The spatial landscape of T cells in the microenvironment of stage III lung adenocarcinoma.

This study aimed to provide more information for prognostic stratification for patients through an analysis of the T-cell spatial landscape. It involved analyzing stained tissue sections of 80 patients with stage III lung adenocarcinoma (LUAD) using multiplex immunofluorescence and exploring the spatial landscape of T cells and their relationship with prognosis in the center of the tumor (CT) and invasive margin (IM). In this study, multivariate regression suggested that the relative clustering of CT CD4+ conventional T cell (Tconv) to inducible Treg (iTreg), natural regulatory T cell (nTreg) to Tconv, terminal CD8+ T cell (tCD8) to helper T cell (Th), and IM Treg to tCD8 and the relative dispersion of CT nTreg to iTreg, IM nTreg to nTreg were independent risk factors for DFS. Finally, we constructed a spatial immunological score named the GT score, which had stronger prognostic correlation than IMMUNOSCORE® based on CD3/CD8 cell densities. The spatial layout of T cells in the tumor microenvironment and the proposed GT score can reflect the prognosis of patients with stage III LUAD more effectively than T-cell density. The exploration of the T-cell spatial landscape may suggest potential cell-cell interactions and therapeutic targets and better guide clinical decision-making. © 2024 The Pathological Society of Great Britain and Ireland.

Loss of NDUFS1 promotes gastric cancer progression by activating the mitochondrial ROS-HIF1α-FBLN5 signaling pathway.

BACKGROUND: Recent studies suggested that NDUFS1 has an important role in human cancers; however, the effects of NDUFS1 on gastric cancer (GC) are still not fully understood. METHODS: We confirmed that NDUFS1 is downregulated in GC cells through western blot immunohistochemistry and bioinformation analysis. The effect of NDUFS1 on GC was studied by CCK-8, colony formation, transwell assay in vitro and Mouse xenograft assay in vivo. Expression and subcellular localization of NDUFS1 and the content of mitochondrial reactive oxygen species (mROS) was observed by confocal reflectance microscopy. RESULTS: Reduced expression of NDUFS1 was found in GC tissues and cell lines. Also, NDUFS1 overexpression inhibited GC cell proliferation, migration, and invasion in vitro as well as growth and metastasis in vivo. Mechanistically, NDUFS1 reduction led to the activation of the mROS-hypoxia-inducible factor 1α (HIF1α) signaling pathway. We further clarified that NDUFS1 reduction upregulated the expression of fibulin 5 (FBLN5), a transcriptional target of HIF1α, through activation of mROS-HIF1α signaling in GC cells. CONCLUSIONS: The results of this study indicate that NDUFS1 downregulation promotes GC progression by activating an mROS-HIF1α-FBLN5 signaling pathway.

Increasing the peroxidase-like activity of the MIL-100(Fe) nanozyme by encapsulating Keggin-type 12-phosphomolybdate and covering three-dimensional graphene.

To improve the peroxidase-like activities of metal-organic frameworks (MOFs) as nanozymes, a ternary MIL-100(Fe)@PMo12@3DGO nanocomposite was designed and fabricated by encapsulating Keggin-type H3PMo12O40 (PMo12) with fast and reversible multi-electron redox processes and an electron-rich structure into MIL-100(Fe), then being covered by three-dimensional graphene (3DGO) with higher conductivity, larger surface area, higher porosity, and better chemical stability. As a consequence, the as-prepared MIL-100(Fe)@PMo12@3DGO nanocomposite exhibits excellent peroxidase-like activities, namely, the lowest limit of detection (0.14 µM) in the range of 1-100 µM for glucose to date, to the best of our knowledge, attributed to the individual and synergistic effects of H3PMo12O40, 3DGO and MIL-100(Fe).

ZIF-67 on Sulfur-Functionalized Graphene Oxide for Lithium-Sulfur Batteries.

