Ubiquitin ligase RFWD2 promotes dendritic spine and synapse formation by activating the ERK/PEA3/c-Jun pathway in rat cerebral cortical neurons.

The regulation of protein degradation through the ubiquitin-proteasome system is essential for normal brain development, axon growth, synaptic growth and plasticity. The E3 ubiquitin ligase RFWD2 plays a key role in the onset and development of neurological diseases, including the pathogenesis of Alzheimer's disease (AD), but the mechanisms controlling the homeostasis of neuronal synaptic proteins are still poorly understood. Here, we showed that the expression level of RFWD2 gradually decreased with the age of the rats and was negatively correlated with the development of cerebral cortical neurons and dendrites in vivo. RFWD2 was shown to localize to presynaptic terminals and some postsynaptic sides of both excitatory synapses and inhibitory synapses via colocalization with neuronal synaptic proteins (SYN, PSD95, Vglut1 and GAD67). Overexpression of RFWD2 promoted dendrite development and dendritic spine formation and markedly decreased the expression of synaptophysin and PSD95 by reducing the expression of ETV1, ETV4, ETV5 and c-JUN in vitro. Furthermore, the whole-cell membrane slice clamp results showed that RFWD2 overexpression resulted in greater membrane capacitance in neuronal cells, inadequate cell repolarization, and a longer time course for neurons to emit action potentials with decreased excitability. RFWD2 regulates dendritic development and plasticity, dendritic spine formation and synaptic function in rat cerebral cortex neurons by activating the ERK/PEA3/c-Jun pathway via a posttranslational regulatory mechanism and can be used as an efficient treatment target for neurological diseases.

Composite water value: A way forward to balance the development and protection of transboundary lakes.

Transboundary lakes are shared by multiple administrative regions. The key to balance the development and protection of transboundary lakes is to properly measure the value of water resources. Most of previous studies on the measurement of lake water resources value have not fully considered the ecosystem service function. This paper proposes a new concept "composite water value" to measure the value of transboundary lakes by integrating the external runoff value and the internal runoff value of water resources. The study constructs a composite water value measurement system for transboundary lakes, further analyzes its influencing factors,and applies the system to the case of Nansi Lake, a representative transboundary lake in eastern China. The results show that: (1) The composite water value of lakes is influenced by various factors, including industrial structure, water withdrawal, and water use methods, which impact the external runoff water value; meanwhile, the composite water quality and fluctuations in lake level are closely associated with the internal runoff water value. From 2008 to 2021, the average annual composite water value of Nansi Lake was 39.628 billion yuan, exhibiting a "rising-falling-fluctuating rising" trend due to pollution control policies, reduced precipitation, and enhanced water-saving technologies successively. (2) From a long-term perspective, it is necessary to focus on the internal runoff water use value of lakes. The internal runoff water value of Nansi Lake has been over 75% of the composite water value, and flood storage and water conservation are important manifestations of its ecosystem service value. (3) The external runoff water value of lake is closely related to the internal runoff water value, and relevant departments need to consider the balance between the water withdrawal of multiple cities along the lake and the retained water volume of the lake to achieve the maximum benefit of composite water value.

Template Synthesis of Cyclometalated Macrocycle Iridium(III) Complexes Based on Photoinduced C-N Cross-Coupling Reactions In Situ.

