ABSTRACT
BACKGROUND: The E1A-associated protein p300 (p300) has emerged as a promising target for cancer therapy due to its crucial role in promoting oncogenic signaling pathways in various cancers, including prostate cancer. This need is particularly significant in prostate cancer. While androgen deprivation therapy (ADT) has demonstrated promising efficacy in prostate cancer, its long-term use can eventually lead to the development of castration-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC). Notably, p300 has been identified as an important co-activator of the androgen receptor (AR), highlighting its significance in prostate cancer progression. Moreover, recent studies have revealed the involvement of p300 in AR-independent oncogenes associated with NEPC. Therefore, the blockade of p300 may emerge as an effective therapeutic strategy to address the challenges posed by both CRPC and NEPC. METHODS: We employed AI-assisted design to develop a peptide-based PROTAC (proteolysis-targeting chimera) drug that targets p300, effectively degrading p300 in vitro and in vivo utilizing nano-selenium as a peptide drug delivery system. FINDINGS: Our p300-targeting peptide PROTAC drug demonstrated effective p300 degradation and cancer cell-killing capabilities in both CRPC, AR-negative, and NEPC cells. This study demonstrated the efficacy of a p300-targeting drug in NEPC cells. In both AR-positive and AR-negative mouse models, the p300 PROTAC drug showed potent p300 degradation and tumor suppression. INTERPRETATION: The design of peptide PROTAC drug targeting p300 is feasible and represents an efficient therapeutic strategy for CRPC, AR-negative prostate cancer, and NEPC. FUNDING: The funding details can be found in the Acknowledgements section.
Subject(s)
E1A-Associated p300 Protein , Peptides , Prostatic Neoplasms , Proteolysis , Xenograft Model Antitumor Assays , Male , Humans , Proteolysis/drug effects , Animals , Mice , Cell Line, Tumor , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , E1A-Associated p300 Protein/metabolism , Peptides/pharmacology , Peptides/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Disease Models, Animal , Receptors, Androgen/metabolism , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/metabolism , Prostatic Neoplasms, Castration-Resistant/pathology , Drug DiscoveryABSTRACT
BACKGROUND: At present, it has been found that many patients have acquired resistance to radiotherapy, which greatly reduces the effect of radiotherapy and further affects the prognosis. CircRNAs is involved in the regulation of radiosensitivity of many kinds of tumor cells. Therefore, the main purpose of this study is to explore the regulatory effect of CircRNA_101491 on radiosensitivity of ESCC and its related mechanism. METHODS: We established ESCC radiation-resistant cell line (KYSE150R cell) by gradient dose method, and tested the difference of KYSE150 between KYSE150R cell and parent cell in vitro. Then, after knocking down the expression of CircRNA_101491, a series of in vitro experiments were conducted to verify the effects of CircRNA_101491 on the phenotype and radiosensitivity of KYSE150R cells, and further analyzed the related regulatory mechanism. In addition, we also used the model of transplanted tumor in nude mice to investigate the effect of CircRNA_101491 on the radiosensitivity of ESCC in vivo. RESULTS: According to a series of in vitro experiments, we confirmed that KYSE150R cells lost the epithelial phenotype and obtained interstitial cell-like phenotype, and found that CircRNA_101491 was highly expressed in KYSE150R cells. In addition, we found that knocking down the expression of CircRNA_101491 will lift the inhibition of miR-125a-5p, and then reverse the process of EMT, accelerate the process of apoptosis, thus play a role in radiosensitization. The in vivo experiment of transplanted tumor in nude mice also showed that knocking down the expression of CircRNA_101491 could enhance the radiosensitivity of ESCC. CONCLUSION: In conclusion, we confirmed that interfering with the expression of CircRNA_101491 can relieve the inhibition of miR-125a-5p, thus reverse the process of interstitial phenotype, accelerate the process of apoptosis, and enhance the radiosensitivity of ESCC.