How to overcome the problem of fast capacity fading and low sulfur utilization is the key to promote the practical applications of lithium-sulfur (Li-S) batteries. Based on the fact that sulfur-functionalized graphene oxide (GO-S) can avoid the loss of sulfur/polysulfides through the strong C-S interaction, and the zeolitic imidazolate framework (ZIF-67) can capture sulfur and catalyze lithium polysulfide (Li2Sx, 4 ≤ x ≤ 8), the combination of ZIF-S (ZIF-67 after combining with sulfur) with GO-S can be expected to be an excellent electrode material for Li-S batteries due to the synergistic effect. Herein, ZIF-S@GO-S (n) nanocomposites (n = 1, 2, and 3 for the mass ratio of ZIF-67/GO of 4:1, 6:1, and 8:1, respectively) as the cathode materials in Li-S batteries were successfully fabricated, and ZIF-S@GO-S (2) showed better electrochemical performances and cycle stability with a high specific capacity of 1529.5 mA h g-1 at the initial cycle and 792 mA h g-1 after 500 cycles at 0.1 C (1 C = 1675 mA h g-1). The fact that ZIF-S@GO-S (n) can simultaneously improve the conductivity and utilization of S (C-S···S8 and C-S···SxLi2) and the conversion kinetics of Li2Sx (4 ≤ x ≤ 8) provides a new avenue for designing and fabricating promising cathodes for high-performance Li-S batteries.

Multi-Class Weed Recognition Using Hybrid CNN-SVM Classifier.

The Convolutional Neural Network (CNN) is one of the widely used deep learning models that offers the chance to boost farming productivity through autonomous inference of field conditions. In this paper, CNN is connected to a Support Vector Machine (SVM) to form a new model CNN-SVM; the CNN models chosen are ResNet-50 and VGG16 and the CNN-SVM models formed are ResNet-50-SVM and VGG16-SVM. The method consists of two parts: ResNet-50 and VGG16 for feature extraction and SVM for classification. This paper uses the public multi-class weeds dataset DeepWeeds for training and testing. The proposed ResNet-50-SVM and VGG16-SVM approaches achieved 97.6% and 95.9% recognition accuracies on the DeepWeeds dataset, respectively. The state-of-the-art networks (VGG16, ResNet-50, GoogLeNet, Densenet-121, and PSO-CNN) with the same dataset are accurate at 93.2%, 96.1%, 93.6%, 94.3%, and 96.9%, respectively. In comparison, the accuracy of the proposed methods has been improved by 1.5% and 2.7%, respectively. The proposed ResNet-50-SVM and the VGG16-SVM weed classification approaches are effective and can achieve high recognition accuracy.

Effect of Fu Yan Qing prescription on pelvic effusion, mass absorption and microenvironment of pelvic blood stasis in patients with sequelae of pelvic inflammatory disease of accumulation of dampness heat and blood stasis type.

Objective: To investigate the effect of Fu Yan Qing prescription on sequelae of pelvic inflammatory disease of accumulation of dampness heat and blood stasis type. Methods: Total 80 patients with sequelae of sequelae of pelvic inflammatory disease of accumulation of dampness heat and blood stasis type were admitted to Baoding No.1 Central Hospital from December, 2018 to April, 2020 and divided into two groups according to the random number table, with 40 cases in each group. Patients in the control group were treated with conventional western medicine, while patients in the observation group were treated with Fu Yan Qing prescription orally. The clinical efficacy, the changes of traditional Chinese medicine (TCM) syndromes, local sign scores, visual analog scale (VAS) of pain, pelvic mass size, pelvic fluid volume and uterine blood flow parameters of the two groups before and after treatment were observed and compared, and the safety of the two groups was evaluated. Results: The total efficacy after treatment in the observation group was 87.5%, which was significantly higher than that of 67.5% in the control group (p<0.05). The TCM syndrome scores, local signs scores, pain scores, size of pelvic mass and pelvic effusion in both groups decreased significantly after treatment (p<0.05), PSV indexes of the two groups were significantly increased after treatment (p<0.05), and these changes were even more pronounced in the observation group (p<0.05). Compared with before treatment, PI and RI indexes of the observation group were significantly decreased after treatment (p<0.05). The observation group experienced an adverse reaction in 7.5% cases considerably lower than the 27.5% of the control group (p<0.05). Conclusion: Fu Yan Qing prescription is a safe and reliable treatment for patients with sequelae of pelvic inflammatory disease of accumulation of dampness heat and blood stasis type. It is worth promotion in clinical practice.

LOXL1 modulates the malignant progression of colorectal cancer by inhibiting the transcriptional activity of YAP.

