Importance of Polyacrylamide Hydrogel Diverse Chains and Cross-Linking Density for Cell Proliferation, Aging, and Death.

Diverse chains and cross-linking density of polymers are important for cell proliferation, aging, and death. In this study, by controlling the component ratio of N,N'-methylenebisacrylamide (Bis)/acrylamide (Acr), we prepared polyacrylamide (PAM) hydrogels with three different polymer structures using ultraviolet irradiation. Moreover, we quantified their Flory's cross-linking densities, gel concentrations, and mechanical properties and evaluated their influence to HL-7702 liver cell behavior and metabolism. Results showed that PAM hydrogel at a ratio of Bis/Acr = 1:50 (Acr-50) owned the highest cross-linking density (0.04), which provided abundant binding sites for cell adhesion and allowed for rapid cell proliferation. On the basis of the binding sites, cells had strong traction interaction from fibrillate adhesion with the polymers, allowed easy cell migration, and induced the living cell aggregations with a diameter of 800 µm. Cells in aggregation exhibited healthy cell phenotypes and functions, and also the mitosis of the cells in aggregation is exactly the same with the cells in tissue. It is concluded that cell proliferation, aging, and death can be controlled by adjusting the cross-linking density and diverse chains of matrix hydrogels. This work will be helpful to design new functional soft biomaterials for tissue regeneration in the future.

Educating adolescents on preventing substance use: The role of 24-h movement behaviors ─ data from 2021 Youth Risk Behavior Surveillance.

BACKGROUND: Little is known about how adhering to the health guidelines for physical activity (PA), screen time (ST), and sleep duration (SD) relates to substance use in adolescents. Thus, this study aims to explore the potential association between adherence to the 24-h movement behavior (24-h MB) guidelines and substance use among adolescents. METHODS: Data from the 2019 Youth Risk Behavior Surveillance was analyzed. Participants reported their weekly PA, ST, SD, and substance use (alcohol and smoking) over the past 30 days. The mean age in the total participants was 15.56, and 48.03 % of the participants were females. Logistic regression was used in this study to explore the potential association between 24-h MB and substance use. Odds ratios (ORs) were reported alongside a 95 % confidence interval to enhance understanding of the observed association. RESULTS: Only 2.22 % participants adhered to all three 24-h MB guidelines, while 47.99 % did not follow any guidelines. Notably, there was no significant difference in the odds of cigarette smoking between participants who followed none of the guidelines and those who followed some or all of them. Nevertheless, adherence to one or more guidelines was found to be associated with higher odds of abstaining from alcohol consumption compared to non-adherence (one guidelines: OR = 1.17 [1.08, 1.28], two guidelines: OR = 1.28 [1.13, 1.44]). CONCLUSIONS: Adhering to 24-h MB guidelines may reduce adolescents' alcohol consumption, but the adherence was not significantly associated with smoking. Longitudinal studies are needed to confirm these findings. These results can inform adolescent health policies and interventions aimed at reducing substance use from the perspective of healthy time-use behaviors, which can be used for researchers and educator.

Construction and analysis of circular RNA-associated competing endogenous RNA network in the hippocampus of aged mice for the occurrence of postoperative cognitive dysfunction.

Circular RNAs are highly stable single-stranded circular RNAs and enriched in the brain. Previous studies showed that circRNAs, as part of competing endogenous RNAs (ceRNAs) network, play an important role in neurodegenerative and psychiatric diseases. However, the mechanism of circRNA-related ceRNA networks in postoperative cognitive dysfunction (POCD) has not been elucidated yet. POCD usually occurs in elderly patients and is characterized by hippocampal dysfunction. Here, aged C57BL/6 mice were subjected to exploratory laparotomy under sevoflurane anesthesia, and this POCD model was verified by Morris water maze test. Whole-transcriptome sequencing was performed on the hippocampus of control group (Con) and surgery group. One hundred and seventy-seven DEcircRNAs, 221 DEmiRNAs and 2,052 DEmRNAs were identified between two groups. A ceRNA network was established with 92 DEcircRNAs having binding sites with 76 DEmiRNAs and 549 target DEmRNAs. In functional enrichment analysis, a pathological pattern of POCD was highlighted in the ceRNA network: Abnormal metabolic process in neural cells, including oxygen metabolism, could promote apoptosis and then affect the synaptic function, which may undermine the neural plasticity and eventually lead to changes in cognitive function and other behavioral patterns. In conclusion, this specific ceRNA network of circRNAs-miRNAs-mRNAs has provided novel insights into the regulatory mechanisms of POCD and revealed potential therapeutic gene targets.

Effect of Anesthesia/Surgery on Gut Microbiota and Fecal Metabolites and Their Relationship With Cognitive Dysfunction.

