Microplastics in different tissues of historical and live samples of endangered mega-fish (Acipenser sinensis) and their potential relevance to exposure pathways.

The Chinese sturgeon (Acipenser sinensis) is an endangered freshwater mega-fish (IUCN-red listed) that survives in the Yangtze River Basin, but the population of which has declined significantly in response to environmental pressures generated by human activities. In order to evaluate the interaction between Chinese sturgeon and microplastics (MPs) for the first time, we examined the gut and gills of historical samples (n = 27), in conjunction with the blood and mucus of live samples (n = 10), to explore the potential pathways involved in MP uptake. We detected MPs in 62.9 % of the field fish, with no significant difference between guts (mean=0.9 items/individual) and gills (mean=0.8 items/individual). The abundance of MPs in fish from 2017 was significantly higher than that from 2015 to 2016 with regards to both gills and gut samples. The size of MPs in gills was significantly smaller than those in guts, yet both contained mostly fibers (90.2 %). No MPs were confirmed in blood, however 62.5 % of mucus samples contained MPs. The MPs in mucus indicated the possibility of MPs entering Chinese sturgeons if their skins were damaged. The body size of Chinese sturgeons affected their MPs uptake by ingestion and inhalation, as less MPs were detected in the gut and gills of smaller individuals. Combining the evidence from historical and live samples, we revealed the presence of MPs in different tissues of Chinese sturgeon and their potential relevance to exposure pathways. Our work expands the understanding of multiple exposure pathways between MPs and long-lived mega-fish, while emphasizing the potential risks of long-term exposure in the field.

Mijiao formula regulates NAT10-mediated Runx2 mRNA ac4C modification to promote bone marrow mesenchymal stem cell osteogenic differentiation and improve osteoporosis in ovariectomized rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The Mijiao (MJ) formula, a traditional herbal remedy, incorporates antlers as its primary constituent. It can effectively treat osteoporosis (OP), anti-aging, enhance immune activity, and change depression-like behavior. In this study, we investigated that MJ formula is a comprehensive treatment strategy, and may provide a potential approach for the clinical treatment of postmenopausal osteoporosis. AIM OF THE STUDY: The purpose of this study was to determine whether MJ formula promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and improved osteoporosis in ovariectomized rats by regulating the NAT10-mediated Runx2 mRNA ac4C modification. MATERIALS AND METHODS: Female Sprague-Dawley (SD) rats were used to investigate the potential therapeutic effect of MJ formula on OP by creating an ovariectomized (OVX) rat model. The expression of osteogenic differentiation related proteins in BMSCs was detected in vivo, indicating their role in promoting bone formation. In addition, the potential mechanism of its bone protective effect was explored via in vitro experiments. RESULTS: Our study showed that MJ formula significantly mitigated bone mass loss in the OVX rat model, highlighting its potential as an OP therapeutic agent. We found that the possible mechanism of action was the ability of this formulation to stabilize Runx2 mRNA through NAT10-mediated ac4C acetylation, which promoted osteogenic differentiation of BMSCs and contributed to the enhancement of bone formation. CONCLUSIONS: MJ formula can treat estrogen deficiency OP by stabilizing Runx2 mRNA, promoting osteogenic differentiation and protecting bone mass. Conceivably, MJ formulation could be a safe and promising strategy for the treatment of osteoporosis.

A comprehensive review of Siraitia grosvenorii (Swingle) C. Jeffrey: chemical composition, pharmacology, toxicology, status of resources development, and applications.