BACKGROUND: LOX-like 1 (LOXL1) is a lysyl oxidase, and emerging evidence has revealed its effect on malignant cancer progression. However, its role in colorectal cancer (CRC) and the underlying molecular mechanisms have not yet been elucidated. METHODS: LOXL1 expression in colorectal cancer was detected by immunohistochemistry, western blotting and real-time PCR. In vitro, colony formation, wound healing, migration and invasion assays were performed to investigate the effects of LOXL1 on cell proliferation, migration and invasion. In vivo, metastasis models and mouse xenografts were used to assess tumorigenicity and metastasis ability. Molecular biology experiments were utilized to reveal the underlying mechanisms by which LOXL1 modulates the Hippo pathway. RESULTS: LOXL1 was highly expressed in normal colon tissues compared with cancer tissues. In vitro, silencing LOXL1 in CRC cell lines dramatically enhanced migration, invasion, and colony formation, while overexpression of LOXL1 exerted the opposite effects. The results of the in vivo experiments demonstrated that the overexpression of LOXL1 in CRC cell lines drastically inhibited metastatic progression and tumour growth. Mechanistically, LOXL1 inhibited the transcriptional activity of Yes-associated protein (YAP) by interacting with MST1/2 and increasing the phosphorylation of MST1/2. CONCLUSIONS: LOXL1 may function as an important tumour suppressor in regulating tumour growth, invasion and metastasis via negative regulation of YAP activity. Video abstract.

Interaction between SNCA gene polymorphisms and T2DM with Parkinson's disease.

AIMS: To investigate the association of several single nucleotide polymorphisms (SNPs) within alpha-synuclein (SNCA) gene and additional gene-environment interaction with Parkinson's disease (PD) risk. METHODS: Hardy-Weinberg equilibrium (HWE) is tested for controls using SNPstats (http://bioinfo.iconcologia.net/SNPstats). Logistic regression is used to calculate the ORs (95% CI) for relations between the four SNPs and PD risk. The generalized multifactor dimensionality reduction (GMDR) model is used to evaluate the synergy between gene and environment. RESULTS: A total of 1161 people were included in this study, including 386 cases of PD and 775 normal controls. In this study, the genotype frequency of the control group was consistent with HWE distribution. Rs356219-G allele frequency was 30.0% in patients and 19.8% in control group. The rs356221-T allele frequency was 29.7% in the patients and 20.8% in the control group. Rs356219-G and rs356221-T alleles were associated with increased PD risk, with adjusted ORs (95% CI) of 1.92 (1.28-2.52) and 1.52 (1.05-2.02), respectively. We also found no significant correlation between rs2301134 and rs2301135 and susceptibility to PD. The best gene-environment interaction models were determined by GMDR analysis, which shown a significant gene-T2DM interaction combinations, but the gene-alcohol drinking interaction combinations were all not significant. We also conducted stratified analysis for interaction effect using logistic regression. We found that T2DM patients with rs356221-AT/ TT genotype have the highest PD risk, compared to subjects with rs356219-AA genotype, OR (95%CI) = 2.67 (1.83-3.46). CONCLUSIONS: The rs356219-G and rs356221-T, gene-environment interaction between rs356221 and T2DM were all associated with increased PD risk.

Ratio-Based Method To Identify True Biomarkers by Normalizing Circulating ncRNA Sequencing and Quantitative PCR Data.

Recent studies have indicated that circulating noncoding RNAs (ncRNAs) such as miRNAs are stable biomarkers for the diagnosis and prognosis of human diseases. However, due to low concentrations of circulating ncRNAs in blood, data normalization in plasma/serum ncRNA experiments using next-generation sequencing and quantitative real time RT-qPCR is a challenge. We found that the current normalization methods based on synthetic external spiked-in controls or published endogenous miRNA controls are inappropriate as they are not stably expressed and therefore fail to reliably detect differentially expressed ncRNAs. Using the alternative of individual ncRNAs as biomarkers, we considered a ratio-based normalization method calculated taking the ratio of any two ncRNAs in the same sample and used the resulting ratios as biomarkers. We mathematically verified the method to be independent of spiked-in and internal controls, and more robust than existing reference control based normalization methods to identify differentially expressed ncRNAs as potential biomarkers for human diseases. Thus, the ratio-based method can solve the difficult normalization problem for circuiting ncRNA data to identify reliable biomarkers to meet real clinical practice.