The synthesis of metal macrocycle complexes holds paramount importance in coordination and supramolecular chemistry. Toward this end, we report a new, mild, and efficient protocol for the synthesis of cyclometalated macrocycle Ir(III) complexes: [Ir(L1)](PF6) (1), [Ir(L2)](PF6) (2), and [Ir(L3)](PF6) (3), where L1 presents 10,17-dioxa-3,6-diaza-2(2,8),7(8,2)-diquinolina-1,8(1,4)-dibenzenacyclooctadecaphane, L2 is 10,13,16,19,22,25-hexaoxa-3,6-diaza-2(2,8),7(8,2)-diquinolina-1,8(1,4)-dibenzenacyclohexacosaphane, and L3 is 4-methyl-10,13,16,19,22,25-hexaoxa-3,6-diaza-2(2,8),7(8,2)-diquinolina-1,8(1,4)-dibenzenacyclohexacosaphane. This synthesis involves the preassembly of two symmetric 2-phenylquinoline arms into C-shape complexes, followed by cyclization with diamine via in situ interligand C-N cross-coupling, employing a metal ion as a template. Moreover, the synthetic yield of these cyclometalated Ir(III) complexes, tethered by an 18-crown-6 ether-like chain, is significantly enhanced in the presence of K+ ion as a template. The resultant cyclometalated macrocycle Ir(III) complexes exhibit high stability, efficient singlet oxygen generation, and superior catalytic activity for the aerobic selective oxidation of sulfides into sulfoxides under visible light irradiation in aqueous media at room temperature. The photocatalyst 2 demonstrates recyclability and can be reused at least 10 times without a significant loss of catalytic activity. These results unveil a new and complementary approach to the design and in situ synthesis of cyclometalated macrocycle Ir(III) complexes via a mild interligand-coupling strategy.

Safflower yellow for injection enhances anti-coagulation of warfarin in rats: implications in pharmacodynamics and pharmacokinetics.

This study investigated whether Safflower Yellow for injection (SYI) would affect the anticoagulation of warfarin in rats.Wistar male rats were divided into six groups randomly and administered with SYI (9 mg/kg, intraperitoneal injection) in single-dose and steady-dose warfarin (0.2 mg/kg, oral gavage), respectively. The pharmacodynamic parameters of PT and APTT were measured by a coagulation analyser. R/S-warfarin concentration was measured by UHPLC-MS/MS, and pharmacokinetic parameters calculated using DAS 2.0 software.The single-dose study demonstrated that SYI, alone or co-administered with warfarin, could significantly increase PT, INR, and APTT values (p < 0.01). R-warfarin Cmax, AUC, and t1/2 values increased by 9.25% (p > 0.05), 25.96% (p < 0.01), and 26.17% (p < 0.01), respectively, whereas the CL/F value reduced by 22.22% (p < 0.01) in the presence of SYI. Meanwhile, S-warfarin Cmax, AUC, and t1/2 values increased by 37.41%, 32.11%, and 31.73% (all p < 0.01), respectively, whereas the CL/F value reduced by 33.33% (p < 0.01). The steady-dose study showed that PT, INR, APTT, and the concentrations of R/S-warfarin increased significantly when SYI was co-administered with warfarin (p < 0.01).SYI can enhance warfarin's anticoagulation intensity and decelerate its metabolism in rats.

Satellite Cell-Derived Exosomes: A Novel Approach to Alleviate Skeletal Muscle Atrophy and Fibrosis.

Skeletal muscle atrophy coincides with extensive fibrous tissue hyperplasia in muscle-atrophied patients, and fibrous tissue plays a vital role in skeletal muscle function and hinders muscle fiber regeneration. However, effective drugs to manage skeletal muscle atrophy and fibrosis remain elusive. This study isolated and characterized exosomes derived from skeletal muscle satellite cells (MuSC-Exo). The study investigated their effects on denervated skeletal muscle atrophy and fibrosis in Sprague Dawley (SD) rats via intramuscular injection. MuSC-Exo demonstrated the potential to alleviate skeletal muscle atrophy and fibrosis. The underlying mechanism using single-cell RNA sequencing data and functional analysis are analyzed. Mechanistic studies reveal close associations between fibroblasts and myoblasts, with the transforming growth factor ß1 (TGF-ß1)-Smad3-Pax7 axis governing fibroblast activation in atrophic skeletal muscle. MuSC-Exo intervention inhibited the TGF-ß1/Smad3 pathway and improved muscle atrophy and fibrosis. In conclusion, MuSC-Exo-based therapy may represent a novel strategy to alleviate skeletal muscle atrophy and reduce excessive fibrotic tissue by targeting Pax7 through the TGF-ß1/Smad3 pathway.

