Green finance, energy consumption, urbanization, and economic growth: Quantile based evidence from China.

This study investigates the relationships between energy consumption, urbanization, green finance, and economic growth in China. By utilizing the quantile ARDL model and considering labor and capital as input factors, we analyze the period from 1999 to 2022. Our findings reveal that green finance and urbanization have negative effects on economic growth across different quantiles, in both the short and long run. Conversely, energy consumption exhibits a significantly positive impact on growth in various quantiles. Policymakers are encouraged to implement sustainable energy measures, promote eco-friendly urban planning, and embrace green technology to achieve both economic growth and environmental sustainability.

Recent findings on miR­370 expression, regulation and functions in cancer (Review).

MicroRNAs (miRNAs/miRs) are a group of small non­coding RNAs that serve as post­transcriptional gene modulators. miRNAs have been demonstrated to serve a pivotal role in carcinogenesis and the dysregulated expression of miRNAs is a well­understood characteristic of cancer. In recent years, miR­370 has been established as a key miRNA in various cancers. The expression of miR­370 is dysregulated in various types of cancer and varies markedly across different tumor types. miR­370 can regulate multiple biological processes, including cell proliferation, apoptosis, migration, invasion, as well as cell cycle progression and cell stemness. Moreover, it has been reported that miR­370 affects the response of tumor cells to anticancer treatments. Additionally, the expression of miR­370 is modulated by multiple factors. The present review summarizes the role and mechanism of miR­370 in tumors, and demonstrates its potential as a molecular marker for cancer diagnosis and prognosis.

Detection of Carbamazepine and Its Metabolites in Blood Samples by LC-MS/MS / 法医学杂志

OBJECTIVES@#To establish a method for the detection of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS).@*METHODS@#The blood samples were treated with 1-butyl-3-methylimidazolium hexafluorophosphate as an extraction solvent. The samples were extracted by ultrasound-assisted extraction and separated by ZORBAX Eclipse Plus C18, 95Å column. The mobile phase A aqueous solution containing 0.1% formic acid and 10 mmol/L ammonium acetate, and mobile phase B mixed organic solvent containing acetonitrile/methanol (Vacetonitrile∶Vmethanol=2∶3) were used for gradient elution at the flow rate of 1.00 mL/min. An electrospray ion source in positive mode was used for detection in the multiple reaction monitoring.@*RESULTS@#The linearities of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples were good within the corresponding range, with correlation coefficients (r) greater than 0.995 6. The limits of detection were 3.00, 0.40 and 1.30 ng/mL, respectively. The limit of quantitation were 8.00, 1.00 and 5.00 ng/mL, respectively. The extraction recoveries ranged from 76.00% to 106.44%. The relative standard deviations of the intra-day and inter-day precisions were less than 16%. Carbamazepine and its main metabolite 10,11-dihydro-10,11-epoxycarbamazepine were detected in blood samples of death cases with a mass concentration of 2.71 μg/mL and 252.14 ng/mL, respectively.@*CONCLUSIONS@#This method has high sensitivity and good selectivity, which is suitable for the detection of carbamazepine and its metabolites in blood samples, and can be used for carbamazepine-related forensic identifications.

CCL19 has potential to be a potential prognostic biomarker and a modulator of tumor immune microenvironment (TIME) of breast cancer: a comprehensive analysis based on TCGA database.

The development of cancer was determined by not only the intrinsic properties of cancer cells, but also the communication between cancer cells and tumor microenvironment (TME). We applied ESTIMATE and CIBERSORT algorithms to calculate the immune/stromal component and tumor-infiltrating immune cells (TICs) in TME of BC. The results showed that immune component in TME predicted patients' survival and associated with progression of BC. Differentially expressed genes (DEGs) were primarily enriched in immune-related activities. Finally, CCL19 was acquired which shared the leading nodes in PPI network and was associated with patients' survival. High expression of CCL19 predicted better prognosis and participated in progression of BC. Genes in CCL19 up-regulated group were enriched in immune-related activities and these functions might depend on the communications between CCL19 and multiple TICs in TIME. In conclusion, CCL19 functioned as a potential prognostic biomarker and a modulator of TIME in BC through communicating with various TICs.

