USP10 promotes cell proliferation, migration, and invasion in NSCLC through deubiquitination and stabilization of EIF4G1.

Lung cancer is one of the most common types of malignant cancer worldwide, causing a serious social and economic burden. It is classified into non-small cell lung cancer (NSCLC) and small cell lung cancer, with NSCLC accounting for 80-85% of cases. Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) is highly expressed in NSCLC, playing an important role in regulating tumor growth, angiogenesis, malignant transformation, and phagocytosis.

Study on the water retention curve of shredded municipal solid waste considering the compressibility of specimens based on the centrifuge method.

The water retention curve (WRC) of municipal solid waste (MSW) is the important hydraulic parameter for the study of unsaturated seepage analysis in landfills. Due to the compressibility and degradability of the waste, the search for a method to quickly and accurately test its water retention curve (WRC) is a current problem that needs to be solved. In this paper, considering the volume change of the waste specimens in test, the test principle of centrifuge testing of WRC is corrected to make it applicable to the testing of waste WRC.

An efficient peptide ligase engineered from a bamboo asparaginyl endopeptidase.

In recent years, a few asparaginyl endopeptidases (AEPs) from certain higher plants have been identified as efficient peptide ligases with wide applications in protein labeling and cyclic peptide synthesis. Recently, we developed a NanoLuc Binary Technology (NanoBiT)-based peptide ligase activity assay to identify more AEP-type peptide ligases. Herein, we screened 61 bamboo species from 16 genera using this assay and detected AEP-type peptide ligase activity in the crude extract of all tested bamboo leaves.

Knockdown of in NSCLC induces CXCL8 secretion.

Non-small cell lung cancer (NSCLC) is the most common type of lung tumor; however, we lack effective early detection indicators and therapeutic targets. Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) is vital to initiate protein synthesis, acting as a scaffolding protein for the eukaryotic protein translation initiation factor complex, EIF4F, which regulates protein synthesis together with EIF4A, EIF4E, and other translation initiation factors. However, EIF4G1's function in NSCLC cancer is unclear.

A review of existing methods for predicting leachate production from municipal solid waste landfills.

Landfilling is one of the predominant methods of municipal solid waste (MSW) disposal worldwide, while the generation of leachate, a kind of toxic wastewater, is among the primary factors behind landfill instability and environmental contamination problems. Precise prediction of leachate production is crucial to landfill safety evaluation and design. This paper presents a comprehensive review of methods for predicting leachate production from MSW landfills.

Nanomolar range of FAM237B can activate receptor GPR83.

Our recent study confirmed that the mature neuropeptide FAM237A, also known as neurosecretory protein GL (NPGL), is an efficient agonist for GPR83. The paralog FAM237B was previously reported as a weak agonist for GPR83. In the present study, we prepared mature human FAM237B via an intein-fusion approach and demonstrated that it could cause a significant activation effect at the nanomolar range (1‒10 nM) in a NanoBiT-based β-arrestin recruitment assay.

The ghrelin receptor GHSR has two efficient agonists in the lobe-finned fish Latimeria chalumnae.

The peptide hormone ghrelin (an agonist) and LEAP2 (an antagonist) play important functions in energy metabolism via their receptor GHSR, an A-class G protein-coupled receptor. Ghrelin, LEAP2, and GHSR are widely present from fishes to mammals. However, our recent study suggested that fish GHSRs have different binding properties to ghrelin: a GHSR from the lobe-finned fish Latimeria chalumnae (coelacanth) is efficiently activated by ghrelin, but GHSRs from the ray-finned fish Danio rerio (zebrafish) and Larimichthys crocea (large yellow croaker) have lost binding to ghrelin.

Prognostic and functional roles of EIF4G1 in lung squamous cell carcinoma.

Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) is highly expressed in many cancers and affects their occurrence and development. However, the effect of EIF4G1 on the prognosis, biological function and the relevant mechanism in lung squamous cell carcinoma (LSCC) is unclear. Through clinical cases, Cox's proportional hazard model and Kaplan-Meier plotter survival analysis, we find the expression levels of EIF4G1 are dependent on age and clinical stage, high expression of EIF4G1 could be used to predict the overall survival of LSCC patients.

FAM237A, rather than peptide PEN and proCCK56-63, binds to and activates the orphan receptor GPR83.

