Excess PLAC8 promotes an unconventional ERK2-dependent EMT in colon cancer

The epithelial-to-mesenchymal transition (EMT) transcriptional program is characterized by repression of E-cadherin (CDH1) and induction of N-cadherin (CDH2), and mesenchymal genes like vimentin (VIM). Placenta-specific 8 (PLAC8) has been implicated in colon cancer; however, how PLAC8 contributes to disease is unknown, and endogenous PLAC8 protein has not been studied. We analyzed zebrafish and human tissues and found that endogenous PLAC8 localizes to the apical domain of differentiated intestinal epithelium. Colon cancer cells with elevated PLAC8 levels exhibited EMT features, including increased expression of VIM and zinc finger E-box binding homeobox 1 (ZEB1), aberrant cell motility, and increased invasiveness. In contrast to classical EMT, PLAC8 overexpression reduced cell surface CDH1 and upregulated P-cadherin (CDH3) without affecting CDH2 expression. PLAC8-induced EMT was linked to increased phosphorylated ERK2 (p-ERK2), and ERK2 knockdown restored cell surface CDH1 and suppressed CDH3, VIM, and ZEB1 upregulation. In vitro, PLAC8 directly bound and inactivated the ERK2 phosphatase DUSP6, thereby increasing p-ERK2. In a murine xenograft model, knockdown of endogenous PLAC8 in colon cancer cells resulted in smaller tumors, reduced local invasion, and decreased p-ERK2. Using MultiOmyx, a multiplex immunofluorescence-based methodology, we observed coexpression of cytosolic PLAC8, CDH3, and VIM at the leading edge of a human colorectal tumor, supporting a role for PLAC8 in cancer invasion in vivo

Particle Formation by Supercritical Fluid Extraction and Expansion Process

Supercritical fluid extraction and expansion (SFEE) patented technology combines the advantages of both supercritical fluid extraction (SFE) and rapid expansion of supercritical solution (RESS) with on-line coupling, which makes the nanoparticle formation feasible directly from matrix such as Chinese herbal medicine. Supercritical fluid extraction is a green separation technology, which has been developed for decades and widely applied in traditional Chinese medicines or natural active components. In this paper, a SFEE patented instrument was firstly built up and controlled by LABVIEW work stations. Stearic acid was used to verify the SFEE process at optimized condition; via adjusting the preexpansion pressure and temperature one can get different sizes of particles. Furthermore, stearic acid was purified during the SFEE process with HPLC-ELSD detecting device; purity of stearic acid increased by 19%, and the device can purify stearic acid

The effects and paths of regional industrial structure transformation on the fluctuation and quality of the marine fisheries economy in China

Industrial structure adjustment is an important component of China’s supply-side structural reforms. This study examines the effect and action path of regional industrial structure transformation, through the lens of advancement and rationalization, on the economic fluctuation and quality of the marine fishery industry. The results show that regional industrial structure advancement (rationalization) promotes (reduces) economic fluctuation. Regarding the action paths, regional industrial structure advancement (rationalization) has a U-shaped (inverted U-shaped) relationship with economic quality. The regional industrial structure advancement level is greater than 5.108 in China’s coastal areas and on the right side of the U shape. Thus, the evolution of the industrial structure in these areas is conducive to improving the economic quality of marine fisheries. Meanwhile, The degree of regional industrial structure rationalization has not reached the optimum level, and most areas are far from optimum level. This suggests that the structural dividends from industrial structure rationalization not fully released and need further regulation. In terms of the overall effect, regional industrial structure transformation can cause economic fluctuations in marine fisheries, with the main force originating from industrial structure advancement. The path of regional industrial structure transformation affecting economic quality of marine fisheries is non-linear. At present, the industrial structure advancement transformation can improve economic quality, but the industrial structure rationalization needs to be further adjusted

Combined examination of sequence and copy number variations in human deafness genes improves diagnosis for cases of genetic deafness

BACKGROUND: Copy number variations (CNVs) are the major type of structural variation in the human genome, and are more common than DNA sequence variations in populations. CNVs are important factors for human genetic and phenotypic diversity. Many CNVs have been associated with either resistance to diseases or identified as the cause of diseases. Currently little is known about the role of CNVs in causing deafness. CNVs are currently not analyzed by conventional genetic analysis methods to study deafness. Here we detected both DNA sequence variations and CNVs affecting 80 genes known to be required for normal hearing. METHODS: Coding regions of the deafness genes were captured by a hybridization-based method and processed through the standard next-generation sequencing (NGS) protocol using the Illumina platform. Samples hybridized together in the same reaction were analyzed to obtain CNVs. A read depth based method was used to measure CNVs at the resolution of a single exon. Results were validated by the quantitative PCR (qPCR) based method. RESULTS: Among 79 sporadic cases clinically diagnosed with sensorineural hearing loss, we identified previously-reported disease-causing sequence mutations in 16 cases. In addition, we identified a total of 97 CNVs (72 CNV gains and 25 CNV losses) in 27 deafness genes. The CNVs included homozygous deletions which may directly give rise to deleterious effects on protein functions known to be essential for hearing, as well as heterozygous deletions and CNV gains compounded with sequence mutations in deafness genes that could potentially harm gene functions. CONCLUSIONS: We studied how CNVs in known deafness genes may result in deafness. Data provided here served as a basis to explain how CNVs disrupt normal functions of deafness genes. These results may significantly expand our understanding about how various types of genetic mutations cause deafness in humans