Functions and Targets of miR-335 in Cancer.

MicroRNAs (miRNAs) are small non-coding RNAs (18~25 nt in length) that act as master regulators of eukaryotic gene expression. They might play an oncogenic or tumor-suppressive role in multiple cancers. In recent decades, several studies have focused on the functions and mechanisms of miR-335 in cancer. The expression level of miR-335 in tissues and cells varies with cancer types, and miR-335 has been proposed as a potential biomarker for the prognosis of cancer. Besides, miR-335 may serve as an oncogene or tumor suppressor via regulating different targets or pathways in tumor initiation, development, and metastasis. Furthermore, miR-335 also influences tumor microenvironment and drug sensitivity. MiR-335 is regulated by various factors such as lncRNAs and microRNAs. In this review, we reveal the functions and targets of miR-335 in various cancers and its potential application as a possible biomarker in prognostic judgment and treatment of malignant tumors.

TGFß1: An Indicator for Tumor Immune Microenvironment of Colon Cancer From a Comprehensive Analysis of TCGA.

BACKGROUND: Tumor microenvironment (TME) and tumor-infiltrating immune cells (TICs) greatly participate in the genesis and development of colon cancer (CC). However, there is little research exploring the dynamic modulation of TME. METHODS: We analyzed the proportion of immune/stromal component and TICs in the TME of 473 CC samples and 41 normal samples from The Cancer Genome Atlas (TCGA) database through ESTIMATE and CIBERSORT algorithms. Correlation analysis was conducted to evaluate the association between immune/stromal component in the TME and clinicopathological characteristics of CC patients. The difference analysis was performed to obtain the differentially expressed genes (DEGs). These DEGs were further analyzed by GO and KEGG enrichment analyses, PPI network, and COX regression analysis. Transforming growth factor ß1 (TGFß1) was finally overlapped from the above analysis. Paired analysis and GSEA were carried out to understand the role of TGFß1 in colon cancer. The intersection between the difference analysis and correlation analysis was conducted to learn the association between TGFß1 and TICs. RESULTS: Our results showed that the immune component in the TME was negatively related with the stages of CC. GO and KEGG enrichment analysis revealed that 1,110 DEGs obtained from the difference analysis were mainly enriched in immune-related activities. The intersection analysis between PPI network and COX regression analysis indicated that TGFß1 was significantly associated with the communication of genes in the PPI network and the survival of CC patients. In addition, TGFß1 was up-regulated in the tumor samples and significantly related with poor prognosis of CC patients. Further GSEA suggested that genes in the TGFß1 up-regulated group were enriched in immune-related activities and the function of TGFß1 might depend on the communications with TICs, including T cells CD4 naïve and T cells regulatory. CONCLUSION: The expression of TGFß1 might be an indicator for the tumor immune microenvironment of CC and serve as a prognostic factor. Drugs targeting TGFß1 might be a potential immunotherapy for CC patients in the future.

PEGylated nano-Rehmannia glutinosa polysaccharide induces potent adaptive immunity against Bordetella bronchiseptica.

Vaccines, in many cases, stimulate only too weak immunogenicity to prevent infection. Therefore, adjuvants are required during their preparation to boost the immune response. We herein developed a PEGylated nano-adjuvant based on Rehmannia glutinosa polysaccharide (RGP). The addition of PEG layer exhibits enhanced immune performance of the nano-RGP. Stimulation of dendritic cells (DCs) with PEGylated nano-RGP (pRL) led to increased proliferation and cytokine production (IL-6, IL-12, IL-1ß and TNF-α). The pRL was internalized into DCs via a rapid and efficient method. The mice immunized with pRL exhibited enhanced antigen-specific serum IgG and Th1-(IFN-γ), Th2-(IL-4), and Th17-(IL-17, IL-6) cytokine production, contributing to a good anti-infection performance. Furthermore, the pRL could effectively deliver the antigen to the lymph nodes (LNs), activate DC in the LN and produce enhanced CD4+and CD8+ T-cells-derived memory (CD44high CD62Lhigh), and effector (CD44high CD62Llow) as well as functional phenotypes. Our results revealed that pRL can act as a promising adjuvant with targeted delivery of antigen due to its effective activation and robust adaptive immunity induction of DCs.

