Job demands, job resources and postdoctoral job satisfaction: An empirical study based on the data from 2020 Nature global postdoctoral survey.

Postdocs encounter numerous hurdles in terms of their professional survival and academic development, as a result of institutional reform and the prevailing academic environment. These challenges significantly impact their job satisfaction, which in turn plays a crucial role in shaping their scientific research career trajectory. To facilitate the advancement of relevant systems and augment the job satisfaction of postdocs, this study employs the 2020 Nature Global Postdoctoral Survey data to conduct a comprehensive analysis. Utilizing descriptive statistics, correlation analysis, and regression analysis, the impact of job characteristic elements on postdoctoral job satisfaction was examined within the theoretical framework of the Job Requirements-Resources (JD-R) model, as well as the mechanisms by which job characteristic elements impact postdoctoral job satisfaction. It was found that job demands and job resources negatively and positively predicted postdoctoral job satisfaction, respectively, with job burnout and job engagement playing a partial mediating role. Job demands can drive postdocs to develop negative coping psychology and limit the motivating effect of job resources on job engagement; job resources can act as a buffer to reduce the probability of postdocs experiencing job burnout as a result of job demands. The aforementioned findings generally support the applicability of the JD-R model to postdocs, theoretically revealing the intrinsic psychological mechanisms by which job characteristics influence postdoctoral job satisfaction and providing theoretical supplements and practical references for postdoctoral training and management.

Focused ultrasound-mediated small-molecule delivery to potentiate immune checkpoint blockade in solid tumors.

In the last decade, immune checkpoint blockade (ICB) has revolutionized the standard of treatment for solid tumors. Despite success in several immunogenic tumor types evidenced by improved survival, ICB remains largely unresponsive, especially in "cold tumors" with poor lymphocyte infiltration. In addition, side effects such as immune-related adverse events (irAEs) are also obstacles for the clinical translation of ICB. Recent studies have shown that focused ultrasound (FUS), a non-invasive technology proven to be effective and safe for tumor treatment in clinical settings, could boost the therapeutic effect of ICB while alleviating the potential side effects. Most importantly, the application of FUS to ultrasound-sensitive small particles, such as microbubbles (MBs) or nanoparticles (NPs), allows for precise delivery and release of genetic materials, catalysts and chemotherapeutic agents to tumor sites, thus enhancing the anti-tumor effects of ICB while minimizing toxicity. In this review, we provide an updated overview of the progress made in recent years concerning ICB therapy assisted by FUS-controlled small-molecule delivery systems. We highlight the value of different FUS-augmented small-molecules delivery systems to ICB and describe the synergetic effects and underlying mechanisms of these combination strategies. Furthermore, we discuss the limitations of the current strategies and the possible ways that FUS-mediated small-molecule delivery systems could boost novel personalized ICB treatments for solid tumors.

Sonoporation of Immune Cells: Heterogeneous Impact on Lymphocytes, Monocytes and Granulocytes.

Microbubble-mediated ultrasound (MB-US) can be used to realize sonoporation and, in turn, facilitate the transfection of leukocytes in the immune system. Nevertheless, the bio-effects that can be induced by MB-US exposure on leukocytes have not been adequately studied, particularly for different leukocyte lineage subsets with distinct cytological characteristics. Here, we describe how that same set of MB-US exposure conditions would induce heterogeneous bio-effects on the three main leukocyte subsets: lymphocytes, monocytes and granulocytes. MB-US exposure was delivered by applying 1-MHz pulsed ultrasound (0.50-MPa peak negative pressure, 10% duty cycle, 30-s exposure period) in the presence of microbubbles (1:1 cell-to-bubble ratio); sonoporated and non-viable leukocytes were respectively labeled using calcein and propidium iodide. Flow cytometry was then performed to classify leukocytes into their corresponding subsets and to analyze each subset's post-exposure viability, sonoporation rate, uptake characteristics and morphology. Results revealed that, when subjected to MB-US exposure, granulocytes experienced the highest loss of viability (64.0 ± 11.0%) and the lowest sonoporation rate (6.3 ± 2.5%), despite maintaining their size and granularity. In contrast, lymphocytes exhibited the lowest loss of viability (20.9 ± 7.0%), while monocytes had the highest sonoporation rate (24.1 ± 13.6%). For these two sonoporated leukocyte subsets, their cell size and granularity were found to be reduced. Also, they exhibited graded levels of calcein uptake, whereas sonoporated granulocytes achieved only mild calcein uptake. These heterogeneous bio-effects should be accounted for when using MB-US and sonoporation in immunomodulation applications.

Dietary phenolic-type Nrf2-activators: implications in the control of toxin-induced hepatic disorders.