Aims: Post-operative cognitive dysfunction (POCD) is the decline in cognitive function of the central nervous system (CNS) after anesthesia/surgery. The present study explored whether anesthesia/surgery altered gut microbiota and fecal metabolites, examining their associations with risk factors of cognitive dysfunction in aged mice. Methods: Sixteen-month-old C57BL/6 mice underwent abdominal surgery under isoflurane anesthesia to establish an animal model of POCD. The Morris water maze test (MWMT) was used as an indicator of memory after surgery. The effects of anesthesia/surgical interventions on gut microbiota, fecal metabolites, hippocampus, and serum levels of inflammatory factors were examined. Results: The anesthesia/surgery induced more serious POCD behavior, increasing brain interleukin (IL)-6, and IL-1ß levels than sham control mice. The relative abundance of bacterial genera Bacteroidales_unclassified, Mucispirillum, and Clostridiales_unclassified declined, whereas that of Escherichia-Shigella, actinomyces, Ruminococcus_gnavus_group, and Lachnospiraceae_FCS020_group were enriched after anesthesia/surgery compared to the baseline controls. Liquid chromatography-mass spectrometry (LC-MS) showed that the metabolites differed between post-anesthesia+surgery (post_A + S) and baseline samples and were associated with the fecal metabolism of tryptophan, kynurenic acid, N-oleoyl γ-aminobutyric acid (GABA), 2-indolecarboxylic acid, and glutamic acid. Furthermore, the differential metabolites were associated with alterations in the abundance of specific bacteria. These results indicate that the POCD intervention may be achieved by targeting specific bacteria associated with neurotransmitter metabolism. Conclusions: A transient cognitive disturbance induced by anesthesia/surgery may be associated with unfavorable alterations in gut microbiota and fecal metabolites, thereby contributing to the POCD development.

Insight into the Mechanism of Internalization of the Cell-Penetrating Carrier Peptide Pep-1 by Conformational Analysis.

Different secondary structures of the pep-1 protein were blamed for transmembrane internalization process of drugs and drug deliveries. But which structure will be important for transmembrane delivery was still not clear. In this study, interactions between pep-1 and cell membranes were studied. Pep-1 in the buffer (Pep-1) and pep-1 on graphene (PDS/G) or they on graphene oxide (PDS/GO) were composed as the transmembrane delivery system to study the different secondary structure of pep-1 that influence for their transmembrane delivery. The curves of chirascan circular dichroism (CD) and all-atom discontinuous molecular dynamics (DMD) simulations illuminate that, in a buffer environment, most pep-1 formed 3-10 helix structures. Meanwhile, when Pep-1 composed graphene slice and formed PDS/G, 3-10 helix and alpha-helix structures can be found in small quantities. When they on graphene oxide and formed PDS/GO, coil or type II beta-turn structure can be found from most of the pep-1 and 3-10 helix structure disappeared. By using sum-frequency generation (SFG) vibrational spectroscopy, we found that pep-1 with 3-10 helix structures in buffer solutions damaged the lipid bilayer violently. PDS/G with less 3-10 helix structures will change the orientation of lipid bilayer effectively but slightly. Pep-1 with coil or type II Beta-turn in PDS/GO cannot influence the structure of lipid bilayers. Hemolysis experiments also proved that when pep-1 composed as PDS/G, they will change the orientation of the plasma membrane of red blood cells effectively but slightly. When they attach on the GO and formed PDS/GO, the plasma membrane of red blood cells cannot be influenced. In conclusion, 3-10 helix structures will be positively correlated with disturbance of membranes. These results will be effectively guided the clinic application of pep-1 as a transporter of the drug delivery system.

Effects of anesthetic technique and surgery on myeloid-derived suppressor cells and prognosis in women who underwent breast cancer surgery: a prospective study.

Background: Surgery and anesthesia-induced immunosuppression may play a critical role in tumor progression and metastasis. Myeloid-derived suppressor cells (MDSCs) are highly immunosuppressive myeloid cells, closely linked with tumor staging, clinical therapeutic efficacy and prognosis. This study aims to investigate the effect of anesthetic technique and surgery on the expression of MDSCs and prognosis in women who received breast cancer surgery. Methods: From March 2016 to January 2017, a total of 80 patients with breast cancer were prospectively enrolled and randomized into two anesthetic groups: sevoflurane-based anesthetic group (SEV; n=38) and propofol-based total intravenous anesthetic group (TIVA; n=42). The expression of MDSCs and prognosis between different anesthetic techniques and stresses of surgical methods were compared. The primary endpoint is the postoperative expression of MDSCs and prognosis between SEV and TIVA groups. The secondary endpoint is the VAS scores at 24 hr post-operation between SEV and TIVA groups. Results: There was no significant difference in postoperative expression of MDSCs (P=0.202) and prognosis (P=0.138) between SEV and TIVA groups. Compared to breast-conserving surgery (BCS), patients who underwent breast mastectomy had significantly fewer MDSCs (P=0.040) and lower VAS score at 24 hr post-operation (P=0.044), while no significant difference in prognosis was found (P=0.953). When MDSCs were classified as subtypes of granulocytic/polymorphonuclear (PMN)-MDSCs and monocytic (Mo)-MDSCs, it showed higher ratio of Mo-MDSCs (P=0.018) or lower ratio of (PMN)-MDSCs (P=0.022) correlates to later tumor stage. Conclusion: Sevoflurane and propofol-based anesthesia do not show significant difference in MDSCs expression and prognosis after breast cancer surgery. Compared to BCS, although mastectomy with high extent of surgical stress exhibits lower levels of MDSCs, there is no significant difference in prognosis. The ratio of MDSCs subtype correlates to tumor stage.