EGFL7 promotes hepatocellular carcinoma cell proliferation and inhibits cell apoptosis through increasing CKS2 expression by activating Wnt/ß-catenin signaling.

Epidermal growth factor-like domain multiple 7 (EGFL7) is an important sport stimulating factor and motility related factors significantly enhanced the tumor cell metastasis and overexpressed in many cancers, including hepatocellular carcinoma (HCC), associated with tumorigenesis. However, the molecular mechanism by which EGFL7 regulates HCC cell proliferation and apoptosis and the correlation between EGFL7 and cyclin-dependent kinases regulatory subunit 2 (CKS2), which is essential for biological function, have not fully explained. In this study, EGFL7 and CKS2 expression in patients with HCC was measured by real-time polymerase chain reaction and immunohistochemistry. After HCC cells respectively transfected with pLKO.1-EGFL7-shRNA, pLVX-Puro-EGFL7 recombined vector or CKS2 small interfering RNA, cell counting kit-8 and flow cytometry was performed to examine the cell proliferation and apoptosis, respectively, and the expression of ß-catenin, CKS2, CDK2, and cleaved caspase-3 was measured by Western blot analysis. We found that EGFL7 and CKS2 were overexpressed in HCC tissues and a positive correlation was found between them. EGFL7 knockdown markedly inhibited proliferation and promoted apoptosis of HCC cells, along with decreased expression of CKS2 and CDK2, but increased cleaved caspase-3 expression, while EGFL7 overexpression showed an opposite effect. EGFL7 silencing in nude mice also showed decreased tumor growth and altered protein expression similar to its effect in HCC cells in vitro. Importantly, CKS2 silencing significantly inhibited EGFL7-induced HCC cell proliferation and protein expression, and Wnt/ß-catenin signaling pathway inhibitor IWR-1-endo significantly inhibited CKS2 expression in HCC cells. Taken together, EGFL7 promotes HCC cell proliferation and inhibits cell apoptosis through increasing CKS2 expression by activating Wnt/ß-catenin signaling.

Protective Effect of Curcumin Against Oxidative Stress-Induced Injury in Rats with Parkinson's Disease Through the Wnt/ ß-Catenin Signaling Pathway.

BACKGROUND/AIMS: The study aimed to investigate the protective effect of curcumin against oxidative stress-induced injury of Parkinson's disease (PD) through the Wnt/ß-catenin signaling pathway in rats. METHODS: The successfully established PD rat models and normal healthy rats were randomly assigned into the 6-hydroxydopamine (6-OHDA), the curcumin (Cur) and the control groups. Immunohistochemistry was used to detect the positive expression of tyrosine hydroxylase (TH), dopamine transporter (DAT) and glial fibrillary acidic protein (GFAP). Deutocerebrum primary cells were extracted and classified into the control, 6-OHDA, Cur (5, 10, 15 µmol/L), Dickkopf-1 (DKK-1) and Cur + DKK-1 groups. MTT assays, adhesion tests and TUNEL staining were used to assess cell viability, adhesion and apoptosis, respectively. Western blotting and qRT-PCR were used to examine the protein and mRNA expressions of Wnt3a and ß-catenin and the c-myc and cyclinD1 mRNA expressions. RESULTS: TH and DAT expressions in the Cur group were elevated and GFAP was reduced compared with the 6-OHDA group. Curcumin enhanced viability, survival and adhesion and attenuated apoptosis of deutocerebrum primary cells by activating the Wnt/ß-catenin signaling pathway. Higher Wnt3a and ß-catenin mRNA and protein expressions and c-myc and cyclinD1 mRNA expressions, enhanced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) contents, decreased malondialdehyde (MDA) content and elevated mitochondrial membrane potential (∆ψm) were found in the 10 and 15 µmol/L Cur groups compared with the 6-OHDA group. However, opposite tendencies were found in the Cur + DKK-1 group compared to the 10 µmol/L Cur group. CONCLUSION: This study suggests that curcumin could protect against oxidative stress-induced injury in PD rats via the Wnt/ß-catenin signaling pathway.