Numerous studies have exemplified the importance of nuclear factor erythroid 2-related factor 2 (Nrf2) activation in the alleviation of toxin-induced hepatic disorders primarily through eliminating oxidative stress. Whereafter, increasingly more efforts have been contributed to finding Nrf2-activators, especially from dietary polyphenols. The present review summarized the phenolic-type Nrf2-activators published in the past few decades, analyzed their effectiveness based on their structural characteristics and outlined their related mechanisms. It turns out that flavonoids are the largest group of phenolic-type Nrf2-activators, followed by nonflavonoids and phenolic acids. When counting on subgroups, the top three types are flavonols, flavones, and hydroxycinnamic acids, with curcuminoids having the highest effective doses. Moreover, most polyphenols work through the phosphorylation of Nrf2. Besides, mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt) are the frequent targets of these Nrf2-activators, which indirectly mediate the behavior of Nrf2. However, current data are not sufficient to conclude any structure-activity relationship.

Circular RNA hsa_circ_0001658 regulates apoptosis and autophagy in gastric cancer through microRNA-182/Ras-related protein Rab-10 signaling axis.

Gastric cancer (GC) is a tumor with high incidence and lack of early diagnostic markers. The aim of this study was to explore novel regulatory circular RNAs (circRNAs) in GC and their underlying mechanisms. Differentially expressed circRNAs were analyzed using the Gene Expression Omnibus (GEO). mRNA and miRNA expression levels were determined using real-time reverse transcription polymerase chain reaction (RT-qPCR). Protein expression was detected using Western blotting. Cellular functions were evaluated using the cell counting kit-8 (CCK-8) assay and flow cytometry analysis. Immunofluorescence analysis was used to visually identify microtubule-associated protein 1 light chain 3 (LC3) puncta on a per-cell basis. Furthermore, dual-luciferase reporter and RNA pull-down assays were performed to verify the interaction between microRNA (miR)-182 and circ_0001658/Ras-related protein Rab-10 (RAB10). Circ_0001658 was identified to be aberrantly expressed in GC tissues and was demonstrated in GC cell lines (AGS and HGC27) in vitro. MiR-182 bound to circ_0001658 and RAB10. Circ_0001658 and RAB10 were upregulated, whereas miR-182 was suppressed in AGS and HGC27 cells. GC cell viability and autophagy were inhibited and apoptosis was promoted after circ_0001658 knockdown, and the cellular functions were reversed by downregulating miR-182. Moreover, upregulated RAB10 neutralized the effects of miR-182 on cell viability, autophagy, and apoptosis of GC cells. Silencing circ_0001658 restrained cell viability, suppressed autophagy, and promoted apoptosis of GC cells by sponging miR-182 to suppress the expression of RAB10. Therefore, circ_0001658 may be a potential therapeutic target for GC.

WITHDRAWN: Usage of deep learning in environmental health risk assessment.

Ahead of Print article withdrawn by publisher.

Sonoporation generates downstream cellular impact after membrane resealing.

Sonoporation via microbubble-mediated ultrasound exposure has shown potential in drug and gene delivery. However, there is a general lack of mechanistic knowledge on sonoporation-induced cellular impact after membrane resealing, and this issue has made it challenging to apply sonoporation efficiently in practice. Here, we present new evidence on how sonoporation, without endangering immediate cell viability, may disrupt downstream cellular hemostasis in ways that are distinguished from the bioeffects observed in other sonicated and unsonoporated cells. Sonoporation was realized on HL-60 leukemia cells by delivering pulsed ultrasound (1 MHz frequency, 0.50 MPa peak negative pressure; 10% duty cycle; 30 s exposure period; 29.1 J/cm2 acoustic energy density) in the presence of lipid-shelled microbubbles (1:1 cell-to-bubble ratio). Results showed that 54.6% of sonoporated cells, despite remaining initially viable, underwent apoptosis or necrosis at 24 h after sonoporation. Anti-proliferation behavior was also observed in sonoporated cells as their subpopulation size was reduced by 43.8% over 24 h. Preceding these cytotoxic events, the percentages of sonoporated cells in different cell cycle phases were found to be altered by 12 h after exposure. As well, for sonoporated cells, their expressions of cytoprotective genes in the heat shock protein-70 (HSP-70) family were upregulated by at least 4.1 fold at 3 h after exposure. Taken altogether, these findings indicate that sonoporated cells attempted to restore homeostasis after membrane resealing, but many of them ultimately failed to recover. Such mechanistic knowledge should be taken into account to devise more efficient sonoporation-mediated therapeutic protocols.

Cellular Bioeffect Investigations on Low-Intensity Pulsed Ultrasound and Sonoporation: Platform Design and Flow Cytometry Protocol.