Effects of sodium ferulate for injection on anticoagulation of warfarin in rats in vivo.

BACKGROUND: Herb-drug interactions may result in increased adverse drug reactions or diminished drug efficacy, especially for drugs with a narrow therapeutic index such as warfarin. The current study investigates the effects of sodium ferulate for injection (SFI) on anticoagulation of warfarin from aspects of pharmacodynamics and pharmacokinetics in rats and predicts the risk of the combination use. METHODS: Rats were randomly divided into different groups and administered single- or multiple-dose of warfarin (0.2 mg/kg) with or without SFI of low dose (8.93 mg/kg) or high dose (26.79 mg/kg). Prothrombin time (PT) and activated partial thromboplastin time (APTT) were detected by a blood coagulation analyzer, and international normalized ratio (INR) values were calculated. UPLC-MS/MS was conducted to measure concentrations of warfarin enantiomers and pharmacokinetic parameters were calculated by DAS2.0 software. RESULTS: The single-dose study demonstrated that SFI alone had no effect on coagulation indices, but significantly decreased PT and INR values of warfarin when the two drugs were co-administered (P < 0.05 or P < 0.01), while APTT values unaffected (P > 0.05). Cmax and AUC of R/S-warfarin decreased but CL increased significantly in presence of SFI (P < 0.01). The multiple-dose study showed that PT, APTT, INR, and concentrations of R/S-warfarin decreased significantly when SFI was co-administered with warfarin (P < 0.01). Warfarin plasma protein binding rate was not significantly changed by SFI (P > 0.05). CONCLUSIONS: The present study implied that SFI could accelerate warfarin metabolism and weaken its anticoagulation intensity in rats.

China Medicinal Plants of the Ampelopsis grossedentata-A Review of Their Botanical Characteristics, Use, Phytochemistry, Active Pharmacological Components, and Toxicology.

Ampelopsis grossedentata (AG) is mainly distributed in Chinese provinces and areas south of the Yangtze River Basin. It is mostly concentrated or scattered in mountainous bushes or woods with high humidity. Approximately 57 chemical components of AG have been identified, including flavonoids, phenols, steroids and terpenoids, volatile components, and other chemical components. In vitro studies have shown that the flavone of AG has therapeutic properties such as anti-bacteria, anti-inflammation, anti-oxidation, enhancing immunity, regulating glucose and lipid metabolism, being hepatoprotective, and being anti-tumor with no toxicity. Through searching and combing the related literature, this paper comprehensively and systematically summarizes the research progress of AG, including morphology, traditional and modern uses, chemical composition and structure, and pharmacological and toxicological effects, with a view to providing references for AG-related research.

Research progress into the application of Mycobacterium phlei in veterinary medicine.

Mycobacterium phlei is a gram-positive acid-fast mycobacterium from the family Mycobacteriaceae. It is a valuable resource for both natural drugs and microecological preparations. It has been widely used in the field of human medicine; however, in the field of animal husbandry and veterinary medicine, the research and application of M. phlei is still in the preliminary exploration stage. This study aims to summarize the research progress of M. phlei in the field of veterinary medicine and provide a valuable reference for future research. Key words, such as 'M. phlei', 'veterinary field', 'immune balancer', 'genome' and other relevant words to this study, were used to search through PubMed, Web of Science, SciELO, Science Direct and Google Scholar databases. The results showed that the culture conditions of M. phlei were relatively simple, but its bacterial composition and genome sequence were relatively complex, and various components in the cell wall may have immunoregulatory effects. Therefore, the inactivated preparation made from M. phlei can have various applications in the veterinary field, such as growth regulation, immune regulation, antitumour, anti-parasite and asthma treatment. The literature review indicates that M. phlei preparation is an efficient and convenient immune system balance agent. Despite the challenges associated with the use of M. phlei preparations, it has a strong potential for application in veterinary medicine.

Effect of Dietary Gelsemium elegans Benth. Extract on the Growth, Slaughter Performance, Meat Quality, Intestinal Morphology, and Microflora of Yellow-Feathered Chickens.