Hypoxia Induces Multidrug Resistance via Enhancement of Epidermal Growth Factor-Like Domain 7 Expression in Non-Small Lung Cancer Cells.

Chemotherapy is widely used in non-small cell lung cancer (NSCLC) treatment, yet multidrug resistance (MDR) is a major chemotherapeutic obstacle in both resectable and advanced NSCLC. Epidermal growth factor-like domain 7 (EGFL7), also known as vascular endothelial stain, is an endothelial cell-derived secreted factor that regulates vascular tube formulation. The aim of this study was to investigate the potential relationships between EGFL7 and MDR in NSCLC cells. We first obtained the CDDP-based MDR phenotype cell line A549/CDDP by repeated exposure to a proper concentration of CDDP (cisplatin) from original A549 cells. These A549/CDDP cells, which maintained relative high levels of EGFL7 and P-glycoprotein (P-gp), were resistant to other chemotherapy drugs, such as carboplatin (CBP), paclitaxel (TAX), and gemcitabine (GEM) (p < 0.05). We also found that hypoxia significantly reduced the chemosensitivity of NSCLC cells, and hypoxia-induced MDR was mediated by P-gp and EGFL7 (p < 0.05). EGFL7 was veryy relevant to NSCLC cell MDR, and downregulation of EGFL7 could significantly increase the chemosensitivity of NSCLC cells (p < 0.05). Thus, our findings first indicate that hypoxia induced NSCLC cell MDR at least partly by enhancing the expression of EGFL7 protein. EGFL7 might be a feasible target for reversing hypoxia-mediated MDR in NSCLC cells and a promising biomarker for predicting the development of MDR in NSCLC patients on chemotherapy.

MiR-335 functions as a tumor suppressor in pancreatic cancer by targeting OCT4.

Octamer-binding transcription factor 4 (OCT4) was closely related to pancreatic cancer progression, but its regulation in pancreatic cancer by microRNA (miRNA) is not fully clear. OCT4-positive and OCT4-negative pancreatic cells were isolated by flow cytometry, and it was found that OCT4-positive cells are enriched in transplanted pancreatic cancer cells compared with the primary ones and showed increasing proliferation and sphere formation. The data of miRNA array assay showed that miR-335 in OCT4-positive pancreatic cancer cells was lower than that in the negative ones. The results were confirmed in pancreatic cancer tissue and cell lines. Through expression analysis, it was found that miR-335 was underexpressed in OCT4(+) pancreatic cancer cells purified from primary tumors. Enforced expression of miR-335 in OCT4(+) pancreatic cancer cells inhibited clonogenic expansion and tumor development. miR-335 re-expression in OCT4(+) pancreatic cancer cells was blocked. Systemically delivered miR-335 inhibited pancreatic cancer metastasis and extended animal survival. Of significance, OCT4 was identified and validated as a direct and functional target of miR-335. Taken together, our results provide evidence that miR-335 might inhibit progression and stem cell properties of pancreatic cancer targeting OCT4.

A randomized clinical trial of nerve block to manage end-stage pancreatic cancerous pain.

Pain control is the most difficult puzzle in patients with terminal pancreatic cancerous pain. Many methods in clinical practice fail in 20 ~ 50% of patients. The present study aims to explore the effect of nerve block on patients with end-stage pancreatic cancerous pain. In this study, 100 subjects with end-stage pancreatic cancerous pain were enrolled and randomly assigned into two groups: 68 in nerve block group (N) and 32 in sham group (S). One group was treated with nerve block and the other group with sham procedure as controls. The pain score (by visual analog scale (VAS)), pain duration, reduction of other analgesic medications, and quality of life (with questionnaire QLQ) were evaluated before and 3 months after interventions. Comparisons were performed between before and after intervention in nerve block group and sham group. The results indicated that compared with sham group, the subjects in nerve block group had significant reduction with pain score, pain duration, and other analgesic medications, as well as improvement of quality of life (P < 0.05, respectively). In conclusion, nerve block is an effective method for treating patients with end-stage pancreatic cancerous pain.

A novel PCR-based approach to discover miRNA target genes.