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Mice, Nude , MicroRNAs , RNA, Circular , Radiation Tolerance , MicroRNAs/genetics , MicroRNAs/metabolism , Animals , RNA, Circular/genetics , Humans , Mice , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Esophageal Neoplasms/radiotherapy , Esophageal Neoplasms/metabolism , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/radiotherapy , Esophageal Squamous Cell Carcinoma/metabolism , Apoptosis , Cell Proliferation , Gene Expression Regulation, Neoplastic , Mice, Inbred BALB C , Cell Line, Tumor , Xenograft Model Antitumor Assays , Tumor Cells, CulturedABSTRACT
Structural engineers are often required to draw two-dimensional engineering sketches for quick structural analysis, either by hand calculation or using analysis software. However, calculation by hand is slow and error-prone, and the manual conversion of a hand-drawn sketch into a virtual model is tedious and time-consuming. This paper presents a complete and autonomous framework for converting a hand-drawn engineering sketch into an analyzed structural model using a camera and computer vision. In this framework, a computer vision object detection stage initially extracts information about the raw features in the image of the beam diagram. Next, a computer vision number-reading model transcribes any handwritten numerals appearing in the image. Then, feature association models are applied to characterize the relationships among the detected features in order to build a comprehensive structural model. Finally, the structural model generated is analyzed using OpenSees. In the system presented, the object detection model achieves a mean average precision of 99.1%, the number-reading model achieves an accuracy of 99.0%, and the models in the feature association stage achieve accuracies ranging from 95.1% to 99.5%. Overall, the tool analyzes 45.0% of images entirely correctly and the remaining 55.0% of images partially correctly. The proposed framework holds promise for other types of structural sketches, such as trusses and frames. Moreover, it can be a valuable tool for structural engineers that is capable of improving the efficiency, safety, and sustainability of future construction projects.
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To detect low-frequency gravitational waves, it is necessary to eliminate the interference of geo-noise and build a laser interference gravitational-wave detection device in space. Space gravitational-wave detection missions, namely Taiji, LISA, and Tianqin, have been planning to achieve picometer sensitivity on an interferometer arm of several million kilometers to meet the gravitational-wave detection requirements. Because of the orbit evolution and the time delay in interferometer arms, the direction of the transmitted laser beam changes; consequently, a remote telescope cannot receive the laser beam to complete the inter-satellite laser interference. In this study, a two-dimensional point-ahead angle mechanism (2DPAAM) is designed and demonstrated to solve the aforementioned problem. Based on the design concept of aligning the rotation center with the mirror surface center, the 2DPAAM employs a four-link flexible-hinge structure, length expanding and contracting piezoelectric stack actuators, and closed-loop control of capacitive sensors to realize two-dimensional picometer-stable, high-precision rotation. A static model is established to analyze the rotational characteristics, and finite element analysis is performed to study the mechanical properties and to verify the rotational characteristics. The yaw and pitch stiffness errors are â¼0.93% and 5.9%, respectively, when the theoretical results are compared with the simulation results. A series of experiments are conducted on the developed 2DPAAM, and the results show that the rotary ranges of yaw and pitch motions attain ±270 and ±268 µrad, respectively. The rotational accuracies of both yaw and pitch motions attain â¼0.35 µrad, and the optical path difference is less than 10pm/Hz when the frequency is between 1 mHz and 1 Hz, by analogy.