The plant species Gelsemium elegans Benth. (GEB) promotes pig and sheep growth; however, little is known about its effects in chickens. In this study, a GEB extract (GEBE) was prepared, and its effects on the growth, slaughter, antioxidant performance, meat quality, serum biochemical indices, intestinal morphology, and microflora of yellow-feathered chickens were evaluated. In total, 600 chickens aged 15 days were randomly divided into four groups with five replicates each and fed a basal diet containing 0% (control), 0.25% (0.25 GEBE), 0.75% (0.75 GEBE), or 1.25% (1.25 GEBE) GEBE until 49 days of age. Chickens were then killed, and their meat, organs, and serum and cecal contents were collected. GEBE reduced the feed conversion ratio, particularly in the 0.75 and 1.25 GEBE groups. Furthermore, the GEBE diet improved meat tenderness and reduced the meat expressible moisture content and liver malondialdehyde content, indicating high meat quality. Whereas the 0.25 GEBE diet increased the level of Lactobacillus acidophilus in the cecum, the 0.75 GEBE diet decreased the Escherichia coli level therein. These findings demonstrate that GEBE may improve the meat quality and cecal microbiota of yellow-feathered chickens, providing a basis for identifying candidate alternatives to conventional antibiotics as growth promoting feed additives.

Flowering repressor CmSVP recruits the TOPLESS corepressor to control flowering in chrysanthemum.

Plant flowering time is induced by environmental and endogenous signals perceived by the plant. The MCM1-AGAMOUSDEFICIENS-Serum Response Factor-box (MADS-box) protein SHORT VEGETATIVE PHASE (SVP) is a pivotal repressor that negatively regulates the floral transition during the vegetative phase; however, the transcriptional regulatory mechanism remains poorly understood. Here, we report that CmSVP, a chrysanthemum (Chrysanthemum morifolium Ramat.) homolog of SVP, can repress the expression of a key flowering gene, a chrysanthemum FLOWERING LOCUS T-like gene (CmFTL3), by binding its promoter CArG element to delay flowering in the ambient temperature pathway in chrysanthemum. Protein-protein interaction assays identified an interaction between CmSVP and CmTPL1-2, a chrysanthemum homologue of TOPLESS (TPL) that plays critical roles as transcriptional corepressor in many aspects of plant life. Genetic analyses revealed the CmSVP-CmTPL1-2 transcriptional complex is a prerequisite for CmSVP to act as a floral repressor. Furthermore, overexpression of CmSVP rescued the phenotype of the svp-31 mutant in Arabidopsis (Arabidopsis thaliana), overexpression of AtSVP or CmSVP in the Arabidopsis dominant-negative mutation tpl-1 led to ineffective late flowering, and AtSVP interacted with AtTPL, confirming the conserved function of SVP in chrysanthemum and Arabidopsis. We have validated a conserved machinery wherein SVP partially relies on TPL to inhibit flowering via a thermosensory pathway.

A study on dynamic simulation and improvement strategies of flood resilience for urban road system.

As one of the most important and directly affected infrastructure by flood disasters in urban areas, the road system plays a crucial role in maintaining the order of human production and life, as well as providing a foundation for the implementation of emergency response work in disaster scenarios. The existing flood resilience quantification methods based on maximum inundation depths of each individual road unit neglects the influences on flood resilience caused by the connectivity of road system. Therefore, this paper focuses on the road system, simulates the flood resilience of the road system in multiple disaster scenarios based on the functionality curve of road system under rainfall-inundation processes, then quantifies the improvement effect of Low Impact Development (LID) measures on flood resilience. A case study is conducted in Yunmen community, Jingdezhen city in China. The results indicate that: (1) The flood resilience of the road system decreases with the increase of rainfall intensity under different scenarios, and the magnitude of the decrease reduces. (2) The road system exhibits strong adaptability during the early stages of rainfall; The duration of functionality loss increases with increasing of rainfall intensity in different scenarios. (3) Implementation of LID measures can significantly improve system robustness by enhancing the reliability of the roads around critical nodes, thereby effectively enhancing flood resilience. The conclusions can provide a theoretical basis for decision-makers to develop urban flood mitigation engineering plans and resilience strategies tailored to local conditions.

