Antiferroptosis therapy alleviated the development of atherosclerosis.

Ferroptosis has been confirmed to be associated with various diseases, but the relationship between ferroptosis and atherosclerosis (AS) remains unclear. Our research detailly clarified the roles of ferroptosis in three continuous and main pathological stages of AS respectively (injury of endothelial cells [ECs], adhesion of monocytes, and formation of foam cells). We confirmed that oxidized low-density lipoprotein (ox-LDL), the key factor in the pathogenesis of AS, strongly induced ferroptosis in ECs. Inhibition of ferroptosis repressed the adhesion of monocytes to ECs by inhibiting inflammation of ECs. Ferroptosis also participated in the formation of foam cells and lipids by regulating the cholesterol efflux of macrophages. Further research confirmed that ox-LDL repressedthe activity of glutathione peroxidase 4 (GPX4), the classic lipid peroxide scavenger. Treatment of a high-fat diet significantly induced ferroptosis in murine aortas and aortic sinuses, which was accompanied by AS lesions and hyperlipidemia. Treatment with ferroptosis inhibitors significantly reduced ferroptosis, hyperlipidemia, and AS lesion development. In conclusion, our research determined that ox-LDL induced ferroptosis by repressing the activity of GPX4. Antiferroptosis treatment showed promising treatment effects in vivo. Ferroptosis-associated indexes also showed promising diagnostic potential in AS patients.

Rapid altitude displacement induce zebrafish appearing acute high altitude illness symptoms.

Rapid ascent to high-altitude areas above 2500 m often leads to acute high altitude illness (AHAI), posing significant health risks. Current models for AHAI research are limited in their ability to accurately simulate the high-altitude environment for drug screening. Addressing this gap, a novel static self-assembled water vacuum transparent chamber was developed to induce AHAI in zebrafish. This study identified 6000 m for 2 h as the optimal condition for AHAI induction in zebrafish. Under these conditions, notable behavioral changes including slow movement, abnormal exploration behavior and static behavior in the Novel tank test. Furthermore, this model demonstrated changes in oxidative stress-related markers included increased levels of malondialdehyde, decreased levels of glutathione, decreased activities of superoxide dismutase and catalase, and increased levels of inflammatory markers IL-6, IL-1ß and TNF-α, and inflammatory cell infiltration and mild edema in the gill tissue, mirroring the clinical pathophysiology observed in AHAI patients. This innovative zebrafish model not only offers a more accurate representation of the high-altitude environment but also provides a high-throughput platform for AHAI drug discovery and pathogenesis research.

TIMM17A overexpression in lung adenocarcinoma and its association with prognosis.

Lung adenocarcinoma (LUAD), a leading cause of cancer-related mortality worldwide, demands a deeper understanding of its molecular mechanisms and the identification of reliable biomarkers for better diagnosis and targeted therapy. Leveraging data from the Cancer Genome Atlas (TCGA), the Clinical Proteomic Tumor Analysis Consortium (CPTAC), and the Human Protein Atlas (HPA), we investigated the mRNA and protein expression profiles of TIMM17A and assessed its prognostic significance through Kaplan-Meier survival curves and Cox regression analysis. Through Gene Set Enrichment Analysis, we explored the regulatory mechanisms of TIMM17A in LUAD progression and demonstrated its role in modulating the proliferative capacity of A549 cells, a type of LUAD cell, via in vitro experiments. Our results indicate that TIMM17A is significantly upregulated in LUAD tissues, correlating with clinical staging, lymph node metastasis, overall survival, and progression-free survival, thereby establishing it as a critical independent prognostic factor. The construction of a nomogram model further enhances our ability to predict patient outcomes. Knockdown of TIMM17A inhibited the growth of LUAD cells. The potential of TIMM17A as a biomarker and therapeutic target for LUAD presents a promising pathway for improving patient diagnosis and treatment strategies.

Super-enhancer-driven LIF promotes the mesenchymal transition in glioblastoma by activating ITGB2 signaling feedback in microglia.