Transcriptome analysis of mild hypothermia protection against radiation / 中南大学学报(医学版)

OBJECTIVES@#To analyze the differentially expressed genes (DEGs) with radiation-induced rat lung injury, and to reveal the protective mechanism for mild hypothermia in the radiation-induced lung injury in rats at the transcriptome level.@*METHODS@#A total of 10 male SD rats aged 6-8 weeks were randomly divided into 2 groups to establish a rat model of radiation-induced lung injury, and one group was treated with mild hypothermia. RNA was extracted from left lung tissue of each group, and sequenced by BGISEQ-500 platform. Significance analysis of DEGs was carried out by edgeR software. Gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to analyze the gene function. Then 5 key DEGs were verified by real-time reverse transcription PCR (real-time RT-PCR).@*RESULTS@#There were 2 790 DEGs (false discovery rate<0.001, |log@*CONCLUSIONS@#The DEGs and pathways related to mild hypothermia protection against radiation-induced lung injury in rats are obtained, which provides an experimental basis for the protection of mild hypothermia against radiation-induced lung injury.

The biological function of m6A demethylase ALKBH5 and its role in human disease.

Human AlkB homolog H5 (ALKBH5) is a primary m6A demethylase, which is dysregulated and acts as a biological and pharmacological role in human cancers or non-cancers. ALKBH5 plays a dual role in various cancers through regulating kinds of biological processes, such as proliferation, migration, invasion, metastasis and tumor growth. In addition, it takes a great part in human non-cancer, including reproductive system diseases. The underlying regulatory mechanisms of ALKBH5 that relys on m6A-dependent modification are implicated with long non-coding RNA, cancer stem cell, autophagy and hypoxia. ALKBH5 is also an independent prognostic indicator in various cancers. In this review, we summarized the current evidence on ALKBH5 in diverse human cancers or non-cancers and its potential as a prognostic target.

Potential regulatory role of lncRNA-miRNA-mRNA axis in osteosarcoma.

Osteosarcoma (OS) is one of the most common malignant bone tumors in childhood and adolescence. Although great efforts have been made in therapeutic methods for OS, the prognosis is not yet satisfactory and the underlying molecular mechanisms of OS pathogenesis have not been fully explored. Meanwhile, non-coding RNAs, especially microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), have long been investigated due to their roles as key players in regulating various biological and pathological processes, such as proliferation, apoptosis, cell-cycle, migration, invasion, metastasis, EMT and drug resistance, through targeting their mRNAs transcriptionally or posttranscriptionally. Although, numerous studies have confirmed a complex cross-regulation among lncRNAs, miRNAs and mRNAs, the underlying molecular mechanism has not been elucidated. In this review, we comprehensively summarized the latest research progress of the regulatory relationship among lncRNAs, miRNAs and mRNAs, and highlighted the role of lncRNA-miRNA-mRNA axis in the development of OS to provide novel approaches for cancer diagnosis and treatment.

Long Noncoding RNA SBF2-AS1 Is Critical for Tumorigenesis of Early-Stage Lung Adenocarcinoma.

