Hypoxia promotes metastasis by relieving miR-598-3p-restricted glycolysis in gastric cancer.

The activation of glycolysis, particularly in the context of reprogrammed energy metabolism, is increasingly recognized as a significant characteristic of cancer. However, the precise mechanisms by which glycolysis is promoted in metastatic gastric cancer cells under normal oxygen conditions remain poorly understood. MicroRNAs (miRNAs) play a crucial role in the development of malignant phenotypes in gastric cancer. Nevertheless, our understanding of the specific involvement of miRNAs in hypoxia-induced metabolic shifting and the subsequent metastatic processes is limited. Hypoxia-induced downregulation of miR-598-3p mechanistically leads to the upregulation of RMP and IGF1r, thereby promoting glycolysis. Either overexpression of miR-598-3p or R406 treatment effectively suppresses the metastasis of gastric cancer cells both in vitro and in vivo. Collectively, the depletion of miR-598-3p alters glucose metabolism from oxidative phosphorylation to glycolysis, thereby exacerbating the malignancy of gastric cancer cells. The present findings indicate a potential target for the development of therapeutics against gastric cancers with increased miR-598-3p expression.

Insight into Formation, Synchronized Release and Stability of Co-Amorphous Curcumin-Piperine by Integrating Experimental-Modeling Techniques.

Intermolecular interactions between drug and co-former are crucial in the formation, release and physical stability of co-amorphous system. However, the interactions remain difficult to investigate with only experimental tools. In this study, intermolecular interactions of co-amorphous curcumin-piperine (i.e., CUR-PIP CM) during formation, dissolution and storage were explored by integrating experimental and modeling techniques. The formed CUR-PIP CM exhibited the strong hydrogen bond interaction between the phenolic OH group of CUR and the CO group of PIP as confirmed by FTIR, ss 13C NMR and molecular dynamics (MD) simulation. In comparison to crystalline CUR, crystalline PIP and their physical mixture, CUR-PIP CM performed significantly increased dissolution accompanied by the synchronized release of CUR and PIP, which arose from the greater interaction energy of H2O-CUR molecules and H2O-PIP molecules than CUR-PIP molecules, breaking the hydrogen bond between CUR and PIP molecules, and then causing a pair-wise solvation of CUR-PIP CM at the molecular level. Furthermore, the stronger intermolecular interaction between CUR and PIP was revealed by higher binding energy of CUR-PIP molecules, which contributed to the excellent physical stability of CUR-PIP CM over amorphous CUR or PIP. The study provides a unique insight into the formation, release and stability of co-amorphous system from MD perspective. Meanwhile, this integrated technique can be used as a practical methodology for the future design of co-amorphous formulations.

Lactate induces C2C12 myoblasts differentiation by mediating ROS/p38 MAPK signalling pathway.

Lactate serves not merely as an energy substrate for skeletal muscle but also regulates myogenic differentiation, leading to an elevation of reactive oxygen species (ROS) levels. The present study was focused on exploring the effects of lactate and ROS/p38 MAPK in promoting C2C12 myoblasts differentiation. Our results demonstrated that lactate increased C2C12 myoblasts differentiation at a range of physiological concentrations, accompanied by enhanced ROS contents. We used n-acetylcysteine (NAC, a ROS scavenger) pretreatment and found that it delayed lactate-induced C2C12 myoblast differentiation by upregulating Myf5 expression on days 5 and 7 and lowering MyoD and MyoG expression. The finding implies that lactate accompanies ROS-dependent manner to promote C2C12 myoblast differentiation. Additionally, lactate significantly increased p38 MAPK phosphorylation to promote C2C12 cell differentiation, but pretreatment with SB203580 (p38 MAPK inhibitor) reduced lactate-induced C2C12 myoblasts differentiation. whereas lactate pretreatment with NAC inhibited p38 MAPK phosphorylation in C2C12 cells, demonstrating that lactate mediated ROS and regulated the p38 MAPK signalling pathway to promote C2C12 cell differentiation. In conclusion, our results suggest that the promotion of C2C12 myoblasts differentiation by lactate is dependent on ROS and the p38 MAPK signalling pathway. These observations reveal a beneficial role for lactate in increasing myogenesis through ROS-sensitive mechanisms as well as providing new ideas regarding the positive impact of ROS in improving the function of skeletal muscle.

The allometric growth relationship between electricity consumption and economics in China.