BACKGROUND: The mesenchymal (MES) subtype of glioblastoma (GBM) is believed to be influenced by both cancer cell-intrinsic alterations and extrinsic cellular interactions, yet the underlying mechanisms remain unexplored. METHODS: Identification of microglial heterogeneity by bioinformatics analysis. Transwell migration, invasion assays, and tumor models were used to determine gene function and the role of small molecule inhibitors. RNA sequencing, chromatin immunoprecipitation, and dual-luciferase reporter assays were performed to explore the underlying regulatory mechanisms. RESULTS: We identified the inflammatory microglial subtype of tumor-associated microglia (TAM) and found that its specific gene ITGB2 was highly expressed in TAM of MES GBM tissues. Mechanistically, the activation of ITGB2 in microglia promoted the interaction between the SH2 domain of STAT3 and the cytoplasmic domain of ITGB2, thereby stimulating the JAK1/STAT3/IL-6 signaling feedback to promote the MES transition of GBM cells. Additionally, microglia communicated with GBM cells through the interaction between the receptor ITGB2 on microglia and the ligand ICAM-1 on GBM cells, while an increased secretion of ICAM-1 was induced by the proinflammatory cytokine LIF. Further studies demonstrated that inhibition of CDK7 substantially reduced the recruitment of SNW1 to the super-enhancer of LIF, resulting in transcriptional inhibition of LIF. We identified notoginsenoside R1 as a novel LIF inhibitor that exhibited synergistic effects in combination with temozolomide. CONCLUSIONS: Our research reveals that the epigenetic-mediated interaction of GBM cells with TAM drives the MES transition of GBM and provides a novel therapeutic avenue for patients with MES GBM.

Genes associated with N6-methyladenosine regulators provide insight into the prognosis and immune response to renal clear cell carcinoma.

As one of the most common messenger ribonucleic acid modifications in eukaryotic organisms, N6-methyladenosine (m6A) is involved in a wide variety of biological functions. The imbalance of m6A RNA modification may be linked to cancer and other disorders, according to a growing body of studies. Its effects on clear cell renal cell carcinoma (KIRC) have not been well discussed, though. Here, we acquired the expression patterns of 23 important regulators of m6A RNA modification and assess how they might fare in KIRC. We observed that 17 major m6A RNA modification regulatory factors had a substantial predictive influence on KIRC. Using the "ConsensusCluster" program, we defined two groupings (Cluster 1 and Cluster 2) depending on the expression of the aforementioned 17 key m6A RNA methylation regulators. The Cluster 2 has a less favorable outcome and is strongly related with a lesser immune microenvironment, according to the findings. We also developed a strong risk profile for three m6A RNA modifiers (METTL14, YTHDF1, and LRPPRC) using multivariate Cox regression analysis. According to further research, the aforementioned risk profile could serve as an independent predicting factor for KIRC, and the chemotherapy response sensitivity was analyzed between two risk groups. Moreover, to effectively forecast the future outlook of KIRC clients, we established a novel prognostic approach according to gender, age, histopathological level, clinical stage, and risk score. Finally, the function of hub gene METTL14 was validated by cell proliferation and subcutaneous graft tumor in mice. In conclusion, we discovered that m6A RNA modifiers play an important role in controlling KIRC and created a viable risk profile as a marker of prediction for KIRC clients.

Inactivated vaccines reduce the risk of liver function abnormality in NAFLD patients with COVID-19: a multi-center retrospective study.

BACKGROUND: Abnormal liver function was frequently observed in nonalcoholic fatty liver disease (NAFLD) patients infected with SARS-CoV-2. Our aim was to explore the effect of SARS-CoV-2 inactivated vaccines on liver function abnormality among NAFLD patients with COVID-19. METHODS: The multi-center retrospective cohort included 517 NAFLD patients with COVID-19 from 1 April to 30 June 2022. Participants who received 2 doses of the vaccine (n = 274) were propensity score matched (PSM) with 243 unvaccinated controls. The primary outcome was liver function abnormality and the secondary outcome was viral shedding duration. Logistic and Cox regression models were used to calculate the odds ratio (OR) and hazard ratio (HR) for the outcomes. Sensitivity analysis was conducted to assess robustness. FINDINGS: PSM identified 171 pairs of vaccinated and unvaccinated patients. Liver function abnormality was less frequent in the vaccinated group (adjusted OR, 0.556 [95% CI (confidence interval), 0.356-0.869], p = 0.010). Additionally, the vaccinated group demonstrated a lower incidence of abnormal bilirubin levels (total bilirubin: adjusted OR, 0.223 [95% CI, 0.072-0.690], p = 0.009; direct bilirubin: adjusted OR, 0.175 [95% CI, 0.080-0.384], p < 0.001) and shorter viral shedding duration (adjusted HR, 0.798 [95% CI, 0.641-0.994], p = 0.044) than the unvaccinated group. Further subgroup analysis revealed similar results, while the sensitivity analyses indicated consistent findings. INTERPRETATION: SARS-CoV-2 vaccination in patients with NAFLD may reduce the risk of liver dysfunction during COVID-19. Furthermore, vaccination demonstrated beneficial effects on viral shedding in the NAFLD population. FUNDING: 23XD1422700, Tszb2023-01, Zdzk2020-10, Zdxk2020-01, 2308085J27 and JLY20180124.