Emerging evidence demonstrates that long non-coding RNAs (lncRNAs) are deeply involved in the development of various cancers. This study identified that SBF2-AS1, an early-stage-specific lncRNA, is critical for the tumorigenesis of lung adenocarcinoma (LUAD). We first analyzed LUAD transcriptome data from The Cancer Genome Atlas and the GEO database by weighted gene co-expression network analysis (WGCNA). Five early LUAD-specific lncRNAs were filtered out, and only SBF2-AS1 was upregulated in LUAD. High expression of SBF2-AS1 indicates poor survival of LUAD, especially the early-stage LUAD, but not lung squamous cell carcinoma. SBF2-AS1 promotes LUAD cells proliferation in vitro, and RNA-sequencing data shows that many cell-cycle-related genes were downregulated after SBF2-AS1 knockdown. Mechanically, SBF2-AS1 could competitively bind with miR-338-3p and miR-362-3p to increase E2F1 expression. Finally, we show that the SBF2-AS1-miR-338-3p/362-3p-E2F1 axis could promote LUAD tumorigenesis in vitro and in vivo. Our study demonstrates that SBF2-AS1, an early-stage-specific lncRNA, promotes LUAD tumorigenesis by sponging miR-338-3p and miR-362-3p and increasing E2F1 expression. The SBF2-AS1-miR-338-3p/362-3p-E2F1 regulatory axis may serve as a prognostic marker and potential therapeutic target for LUAD.

Inhibitory Effects of Berberine Hydrochloride on Trichophyton mentagrophytes and the Underlying Mechanisms.

BACKGROUND: T. mentagrophytes can infect all mammals, including rabbits, causing serious infections with remarkable economic losses for rabbit farmers. Berberine is an alkaloid that is effective against a variety of microbial infections such as T. mentagrophytes. Growth curve by dry weight determination and in-vivo antifungal assay were carried out to clarify the inhibitory effect of berberine hydrochloride against T. mentagrophytes. Transcriptomics analyses were also carried out for better understanding of the underlying mechanisms. RESULTS: The growth rate of T. mentagrophytes was significantly higher in control condition than under berberine hydrochloride or clotrimazole for 60 h. The growth rate of T. mentagrophytes was significantly slighter higher in berberine condition (1 mg) than under clotrimazole for 46 h. T. mentagrophytes seriously shrunk after berberine or clotrimazole treatment, as observed by TEM and in SEM. Significant recovery was evident in three berberine groups on day 6 compared with the DMSO group. Results from transcriptomics analyses showed 18,881 identified unigenes, including 18,754 and 12,127 in the NT and SwissProt databases. Among these, 12,011, 9174, and 11,679 unigenes belonged to 3 Gene Ontology (GO), 43 KEGG, and 25 KOG categories, respectively. Interestingly, we found that down-regulation of 14α-demethylase exposed to various medicines was slightly different, i.e., berberine hydrochloride (fold change -3.4956) and clotrimazole (fold change -2.1283) caused various degrees of alteration. CONCLUSIONS: Berberine hydrochloride could inhibit the growth of T. mentagrophytes. Berberine hydrochloride could also cure dermatosis induced by T. mentagrophytes. Down-regulation of 14α-demethylase exposed to various medicines was slightly different and might be one of the anti-resistance mechanisms of berberine hydrochloride in T. mentagrophytes. The present investigation provides considerable transcript sequence data that would help further assess the antifungal mechanisms against T. mentagrophytes, for antifungal medicine development.

FDA guidelines for preclinical evaluation of radiopharmaceuticals / 中华核医学与分子影像杂志

Preclinical evaluation is related to the clinical safety of radiopharmaceuticals.There are different research foci on preclinical evaluation of different radiopharmaceuticals.This article summarizes the Food and Drug Administration (FDA) preclinical evaluation guidelines of diagnostic and therapeutic radiopharmaceuticals,in order to provide reference for domestic research and preclinical evaluation of radiopharmaceuticals.

Application of the red fluorescent protein mCherry in mycelial labeling and organelle tracing in the dermatophyte Trichophyton mentagrophytes.

Trichophyton mentagrophytes is a fungus that causes skin disease in humans and other animals worldwide. Studies on molecular biology and fluorescent labeling of the fungus are limited. Here, we applied mCherry for the first time in T. mentagrophytes to label the fungus and its organelles. We constructed four expression vectors of mCherry or mCherry fusions containing a variety of resistance markers and promoters, which were then integrated, together with two previous mCherry expression vectors, in T. mentagrophytes via Agrobacterium tumefaciens-mediated transformation (AtMT). The resulting transformants emitted bright red fluorescence. We used the histone protein H2B and the peroxisome targeting signal 1 (PTS1) peptide to target the nucleus and peroxisomes, respectively, in T. mentagrophytes. In the transformants expressing mCherry-fused H2B, the fluorescence was distinctly localized to the nuclei in hyphae, spores and the fungal cells in infected animal tissue. In the T. mentagrophytes transformants where the peroxisome was targeted, the mCherry was present as small dots (0.2-1 µm diameter) throughout the spores and the hyphae. We also constructed a T. mentagrophytes AtMT library containing more than 1000 hygromycin-resistant transformants that were genetically stable. Our results provide useful tools for further investigations on molecular pathogenesis of T. mentagrophytes.