Solvent-Induced Umpolung Reaction from Dioxygenation to C-S Coupling in Bis(2-phenylquinoline) Iridium(III) Thiolate Complexes.

The construction of C-S bonds is of great importance in the field of synthetic and medicinal chemistry. Herein, solvent-induced umpolung reactions from dioxygenation to interligand C-S cross-coupling in bis(cyclometalated) Ir(III) thiolate complexes are reported in good to excellent yields at room temperature. Specifically, the reaction of rac-[Ir(pq)2(aet)] (where pq is 2-phenylquinoline and aet is 2-aminoethanethiolate) can be selectively switched to dioxygenation in acetonitrile solution in the presence of O2, resulting in the formation of a sulfinato complex rac-[Ir(pq)2(aes)] (where aes is 2-aminoethanesulfinato). Alternatively, the reaction in trifluoroethanol solution leads to interligand C-S cross-coupling, affording a rac-[Ir(pq)(pqaet)](PF6) [where pqaet is 2-((2-phenylquinolin-8-yl)thio)ethan-1-amine] complex, which generates a new tetradentate ligand in situ. Mechanistically, the formation of electrophilic metal thiyl radicals is proposed as a key intermediate in the interligand C-S coupling reaction. Furthermore, the sequential oxidation of a thioether complex into a sulfoxide complex is also observed at room temperature using H2O2 as an oxidant. Additionally, a new approach for the synthesis of a hexadentate ligand is developed through sequential C-S and C-N interligand coupling of metal thiolate complexes in situ under visible light irradiation in the presence of O2.

Study on the mechanism of Baihe Dihuang decoction in treating menopausal syndrome based on network pharmacology.

Menopausal syndrome (MS) refers to a series of symptoms with autonomic nervous system dysfunction caused by decreased sex hormones before and after menopause. Baihe Dihuang (BHDH) decoction positively affects MS, but its mechanism remains unclear. This study aimed to reveal the underlying mechanism through network pharmacology. The components of the BHDH Decoction were found through HERB, while corresponding targets were obtained from the HERB, Drug Bank, NPASS, Targetnet, and Swisstarget databases. The MS targets were obtained from GeneCards and OMIM. STRING was used to construct the protein-protein interaction networks. OmicShare tools were used for Gene Ontology and Kyoto encyclopedia of genes and genomes analyses. Finally, Autodock Vina 1.1.2 software (https://vina.scripps.edu/downloads/) was used for molecular alignment to verify whether the main active ingredients and key targets had good binding activity. We screened out 27 active ingredients and 251 effective targets of BHDH Decoction, 3405 MS-related targets, and 133 intersection targets between BHDH Decoction and MS. Protein-protein interaction network identified tumor protein P53, Serine/threonine-protein kinase AKT, epidermal growth factor receptor, Estrogen Receptor 1, and jun proto-oncogene as critical targets. Gene ontology analysis showed that these targets were mainly involved in the cellular response to chemical stimulus, response to oxygen-containing compound, cellular response to endogenous stimulus, response to an organic substance, and response to chemical, etc. Kyoto encyclopedia of genes and genomes pathways were mainly enriched in endocrine resistance, pathways in cancer, and the ErbB signaling pathway, etc. Molecular docking results showed that emodin and stigmasterol are strongly associated with Serine/threonine-protein kinase AKT, Estrogen Receptor 1, epidermal growth factor receptor, sarcoma gene, and tumor protein P53. This study preliminarily revealed the multi-component, multi-target, and multi-channel mechanism of BHDH Decoction in treating MS. It provides a reference for in vitro and in vivo research and clinical application of BHDH Decoction in the treatment of MS.

[Establishment and characterization of bone marrow mesenchymal stem cell lines stably synthesizing high-level dopamine].