Siraitia grosvenorii (Swingle) C. Jeffrey (S. grosvenorii), a perennial indigenous liana from the Cucurbitaceae family, has historically played a significant role in southern China's traditional remedies for various ailments. Its dual classification by the Chinese Ministry of Health for both medicinal and food utility underscores its has the potential of versatile applications. Recent research has shed light on the chemical composition, pharmacological effects, and toxicity of S. grosvenorii. Its active ingredients include triterpenoids, flavonoids, amino acids, volatile oils, polysaccharides, minerals, vitamins, and other microconstituents. Apart from being a natural sweetener, S. grosvenorii has been found to have numerous pharmacological effects, including alleviating cough and phlegm, preventing dental caries, exerting anti-inflammatory and anti-allergic effects, anti-aging and anti-oxidative, hypoglycemic, lipid-lowering, anti-depression, anti-fatigue, anti-schizophrenic, anti-Parkinson, anti-fibrotic, and anti-tumor activities. Despite its versatile potential, there is still a lack of systematic research on S. grosvenorii to date. This paper aims to address this gap by providing an overview of the main active components, pharmacological efficacy, toxicity, current status of development and application, development dilemmas, and strategies for intensive exploitation and utilization of S. grosvenorii. This paper aims to serve as a guide for researchers and practitioners committed to exploiting the biological resources of S. grosvenorii and further exploring its interdisciplinary potential.

Reconstructing Hydrogen-Bond Network for Efficient Acidic Oxygen Evolution.

Developing highly active oxygen evolution reaction (OER) catalysts in acidic conditions is a pressing demand for proton-exchange membrane water electrolysis. Manipulating proton character at the electrified interface, as the crux of all proton-coupled electrochemical reactions, is highly desirable but elusive. Herein we present a promising protocol, which reconstructs a connected hydrogen-bond network between the catalyst-electrolyte interface by coupling hydrophilic units to boost acidic OER activity. Modelling on N-doped-carbon-layer clothed Mn-doped-Co3O4 (Mn-Co3O4@CN), we unravel that the hydrogen-bond interaction between CN units and H2O molecule not only drags the free water to enrich the surface of Mn-Co3O4 but also serves as a channel to promote the dehydrogenation process. Meanwhile, the modulated local charge of the Co sites from CN units/Mn dopant lowers the OER barrier. Therefore, Mn-Co3O4@CN surpasses RuO2 at high current density (100 mA cm-2 @ ~538 mV).

Identification of gastric cancer types based on hyperspectral imaging technology.

Gastric cancer is becoming the second biggest cause of death from cancer. Treatment and prognosis of different types of gastric cancer vary greatly. However, the routine pathological examination is limited to the tissue level and is easily affected by subjective factors. In our study, we examined gastric mucosal samples from 50 normal tissue and 90 cancer tissues. Hyperspectral imaging technology was used to obtain spectral information. A two-classification model for normal tissue and cancer tissue identification and a four-classification model for cancer type identification are constructed based on the improved deep residual network (IDRN). The accuracy of the two-classification model and four-classification model are 0.947 and 0.965. Hyperspectral imaging technology was used to extract molecular information to realize real-time diagnosis and accurate typing. The results show that hyperspectral imaging technique has good effect on diagnosis and type differentiation of gastric cancer, which is expected to be used in auxiliary diagnosis and treatment.

Morroniside improves the symptoms of post-stroke depression in mice through the BDNF signaling pathway mediated by MiR-409-3p.

BACKGROUND: Post-stroke depression (PSD) is a common psychiatric symptom after a stroke. Morroniside, an iridoid glycoside found in Cornus officinalis, has garnered significant attention for its potential to alleviate symptoms associated with depression. PURPOSE: This study aims to highlight the potential use of morroniside in the treatment of PSD and elucidate the underlying molecular mechanisms. METHODS: To establish a reliable PSD model, male C57BL/6 mice were subjected to brief MCAO in conjunction with CUMS. Post-morroniside administration, neuronal viability, and hippocampal cell apoptosis were evaluated by Nissl staining and TUNEL detection, respectively. Depression-like behaviors were evaluated using SPT, TST, and FST. The Longa score and cylinder test were used to evaluate the effect of morroniside on motor function. Furthermore, to investigate the underlying molecular mechanisms, bioinformatic analysis and the dual luciferase assay were performed to investigate the MiR-409-3p-BDNF interaction. In addition, subsequent to MiR-409-3p overexpression via AAV virus, we assessed mRNA expression and protein levels of key components within the BDNF/TrkB signaling pathway using RT-qPCR, immunohistochemistry, and western blot analysis. RESULTS: The observed decrease in apoptosis and amelioration of depression-like behaviors strongly indicate the potential of morroniside as a therapeutic agent for PSD. Furthermore, the upregulation of key proteins within the BDNF/TrkB signaling pathway in the cortex suggests that morroniside activates this pathway. Through bioinformatics analysis, MiR-409-3p was identified and found to bind to the BDNF gene, resulting in the inhibition of BDNF expression. Importantly, we demonstrate that morroniside mitigates this inhibitory effect of MiR-409-3p on BDNF, thereby facilitating the activation of the BDNF/TrkB signaling pathway. CONCLUSION: The findings suggest that morroniside demonstrates the ability to improve PSD symptoms through the BDNF/TrkB signaling pathway mediated by MiR-409-3p. These results emphasize the importance of the BDNF signaling pathway in improving PSD symptoms and provide a possible mechanism for morroniside to treat PSD.