Introduction of radiopharmaceutical administration policy of FDA / 中华核医学与分子影像杂志

Radiopharmaceuticals have been widely used in the diagnosis, treatment and monitoring of diseases, and they play an important role in new drug development. Food and Drug Administration(FDA) has rich experience in the administration of radiopharmaceuticals. This article mainly interprets the regulato-ry policy of FDA for radiopharmaceuticals from the aspects of definition, regulations and registration, trying to provide reference for domestic research of radiopharmaceuticals.

Effect of Blocking PYR Complex Binding to DNA Site by Peptide Nucleic Acid on γ-Globin Gene Expression / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of blocking polypyrimidine complex binding to DNA site by using peptide nucleic acid (PNA) on γ-globin gene expression.</p><p><b>METHODS</b>PYR-PNA, β-PNA and RS-PNA (random sequence-PNA) were designed and synthesized, then were transfected into K562 cells with the cationic liposome lipofectamine 2000 used as vector. The expression of γ-globin gene at both the transcriptional and translational level was detected by RT-PCR and the Western blot respectively at 24 h, 48 h and 72 h after transfection with PNAs.</p><p><b>RESULTS</b>Compared with RS-PNA and control groups, the expression of γ-globin gene at mRNA and protein levels in PYR-PNA group was significantly up-regulated(P<0.05), especially at 48 h after tranfection, the levels of mRNA and protein in PYR-PNA group were increased by 2.0 and 2.5 times than those in control group, respectively.</p><p><b>CONCLUSION</b>PYR-PNA can significantly up-regulate the expression of γ-globin gene in K562 cells, this study may provide a new research idea for gene therapy of β-thalassemia.</p>

The Protective Effect of Jatrorrhizine Against Oxidative Stress in Primary Rat Cortical Neurons.

OBJECTIVES: This study investigated the neuroprotective effects of Jatrorrhizine in rat cortical neurons. METHOD: The effects of Jatrorrhizine on hydrogen peroxide (H2O2)-induced cell lesion, levels of lipid peroxidation and antioxidant enzyme activities were investigated in rat cortical neurons. Levels of mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) were measured by fluorescent rhodamine staining and 2',7'-dichlorfluorescein-diacetate staining, respectively. ATP content was measured by a high performance liquid chromatography. The protein levels for Bax, Bcl2 and cleaved caspase-3 were analyzed by western blot protein expression. RESULTS: There was a significant reduction in cell viability and activities of Superoxide dismutase and glutathione peroxidase for the cortical neurons after exposure to 50µM H2O2 for 12h. The hydrogen peroxide increased the production of malondialdehyde and ROS but decreased MMP and ATP in the neurons. However, pretreatment with different concentrations of Jatrorrhizine (5-20µM) inhibited H2O2-induced neurotoxicity markedly. Jatrorrhizine also attenuated the H2O2-induced Bcl-2/Bax ratio reduction and caspase-3 activation in these neurons. CONCLUSIONS: Our findings suggest that Jatrorrhizine plays a critical neuroprotective role in H2O2 - induced apoptosis through its anti-oxidative actions. This may allow Jatrorrhizine to be a novel therapeutic with its high bioavailability to treat Alzheimer's disease.