G protein-coupled receptor 83 (GPR83) is primarily expressed in the brain and is implicated in the regulation of energy metabolism and some anxiety-related behaviours. Recently, the PCSK1N/proSAAS-derived peptide PEN, the procholecystokinin-derived peptide proCCK56-63, and family with sequence similarity 237 member A (FAM237A) were all reported as efficient agonists of GPR83. However, these results have not yet been reproduced by other laboratories and thus GPR83 is still officially an orphan receptor.

LEAP2 is a more conserved ligand than ghrelin for fish GHSRs.

Recently, liver-expressed antimicrobial peptide 2 (LEAP2) was identified as an endogenous antagonist and an inverse agonist of the ghrelin receptor GHSR. However, its functions in lower vertebrates are not well understood. Our recent study demonstrated that both LEAP2 and ghrelin are functional towards a fish GHSR from Latimeria chalumnae, an extant coelacanth believed to be one of the closest ancestors of tetrapods.

Atomistic insights into migration mechanism of graphene-based membranes on soil mineral phases.

Graphene-based membranes (GBM) will migrate in the soil and enter the groundwater system or plant roots, which will eventually pose potential risks to human beings. The migration mechanism of GBM depends on the interface behavior of complex soil components. Herein, we use molecular dynamics (MD) simulations to probe the interface behavior between GBM and three type minerals (quartz, calcite and kaolinite).

Study of leachate recharge model and vertical well design method for bioreactor landfills.

Leachate recharging not only solves the leachate treatment problem but also has tremendous environmental and engineering benefits. In this study, a recharge model was developed based on consideration of the inhomogeneous characteristics of the pile and the degree of clogging of the leachate collection and removal system (LCRs), and a design diagram of the maximum injection pressure P and the minimum setback distance d was given. The following conclusions are obtained: the rate of diffusion in the horizontal and burial depth directions depends on anisotropy coefficient A, and the rate of development of the blocked water level on the LCRs depends on the degree of blockage h.

Development of Esterase-Resistant and Highly Active Ghrelin Analogs via Thiol-Ene Click Chemistry.

The orexigenic peptide ghrelin exerts important functions in energy metabolism and has therapeutic potential to treat certain diseases. Native ghrelin carries an essential -fatty acyl moiety; however, this post-translational modification is susceptible to hydrolysis by certain esterases in circulation, representing a major route of its in vivo inactivation. In the present study, we developed a novel approach to prepare various esterase-resistant ghrelin analogs via photoinduced thiol-ene click chemistry.

Cationic amino acid transporter-1 (CAT-1) promotes fibroblast-like synoviocyte proliferation and cytokine secretion by taking up L-arginine in rheumatoid arthritis.

Background: Abnormal proliferation of fibroblast-like synoviocytes (FLSs) in the synovial lining layer is the primary cause of synovial hyperplasia and joint destruction in rheumatoid arthritis (RA). Currently, the relationship between metabolic abnormalities and FLS proliferation is a new focus of investigation. However, little is known regarding the relationship between amino acid metabolism and RA.

Blockade of the amino acid transporter SLC6A14 suppresses tumor growth in colorectal Cancer.

Background: The amino acid transporter SLC6A14, which transports 18 of the 20 proteinogenic amino acids, is too low to be detected in healthy normal tissues but is significantly increased in some solid cancers. However, little is known about the roles of SLC6A14 in colorectal cancer (CRC).

Methods: The mRNA and protein levels of SLC6A14 were detected using TCGA database, real-time polymerase chain reaction, western blot, and tissue microarrays, respectively.

The Prognostic Value and Immune Infiltration of USP10 in Pan-Cancer: A Potential Therapeutic Target.

Ubiquitin-specific peptidase 10 (USP10) can sustain cellular functions and regulate cellular processes. It plays an essential role in cancer inhibition or facilitation by reversing ubiquitin-proteasome degradation. Studies have identified USP10 to be involved in tumor progression in various cancers.

A case study: a continuous improvement project of lecturing skills for clinical teachers in Chinese residency standardized training.

Background: Aiming at the poor quality of small lectures due to the lack of lecturing skills of the clinical teachers in residency standardized training, the Teaching and Training Department of Shanghai East Hospital set up a continuous improvement project of lecturing skills for the clinical teachers to search for effective ways to improve lecture quality, then the effect was evaluated.

