Intensive care unit-acquired weakness (ICU-AW), a common neuromuscular complication associated with patients in the ICU, is a type of skeletal muscle dysfunction that commonly occurs following sepsis, mobility restriction, hyperglycemia, and the use of glucocorticoids or neuromuscular blocking agents. ICU-AW can lead to delayed withdrawal of mechanical ventilation and extended hospitalization. Patients often have poor prognosis, limited mobility, and severely affected quality of life. Currently, its pathogenesis is uncertain, with unavailability of specific drugs or targeted therapies. ICU-AW has gained attention in recent years. This manuscript reviews the current research status of the epidemiology, pathogenesis, diagnosis, and treatment methods for ICU-AW and speculates the novel perspectives for future research.
Hydrogen sulfide (H2S), a gaseous signaling molecule, is associated with the development of various malignancies via modulating various cellular signaling cascades. Published research has established the fact that inhibition of endogenous H2S production or exposure of H2S donors is an effective approach against cancer progression. However, the effect of pharmacological inhibition of endogenous H2S-producing enzymes (cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MPST)) on the growth of breast cancer (BC) remains unknown. In the present study, DL-propargylglycine (PAG, inhibitor of CSE), aminooxyacetic acid (AOAA, inhibitor of CBS), and L-aspartic acid (L-Asp, inhibitor of 3-MPST) were used to determine the role of endogenous H2S in the growth of BC by in vitro and in vivo experiments. An in silico study was also performed to confirm the results. Corresponding to each enzyme in separate groups, we treated BC cells (MCF-7 and MDA-MB-231) with 10 mM of PAG, AOAA, and L-Asp for 24 h. Findings reveal that the combined dose (PAG + AOAA + L-Asp) group showed exclusive inhibitory effects on BC cells’ viability, proliferation, migration, and invasion compared to the control group. Further, treated cells exhibited increased apoptosis and a reduced level of phospho (p)-extracellular signal-regulated protein kinases such as p-AKT, p-PI3K, and p-mTOR. Moreover, the combined group exhibited potent inhibitory effects on the growth of BC xenograft tumors in nude mice, without obvious toxicity. The molecular docking results were consistent with the wet lab experiments and enhanced the reliability of the drugs. In conclusion, our results demonstrate that the inhibition of endogenous H2S production can significantly inhibit the growth of human breast cancer cells via the AKT/PI3K/mTOR pathway and suggest that endogenous H2S may act as a promising therapeutic target in human BC cells. Our study also empowers the rationale to design novel H2S-based anti-tumor drugs to cure BC.
PEST-containing nuclear protein (PCNP) is a short-lived novel nuclear protein. It has been well evaluated that PCNP mediates the progression of several cancers, but the exact mechanisms are still under investigation. In this study, we provided an e-science view of PCNP protein from the aspects of protein structure, interactions, and bioinformatics-based analysis related to evolutionary features as well as proteomic profile. The phylogenetic relationship results reveal that PCNP is closely related to Pan troglodytes and the Bovidae family, while being distantly related to the Muridae family. The analysis of the physicochemical properties of PCNP demonstrated that it is a thermolabile protein which is slightly acidic and hydrophilic in nature. Further, coexpression and protein-protein interaction analyses were carried out, which demonstrated that the PCNP gene was remarkably expressed with MORF4LI and RSL24D1 genes and has close interactions with TRAM1, PSMC6, SRP9, PRKRIR, UHRF2, and BMI1 proteins. Gene ontology and pathway enrichment analyses showed that PCNP has a high tendency to work in cell cycle regulation. Moreover, among the four 3D structure generating tools, I-TASSER-generated structure had the highest quality factor score. The validation analysis revealed that the I-TASSER-generated structure exhibited the best quality factor score with maximum amino acids in the favored region. In addition, molecular dynamic simulation analysis approved the stable structure of the PCNP. This is the first study that highlights the usefulness of the understanding of the structural and functional analysis of the PCNP, which lays the groundwork for further experimental studies to validate the outcome.
We theoretically investigate the residual current of linearly polarized light incident on graphene under the combined effect of carrier envelope phase and chirp. Phase shift and peak residual current enhancement are significantly obtained. Phase shift is the natural result of introducing a linear chirp in the presence of carrier envelope phase. By comparing the residual current integrated along the kx direction for different chirp rates and carrier envelope phases, the enhancement can be observed from two regions, where multiphoton interference is involved. By increasing the chirp rate, the light-graphene interaction turns from a non-perturbative to a perturbative regime. Thus the results of the combined effect can help to find suitable parameters to study regime transition and control of electronic dynamics. We expect that this study contributes to the signal processing at optical frequencies and to the development of optoelectronic integrated device applications.
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