Gallium-Doped Hydroxyapatite: Shape Transformation and Osteogenesis Activity.

In this study, we employed a chemical precipitation method to successfully synthesize nanoparticles of gallium-doped hydroxyapatite (Ga-HAp). The microstructure of Ga-HAp was precisely tailored by modulating the concentration of gallium ions. Our findings unequivocally demonstrate that gallium ions exert a pronounced inhibitory influence on the growth of HAp crystals, and this inhibitory potency exhibits a direct correlation with the concentration of gallium. Furthermore, gallium ions facilitate the metamorphosis of HAp nanoparticles, transitioning them from nanoneedles to nanosheets. It is worth noting, however, that gallium ions exhibit a limited capacity to substitute for calcium ions within the crystal lattice of HAp, with the maximum substitution rate capped at 4.85%. Additionally, gallium plays a pivotal role in constraining the release of ions from HAp, and this behavior remains consistent across samples with varying Ga doping concentrations. Our in vitro experiments confirm that Ga-doped HAp amplifies both the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells.

Rhein attenuates cerebral ischemia-reperfusion injury via inhibition of ferroptosis through NRF2/SLC7A11/GPX4 pathway.

BACKGROUND: Ischemic stroke, a major cause of death and disability worldwide, results from reduced blood flow to the brain, leading to irreversible neuronal damage. Recent evidence suggests that ferroptosis, a form of regulated cell death, plays a critical role in the pathogenesis of ischemic stroke. Rhein, a natural anthraquinone compound, has demonstrated neuroprotective effects; However, its role in ferroptosis and the underlying mechanisms remain unclear. Here, we investigated the protective effects of Rhein against ischemia/reperfusion (I/R) injury in a rat model of middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cells. Rhein treatment dose-dependently ameliorated neurological deficits, reduced infarct volume, and attenuated blood-brain barrier (BBB) disruption in the MCAO model. Furthermore, Rhein suppressed oxidative stress, intracellular ROS generation, and ferroptosis-related protein expression in both in vivo and in vitro models. Mechanistically, Rhein protected against OGD/R-induced HT22 cell injury by regulating the NRF2/SLC7A11/GPX4 signaling pathway. This effect was abolished upon NRF2 inhibition, suggesting that Rhein's neuroprotective action is NRF2-dependent. Molecular docking and microscale thermophoresis analyses further supported the direct interaction between Rhein and the ferroptosis-related protein NRF2. Collectively, our findings reveal that Rhein confers neuroprotection against cerebral I/R injury by inhibiting ferroptosis via the NRF2/SLC7A11/GPX4 axis, providing a potential therapeutic avenue for ischemic stroke. AIMS: To investigate the neuroprotective effects of Rhein, a natural anthraquinone compound, against ischemia/reperfusion (I/R) injury and elucidate the underlying mechanisms involving ferroptosis and the NRF2/SLC7A11/GPX4 pathway. METHODS: A rat model of middle cerebral artery occlusion (MCAO) was employed for in vivo assessments, while oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cells were used as an in vitro model. Comprehensive analyses, including neurological score assessment, triphenyl tetrazolium chloride staining, Evans Blue leakage assay, intracellular ROS detection, MTT assay, dual-luciferase reporter assay, oxidative stress and Fe2+ content assessment, immunofluorescence, Western blot, flow cytometry, molecular docking, and microscale thermophoresis, were performed to evaluate the effects of Rhein on I/R injury and ferroptosis. RESULTS: Rhein conferred dose-dependent neuroprotection against cerebral I/R injury, reducing infarct volume and blood-brain barrier (BBB) disruption in the MCAO model. In both in vivo and in vitro models, Rhein suppressed oxidative stress, intracellular ROS generation, and ferroptosis-related protein expression. Furthermore, Rhein protected HT22 cells from OGD/R-induced injury by regulating the NRF2/SLC7A11/GPX4 signaling pathway, with NRF2 inhibition abolishing these therapeutic effects. Molecular docking and microscale thermophoresis analyses supported a direct interaction between Rhein and NRF2, a ferroptosis-related protein. CONCLUSION: Rhein attenuates cerebral I/R injury by inhibiting ferroptosis via the NRF2/SLC7A11/GPX4 axis, highlighting its potential as a therapeutic agent for ischemic stroke.

