PO-234 Research progress of exercise therapy on type 1 diabetes mellitus

Objective  Type 1 diabetes mellitus (T1DM) is an autoimmune disease with a clear genetic basis, and early islet cell function appears clearly in recession or even lost. Insulin deficiency allows patients to rely on exogenous insulin for life, and long-term complications seriously affect quality of life and shorten life expectancy.  Methods This paper retrieves 1998-2018 years' literatures on "Sports" and "type 1 diabetes" through the PubMed database, and collate and analyze the progress of the research and induction of type 1 diabetes exercise therapy. Results Numerous studies have shown that regular physical exercise can reduce the daily insulin dose in patients with T1DM.At the same time, they should master the contraindications in order to avoid the risks of movement. Currently a recommendation for all T1DM patients is engaging in at least 150 min/week of moderate to vigorous intensity aerobic exercise, sustainability or HIIT, combined with resistance training such as resistance machines and bands, as well as other stretching and balance exercises such as yoga, tai chi, 3 to 7 times per week which is depended on the physical condition of patients and exercise intensity, and resistance training can be performed on nonconsecutive days. Conclusions So patients need to be clear how to safely increase their physical activity, and incorporate more independent physical activity into daily life. &nbsp

Experimental Characterization of Laser Trepanned Microholes in Superalloy GH4220 with Water-Based Assistance

An experiment using water-assisted millisecond laser trepanning on superalloy GH4220 was carried out, and the effects of pulse energy on the hole entrance morphology, diameter, roundness, cross-section morphology, taper angle, sidewall roughness, and recast layer in air and with water-based assistance were compared and analyzed. The results show that, compared with the air condition, the water-based assistance improved the material removal rate and hole quality, increased the diameter of the hole entrance and exit, increased the hole roundness, decreased the hole taper angle, decreased the hole sidewall roughness, and reduced the recast layer thickness. In addition, under the combined action of water and steam inside the hole, the sidewall surface morphology quality was improved. Compared with the air condition, the spatter around the hole entrance was reduced, but the oxidation phenomenon formed by the thermal effect surrounding the hole entrance with water-based assistance was more obvious. The research provided technical support for the industrial application of millisecond laser drilling

Achieving simultaneous nitrogen and antibiotic removal in one-stage partial nitritation-Anammox (PN/A) process

Partial nitritation-Anammox (PN/A) process has been recognized as a sustainable process for biological nitrogen removal. Although various antibiotics have been ubiquitously detected in influent of wastewater treatment plants, little is known whether functional microorganisms in the PN/A process are capable of biodegrading antibiotics. This study aimed to investigate simultaneous nitrogen and antibiotic removal in a lab-scale one-stage PN/A system treating synthetic wastewater containing a widely-used antibiotic, sulfadiazine (SDZ). Results showed that maximum total nitrogen (TN) removal efficiency of 86.1% and SDZ removal efficiency of 95.1% could be achieved when treating 5 mg/L SDZ under DO conditions of 0.5–0.6 mg/L. Compared to anammox bacteria, ammonia-oxidizing bacteria (AOB) made a major contribution to SDZ degradation through their cometabolic pathway. A strong correlation between amoA gene and SDZ removal efficiency was found (p < 0.01). In addition, the degradation products of SDZ did not exhibit any inhibitory effects on Escherichia coli. The findings suggest that it is promising to apply the PN/A process to simultaneously remove antibiotics and nitrogen from contaminated wastewater

Integrin β3 Promotes Resistance to EGFR-TKI in Non-Small-Cell Lung Cancer by Upregulating AXL through the YAP Pathway

Integrin β3 plays a key role in the resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI), but the development of integrin β3 inhibitors has been stalled due to the failure of phase III clinical trials for cancer treatment. Therefore, it is imperative to find a potentially effective solution to the problem of acquired resistance to EGFR-TKI for patients with integrin-β3 positive non-small-cell lung cancer (NSCLC) by exploring novel downstream targets and action mechanisms of integrin β3. In the present study, we observed that the expression of integrin β3 and AXL was significantly upregulated in erlotinib-resistant NSCLC cell lines, which was further confirmed clinically in tumor specimens from patients with NSCLC who developed acquired resistance to erlotinib. Through ectopic expression or knockdown, we found that AXL expression was positively regulated by integrin β3. In addition, integrin β3 promoted erlotinib resistance in NSCLC cells by upregulating AXL expression. Furthermore, the YAP pathway, rather than pathways associated with ERK or AKT, was involved in the regulation of AXL by integrin β3. To investigate the clinical significance of this finding, the current well-known AXL inhibitor R428 was tested, demonstrating that R428 significantly inhibited resistance to erlotinib, colony formation, epithelial–mesenchymal transformation and cell migration induced by integrin β3. In conclusion, integrin β3 could promote resistance to EGFR-TKI in NSCLC by upregulating the expression of AXL through the YAP pathway. Patients with advanced NSCLC, who are positive for integrin β3, might benefit from a combination of AXL inhibitors and EGFR-TKI therapy