Harnessing immunotherapy for brain metastases: insights into tumor-brain microenvironment interactions and emerging treatment modalities.

Brain metastases signify a deleterious milestone in the progression of several advanced cancers, predominantly originating from lung, breast and melanoma malignancies, with a median survival timeframe nearing six months. Existing therapeutic regimens yield suboptimal outcomes; however, burgeoning insights into the tumor microenvironment, particularly the immunosuppressive milieu engendered by tumor-brain interplay, posit immunotherapy as a promising avenue for ameliorating brain metastases. In this review, we meticulously delineate the research advancements concerning the microenvironment of brain metastases, striving to elucidate the panorama of their onset and evolution. We encapsulate three emergent immunotherapeutic strategies, namely immune checkpoint inhibition, chimeric antigen receptor (CAR) T cell transplantation and glial cell-targeted immunoenhancement. We underscore the imperative of aligning immunotherapy development with in-depth understanding of the tumor microenvironment and engendering innovative delivery platforms. Moreover, the integration with established or avant-garde physical methodologies and localized applications warrants consideration in the prevailing therapeutic schema.

AL360181.1 promotes proliferation and invasion in colon cancer and is one of ten m6A-related lncRNAs that predict overall survival.

Background: N6-methyladenosine (m6A) exerted a pivotal role in colon cancer. Nevertheless, the long non-coding RNAs (lncRNAs) associated with this process have yet to be elucidated. Methods: The open-access data used for analysis was downloaded from The Cancer Genome Atlas (TCGA) database for analysis, employing the R software for computational evaluations. The RNA level of specific molecules was assessed using the quantitative real-time PCR. CCK8, colony formation and transwell assay were used to evaluate the proliferation, invasion and migration ability of colon cancer cells. Results: Here, we identified the m6A regulators from TCGA data and subsequently pinpointed lncRNAs with a -Cor- > 0.3 and P < 0.05, categorizing them as m6A-associated lncRNAs. Moreover, we formulated a prognosis signature rooted in ten m6A-related lncRNAs, consisting of AL360181.1, PCAT6, SNHG26, AC016876.1, AC104667.2, AL114730.3, LINC02257, AC147067.1, AP006621.3 and AC009237.14. This signature exhibited notable predictive accuracy in gauging patient survival. Immune-related evaluations revealed varied immune cell infiltration patterns across different risk groups, with our findings suggesting superior immunotherapy response in low-risk patients. Biological enrichment analysis indicated that the high-risk patients had a higher activity of multiple carcinogenic pathways, including glycolysis. The previously unreported lncRNA, AL360181.1, displayed a connection to glycolytic activity and diminished survival rates, warranting further investigation. The result indicated that AL360181.1 was correlated with more aggressive clinical characteristics. Immune infiltration assessments found AL360181.1 to have a positive correlation with Tcm infiltration, but an inverse relationship with entities like Th2 cells, T cells, neutrophils and macrophages. Biological enrichment analysis indicated that the pathways of WNT/ß-catenin, pancreas beta cells, hedgehog signaling and some metabolism pathways were upregulated in high AL360181.1 patients. In vitro experiments showed that AL360181.1 was upregulated in the colon cancer cells. Moreover, AL360181.1 significantly promotes the proliferation, invasion and migration of colon cancer cells. Conclusions: Our results can provide direction for future studies on m6A-related lncRNA in colon cancer.

Online dynamic nomogram for predicting pain recurrence after microvascular decompression in trigeminal neuralgia.