Transcriptome sequencing and network pharmacology-based approach to reveal the effect and mechanism of Ji Chuan Jian against Parkinson's disease.

BACKGROUND: Ji Chuan Jian (JCJ), a classic Traditional Chinese Medicine (TCM) formula, has been widely applied in treating Parkinson's disease (PD) in China, However, the interaction of bioactive compounds from JCJ with the targets involved in PD remains elusive. METHODS: Based on the transcriptome sequencing and network pharmacology approaches, the chemical compounds of JCJ and gene targets for treating PD were identified. Then, the Protein-protein interaction (PPI) and "Compound-Disease-Target" (C-D-T) network were constructed by using of Cytoscape. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to these target proteins. Finally, AutoDock Vina was used for applying molecular docking. RESULTS: In the present study, a total number of 2669 differentially expressed genes (DEGs) were identified between PD and healthy controls using whole transcriptome RNA sequencing. Then, 260 targets of 38 bioactive compounds in JCJ were identified. Of these targets, 47 were considered PD-related targets. Based on the PPI degree, the top 10 targets were identified. In C-D-T network analysis, the most important anti-PD bioactive compounds in JCJ were determined. Molecular docking revealed that potential PD-related targets, matrix metalloproteinases-9 (MMP9) were more stably bound with naringenin, quercetin, baicalein, kaempferol and wogonin. CONCLUSION: Our study preliminarily investigated the bioactive compounds, key targets, and potential molecular mechanism of JCJ against PD. It also provided a promising approach for identifying the bioactive compounds in TCM as well as a scientific basis for further elucidating the mechanism of TCM formulae in treating diseases.

Accumulation and re-distribution of microplastics via aquatic plants and macroalgae - A review of field studies.

The aquatic plants and macroalgae are primary producers with major roles regarding the maintenance of ecosystems but their interaction with microplastics (MPs) has received less attention than animals. We summarize the methodologies used, the MPs abundances and their characteristics across the literature on MPs pollution in aquatic plants and macroalgae. The sampling and quantification of MPs still lacks consistency between studies, which increased the uncertainty in cross-comparisons. The abundance of MPs varied by orders of magnitude between species and were mostly fibers and polymers with large degrees of production and applications. Filamentous species contained more MPs than others. The average ratio of MPs between vegetated and unvegetated sites reached 3:1. The average ratio of MPs between the biotic and abiotic fractions reached 2193:1, suggesting a high level of retention in fields. Our findings supported that aquatic plants and macroalgae are critical in the plastic flux within the marine environments.

GSPT1 Functions as a Tumor Promoter in Human Liver Cancer.