ABSTRACT
The Large Plasma Device (LAPD) at UCLA (University of California, Los Angeles) produces an 18 m long, magnetized, quiescent, and uniform plasma at a high repetition rate to enable studies of fundamental plasma physics. Here, we report on a major upgrade to the LAPD plasma source that allows for more robust operation and significant expansion of achievable plasma parameters. The original plasma source made use of a heated barium oxide (BaO) coated nickel sheet as an electron emitter. This source had a number of drawbacks, including a limited range of plasma density (â²4.0 × 1012 cm-3), a limited discharge duration (â¼10 ms), and susceptibility to poisoning following oxygen exposure. The new plasma source utilizes a 38 cm diameter lanthanum hexaboride (LaB6) cathode, which has a significantly higher emissivity, allowing for a much larger discharge power density, and is robust to exposure to air. Peak plasma density of up to 3.0 × 1013 cm-33 in helium gas has been achieved. The typical operating pressure is â¼10-5 Torr, while dynamic pressure can be achieved through the gas-puffing technique. Discharges as long as 70 ms have been produced, enabling a variety of long-time-scale studies of processes, such as turbulent particle transport. The new source has been in continuous operation for 14 months, having survived air leaks, power outages that led to rapid temperature changes on the cathode and heater, and planned machine openings. We describe the design, construction, and initial operation of this novel new large-area LaB6 plasma source.
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Multicomponent metallacages can integrate the functions of their different building blocks to achieve synergetic effects for advanced applications. Herein, based on metal-coordination-driven self-assembly, we report the preparation of a series of isoreticular tetraphenylethylene-based metallacages, which are well characterized by multinuclear NMR, ESI-TOF-MS and single-crystal X-ray diffraction techniques. The suitable integration of photosensitizing tetraphenylethylene units as faces and Re catalytic complexes as the pillars into a single metallacage offers a high photocatalytic hydrogen production rate of 1707â µmol g-1 h-1 , which is one of the highest values among reported metallacages. Femtosecond transient absorption and DFT calculations reveal that the metallacage can serve as a platform for the precise and organized arrangement of the two building blocks, enabling efficient and directional electron transfer for highly efficient photocatalytic performance. This study provides a general strategy to integrate multifunctional ligands into a certain metallacage to improve the efficiency of photocatalytic hydrogen production, which will guide the future design of metallacages towards photocatalysis.
ABSTRACT
Biosurfactants have significant applications in various industries, including microbial-enhanced oil recovery (MEOR). While the state-of-the-art genetic approaches can generate high-yield strains for biosurfactant production in fermenters, there remains a critical challenge in enhancing biosurfactant-producing strains for use in natural environments with minimal ecological risks. The objectives of this work are enhancing the strain's capacity for rhamnolipids production and exploring the genetic mechanisms for its improvement. In this study, we employed atmospheric and room-temperature plasma (ARTP) mutagenesis to enhance the biosynthesis of rhamnolipids in Pseudomonas sp. L01, a biosurfactant-producing strain isolated from petroleum-contaminated soil. Following ARTP treatment, we identified 13 high-yield mutants, with the highest yield of 3.45 ± 0.09 g/L, representing a 2.7-fold increase compared to the parent strain. To determine the genetic mechanisms behind the enhanced rhamnolipids biosynthesis, we sequenced the genomes of the strain L01 and five high-yield mutants. A comparative genomic analysis suggested that mutations in genes related to the synthesis of lipopolysaccharides (LPS) and the transport of rhamnolipids may contribute to the improved biosynthesis. To the best of our knowledge, this is the first instance of utilizing the ARTP approach to improve rhamnolipid production in Pseudomonas strains. Our study provides valuable insights into the enhancement of biosurfactant-producing strains and the regulatory mechanisms of rhamnolipids biosynthesis.
ABSTRACT
Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.