Trigeminal neuralgia (TN) is one of the most common causes of facial pain. Microvascular decompression (MVD) is the first-choice surgical treatment. The present study aimed to develop a novel practical assessment system based on preoperative clinical and imaging factors for clinicians to predict the likelihood of pain recurrence following MVD in TN. A total of 56 patients with primary unilateral TN who underwent MVD were retrospectively analyzed. Patients were followed up to observe pain recurrence 1 year after MVD. An online dynamic nomogram was constructed for predicting the probability of pain recurrence after MVD in patients with TN based on multivariate logistic model. The concordance index (C-index) and receiver operating characteristic (ROC) were used to measure model discrimination. Bootstrap resampling was used for internal validation of the model and calibration curve was constructed. Decision curve analysis (DCA) was used to assess clinical applicability. Factors such as numeric rating scale (to score pain degree of patients with TN), response to neuroanalgesic drugs and neurovascular contact on magnetic resonance imaging were independent risk factors affecting the pain recurrence rate (all P<0.05). C-index was 0.973 (95%CI, 0.938-1.000) and the area under the ROC was 0.973 (95%CI, 0.938-1.000). Calibration curve with a 1,000 bootstrap resampling showed a good fit between dynamic nomogram prediction and actual observations. The DCA showed that at a threshold probability between 0 and 100%, this model can achieve a greater net benefit than if all patients had surgery or none had surgery. In conclusion, this online dynamic nomogram reliably predicted risk of pain recurrence in patients with TN following MVD.

Rapid Assessment of Ocular Toxicity from Environmental Contaminants Based on Visually Mediated Zebrafish Behavior Studies.

The presence of contaminants in the environment has increased in recent years, and studies have demonstrated that these contaminants have the ability to penetrate the blood-retinal barrier and directly affect the visual systems of organisms. Zebrafish are recognized as an ideal model for human eye diseases due to their anatomical and functional similarities to the human eye, making them an efficient and versatile organism for studying ocular toxicity caused by environmental contaminants in the field of environmental toxicology. Meanwhile, zebrafish exhibit a diverse repertoire of visually mediated behaviors, and their visual system undergoes complex changes in behavioral responses when exposed to environmental contaminants, enabling rapid assessment of the ocular toxicity induced by such pollutants. Therefore, this review aimed to highlight the effectiveness of zebrafish as a model for examining the effects of environmental contaminants on ocular development. Special attention is given to the visually mediated behavior of zebrafish, which allows for a rapid assessment of ocular toxicity resulting from exposure to environmental contaminants. Additionally, the potential mechanisms by which environmental contaminants may induce ocular toxicity are briefly outlined.

Nanosonosensitizers-engineered injectable thermogel for augmented chemo-sonodynamic therapy of melanoma and infected wound healing.

Easy recurrence and bacteria infected-wound healing after surgery excision pose severe challenges to clinical melanoma therapy. Herein, an injectable CuO2 nanodots-engineered thermosensitive chitosan hydrogel (CuO2-BSO@Gel) for enhanced melanoma chemo-sonodynamic therapy and improved infected wound healing was rationally constructed by facilely integrating the CuO2 nanodots and L-Buthionine-(S, R)-sulfoximine (BSO) with thermoresponsive hydrogel. Favored by the Fenton catalytic activity of Cu2+, the CuO2 nanodots can achieve enhanced chemodynamic therapy (CDT) by self-supplying H2O2 under acidic tumor microenvironment. Simultaneously, the CuO2 nanodots with a narrow bandgap (2.29 â€‹eV) were proven to be the efficient sonosensitizers, and the corresponding quantum yield of singlet oxygen (1O2) could be boosted by the O2 generation during Fenton-like reactions. Additionally, combining with the glutathione (GSH) depletion of loaded BSO, intracellular oxidative stress induced by SDT and CDT was further amplified, leading to the specific ferroptosis. Importantly, this multifunctional hydrogel significantly promoted the proliferation of normal skin cells and accelerated the bacteria-infected wound healing by the effective chemo-sonodynamic antibacterial activity and the enhanced angiogenesis. Thus, the engineered thermogel features the distinct chemo-sonodynamic performance, desirable biocompatibility and bioactivity, providing a competitive strategy for eradicating melanoma and infected wound healing.

CircRNA RNA hsa_circ_0008234 Promotes Colon Cancer Progression by Regulating the miR-338-3p/ETS1 Axis and PI3K/AKT/mTOR Signaling.