A triple-transgenic (tyrosine hydroxylase/dopamine decarboxylase/GTP cyclohydrolase 1, TH/DDC/GCH1) bone marrow mesenchymal stem cell line (BMSCs) capable of stably synthesizing dopamine (DA) transmitters were established to provide experimental evidence for the clinical treatment of Parkinson's disease (PD) by using this cell line. The DA-BMSCs cell line that could stably synthesize and secrete DA transmitters was established by using the triple transgenic recombinant lentivirus. The triple transgenes (TH/DDC/GCH1) expression in DA-BMSCs was detected using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence. Moreover, the secretion of DA was tested by enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC). Chromosome G-banding analysis was used to detect the genetic stability of DA-BMSCs. Subsequently, the DA-BMSCs were stereotactically transplanted into the right medial forebrain bundle (MFB) of Parkinson's rat models to detect their survival and differentiation in the intracerebral microenvironment of PD rats. Apomorphine (APO)-induced rotation test was used to detect the improvement of motor dysfunction in PD rat models with cell transplantation. The TH, DDC and GCH1 were expressed stably and efficiently in the DA-BMSCs cell line, but not expressed in the normal rat BMSCs. The concentration of DA in the cell culture supernatant of the triple transgenic group (DA-BMSCs) and the LV-TH group was extremely significantly higher than that of the standard BMSCs control group (P < 0.000 1). After passage, DA-BMSCs stably produced DA. Karyotype G-banding analysis showed that the vast majority of DA-BMSCs maintained normal diploid karyotypes (94.5%). Moreover, after 4 weeks of transplantation into the brain of PD rats, DA-BMSCs significantly improved the movement disorder of PD rat models, survived in a large amount in the brain microenvironment, differentiated into TH-positive and GFAP-positive cells, and upregulated the DA level in the injured area of the brain. The triple-transgenic DA-BMSCs cell line that stably produced DA, survived in large numbers, and differentiated in the rat brain was successfully established, laying a foundation for the treatment of PD using engineered culture and transplantation of DA-BMSCs.

System comprehensive risk assessment of urban rainstorm-induced flood-water pollution disasters.

The urban rainstorm-induced flood-water pollution disaster is a kind of systematic risk, which may induce secondary disasters that can lead to more serious damage, so this paper first adopts the fuzzy comprehensive evaluation method to determine the flood risk by combining with the submergence depth derived from the risk field and other factors data, and then the grid environmental risk evaluation method, which is improved by increasing the induced possibility based on Bayesian theory, is used to evaluate the flood-induced water pollution risk, and the system comprehensive risk of rainstorm-induced flood-water pollution disasters is finally obtained by constructing risk level matrix, which can well depict the coupling superposition effect. Shenzhen City is selected as the study area, and the results showed that the area with high-risk of both flood and water pollution only accounts for about 0.14% of the total area, mainly distributed in the eastern junction of Longgang district and Pingshan district, where the rainstorms occur frequently and the enterprise risk sources are dense. The system comprehensive risk is mostly very low-low and very high-low, accounting for more than 76% of the total area. It is always necessary to pay attention not only to the areas with high risk level of both disasters, but also to the areas with high risk level of one disaster. The method proposed in this study can not only quantitatively reveal the formation of the induced risk, but also provide reference for early warning.

Neural progenitor cells derived from fibroblasts induced by small molecule compounds under hypoxia for treatment of Parkinson's disease in rats.