At low-intensity levels, ultrasound can potentially generate therapeutic effects on living cells, and it can trigger sonoporation when microbubbles (MBs) are present to facilitate drug delivery. Yet, our foundational knowledge of low-intensity pulsed ultrasound (LIPUS) and sonoporation remains to be critically weak because the pertinent cellular bioeffects have not been rigorously studied. In this article, we present a population-based experimental protocol that can effectively foster investigations on the mechanistic bioeffects of LIPUS and sonoporation over a cell population. Walkthroughs of different methodological details are presented, including the fabrication of the ultrasound exposure platform and its calibration, as well as the design of a bioassay procedure that uses fluorescent tracers and flow cytometry to isolate sonicated cells with similar characteristics. An application example is also presented to illustrate how our protocol can be used to investigate the downstream cellular bioeffects of leukemia cells. We show that, with 1-MHz LIPUS exposure (with 29.1 J/cm2 delivered acoustic energy density), variations in viability and morphology would be found among different types of sonicated leukemia cells (HL-60, Molt-4) in the absence and presence of MBs. Taken altogether, this article provides a reference on how cellular bioeffect experiments on LIPUS and sonoporation can be planned meticulously to acquire strong observations that are critical to establish the biological foundations for therapeutic applications.

Oxidative Stress Alters the Morphological Responses of Myoblasts to Single-Site Membrane Photoporation.

The responses of single cells to plasma membrane damage is critical to cell survival under adverse conditions and to many transfection protocols in genetic engineering. While the post-damage molecular responses have been much studied, the holistic morphological changes of damaged cells have received less attention. Here we document the post-damage morphological changes of the C2C12 myoblast cell bodies and nuclei after femtosecond laser photoporation targeted at the plasma membrane. One adverse environmental condition, namely oxidative stress, was also studied to investigate whether external environmental threats could affect the cellular responses to plasma membrane damage. The 3D characteristics data showed that in normal conditions, the cell bodies underwent significant shrinkage after single-site laser photoporation on the plasma membrane. However for the cells bearing hydrogen peroxide oxidative stress beforehand, the cell bodies showed significant swelling after laser photoporation. The post-damage morphological changes of single cells were more obvious after chronic oxidative exposure than that after acute ones. Interestingly, in both conditions, the 2D projection of nucleus apparently shrank after laser photoporation and distanced itself from the damage site. Our results suggest that the cells may experience significant multi-dimensional biophysical changes after single-site plasma membrane damage. These post-damage responses could be dramatically affected by oxidative stress.

Oxidative Stress and Plasma Membrane Repair in Single Myoblasts After Femtosecond Laser Photoporation.

Cell membranes are susceptible to biophysical damages. These biophysical damages often present themselves in challenging oxidative environments, such as in chronic inflammation. Here we report the damage evolution after single myoblasts were individually subjected to femtosecond (fs) laser photoporation on their plasma membranes under normal and oxidative conditions. A well-characterized tunable fs laser was coupled with a laser scanning confocal microscope. The post-damage wound evolution was documented by real-time imaging. The fs laser could generate a highly focused hole at a targeted site of the myoblast plasma membrane. The initial hole size depended on the laser dosage in terms of power and exposure duration. With the same laser power and irradiation duration, photoporation invoked bigger holes in the oxidative groups than in the control. Myoblasts showed difficulty in repairing holes with initial size beyond certain threshold. Within the threshold, holes could apparently be resealed within 100 s under the normal condition; while in oxidative condition, the resealing process could take 100-300 s. The hole-resealing capacity of myoblasts was compromised under oxidative stress particularly when the oxidative exposure was chronic. It is interesting to note that brief exposure to oxidative stress apparently could promote resealing in myoblasts after photoporation.

Distraction reduces theta synchronization in emotion regulation during adolescence.

We sought to determine if attentional distraction in adolescents can modulate event-related desynchronization or synchronization (ERD or ERS) of the theta band during emotion regulation. Event-related theta oscillations were collected from 48 adolescents and young adults as they performed a distraction (counting) task while viewing affective pictures. Consistent with data from adult participants, positive and negative pictures elicited a larger theta ERS than did neutral pictures within a 100-400 ms window, indicating that early theta ERS is indicative of motivated attention to biologically salient stimuli. Counting as a distraction strategy attenuated early affective modulation of theta ERS. Moreover, theta ERS increased with age in the anterior regions of the brain regardless of valence; however, no age differences were found in the posterior regions. These results suggest that distraction depends on a top-down attentional mechanism that disrupts theta ERS for affective pictures at an early stage. Furthermore, adolescents undergo a developmental increase in oscillatory brain reorganization.