Methods: Based on the ADDIE model of training design, the department conducted the project in accordance with a process of analysis, design, development, implementation and evaluation. A special course "Clinical Teacher Presentation Training" (CTPT) was developed to convey and train the 5 key behaviors in presentation to improving lecture quality of the clinical teachers.

Development of a general bioluminescent activity assay for peptide ligases.

In recent years, some peptide ligases have been identified, such as bacterial sortases and certain plant asparaginyl or prolyl endopeptidases. Peptide ligases have wide applications in protein labelling and cyclic peptide synthesis. To characterize various known peptide ligases or identify new ones, we propose a general bioluminescent activity assay via the genetic fusion of a recognition motif of peptide ligase(s) to the C-terminus of an inactive large NanoLuc fragment (LgBiT) and the chemical introduction of a nucleophilic motif preferred by the peptide ligase(s) to the N-terminus of the low-affinity SmBiT complementation tag.

LEAP2 has antagonized the ghrelin receptor GHSR1a since its emergence in ancient fish.

Recent studies have demonstrated that liver-expressed antimicrobial peptide 2 (LEAP2) antagonizes the ghrelin receptor GHSR1a in mammals. However, its antagonistic function in lower vertebrates has not yet been tested. LEAP2 orthologs have been identified from a variety of fish species; however, previous studies all focused on their antimicrobial activity.

Unusual orthologs shed new light on the binding mechanism of ghrelin to its receptor GHSR1a.

The gastric peptide ghrelin has important functions in energy metabolism and cellular homeostasis by activating growth hormone secretagogue receptor type 1a (GHSR1a). The N-terminal residues of ghrelin orthologs from all vertebrates are quite conserved; however, in orthologs from Cavia porcellus and Phyllostomus discolor, Ser2 and Leu5 are replaced by a smaller Ala and a positively charged Arg, respectively. In the present study, we first demonstrated that the hydrophobic Leu5 is essential for the function of human ghrelin, because Ala replacement caused an approximately 100-fold decrease in activity.

Elevation of EIF4G1 promotes non-small cell lung cancer progression by activating mTOR signalling.

Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1), as the key component of the transcription initiation factor complex EIF4F, is significantly upregulated in multiple solid tumours, including lung cancer. However, the function and mechanism of EIF4G1 in the regulation of non-small-cell lung cancer (NSCLC) remain unclear. Here, using the clinical samples and the comprehensive survival analysis platforms Kaplan-Meier plotter, we observed aberrant upregulation of EIF4G1 in NSCLC tissues; furthermore, high expression of EIF4G1 showed association with low differentiation of lung cancer cells and poor overall survival in NSCLC patients.

Hydrophobic interactions of relaxin family peptide receptor 3 with ligands identified using a NanoBiT-based binding assay.

Relaxin family peptide receptor 3 (RXFP3) is a G protein-coupled receptor implicated in the regulation of food intake and stress response upon activation by the neuropeptide relaxin-3. In recent studies, interactions of RXFP3 with some natural or synthetic ligands have been investigated. In the present study, we identified the hydrophobic interactions of human RXFP3 with the chimeric agonist R3/I5 and the chimeric antagonist R3(ΔB23-27)R/I5 using a newly developed NanoBiT-based homogenous binding assay.

Identifying key residues and key interactions for the binding of LEAP2 to receptor GHSR1a.

Liver-expressed antimicrobial peptide 2 (LEAP2) was recently identified as a competitive antagonist for the G protein-coupled receptor GHSR1a, the cognate receptor for the gastric peptide ghrelin. LEAP2 plays important functions in energy metabolism by tuning the ghrelin-GHSR1a system. However, the molecular mechanism by which LEAP2 binds to GHSR1a is largely unknown.

Exploring electrostatic interactions of relaxin family peptide receptor 3 and 4 with ligands using a NanoBiT-based binding assay.

Relaxin family peptides perform a variety of biological functions by activating four G protein-coupled receptors, namely relaxin family peptide receptor 1-4 (RXFP1-4). We recently disclosed electrostatic interactions of the homologous RXFP3 and RXFP4 with some agonists based on activation complementation. However, this activation assay-based approach cannot be applied to antagonists that do not activate receptors.