Neural progenitor cells (NPCs) capable of self-renewal and differentiation into neural cell lineages offer broad prospects for cell therapy for neurodegenerative diseases. However, cell therapy based on NPC transplantation is limited by the inability to acquire sufficient quantities of NPCs. Previous studies have found that a chemical cocktail of valproic acid, CHIR99021, and Repsox (VCR) promotes mouse fibroblasts to differentiate into NPCs under hypoxic conditions. Therefore, we used VCR (0.5 mM valproic acid, 3 µM CHIR99021, and 1 µM Repsox) to induce the reprogramming of rat embryonic fibroblasts into NPCs under a hypoxic condition (5%). These NPCs exhibited typical neurosphere-like structures that can express NPC markers, such as Nestin, SRY-box transcription factor 2, and paired box 6 (Pax6), and could also differentiate into multiple types of functional neurons and astrocytes in vitro. They had similar gene expression profiles to those of rat brain-derived neural stem cells. Subsequently, the chemically-induced NPCs (ciNPCs) were stereotactically transplanted into the substantia nigra of 6-hydroxydopamine-lesioned parkinsonian rats. We found that the ciNPCs exhibited long-term survival, migrated long distances, and differentiated into multiple types of functional neurons and glial cells in vivo. Moreover, the parkinsonian behavioral defects of the parkinsonian model rats grafted with ciNPCs showed remarkable functional recovery. These findings suggest that rat fibroblasts can be directly transformed into NPCs using a chemical cocktail of VCR without introducing exogenous factors, which may be an attractive donor material for transplantation therapy for Parkinson's disease.

Overexpression of TCERG1 as a prognostic marker in hepatocellular carcinoma: A TCGA data-based analysis.

Objective: Transcription elongation factor 1 (TCERG1) is a nuclear protein consisted of multiple protein structural domains that plays an important role in regulating the transcription, extension, and splicing regulation of RNA polymerase II. However, the prognostic and immunological role of TCERG1 in human cancer remains unknown. In this study, we analyzed the expression of TCERG1 gene in hepatocellular carcinoma (HCC) patients, its clinical significance, and its possible prognostic value by bioinformatics. Methods: RNA sequencing data and clinicopathological characteristics of patients with HCC were collected from TCGA and CCLE databases. The Wilcoxon rank-sum test was used to analyze the expression of TCERG1 in HCC tissues and normal tissues. The protein levels of TCERG1 between normal and liver cancer tissues were analyzed by the Human Protein Atlas Database (HPA) (www.proteinatlas.org). Validation was performed using the Gene Expression Omnibus (GEO) dataset of 167 samples. The expression of TCERG1 in HCC cells were verified by qRT-PCR, and CCK-8, scratch assay and Transwell assay were performed to detect cell proliferation, migration and invasion ability. According to the median value of TCERG1 expression, patients were divided into high and low subgroups. Logistic regression, GSEA enrichment, TME, and single-sample set gene enrichment analysis (ssGSEA) were performed to explore the effects of TCERG1 on liver cancer biological function and immune infiltrates. TCERG1 co-expression networks were studied through the CCLE database and the LinkedOmics database to analyze genes that interact with TCERG1. Results: The expression levels of TCERG1 in HCC patient tissues were significantly higher than in normal tissues. Survival analysis showed that high levels of TCERG1 expression were significantly associated with low survival rates in HCC patients. Multifactorial analysis showed that high TCERG1 expression was an independent risk factor affecting tumor prognosis. This result was also verified in the GEO database. Cellular experiments demonstrated that cell proliferation, migration and invasion were inhibited after silencing of TCERG1 gene expression. Co-expression analysis revealed that CPSF6 and MAML1 expression were positively correlated with TCERG1. GSEA showed that in samples with high TCERG1 expression, relevant signaling pathways associated with cell cycle, apoptosis, pathways in cancer and enriched in known tumors included Wnt signaling pathway, Vegf signaling pathway, Notch signaling pathway, MAPK signaling pathway and MTOR pathways. The expression of TCERG1 was positively correlated with tumor immune infiltrating cells (T helper two cells, T helper cells). Conclusion: TCERG1 gene is highly expressed in hepatocellular carcinoma tissues, which is associated with the poor prognosis of liver cancer, and may be one of the markers for the diagnosis and screening of liver cancer and the prediction of prognosis effect. At the same time, TCERG1 may also become a new target for tumor immunotherapy.

LncRNA MNX1-AS1 contributes to lung adenocarcinoma progression by targeting the miR-34a/SIRT1 axis.