Identification of MTHFD2 as a prognostic biomarker and ferroptosis regulator in triple-negative breast cancer

BackgroundMethylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a mitochondrial bifunctional enzyme encoded in the nucleus. It plays a significant role in the regulation of glucose, nucleic acid, and folate metabolism, and maintains redox balance in the cells. The present study aimed at elucidating the potential function and mechanisms of MTHFD2 and explored the correlation between ferroptosis and MTHFD2 in triple-negative breast cancer.MethodsMTHFD2 expression, survival analysis, and clinical correlation were performed using data from various online databases including TCGA, GEO, HPA, GTEX, Kaplan–Meier Plotter, PrognoScan, and UALCAN databases. Genomic alterations and CNV analysis were performed using the cBioPortal and GSCA databases. Potential functions and mechanisms were explored by enrichment analysis. The tumor microenvironment was identified by the TIMER database. In vitro, RT-qPCR and western blot assays were utilized to identify the MTHFD2 expression and the knockdown effects in breast cancer. CCK8, cell wound healing, transwell, and flow cytometry assays were used to identify the potential function of MTHFD2 in TNBC cells. MDA, GSH detection, and flow cytometry assays were performed to identify ferroptosis. Western blot assays were performed to measure the protein expression of all target genes.ResultsMTHFD2 expression levels were up-regulated in the majority of cancers and particularly in TNBC, in which higher expression levels indicated a poorer prognosis. Enrichment analyses showed that MTHFD2 is involved in various tumor-related biological processes. MTHFD2 expression was found to strongly correlate with multiple immune cell infiltration. In vitro, the knockdown of MTHFD2 suppresses the proliferation, apoptosis, migration, and invasion in TNBC cells. In addition, the MTHFD2 knockdown significantly enhanced intracellular ROS and lipid peroxidation and decreased intracellular GSH. The expressions of SLC7A11, GPX4, and NRF2 were down-regulated by the MTHFD2 knockdown.ConclusionMTHFD2 could be a crucial molecular biomarker for predicting patient prognosis and a novel therapeutic target in TNBC. In addition, MTHFD2 is a potential ferroptosis regulatory gene in TNBC

Natural lipid nanoparticles extracted from Morus nigra L. leaves for targeted treatment of hepatocellular carcinoma via the oral route

The clinical application of conventional medications for hepatocellular carcinoma treatment has been severely restricted by their adverse effects and unsatisfactory therapeutic effectiveness. Inspired by the concept of â medicine food homologyâ , we extracted and purified natural exosome-like lipid nanoparticles (LNPs) from black mulberry (Morus nigra L.) leaves. The obtained MLNPs possessed a desirable hydrodynamic particle size (162.1 nm), a uniform size distribution (polydispersity indexâ =â 0.025), and a negative surface charge (-26.6 mv). These natural LNPs were rich in glycolipids, functional proteins, and active small molecules (e.g., rutin and quercetin 3-O-glucoside). In vitro experiments revealed that MLNPs were preferentially internalized by liver tumor cell lines via galactose receptor-mediated endocytosis, increased intracellular oxidative stress, and triggered mitochondrial damage, resulting in suppressing the viability, migration, and invasion of these cells. Importantly, in vivo investigations suggested that oral MLNPs entered into the circulatory system mainly through the jejunum and colon, and they exhibited negligible adverse effects and superior anti-liver tumor outcomes through direct tumor killing and intestinal microbiota modulation. These findings collectively demonstrate the potential of MLNPs as a natural, safe, and robust nanomedicine for oral treatment of hepatocellular carcinoma.NSFC -National Natural Science Foundation of China(SKLTCM2022067

Prediction of hydrogen consumption scale and hydrogen price based on LEAP model and two-factor learning curve

Under the dual-carbon target, hydrogen energy, as a zero-carbon secondary energy source, has great scope for replacing fossil feedstocks in the fields of energy, transportation and industry. However, the current research on the competitiveness of hydrogen energy in various fields is not sufficiently addressed. In this paper, we use the LEAP model to predict the future scale of hydrogen use and the two-factor learning curve to predict the trend of hydrogen price change from 2025 to 2050, using Qinghai Province as the research background. At the same time, considering the carbon emission reduction benefits and raw material costs, the competitiveness of hydrogen energy in energy, transportation, industry and other fields in the future is compared. The results show that: 1) The hydrogen load scale in Qinghai Province will grow fast from 2025 to 2030. From 2030 to 2040, it slows under the steady and basic scenarios but remains high under the accelerated one. By 2040, the consumption scales are 1.057 million, 649,000 and 442,000 tons respectively. 2) The price of hydrogen energy will drop rapidly from the current 28 CNY/kg to about 20 CNY/kg in the next 5 years. By 2040, the price of hydrogen energy will be reduced to about 17 CNY/kg. 3) In terms of hydrogen energy competitiveness, when carbon emissions are not taken into account, hydrogen energy is currently competitive in the transportation field. During 2032–2038, it will be competitive in the field of methanol synthesis. By 2040, hydrogen energy will not be competitive in the fields of ammonia synthesis and power/heating. When considering carbon emissions, the competitiveness of hydrogen energy in the transportation field will become greater. The competitive year in the field of methanol synthesis will be 1–2 years ahead. By 2040, it will not be competitive in the field of synthetic ammonia and power/heating, but the gap will be significantly reduced due to the consideration of carbon emissions