OBJECTIVE: This study analyzed the role of G1 to S phase transition 1 protein (GSPT1) in promoting progression of liver cancer cells. METHODS: A bioinformatics database was used to analyze the expression levels of GSPT1 in liver cancer tissues and the prognosis of patients. Subsequently, Western blotting and quantitative PCR were used to verify the expression levels of GSPT1 between normal hepatocytes and hepatoma cells. We used a CRISPR/Cas9 system to construct knockouts of GSPT1 in HepG2 and HCCLM9 liver cancer cells. The effect of GSPT1 on liver cancer cell migration and invasion was analyzed using flow cytometry, migration, and tumor formation assays. RESULTS: The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset indicated that GSPT1 expression was upregulated in liver cancer cell lines, and patients with liver cancer had poor prognosis. Knockout of GSPT1 in cells significantly inhibited tumor proliferation, cell migration, and growth in vivo. CONCLUSION: In this study, we found that GSPT1 promotes the migration and invasion of liver cancer cells.

Cysteine and glycine rich protein 2 exacerbates vascular fibrosis in pulmonary hypertension through the nuclear translocation of yes-associated protein and transcriptional coactivator with PDZ-binding motif.

Pulmonary hypertension (PH) is a serious cardiovascular disease with a poor prognosis and high mortality. The pathogenesis of PH is complex, and the main pathological changes in PH are abnormal hypertrophy and vessel stiffness. Cysteine and glycine rich protein 2 (Csrp2), a member of the LIM-only family plays a key role in the response to vascular injury. However, its roles in vascular fibrosis and PH have not been clarified. Therefore, this study aimed to investigate whether Csrp2 can promote vascular fibrosis and to further explore the possible mechanisms. Csrp2 expression was increased in both the pulmonary vasculature of rats with PH and hypoxic pulmonary vascular smooth muscle cells (PASMCs). Hypoxia activated TGF-ß1 and its downstream effector, SP1. Additionally, hypoxia activated the ROCK pathway and inhibited KLF4 expression. Silencing SP1 and overexpressing KLF4 reversed the hypoxia-induced increase in Csrp2 expression. Csrp2 knockdown decreased the expression of extracellular matrix (ECM) proteins and inhibited the nuclear translocation and expression of YAP/TAZ in hypoxic PASMCs. These results indicate that hypoxia induces Csrp2 expression through the TGF-ß1/SP1 and ROCK/KLF4 pathways. Elevated Csrp2 promoted the nuclear translocation and expression of YAP/TAZ, leading to vascular fibrosis and the development of PH.

Inhibition of UV-B stress in lettuce through enzyme-like Scutellaria baicalensis carbon dots.

Oxidative stress in plants caused by UV-B stress has always been a great challenge to the yield of agricultural products. Carbon dots (CDs) with enzyme-like activity have been developed, and inhibiting oxidative stress in animals has been achieved, but little is known about abiotic stress resistance in plants, especially UV-B stress. In this study, CDs were synthesized from Scutellaria baicalensis via a hydrothermal method. The ability of CDs to scavenge reactive oxygen species (ROS) in vivo and in vitro and to enhance antioxidant resistance in vivo was evaluated. The results show that CDs promoted the nutrient assimilation ability of lettuce seedlings and protected the plants from UV-B stress by increasing the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), glutathione reductase (GR), and ascorbate peroxidase (APX). Moreover, the antioxidant metabolism of plants can be activated by CDs and the expression levels of aquaporin (AQP) genes PIP1 and PIP2 are also up-regulated. These results facilitate the design and fabrication of CDs to meet the challenge of abiotic stress in food production.

Ergosterol production at elevated temperatures by Upc2-overexpressing Kluyveromyces marxianus using Jerusalem artichoke tubers as feedstock.