Circular RNAs (circRNAs) have been shown to play a crucial role in cancer occurrence and progression. This present work investigated the link between hsa_circ_0008234 and colon cancer. Data retrieved from GSE172229 was used to compare the circRNA profiles of colon cancer and surrounding non-tumorous tissues. The amount of RNA and protein in the molecules was determined using quantitative real-time PCR (qRT-PCR) and Western blot analysis, respectively. The cell proliferation ability was assessed using CCK8, EdU, colon formation, and nude mice tumorigenesis tests. Cell invasion and migration abilities were evaluated using transwell wound healing and mice lung metastasis model. Hsa_circ_0008234 piqued our interest because bioinformatics and qRT-PCR analyses revealed that it is upregulated in colon cancer tissue. Cell phenotypic studies suggest that hsa_circ_0008234 may significantly increase colon cancer cell aggressiveness. Mice experiments revealed that inhibiting hsa_circ_0008234 significantly reduced tumor growth and metastasis. Moreover, the fluorescence in situ hybridization experiment demonstrated that hsa_circ_0008234 is primarily found in the cytoplasm, implying that it potentially functions via a competitive endogenous RNA pathway. These findings indicated that hsa_circ_0008234 may act as a "molecular sponge" for miR-338-3p, increasing the expression of miR-338-target 3p's ETS1. In addition, the traditional oncogenic pathway PI3K/AKT/mTOR signaling was found to be the potential downstream pathway of the hsa_circ_0008234/miR-338-3p/ETS1 axis. In conclusion, hsa_circ_0008234 increases colon cancer proliferation, infiltration, and migration via the miR-338-3p/ETS1/PI3K/AKT axis; therefore, it could serve as a target and a focus for colon cancer therapy.

CASPR2 antibody associated neurological syndromes in children.

To strengthen the understanding of the clinical features for CASPR2 neurological autoimmunity in children. A multicenter retrospective and prospective analysis of CASPR2 autoimmunity was conducted. Twenty-six patients were enrolled, including 25 with serum positivity and 3 with cerebrospinal fluid (CSF) positivity; 5 patients were co-positive with anti-NMDAR or anti-GABABR antibodies. Eleven patients (who manifested with refractory epilepsy, psychobehavioral abnormalities or germinoma) presented with low antibody titers, relatively normal MRI/EEG/CSF examinations, and poor response to immunotherapy and were thus considered false positive (42.3%). Fifteen patients were diagnosed with autoimmune encephalitis/ encephalopathy/ cerebellitis (including 1 whose condition was secondary to Japanese encephalitis). The most common symptoms included disorders of consciousness (10/15), fever (8/15), psychological symptoms/abnormal behaviors (8/15), sleep disorders (8/15), seizures (7/15), movement disorders (5/15), autonomic symptoms (5/15). Brain MRI revealed abnormalities in 10 patients (66.7%). Electroencephalography (EEG) recordings revealed a slow wave background in 13 patients (86.7%). Five patients showed elevated WBCs in CSF, and 4 patients showed elevated protein levels in the CSF. Thirteen patients received immunotherapy (rituximab was adopted in 2 cases) and recovered well. Two patients received symptomatic treatment, and the recovery was slow and accompanied by emotional abnormalities and developmental delay. Autoimmune encephalitis is the most common clinical phenotype; it can be secondary to Japanese encephalitis. Rituximab can be used in patients who respond poorly to conventional immunotherapy. The high false-positive rate of anti-CASPR2 in refractory epilepsy and the psychobehavioral abnormalities needs to be explored further.

Ellagic acid induces apoptosis and autophagy in colon cancer through the AMPK/mTOR pathway.

Ellagic acid (EA), found in fruits and foods, has been shown to be effective in the treatment of breast, colon and bladder cancer. However, due to the complexity of colon cancer, the therapeutic mechanism of EA for colon cancer is still unclear. Cell Counting Kit-8 (CCK-8) assay were employed to investigate the cell proliferation. Western blotting and flow cytometry assays were utilized to investigate apoptosis and autophagy in CRC cells (HCT116), respectively. Moreover, western blotting and luciferase reporter assays were evaluated the effect of EA on AMPK/mTOR pathway. Through flow cytometry analysis, EA could promote the apoptosis of HCT116 cells. In addition, EA can reduce the phosphorylation of mTOR, promoted phosphorylation of AMPK, and induced autophagy in HCT116 cells. Also, Dorsomorphin pretreatment can reduce the expression of autophagy protein, which indicates that EA induces autophagy through AMPK/mTOR pathway. These results suggest that EA inhibits the growth of colon cancer through AMPK/mTOR pathway and induces apoptosis and protective autophagy.

Selective Penetration and Profile Control Performance of Preformed Particle Gels for Heterogeneous Oil Reservoirs.