Subject(s)
Prostatic Neoplasms , Von Hippel-Lindau Tumor Suppressor Protein , Male , Humans , Von Hippel-Lindau Tumor Suppressor Protein/genetics , Von Hippel-Lindau Tumor Suppressor Protein/metabolism , DNA-Binding Proteins/metabolism , Prolyl Hydroxylases/metabolism , Hypoxia , Prostatic Neoplasms/pathology , Glycolysis , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Cell Line, Tumor , DNA Helicases/metabolismABSTRACT
Scientific collaboration plays a significant role in scientists' research performance. When scientists move from one institution to another and leave the team they belong to or lead, they may continue collaborating with the former team because engaging in or building a new team takes time. In this study, we collected data from the Open Researcher and Contributor ID (ORCID) website on 2,922 scientists who published first-tier journal papers defined by the Chinese Academy of Science (CAS) before they moved to a new institution. By applying a Poisson regression model to the dataset, we explored the correlation between continued collaboration and the transition period after scientists moved, which is defined as the time span between the year of the move and the year when they published their first top-tier journal paper after moving. Our findings indicated that: (1) continued collaboration significantly shortens the transition period by 27.2%; (2) continued collaboration significantly shortens the transition period of senior scientists to a larger extent than that of junior scientists; (3) continued collaboration significantly shortens the transition period of social scientists to a larger extent than that of natural scientists; (4) the transition period is shorter after moves for scientists with higher inherent potential; and (5) there is no evidence that the transition period is associated with culture-related differences between the origin country and the destination country after the move, or whether they had lived in the destination country before.
ABSTRACT
Acute respiratory tract infections are a major public health problem and the leading cause of morbidity in children younger than 5 years old. This study investigated the potential reasons of unexplained acute respiratory infections in children in Xuzhou and its environs during 2018-2019.We collected pharyngeal swab samples from 411 children under the age of five who presented with symptoms of unexplained acute respiratory infection and were negative for bacteria, mycoplasma, and influenza viruses. Using viral metagenomic techniques, viral nucleic acids were extracted, enriched, and sequenced from the samples. Results indicated that Picornaviridae, Parvoviridae, Paramyxoviridae, Coronaviridae, and Anelloviridae were the five virus families with the highest relative content of sequence reads. And we detected 35 HBoV-positive and 12 HEV-positive samples out of 411 samples by the polymerase chain reaction (PCR). Partial or nearly complete genome sequences of viruses belonging to the families Picornaviridae, Parvoviridae, and Anelloviridae were characterized, and phylogenetic trees were constructed based on the nucleic acid or amino acid sequences of the predicted viral open reading frames (ORFs), as well as genotyping of the viruses. In addition, we observed recombination events in the Saffold virus and Coxsackievirus A9 by analyzing the genetic characteristics of the viruses revealed in this study. This study provides vital information for the prevention and treatment of acute respiratory infections in children younger than five years old.
Subject(s)
Nucleic Acids , Picornaviridae , Respiratory Tract Infections , Viruses , Child , Child, Preschool , Humans , Infant , Metagenomics , Phylogeny , Viruses/geneticsABSTRACT
Osmanthus fragrans (scientific name: Osmanthus fragrans (Thunb.) Lour.) is a species of the Osmanthus genus in the family Oleaceae, and it has a long history of cultivation in China. O. fragrans is edible and is well known for conferring a natural fragrance to desserts. This flowering plant has long been cultivated for ornamental purposes. Most contemporary literature related to O. fragrans focuses on its edible value and new species discovery, but the functional use of O. fragrans is often neglected. O, fragrans has many properties that are beneficial to human health, and its roots, stems, leaves, flowers and fruits have medicinal value. These characteristics are recorded in the classics of traditional Chinese medicine. Studies on the metabolites and medicinal value of O. fragrans published in recent years were used in this study to evaluate the medicinal value of O. fragrans. Using keywords such as metabolites and Osmanthus fragrans, a systematic and nonexhaustive search of articles, papers and books related to the medicinal use of Osmanthus fragrans metabolites was conducted. Fifteen metabolites were identified through this literature search and classified into three categories according to their properties and structure: flavonoids, terpenes and phenolic acids. It was found that the pharmacological activities of these secondary metabolites mainly include antioxidant, anticancer, anti-inflammatory and antibacterial activities and that these metabolites can be used to treat many human diseases, such as cancer, skin diseases, cardiovascular diseases, and neurological diseases. Most of the reports that are currently available and concern the secondary metabolites of Osmanthus fragrans have limitations. Some reports introduce only the general classification of compounds in Osmanthus fragrans, and some reports introduce only a single compound. In contrast, the introduction section of this paper includes both the category and the functional value of each compound. While reviewing the data for this study, the authors found that the specific action sites of these compounds and their mechanisms of action in plants are relatively weak, and in the future, additional research should be conducted to investigate this topic further.
