodulatory signature, whereas Clec4a4− eosinophils manifested a proinflammatory profile.

A New Concept of Work Engagement Theory in Cognitive Engagement, Emotional Engagement, and Physical Engagement.

The concept of work engagement (WE) has aroused the interest of many scholars. However, there has been limited academic research in examining how authentic leadership (AL) can influence WE, which consequently influences organizational citizenship behavior (OCB) and task performance (TP). In particular, this study divides WE into cognitive engagement, emotional engagement, and physical engagement to fully reflect the engagement theory.

PERK is a critical metabolic hub for immunosuppressive function in macrophages.

Chronic inflammation triggers compensatory immunosuppression to stop inflammation and minimize tissue damage. Studies have demonstrated that endoplasmic reticulum (ER) stress augments the suppressive phenotypes of immune cells; however, the molecular mechanisms underpinning this process and how it links to the metabolic reprogramming of immunosuppressive macrophages remain elusive. In the present study, we report that the helper T cell 2 cytokine interleukin-4 and the tumor microenvironment increase the activity of a protein kinase RNA-like ER kinase (PERK)-signaling cascade in macrophages and promote immunosuppressive M2 activation and proliferation.

Fatty acids secreted from head and neck cancer induce M2-like Macrophages.

Tumor-infiltrating monocytes can mature into Macrophages that support tumor survival or that display antitumor properties. To explore mechanisms steering Macrophage maturation, we assessed the effects of supernatants from squamous cell carcinoma cell lines (FaDu and SCC) on monocyte-derived Macrophage maturation. Purified monocytes were incubated in medium or medium supplemented with supernatants from FaDu and SCC9 or the leukemia monocytic cell line, THP-1.

Transforming the Emotional Intelligence of the Feeders in Agribusinesses into the Development of Task Performance and Counterproductive Work Behaviors during the COVID-19 Pandemic.

The present research poses a novel multilevel model to describe how transformational leadership can significantly affect task performance and counterproductive work behavior through intermediary effects of emotional intelligence, work engagement, and work burnout. The empirical data is from 240 livestock feeders from 80 Taiwanese livestock production agribusinesses. The empirical results demonstrate that leadership could indeed transform the emotional intelligence of livestock feeders into positive task performance and negative counterproductive work behavior.

Tumor-induced reshuffling of lipid composition on the endoplasmic reticulum membrane sustains macrophage survival and pro-tumorigenic activity.

Tumor-associated macrophages (TAMs) display pro-tumorigenic phenotypes for supporting tumor progression in response to microenvironmental cues imposed by tumor and stromal cells. However, the underlying mechanisms by which tumor cells instruct TAM behavior remain elusive. Here, we uncover that tumor-cell-derived glucosylceramide stimulated unconventional endoplasmic reticulum (ER) stress responses by inducing reshuffling of lipid composition and saturation on the ER membrane in macrophages, which induced IRE1-mediated spliced XBP1 production and STAT3 activation.

Toward a Unified Theory of Customer Continuance Model for Financial Technology Chatbots.

With the popularity of financial technology (fintech) chatbots equipped with artificial intelligence, understanding the user's response mechanism can help bankers formulate precise marketing strategies, which is a crucial issue in the social science field. Nevertheless, the user's response mechanism towards financial technology chatbots has been relatively under-investigated. To fill these literature gaps, latent growth curve modeling was adopted by the present research to survey Taiwanese users of fintech chatbots.

Transformational Leadership, Ethical Leadership, and Participative Leadership in Predicting Counterproductive Work Behaviors: Evidence From Financial Technology Firms.

Counterproductive work behaviors are a crucial issue for practice and academic because it influences employees' job performance and career development. The present research conceptualizes Kahn's employee engagement theory and employs transformational leadership, ethical leadership, and participative leadership as its antecedents to predict counterproductive work behaviors through a latent growth model. The present research collected empirical data of 505 employees of fintech businesses in Great China at three waves over 6 months.

Is glucose the scapegoat for tumor evasion?

Tumor cells undergo rapid aerobic glycolysis to fuel growth and proliferation. A recent finding in Nature reveals that tumor-infiltrating myeloid cells demonstrate greater capacity for glucose uptake than tumor cells and consume significant amounts within the tumor milieu. Unexpectedly, tumor cells account for the highest glutamine utilization in the tumor microenvironment.

Molecular Chaperones: Molecular Assembly Line Brings Metabolism and Immunity in Shape.

Molecular chaperones are a set of conserved proteins that have evolved to assist the folding of many newly synthesized proteins by preventing their misfolding under conditions such as elevated temperatures, hypoxia, acidosis and nutrient deprivation. Molecular chaperones belong to the heat shock protein (HSP) family. They have been identified as important participants in immune functions including antigen presentation, immunostimulation and immunomodulation, and play crucial roles in metabolic rewiring and epigenetic circuits.

Circles of Life: linking metabolic and epigenetic cycles to immunity.

Metabolites are the essential substrates for epigenetic modification enzymes to write or erase the epigenetic blueprint in cells. Hence, the availability of nutrients and activity of metabolic pathways strongly influence the enzymatic function. Recent studies have shed light on the choreography between metabolome and epigenome in the control of immune cell differentiation and function, with a major focus on histone modifications.

Carbohydrate and Amino Acid Metabolism as Hallmarks for Innate Immune Cell Activation and Function.

Immune activation is now understood to be fundamentally linked to intrinsic and/or extrinsic metabolic processes which are essential for immune cells to survive, proliferate, and perform their effector functions. Moreover, disruption or dysregulation of these pathways can result in detrimental outcomes and underly a number of pathologies in both communicable and non-communicable diseases. In this review, we discuss how the metabolism of carbohydrates and amino acids in particular can modulate innate immunity and how perturbations in these pathways can result in failure of these immune cells to properly function or induce unfavorable phenotypes.

BHLHE40 Promotes T2 Cell-Mediated Antihelminth Immunity and Reveals Cooperative CSF2RB Family Cytokines.

The transcription factor BHLHE40 is an emerging regulator of the immune system. Recent studies suggest that BHLHE40 regulates type 2 immunity, but this has not been demonstrated in vivo. We found that BHLHE40 is required in T cells for a protective T2 cell response in mice infected with the helminth elicited changes in gene and cytokine expression by lamina propria CD4 T cells, many of which were BHLHE40 dependent, including production of the common β (CSF2RB) chain family cytokines GM-CSF and IL-5.

Longitudinal Functional Assessment of Brain Injury Induced by High-Intensity Ultrasound Pulse Sequences.

Exposure of the brain to high-intensity stress waves creates the potential for long-term functional deficits not related to thermal or cavitational damage. Possible sources of such exposure include overpressure from blast explosions or high-intensity focused ultrasound (HIFU). While current ultrasound clinical protocols do not normally produce long-term neurological deficits, the rapid expansion of potential therapeutic applications and ultrasound pulse-train protocols highlights the importance of establishing a safety envelope beyond which therapeutic ultrasound can cause neurological deficits not detectable by standard histological assessment for thermal and cavitational damage.

ILC3s integrate glycolysis and mitochondrial production of reactive oxygen species to fulfill activation demands.

Group 3 innate lymphoid cells (ILC3s) are the innate counterparts of Th17 that require the transcription factor RORγt for development and contribute to the defense against pathogens through IL-22 and IL-17 secretion. Proliferation and effector functions of Th17 require a specific mTOR-dependent metabolic program that utilizes high-rate glycolysis, while mitochondrial lipid oxidation and production of reactive oxygen species (mROS) support alternative T reg cell differentiation. Whether ILC3s employ a specific metabolic program is not known.