Electric power is the basic industry of a modern country. The rapid development of the power industry has promoted economic development and social progress. With the establishment of the carbon neutrality target of carbon peak, China's power industry is also facing new situations and new challenges. This paper innovatively introduces the concept of allometric growth in biology, and uses the data of provincial electricity consumption and economic development from 1972 to 2017, to study the allometric growth relationship between electricity consumption and economics in China at multiple scales. Combined with the spatial autocorrelation analysis method, the temporal and spatial characteristics of allometric growth between electricity consumption and economic development were researched based on the analysis of spatial correlation of GDP electricity consumption intensity. The results show that: (1) The provincial GDP electricity consumption intensity shows an aggregate distribution, and the local aggregate pattern changed significantly from 1972 to 2017. (2) The High-High Cluster gradually disappeared, and the Low-Low Cluster moved southward, appearing in the middle and lower reaches of the Yangtze River. (3) The differential growth coefficient of electricity consumption and economic development increased initially and decreased from 1972 to 2017. (4) GDP would increase by 7.4%, 20.1%, and 15.6% in the simulation of electricity consumption, increasing 10% at the three stages of China's economic development. (5) The allometric growth coefficients of electricity consumption and economic development are very different in the three economic belts, eight economic zones, and provinces with different characteristics at the different stages of economic development. Formulating differentiated regulation policies for regional economic development and electricity consumption will be conducive to the coordinated development of electric power production and the national economy.

Amorphous solid dispersions: Stability mechanism, design strategy and key production technique of hot melt extrusion.

Solid dispersion (SD) system has been used as an effective formulation strategy to increase in vitro and in vivo performances of poorly water-soluble drugs, such as solubility/dissolution, stability and bioavailability. This review provides a comprehensive SD classification and identifies the most popular amorphous solid dispersions (ASDs). Meanwhile, this review further puts forward the systematic design strategy of satisfactory ASDs in terms of drug properties, carrier selection, preparation methods and stabilization mechanisms. In addition, hot melt extrusion (HME) as the continuous manufacturing technique is described including the principle and structure of HME instrument, key process parameters and production application, in order to guide the scale-up of ASDs and develop more ASD products to the market in pharmaceutical industry.

Ubiquitin E3 ligase SPOP is a host negative regulator of enterovirus 71-encoded 2A protease.

IMPORTANCE: EV71 poses a significant health threat to children aged 5 and below. The process of EV71 infection and replication is predominantly influenced by ubiquitination modifications. Our previous findings indicate that EV71 prompts the activation of host deubiquitinating enzymes, thereby impeding the host interferon signaling pathway as a means of evading the immune response. Nevertheless, the precise mechanisms by which the host employs ubiquitination modifications to hinder EV71 infection remain unclear. The present study demonstrated that the nonstructural protein 2Apro, which is encoded by EV71, exhibits ubiquitination and degradation mediated by the host E3 ubiquitin ligase SPOP. In addition, it is the first report, to our knowledge, that SPOP is involved in the host antiviral response.

K2LiScF6:Cr3+/Mn4+ fluoride phosphor with enhanced broadband emission for NIR pc-LEDs.

Trivalent chromium ion-activated broadband near-infrared (NIR) luminescence materials have shown great application prospects as next-generation NIR light sources, but improvement of the luminescence efficiency remains a challenge. Herein, novel K2LiScF6:Cr3+ and K2LiScF6:Cr3+/Mn4+ broadband fluoride NIR phosphors are designed and prepared by a combination of hydrothermal and cation exchange methods for the first time. The crystal structure and photoluminescence (PL) properties of K2LiScF6:Cr3+ are studied in detail, which shows strong absorption in the blue light region (λex = 432 nm) and broadband NIR emission (λem = 770 nm) with a PL quantum efficiency of 77.6%. More importantly, the NIR emission of Cr3+ can be enhanced by co-doping with Mn4+, which may provide an alternative way for improving the PL intensity of Cr3+-activated broadband NIR phosphors. Finally, a NIR phosphor-converted LED (pc-LED) device is fabricated using the as-prepared NIR phosphor and its application in bio-imaging and night vision has been evaluated.

Metastatic colon cancer treated using traditional Chinese medicine combined with chemotherapy: A case report.

BACKGROUND: Colon cancer (CC) is one of the leading causes of cancer-related morbidity and mortality worldwide. Traditional Chinese medicine (TCM) is widely used in the treatment of various chronic diseases. CC easily metastasizes and results in high morbidity and mortality rates. CASE SUMMARY: A 71-year-old man with a 12-year history of old myocardial infarction and a 7-year history of type 2 diabetes mellitus was diagnosed with CC and underwent right hemicolectomy 1 year ago. Tumor biopsy revealed moderately poorly differentiated adenocarcinoma. Subsequently, chemotherapy with oxaliplatin and paclitaxel was administered. Anastomosis recurrence and pelvic metastasis were noted 37 d later. The patient received eight 21-d cycles of adjuvant chemotherapy with oxaliplatin and capecitabine after recurrence. However, the tumor persisted, and chemotherapy-related liver damage developed gradually. Thus, he was advised to take TCM for the recurrence and pelvic metastasis. The patient's metastatic CC was cured after receiving TCM combined with long-term chemotherapy. CONCLUSION: TCM may be an effective adjunct therapy in the treatment of patients with metastatic CC.