ABSTRACT
BACKGROUND: Members of the genus Circovirus with the family Circoviridae are responsible for fatal diseases that can affect mammals and birds. Beak and feather disease virus (BFDV) is responsible for fatal diseases that could affect birds, causing the psittacine beak and feather disease. The current study discovered a new Circovirus from feces of laboratory rabbits and name it RabCV, which shows close relationship to BFDVs. RESULTS: We investigated the feces virome of 10 laboratory rabbits using the viral metagenomic method. In these samples, we detected a new rabbit-associated Circovirus (RabCV) and performed phylogenetic analysis based on replication-associated (Rep) protein. The result showed that the RabCV was closely clustered with BFDVs, sharing the identity of 56.7%-57.2% with them based on the whole genome sequence. PCR screening in a cohort of 38 laboratory rabbits showed that 3 out of the 38 rabbits were positive for this new rabbit-associated Circovirus. CONCLUSION: A new Circovirus was discovered from feces of rabbits, which showed low prevalence in the healthy laboratory rabbits. BFDV is responsible for fatal diseases that could affect birds, which suggested that the potential threat of the new rabbit-associated Circovirus to the health of laboratory rabbits needs further study.
Subject(s)
Bird Diseases , Circoviridae Infections , Circovirus , Animals , Birds , Circovirus/genetics , Feces , Humans , Mammals , Phylogeny , RabbitsABSTRACT
BACKGROUND AND OBJECTIVES: To investigate the association between various medication classes and the periodic limb movement index (PLMI) in a clinical cohort of adults who completed in-laboratory polysomnography. METHODS: A single, diagnostic, overnight, in-laboratory polysomnogram was completed for 3,488 patients consecutively referred from 2010 to 2015 to determine PLMI. Medication use and medical comorbidities were collected through patient questionnaires. Associations between medication classes and PLMI were ascertained using multivariable ordinal logistic regression models. RESULTS: The median age of the cohort was 56.0 years (48.2% male). After adjusting for age, sex, body mass index, relevant comorbidities, and sleep measures, the use of selective serotonin reuptake inhibitors (SSRIs) (odds ratio [OR] 1.52) and serotonin-norepinephrine reuptake inhibitors (SNRIs) (OR 1.99) was associated with increased PLMI. Conversely, gabapentinoids (OR 0.71), stimulants (OR 0.52), benzodiazepines (OR 0.79), and dopamine agonists (OR 0.38) were associated with decreased PLMI. A non-statistically significant trend for decreased PLMI with neuroleptic use was observed. No significant associations were found between PLMI and the use of antihypertensives, statins, tricyclic antidepressants, bupropion, anticoagulants, antiplatelets, modafinil, and antihistamines. DISCUSSION: The use of SSRIs and SNRIs was associated with elevated PLMI while the use of gabapentinoids, stimulants, benzodiazepines, and dopamine agonists was associated with decreased PLMI. These results can assist physicians in managing periodic limb movements in sleep (PLMS) and invite further research into the relationship between PLMS and medications with the modulating effects of dose, formulation type, and time of administration. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that SSRIs and SNRIs are associated with elevated PLMI while gabapentinoids, stimulants, benzodiazepines, and dopamine agonists are associated with decreased PLMI.