pH-Triggered Sheddable Shielding System for Polycationic Gene Carriers

For improving the therapeutic efficiency of tumors and decreasing undesirable side effects, ternary complexes were developed by coating pH-sensitive PEG-b-PLL-g-succinylsulfathiazole (hereafter abbreviated as PPSD) with DNA/PEI polyplexes via electrostatic interaction. PPSD can efficiently shield the surface charge of DNA/PEI. The gene transfection efficiency of ternary complexes was lower than that of DNA/PEI at pH 7.4; however, it recovered to the same level as that of DNA/PEI at pH 6.0, attributed to the pH-triggered release of DNA/PEI from ternary complexes. Cell uptake results also exhibited the same trend as transfection at different pH values. The suitable ability for pH-triggered shielding/deshielding estimated that PPSD demonstrates potential as a shielding system for use in in vivo gene delivery

CYLD regulates cell ferroptosis through Hippo/YAP signaling in prostate cancer progression

Abstract Prostate cancer (PCa) is one of the most common malignancy in men. However, the molecular mechanism of its pathogenesis has not yet been elucidated. In this study, we demonstrated that CYLD, a novel deubiquitinating enzyme, impeded PCa development and progression via tumor suppression. First, we found that CYLD was downregulated in PCa tissues, and its expression was inversely correlated with pathological grade and clinical stage. Moreover, we discovered that CYLD inhibited tumor cell proliferation and enhanced the sensitivity to cell ferroptosis in PCa in vitro and in vivo, respectively. Mechanistically, we demonstrated that CYLD suppressed the ubiquitination of YAP protein, then promoted ACSL4 and TFRC mRNA transcription. Then, we demonstrated that CYLD could enhance the sensitivity of PCa xenografts to ferroptosis in vivo. Furthermore, we discovered for the first time that there was a positive correlation between CYLD expression and ACSL4 or TFRC expression in human PCa specimens. The results of this study suggested that CYLD acted as a tumor suppressor gene in PCa and promoted cell ferroptosis through Hippo/YAP signaling

Magnesium Isotopes of Carbonate Reveal Seasonal Climate Variation in the Central East Asia During the Middle Eocene

Abstract It is debated whether there was strong climate seasonality during the Eocene, which provides a close geological analogy for near‐future scenarios of greenhouse gas emissions. Lithological data suggest the existence of a broad arid zone centered around 30°N paleo‐latitude, while a humid climate was supported by palaeobotanic assemblages in East Asia. Here, we report the occurrence of massive primary lacustrine dolomite and magnesite in the central East Asia during the middle Eocene. We provide a novel perspective from magnesium isotopes to link the formation of Mg‐carbonates to seasonal dry‐wet cycles. Rapid magnesium input during the rainy season and intense evaporation in the dry season likely caused the formation of magnesium carbonates in an enclosed lake. These findings provide insights into hydroclimatic seasonality during the Eocene, contributing to our understanding of the hydrological cycle response to a greenhouse climate

Proteasome Inhibitor YSY01A Abrogates Constitutive STAT3 Signaling via Down-regulation of Gp130 and JAK2 in Human A549 Lung Cancer Cells

Proteasome inhibition interfering with many cell signaling pathways has been extensively explored as a therapeutic strategy for cancers. Proteasome inhibitor YSY01A is a novel agent that has shown remarkable anti-tumor effects; however, its mechanisms of action are not fully understood. Here we report that YSY01A is capable of suppressing cancer cell survival by induction of apoptosis. Paradoxically, we find that YSY01A abrogates constitutive activation of STAT3 via proteasome-independent degradation of gp130 and JAK2, but not transcriptional regulation, in human A549 non-small cell lung cancer cells. The reduction in gp130 and JAK2 can be restored by co-treatment with 3-methyladenine, an early-stage autophagy lysosome and type I/III PI3K inhibitor. YSY01A also effectively inhibits cancer cell migration and lung xenograft tumor growth with little adverse effect on animals. Thus, our findings suggest that YSY01A represents a promising candidate for further development of novel anticancer therapeutics targeting the proteasome