MiRNAs are potent regulators of gene expression, and most miRNAs have from several to several thousands of gene targets. Validating the numerous gene targets of a given miRNA remains challenging despite the existence of various tools and databases that predict candidate gene-miRNA pairs. In the present study, we present a high-throughput but flexible method that applies a PCR-based application to simulate the binding of miRNAs to their gene targets. Using hsa-miR-377 as an illustrative example, our method was able to identify 13 potential targets of hsa-miR-377. Moreover, our results include 2 genes (SOD2 and PPM1A) that have already been verified as targets of hsa-miR-377. Our method may provide an alternative way of identifying the gene targets of miRNAs for future research.

[Treatment of nonalcoholic steatohepatitis by Jianpi Shugan Recipe: a multi-center, randomized, controlled clinical trial].

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine (CM) intervention in the treatment of nonalcoholic steatohepatitis (NASH) from liver enzyme (ALT), imaging (the liver/spleen CT ratio) and syndrome scores, and to establish standard methods for diagnosis and therapeutic efficacy evaluation with characteristics of CM. METHODS: A multi-center, stratified randomized, parallel controlled, blindness-method evaluated, superiority trial was performed. Totally 204 patients were randomly allocated into two groups, 102 patients in the experimental group (treated with CM) and 102 patients in the control group [treated with Western medicine (WM)]. The alanine aminotransferase (ALT), liver/spleen CT ratio, and clinical symptoms were observed in both groups. RESULTS: Of the randomly allocated 204 cases from 4 hospitals, 3 patients were rejected, and 25 were lost. Totally 176 cases con- formed to the plan with complete follow-ups. After 3 months of treatment, syndrome scores and the improvement of partial clinical symptoms (fatigue and sallow complexion) were superior in the experimental group to those in the control group (P < 0.05). After 3 months of follow-up, the syndrome scores and improvement of partial clinical symptoms (fatigue and sallow complexion) were superior in the experimental group to those in the control group (P < 0.05). There was no statistical difference in improving liver enzymes or the liver/spleen CT ratio between the two groups (P > 0.05). There were 4 adverse reactions/adverse events in the two groups in the process of treatment, mainly covering drug-induced liver injury, diarrhea, and epigastric distension. Adverse reactions had nothing to do with CM treatment. CONCLUSIONS: Jianpi Shugan Recipe had obvious efficacy in treatment of NASH. It could remove the liver fat and play a role in anti-inflammation and liver protection. It also could improve the indices of liver enzymes and the liver/spleen CT ratio effectively, which was superior to Polyene Phosphatidylcholine Capsule (PPC) in improving clinical symptoms, especially for such symptoms as fatigue and sallow complexion.

Effect of Butylphthalide soft capsules on cognitive function and dementia-related factors in elderly patients with Parkinson's disease dementia during the COVID-19 pandemic.

OBJECTIVE: To observe the effect of Butylphthalide soft capsules on improving cognitive function, activity of daily living, and dementia-related factors of elderly patients with Parkinson's disease dementia (PDD) during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: The clinical data of 126 elderly patients with PDD admitted to the Second Affiliated Hospital of Zhengzhou University during the COVID-19 pandemic were analyzed retrospectively. Patients were assigned to a control group (conventional clinical treatment, n=50) and a research group (conventional clinical treatment combined with Butylphthalide soft capsules, n=76). The clinical response, clinical symptoms, cognitive function, activity of daily living (ADL), cerebral blood flow velocity, serum inflammatory factors, oxidative stress indices, neurotrophic factors, dementia-related factors, and drug safety were analyzed and compared between the two groups. RESULTS: The overall response rate was significantly higher in the research group than in the control group (97.37% vs. 84.00%, P=0.017). After treatment, the clinical symptom-based scores and levels of serum inflammatory factors, malondialdehyde, and Parkinson disease protein 7 were significantly lower in the research group than in the control group (all P<0.001); the cognitive function and ADL scores, cerebral blood flow velocities, and levels of catalase, glutathione peroxidase, superoxide dismutase, neurotrophic factors, and neurotrophin-3 were significantly higher in the research group (all P<0.001). The incidence of adverse reactions was comparable between the two groups (4.00% vs. 6.58%, P=0.825). CONCLUSION: Butylphthalide soft capsules have a definite effect and good safety in elderly patients with PDD during the COVID-19 pandemic.