Alteration of gene expression profile in Beagle dogs' peripheral blood lymphocytes after acute γ-ray irradiation / 中华放射医学与防护杂志

Objective To investigate the changes of gene expression profile in Beagle dogs' peripheral blood lymphocytes after acute irradiation.Methods Totally 20 male adult Beagle dogs were randomly divided into four groups including non-treatment blank control group and three radiation groups exposed to 0.5,2.0,and 5.0 Gy of γ-rays,respectively.Six hours after radiation,the peripheral blood were collected for lymphocytes isolation.Total RNA was extracted from the lymphocytes and analyzed by microarray hybridization.The differential gene profiles of radiation groups were analyzed by gene ontology (GO) analysis and kyoto encyclopedia of genes and genomes (KEGG) pathways analysis,and the alerted genes were further confirmed by the real time quantitative PCR (qRT-PCR) assay.Results Compared to the blank control group,the expressions of 308 genes in the radiation groups were perturbed over 2-fold of control,including 61 genes up-regulated and 247 genes down-regulated,which were mainly associated with immune response and cancer occurrence.The GO analysis indicated that the differential expressed genes were associated with cell connection,signal transduction,oxidation-reduction reaction and metabolism.The KEGG pathway analysis showed that some physiological and biochemical processes were involved,such as phagocytosis,tumor pathway,p53 signaling pathway,JAK-STAT signal pathway,cell differentiation,and proliferation,oxidative phosphorylation,glycogen dysplasia and other pathways.The microarray data of the alterations of apoptosis enhancing nuclease (AEN) and mitogenactivated protein kinase 13 (MAP3K13) gene expressions were further confirmed by qRT-PCR.Conclusions Exposure to different doses of acute γ-ray irradiation had significant impact on the gene expressions in Beagle dogs' peripheral blood lymphocytes and those differential expressed genes were related to a series of biological processes and pathways including immune response,metabolism and carcinogenesis.

Homology modeling and virtual screening for inhibitors of lipid kinase PI(4)K from Plasmodium.

Malaria parasite strains have emerged to tolerate the therapeutic effects of the prophylactics and drugs presently available. Recent studies have shown that KAI715 and its analogs inhibit malaria parasites growth by binding to lipid kinase PI(4)K (phosphatidylinositol-4-OH kinase) of the parasites. Therefore, targeting PI(4)K may open up new avenues of target-based drug discovery to identify novel anti-malaria drugs. In this investigation, we describe the discovery of novel potent PfPI(4)K (PI(4)K from P. falciparum) inhibitors by employing a proposed hybrid virtual screening (VS) method, including pharmacophore model, drug-likeness prediction and molecular docking approach. 3D structure of PfPI(4)K has been established by homology modeling. Pharmacophore model HypoA of PfPI(4)K inhibitors has been developed based on the ligand complexed with its corresponding receptor. 174 compounds with good ADMET properties were carefully selected by a hybrid virtual screening method. Finally, the 174 hits were further validated by using a new pharmacophore model HypoB built based on the docking pose of BQR685, and 95 compounds passed the last filter. These compounds would be further evaluated by biological activity assays. The molecular interactions of the top two potential inhibitors with the active site residues are discussed in detail. These identified hits can be further used for designing the more potent inhibitors against PfPI(4)K by scaffold hopping, and deserve consideration for further structure-activity relationship (SAR) studies.

Synthesis of novel galactose functionalized gold nanoparticles and its radiosensitizing mechanism.

BACKGROUND: Biocompatible gold nanoparticles (GNPs) are potentially practical and efficient agents in cancer radiotherapy applications. In this study, we demonstrated that GNPs can significantly modulate irradiation response of hepatocellular carcinoma cells in vitro and investigated the underlying mechanisms. We co-grafted galactose (GAL) targeting hepatocyte specific asialoglycoprotein receptor and Polyethylene Glycol (PEG) onto GNPs surfaces to increase GNPs targeting specificity and stability. RESULTS: This novel GAL-PEG-GNPs and bare GNPs show similar appearance and cytotoxicity profiles, while more GAL-PEG-GNPs can be effectively uptaken and could enhance cancer cell killing. CONCLUSION: GAL-PEG-GNPs have better radiosensitization to HepG2. The sensitization mechanism of GAL-PEG-GNPs is related to the apoptotic gene process activated by generation of a large amount of free radicals induced by GNPs.