LncRNA MNX1-AS1 is known to be involved in progression of several tumor types. However, few studies have investigated the molecular mechanism of MNX1-AS1 in lung adenocarcinoma (LAC). To explore the function of MNX1-AS1 in the pathogenesis of LAC, qRT-PCR was performed to show MNX1-AS1 expression. MNX1-AS1 expression in LAC cells was suppressed by siRNA to detect the biologic behavior. The relationships among miR-34a, MNX1-AS1 and SIRT1 were confirmed by pull-down and dual-luciferase reporter assay. Whether MNX1-AS1 was involved in LAC by targeting miR-34a/SIRT1 axis was verified. MNX1-AS1 was up-regulated in LAC, and over-expression of MNX1-AS1 was significantly associated with lymph node metastasis and poor prognosis. In A549 and H1299 cells, cell proliferation, migration, and invasion were suppressed, the cell cycle was regulated, as well as apoptosis was increased after silencing MNX1-AS1. Mechanistically, MNX1-AS1 served as a ceRNA of miR-34a to down-regulate miR-34a expression. SIRT1 is targeted by miR-34a and its expression is regulated by MNX1-AS1 and miR-34a. Up-regulation of SIRT1 salvaged the effect of silencing MNX1-AS1 on A549 and H1299 cells, to some extent. These results showed that MNX1-AS1 contributes to LAC progression by targeting the miR-34a/SIRT1 axis.

Change of motifs in C. elegans reveals developmental principle of neural network.

Revealing the organizing principles of developing neural networks is a difficult but significant task in neuroscience. As a creature with a rather compact and well-studied neural network, C. elegans is an ideal subject for neuroscience study. However, the researches on its developing neural network remain challenging. The changes in specific properties of neural network across development may uncover part of its principles. Motif is a typical structure property that can be well applied to various complex networks. Here, we study the motif changes in C. elegans neural network across development. By counting the occurrence number of all three-node subgraph motif structures in its neural network at different stages of C. elegans development, along with those in corresponding random networks, we determine which of these structures are motifs for C. elegans, finding out the regular changes of motifs during its development. Combined with the potential function of these subgraph motifs and synaptic information, we gain insight into the organizing principle of neural network during development, which may increase our understanding of neuroscience and inspire the construction of artificial neural network.

The Application of Mixed Organic and Inorganic Fertilizers Drives Soil Nutrient and Bacterial Community Changes in Teak Plantations.

Appropriate fertilization can enhance forest productivity by maintaining soil fertility and improving the structure of the bacterial community. However, there is still uncertainty surrounding the effects of combined application of organic and inorganic fertilizers on soil nutrient status and bacterial community structure. A fertilization experiment was set up in an eight-year-old teak plantation with five treatments involved: mixed organic and NPK compound fertilizers (OCF), mixed organic and phosphorus fertilizers (OPF), mixed organic, NPK and phosphorus fertilizers (OCPF), mixed NPK and phosphorus fertilizers (CPF) and no fertilization (CK). Soil chemical properties and bacterial communities were investigated, and the co-occurrence pattern of the bacterial community under different fertilization treatments was compared. The results showed that the contents of soil organic matter and nitrate nitrogen, and the soil pH values were the highest after OCPF treatment, which were 20.39%, 90.91% and 8.16% higher than CK, respectively. The richness and diversity of bacteria underwent no obvious changes, but the structure of the soil's bacterial community was significantly altered by fertilization. Of the dominant bacteria taxa, the relative abundance increased for Gemmatimonadetes, Myxococcota, ADurb.Bin063-13 and Candidatus_Koribacter, and decreased for Chloroflexi, Proteobacteria, JG30-KF-AS9 and Acidothermus under OCPF treatment in comparison to CK. The number of nodes and edges, the average degree and the network density of bacterial community co-occurrence networks were the greatest in OCPF treatment, indicating that application of OCPF could make the network structure of soil bacteria more stable and complex. Moreover, soil pH and organic matter were significantly correlated with bacterial community structure and were considered the main influencing factors. These findings highlight that the combined application of organic, NPK and phosphorus fertilizers is highly beneficial for improving soil quality and optimizing bacterial community structure in teak plantations.