Ergosterol is an important precursor in the pharmaceutical industry for the production of numerous drugs. In this study, Kluyveromyces marxianus that showed more potential for ergosterol production than some other yeasts was reported. The effects of transcription factors UPC2, MOT3, and ROX1 of K. marxianus on ergosterol synthesis were explored, and a Upc2-overexpressing strain produced 1.78 times more ergosterol (167.33 mg/L) than the wild-type strain (60.04 mg/L). A total of 239.98 mg/L ergosterol was produced when glucose was replaced with fructose to limit ethanol production. Enhanced aeration increased ergosterol titer from 63.09 mg/L to 128.46 mg/L at 42 °C. The ergosterol titer reached 304.37 mg/L in a shake flask at 37 °C, or 1124.38 and 948.32 mg/L at 37 °C and 42 °C, respectively, in a 5 L bioreactor, using Jerusalem artichoke tubers as the sole carbon source. This study establishes a platform for ergosterol biosynthesis using inexpensive materials.

Cysteine and glycine-rich protein 2 promotes hypoxic pulmonary vascular smooth muscle cell proliferation through the Wnt3α-ß-catenin/lymphoid enhancer-binding factor 1 pathway.

Pulmonary hypertension (PH) is mainly characterized by abnormal pulmonary vascular hyperplasia and vascular remodeling, but its mechanism is complicated and currently unclear. Cysteine and glycine-rich protein 2 (Csrp2) has been reported to promote cell proliferation and migration, and affect cell cycle progression. As a new invasive actin-binding factor, Csrp2 increased the invasion and even metastasis of some cancer cells. It was associated with tumor recurrence and chemotherapy resistance. However, the role of Csrp2 in PH remains unknown. We found that Csrp2 expression was increased both in pulmonary arteries (PAs) and smooth muscle cells (PASMCs) in PH. Csrp2 enhanced PASMC proliferation and phenotypic transition. The Wnt3α-ß-catenin/lymphoid enhancer-binding factor 1 (LEF1) pathway is involved in cell proliferation and phenotypic transition regulated by Csrp2 expression. These results suggest that hypoxia downregulates YinYang-1 (YY1) and then increases Csrp2 expression. Increased Csrp2 promotes PASMC proliferation and phenotypic transition by activating the Wnt3α-ß-catenin/LEF1 pathways, which leads to pulmonary vascular remodeling and even provides a new theoretical basis for studying the pathogenesis and therapeutic targets of PH.

Salvia miltiorrhiza Derived Carbon Dots and Their Heat Stress Tolerance of Italian Lettuce by Promoting Growth and Enhancing Antioxidant Enzyme Activity.

With global warming, plants often suffer damage from high temperatures during the growth process, which inhibits their growth. In this work, carbon dots (CDs), synthesized by Salvia miltiorrhiza (S. miltiorrhiza) with a one-step hydrothermal method, were selected as heat-resistant enhancement agents for plants. Inspired by this background, this work studied Italian lettuce grown at 25, 35, and 45 °C and treated with CD and deionized water control (sprayed on leaves). The results showed that the biomass, chlorophyll content, net photosynthetic rate, activities of SOD (superoxide dismutase), POD (peroxidase), CAT (catalase), soluble sugar, and soluble protein contents of lettuce treated by CDs were increased while the contents of malondialdehyde (MDA) and proline (Pro) were decreased at 35 and 45 °C. The application of CDs at 35 and 45 °C could maintain the growth of plants by reducing oxidative damage and lipid peroxidation especially at the temperature of 35 °C, the growth status of lettuce treated by CDs was no different from that of lettuce grown naturally at the optimal temperature of 25 °C, or even better than the latter. This finding verified that the CDs could significantly improve the high-temperature tolerance of lettuce, thus alleviating the heat stress of plants.

GMFG Has Potential to Be a Novel Prognostic Marker and Related to Immune Infiltrates in Breast Cancer.