The preformed particle gel (PPG) has been proved to be an effective chemical agent to reduce fluid channeling and increase the sweeping efficiency. However, we still lack a clear understanding of the field-scale matching relationship between PPG size, elastic modulus and a heterogeneous reservoir. In this respect, the paper carried out various sand pack displacement experiments. The results indicated that an excessively large PPG or elastic modulus would plug a low-permeability sand pack and even increase the severity of fluid channeling. On the contrary, an excessively small PPG or elastic modulus allowed a certain degree of profile control, but the PPG could easily migrate out of high-permeability sand packs with water. If the elastic modulus remained unchanged, the suitable PPG size increased as the reservoir permeability ratio increased. On the other hand, the suitable elastic modulus increased with the increase of the reservoir permeability ratio when the PPG size was kept the same. By using regression analysis, quantitative expressions were established in order to determine the best suitable PPG size for a certain heterogeneous reservoir. When the elastic modulus was fixed, the best suitable PPG mesh exhibited a linear relation with the permeability ratio. This paper provides a useful reference to select the most convenient PPG size and elastic modulus for a potential heterogeneous reservoir, suitable to enhance oil recovery.

Experimental Study on Matched Particle Size and Elastic Modulus of Preformed Particle Gel for Oil Reservoirs.

Suitable elastic modulus and particle size of preformed particle gel are the keys to both diverting water flow and avoiding permanent impairment to reservoirs. Therefore, the paper aims at finding the best matched preformed particle gel for given reservoirs using sand-pack displacement experiments. The results show that the injection pressure of preformed particle gel with excessively small size and elastic modulus is relatively low, indicating poor capacity to increase flow resistance and reduce water channeling. On the other hand, if the particle size and elastic modulus of preformed particle gel are excessively large, the reservoir may be plugged and irreversibly damaged, affecting oil development performance. In fact, the best matched particle size and elastic modulus of preformed particle gel increase with the increase in reservoir permeability. Furthermore, the paper establishes a quantitative logarithmic model between the particle size of preformed particle gel and reservoir permeability. Finally, the established matching relationship is validated via microscopic visualization oil displacement experiments using a glass etching model. The validation experiments indicate that the preformed particle gel (60-80 mesh; 2-4 Pa) selected according to the matching relationship can effectively reduce water channeling and increase sweeping efficiency by as much as 55% compared with water flooding in the glass etching model with an average permeability of 2624 × 10-3 µm2. Therefore, the established matching relationship can provide an effective guide when selecting the best suitable preformed particle gel for a given reservoir in more future applications.

Extraction, isolation, structural characterization, and antioxidant activity of polysaccharides from elderberry fruit.

The isolation, purification, and antioxidant activity of polysaccharides extracted from elderberry fruits were studied. Two neutral polysaccharides (EFP-0 and EFP-1) and three acidic polysaccharides (EFP-2, EFP-3, and EFP-4) were isolated from elderberry. EFP-0, EFP-1, EFP-2, EFP-3, and EFP-4 all contain arabinose, galactose, glucose, and mannose, with molecular weights of 1.7981 × 106, 7.0523 × 106, 7.7638 × 106, 4.3855 × 105, and 7.3173 × 105 Da, respectively. Structural characterization showed that the backbone of EFP-2 consisted of →4)-Manp (1→4)-ß-D-Glcp (1→ and →4)-ß-D-Glcp (1→5)-α-L-Araf (1→units, and T-α-L-Araf (1→ and T-ß-D-Galp (1→ residues were detected by methylation analysis and NMR analysis. In addition, the MTT assay and zebrafish oxidative damage assay showed that EFP-2 had a protective effect on H2O2-damaged RAW264.7 cells in a dose-dependent manner, and zebrafish with the addition of EFP-2 would have low levels of ROS in vivo which showed significant antioxidant activity. Therefore, the results showed that the elderberry polysaccharides have antioxidant activity and can be used as potential antioxidants in functional foods.

Long Non-Coding RNA CKMT2-AS1 Reduces the Viability of Colorectal Cancer Cells by Targeting AKT/mTOR Signaling Pathway.