LINC01977 promotes colorectal cancer growth and metastasis by enhancing aerobic glycolysis via the ERK/c-Myc axis.

Background: How colorectal cancer (CRC) gain the ability to growth and metastasis remains largely unknown. Findings from preceding studies have revealed the participation of long non-coding RNAs (lncRNAs) in CRC progression. However, the role of LINC01977 in CRC remains unexplored. This study aims to explore the function and underlying mechanism of LINC01977 in CRC. Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to analyze the expression of LINC01977 in CRC and its correlation with CRC prognosis. In our research, we explored the influence of LINC01977 on CRC progression such as cell proliferation, migration, invasion, and aerobic glycolysis, and identified its fundamental molecular mechanism using in vitro CRC cell lines and in vivo mouse xenograft models. Results: LINC01977 exhibited significantly elevated expression in CRC tissues and cell lines, and its level was significantly correlated with malignant clinicopathological characteristics and negative prognosis. Furthermore, both in vivo and in vitro tests revealed LINC01977's role in facilitating CRC cell proliferation and metastasis. LINC01977's significant part in CRC aerobic glycolysis was also discovered. With an aim to uncover the underlying mechanism, we investigated LINC01977's effect on c-Myc, a key gene in glycolysis. The results showed that LINC01977 regulated c-Myc stability via extracellular signal-regulated kinase (ERK)-mediated phosphorylation, and LINC01977-mediated c-Myc activated the level of vital glycolysis-related genes such as HK2, PGK1, LDHA, and GLUT1. Rescue experiments further confirmed that LINC01977 promoted CRC proliferation, metastasis, and aerobic glycolysis via c-Myc. Conclusions: This study is the first to report that LINC01977 facilitates CRC proliferation, metastasis, and aerobic glycolysis through c-Myc, suggesting its potential as a therapeutic target for CRC treatment.

Host genetics and larval host plant modulate microbiome structure and evolution underlying the intimate insect-microbe-plant interactions in Parnassius species on the Qinghai-Tibet Plateau.

Insects harbor a remarkable diversity of gut microbiomes critical for host survival, health, and fitness, but the mechanism of this structured symbiotic community remains poorly known, especially for the insect group consisting of many closely related species that inhabit the Qinghai-Tibet Plateau. Here, we firstly analyzed population-level 16S rRNA microbial dataset, comprising 11 Parnassius species covering 5 subgenera, from 14 populations mostly sampled in mountainous regions across northwestern-to-southeastern China, and meanwhile clarified the relative importance of multiple factors on gut microbial community structure and evolution. Our findings indicated that both host genetics and larval host plant modulated gut microbial diversity and community structure. Moreover, the effect analysis of host genetics and larval diet on gut microbiomes showed that host genetics played a critical role in governing the gut microbial beta diversity and the symbiotic community structure, while larval host plant remarkably influenced the functional evolution of gut microbiomes. These findings of the intimate insect-microbe-plant interactions jointly provide some new insights into the correlation among the host genetic background, larval host plant, the structure and evolution of gut microbiome, as well as the mechanisms of high-altitude adaptation in closely related species of this alpine butterfly group.

Differentiation of hUC-MSC into dopaminergic-like cells after transduction with hepatocyte growth factor.

Parkinson's disease (PD) is a common neurodegenerative condition causing significant disability and thus negatively impacting quality of life. The recent advent of stem cell-based therapy has heralded the prospect of a potential restorative treatment option for PD. In particular, mesenchymal stem cells derived from human umbilical cord (hUC-MSCs) have great potential for developing a therapeutic agent as such. Furthermore, hepatocyte growth factor (HGF), which shows mitogenic and morphogenetic activities in a variety of cells, including MSC, and may be implicated in the pathophysiology of PD. As such, HGF may represent a new therapeutic target for the disease. In this study, we successfully isolated and facilitated the transduction of an adenoviral vector expressing HGF (Ad-HGF) into isolated hUC-MSCs. Following transduction, the hUC-MSCs can differentiate into dopaminergic neuron-like cells secreting dopamine, tyrosine hydroxylase, and dopamine transporter. Our data suggest that hUC-MSCs have the ability to differentiate into dopaminergic neurons after transduction with Ad-HGF, providing encouraging evidence to further explore this approach to the treatment of PD.