A growing amount of evidence has indicated immune genes perform a crucial position in the development and progression of breast cancer microenvironment. The purpose of our study was to identify immunogenic prognostic marker and explore potential regulatory mechanisms for breast cancer. We identified the genes related to ImmuneScore using ESTIMATE algorithm and WGCNA analysis, and we identified the differentially expressed gene (DEGs). Then, Glia maturation factor γ (GMFG) was determined as a predictive factor by intersecting immune-related genes with DEGs and survival analysis. We found the expression of GMFG was lower in breast cancer tissues compared with normal breast tissues, which was further verified by immunohistochemical (IHC). Moreover, the decreased expression of GMFG was significantly related to the poor prognosis. Besides, the expression of GMFG was related to the age, ER status, PR status, HER2 status and tumor size, which further suggested that the expression of GMFG was correlated with the subtype and the growth of tumor. The univariate and multivariate Cox regression analyses revealed that age, stage, the expression level of GMFG and radiotherapy were independent factors for predicting the prognosis of breast cancer patients. Subsequently, a prognostic model to predict the 3-year, 5-year and 10-year overall survival rate was developed based on the above four variables, and visualized as a nomogram. The values of area under the curve of the nomogram at 3-year, 5-year and 10-year were 0.897, 0.873 and 0.922, respectively, which was higher than stage in prognostic accuracy. In addition, we also found that GMFG expression level was correlated with sensitivity of some breast cancer chemotherapy drugs. Furthermore, the results of GSEA indicated immune-related pathways were mainly enriched in GMFG-high-expression group. CIBERSORT analysis for the proportion of tumor-infiltrating immune cells (TIICs) suggested that expression of GMFG was positively association with multiple kinds T-cell in BC. Among them, CD8+ T cells had the strongest correlation with GMFG expression, which revealed that GMFG might has an antitumor effect by increasing the infiltration of CD8+ T cells in breast cancer. Accordingly, GMFG has the potential to become a novel immune biomarker for the diagnosis and treatment of breast cancer.

Glycolysis-Related Gene Expression Profiling Screen for Prognostic Risk Signature of Pancreatic Ductal Adenocarcinoma.

Objective: Pancreatic ductal adenocarcinoma (PDAC) is highly lethal. Although progress has been made in the treatment of PDAC, its prognosis remains unsatisfactory. This study aimed to develop novel prognostic genes related to glycolysis in PDAC and to apply these genes to new risk stratification. Methods: In this study, based on the Cancer Genome Atlas (TCGA) PAAD cohort, the expression level of glycolysis-related gene at mRNA level in PAAD and its relationship with prognosis were analyzed. Non-negative matrix decomposition (NMF) clustering was used to cluster PDAC patients according to glycolytic genes. Prognostic glycolytic genes, screened by univariate Cox analysis and LASSO regression analysis were established to calculate risk scores. The differentially expressed genes (DEGs) in the high-risk group and the low-risk group were analyzed, and the signal pathway was further enriched to analyze the correlation between glycolysis genes. In addition, based on RNA-seq data, CIBERSORT was used to evaluate the infiltration degree of immune cells in PDAC samples, and ESTIMATE was used to calculate the immune score of the samples. Results: A total of 319 glycolysis-related genes were retrieved, and all PDAC samples were divided into two clusters by NMF cluster analysis. Survival analysis showed that PDAC patients in cluster 1 had shorter survival time and worse prognosis compared with cluster 2 samples (P < 0.001). A risk prediction model based on 11 glycolysis genes was constructed, according to which patients were divided into two groups, with significantly poorer prognosis in high-risk group than in low-risk group (P < 0.001). Both internal validation and external dataset validation demonstrate good predictive ability of the model (AUC = 0.805, P < 0.001; AUC = 0.763, P < 0.001). Gene aggregation analysis showed that DEGs highly expressed in high-risk group were mainly concentrated in the glycolysis level, immune status, and tumor cell proliferation, etc. In addition, the samples in high-risk group showed immunosuppressed status and infiltrated by relatively more macrophages and less CD8+T cell. Conclusions: These findings suggested that the gene signature based on glycolysis-related genes had potential diagnostic, therapeutic, and prognostic value for PDAC.

Clinical outcomes of dialysis patients with COVID-19 in the initial phase of the COVID-19 outbreak in Wuhan, China.