Background: Colorectal cancer (CRC) has not only seriously affected people's lives, but also burdened the government healthcare system. Long non-coding RNAs (lncRNA) have attracted more and more attention in the cancer study field. Methods: Experiments were completed in the Medical Research and Innovation Center of Shanghai Pudong Hospital, China from 2019 to 2020. Cell cycle was detected by western blot analyzing and flow cytometry. Apoptosis analysis were determined using flow cytometry or western blot analysis. LncRNA CKMT2-AS1 was knocked down by shRNA transfection. Results: We found CKMT2-AS1 was the most significant=0.0105 for SW480 and P=0.0071 for HCT116) difference lncRNA between colorectal cancer treated with autophagy inducer and colorectal cancer without any treatment. Effective shRNA-CKMT2-AS1 was also designed. Following, we found the treatment of autophagy inducer and autophagy inducer + shRNA-NC were able to suppress the proliferation of both SW480 and HCT116 cells. In addition, the treatment of autophagy inducer + shRNA-CKMT2-AS1 significantly reduced the apoptosis of SW480 and HCT116 cells induced by autophagy. Furthermore, we found the phosphorylation of mTOR, AKT was enhanced in SW480, and HCT116 cells treated with autophagy inducer + shRNA-CKMT2-AS1 compared to the cells treated with autophagy inducer of autophagy inducer + shRNA-NC. Conclusion: Enhancing the expression of CKMT2-AS1 will become a promising strategy to prevent the progress of colorectal cancer.

MicroRNA and Degradome Profiling Uncover Defense Response of Fraxinus velutina Torr. to Salt Stress.

Soil salinization is a major environmental problem that seriously threatens the sustainable development of regional ecosystems and local economies. Fraxinus velutina Torr. is an excellent salt-tolerant tree species, which is widely planted in the saline-alkaline soils in China. A growing body of evidence shows that microRNAs (miRNAs) play important roles in the defense response of plants to salt stress; however, how miRNAs in F. velutina exert anti-salt stress remains unclear. We previously identified two contrasting F. velutina cuttings clones, salt-tolerant (R7) and salt-sensitive (S4) and found that R7 exhibits higher salt tolerance than S4. To identify salt-responsive miRNAs and their target genes, the leaves and roots of R7 and S4 exposed to salt stress were subjected to miRNA and degradome sequencing analysis. The results showed that compared with S4, R7 showed 89 and 138 differentially expressed miRNAs in leaves and roots, respectively. Specifically, in R7 leaves, miR164d, miR171b/c, miR396a, and miR160g targeting NAC1, SCL22, GRF1, and ARF18, respectively, were involved in salt tolerance. In R7 roots, miR396a, miR156a/b, miR8175, miR319a/d, and miR393a targeting TGA2.3, SBP14, GR-RBP, TCP2/4, and TIR1, respectively, participated in salt stress responses. Taken together, the findings presented here revealed the key regulatory network of miRNAs in R7 responding to salt stress, thereby providing new insights into improving salt tolerance of F. velutina through miRNA manipulation.

Comparative Transcriptome Analysis Unravels Defense Pathways of Fraxinus velutina Torr Against Salt Stress.

Fraxinus velutina Torr with high salt tolerance has been widely grown in saline lands in the Yellow River Delta, China. However, the salt-tolerant mechanisms of F. velutina remain largely elusive. Here, we identified two contrasting cutting clones of F. velutina, R7 (salt-tolerant), and S4 (salt-sensitive) by measuring chlorophyll fluorescence characteristics (Fv/Fm ratio) in the excised leaves and physiological indexes in roots or leaves under salt treatment. To further explore the salt resistance mechanisms, we compared the transcriptomes of R7 and S4 from leaf and root tissues exposed to salt stress. The results showed that when the excised leaves of S4 and R7 were, respectively, exposed to 250 mM NaCl for 48 h, Fv/Fm ratio decreased significantly in S4 compared with R7, confirming that R7 is more tolerant to salt stress. Comparative transcriptome analysis showed that salt stress induced the significant upregulation of stress-responsive genes in R7, making important contributions to the high salt tolerance. Specifically, in the R7 leaves, salt stress markedly upregulated key genes involved in plant hormone signaling and mitogen-activated protein kinase signaling pathways; in the R7 roots, salt stress induced the upregulation of main genes involved in proline biosynthesis and starch and sucrose metabolism. In addition, 12 genes encoding antioxidant enzyme peroxidase were all significantly upregulated in both leaves and roots. Collectively, our findings revealed the crucial defense pathways underlying high salt tolerance of R7 through significant upregulation of some key genes involving metabolism and hub signaling pathways, thus providing novel insights into salt-tolerant F. velutina breeding.