PURPOSE: Since the end of 2019, dialysis patients have been at risk of coronavirus disease 2019 (COVID-19) as well as other potential complications. Hence, we sought to describe the clinical characteristics of dialysis patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We reviewed clinical outcomes, which consisted of clinical data extracted from the medical records of 695 registered dialysis patients at the Dialysis Center of Central Hospital of Wuhan from January 13th, 2020, to February 29th, 2020, and performed statistical analysis. According to the results, there were 447, 227 and 21 hemodialysis (HD), peritoneal dialysis (PD) and combined HD and PD (HD&PD) cases, respectively. RESULTS: During the outbreak of COVID-19, 36 dialysis patients were infected by SARS-CoV-2. Among those 36 patients, 32 (7.2%) were on HD, and 4 (1.8%) were on PD. When comparing SARS-CoV-2 infection between HD and PD, the relative risk was 4.07 (RR = 4.07, 95% CI 1.46-11.35). We noted a median age of 66 years during the observation period, and the number of male patients was 23 (63.9%). There were 15 fatal cases tested positive for SARS-CoV-2 (13 cases on HD and 2 cases on PD). By comparing mortality in the same period of 2018, 2019 and 2020, the all-cause mortality of hemodialysis patients was significantly higher in 2020 (4.89%) than in either 2018 (2.55%) or 2019 (1.97%). There was no significant difference in mortality from all causes excluding COVID-19, during the same period among the 3-year period. However, during the COVID-19 outbreak, the mortality from all causes excluding COVID-19 was 2.73%, which was slightly higher than that from COVID-19 (2.16%). CONCLUSIONS: Although COVID-19 seriously threatens the health of people with uremia, deaths from all causes excluding COVID-19 during the epidemic cannot be ignored.

Hypoxia-Associated Prognostic Markers and Competing Endogenous RNA Co-Expression Networks in Breast Cancer.

Objective: Many primary tumors have insufficient supply of molecular oxygen, called hypoxia. Hypoxia is one of the leading characteristics of solid tumors resulting in a higher risk of local failure and distant metastasis. It is quite necessary to investigate the hypoxia associated molecular hallmarks in breast cancer. Materials and Methods: According to the published studies, we selected 13 hypoxia related gene expression signature to define the hypoxia status of breast cancer using ConsensusClusterPlus package based on the data from The Cancer Genome Atlas (TCGA). Subsequently, we characterized the infiltration of 24 immune cell types under different hypoxic conditions. Furthermore, the differentially expressed hypoxia associated microRNAs, mRNAs and related signaling pathways were analyzed and depicted. On this basis, a series of prognostic markers related to hypoxia were identified and ceRNA co-expression networks were constructed. Results: Two subgroups (cluster1 and cluster2) were identified and the 13 hypoxia related gene signature were all up-regulated in cluster1. Thus, we defined the cluster1 as "hypoxic subgroup" compared with cluster2. The infiltration of CD8+ T cell and CD4+ T cell were lower in cluster1 while the nTreg cell and iTreg cell were higher, indicating that there was immunosuppressive status in cluster1. We observed widespread hypoxia-associated dysregulation of microRNAs and mRNAs. Next, a risk signature for predicting prognosis of breast cancer patients was established based on 12 dysregulated hypoxia associated prognostic genes. Two microRNAs, hsa-miR-210-3p and hsa-miR-190b, with the most significant absolute logFC value were related to unfavorable and better prognosis, respectively. Several long non-coding RNAs were predicted to be microRNA targets and positively correlated with two selected mRNAs, CPEB2 and BCL11A. Predictions based on the SNHG16-hsa-miR-210-3p-CPEB2 and LINC00899/PSMG3-AS1/PAXIP-AS1-hsa-miR-190b-BCL11A ceRNA regulation networks indicated that the two genes might act as tumor suppressor and oncogene, respectively. Conclusion: Hypoxia plays an important role in the initiation and progression of breast cancer. Our research provides potential mechanisms into molecular-level understanding of tumor hypoxia.