Subject(s)
Nocturnal Myoclonus Syndrome , Serotonin and Noradrenaline Reuptake Inhibitors , Adult , Benzodiazepines/therapeutic use , Cohort Studies , Dopamine Agonists/adverse effects , Female , Humans , Male , Middle Aged , Nocturnal Myoclonus Syndrome/complications , Nocturnal Myoclonus Syndrome/epidemiology , Retrospective Studies , Selective Serotonin Reuptake Inhibitors/adverse effectsABSTRACT
The cone angle of a hydrocyclone is believed to be an important parameter to affect the separation performance. For the recycling of waste plastics, this paper focused on the study of the influence of cone angles on the separation of light dispersed plastics (PET) and heavy dispersed plastics (PVC) by experiments and numerical simulations. The cone angle was changed from 3° to 28° either at given length of the cylindrical section or at fixed total length of the hydrocyclone. The separation performance varied with cone angles at given length of the cylindrical section more greatly than that at fixed total length of the hydrocyclone. Results show that particles with different sizes in mixture exhibited discrepant separation behaviors at various cone angles. There was an optimum cone angle at which the Newton efficiency peaked as 90.2%, while the purity of PET could also reach the highest. The proportion of cylindrical section could be properly small for the enhancement of Newton efficiency.
Subject(s)
Plastics , Refuse Disposal , RecyclingABSTRACT
The optical reference cavity in an ultrastable laser is sensitive to vibrations; the microvibrations in a space platform affect the accuracy and stability of such lasers. In this study, an active vibration isolation controller is proposed to reduce the effect of vibrations on variations in the cavity length and improve the frequency stability of ultrastable lasers. Based on the decentralized control strategy, we designed a state-differential feedback controller with a linear quadratic regulator (LQR) and added a disturbance observer (DOB) to estimate the source noise. Experiments were conducted using an active vibration isolation system; the results verified the feasibility and performance of the designed controller. The accelerations along the axis (Z-, X-, Y-) directions were suppressed in the low-frequency band within 200 Hz, and the root-cumulative power spectral densities (PSDs) declined to 1.17 × 10-5, 7.16 × 10-6, and 8.76 × 10-6 g. This comprehensive vibration met the requirements of an ultrastable laser.
ABSTRACT
Surfactant aggregates have long been considered as a tool to improve drug delivery and have been widely used in medical products. The pH-responsive aggregation behavior in anionic gemini surfactant 1,3-bis(N-dodecyl-N-propanesulfonate sodium)-propane (C12C3C12(SO3)2) and its mixture with a cationic monomeric surfactant cetyltrimethylammonium bromide (CTAB) have been investigated. The spherical-to-wormlike micelle transition was successfully realized in C12C3C12(SO3)2 through decreasing the pH, while the rheological properties were perfectly enhanced for the formation of wormlike micelles. Especially at 140 mM and pH 6.7, the mixture showed high viscoelasticity, and the maximum of the zero-shear viscosity reached 1530 Pa·s. Acting as a sulfobetaine zwitterionic gemini surfactant, the electrostatic attraction, the hydrogen bond and the short spacer of C12C3C12(SO3)2 molecules were all responsible for the significant micellar growth. Upon adding CTAB, the similar transition could also be realized at a low pH, and the further transformation to branched micelles occurred by adjusting the total concentration. Although the mixtures did not approach the viscosity maximum appearing in the C12C3C12(SO3)2 solution, CTAB addition is more favorable for viscosity enhancement in the wormlike-micelle region. The weakened charges of the headgroups in a catanionic mixed system minimizes the micellar spontaneous curvature and enhances the intermolecular hydrogen-bonding interaction between C12C3C12(SO3)2, facilitating the formation of a viscous solution, which would greatly induce entanglement and even the fusion of wormlike micelles, thus resulting in branched microstructures and a decline of viscosity.
Subject(s)
Rheology , Surface-Active Agents/chemistry , Cetrimonium/chemistry , Glutamates/chemistry , Hydrogen-Ion Concentration , Micelles , ViscosityABSTRACT
Protein phosphorylation is one of the most important posttranslational modifications. The phosphorylation and dephosphorylation of proteins regulate almost every cellular process, and the understanding of their functions can provide insights into the regulation of living systems at the molecular level. In recent years, both the rapid developments of enrichment approaches for phosphoproteins and MS techniques have improved the research scope and depth of phosphoproteomics. Using NaCl-treated soybean roots as the experimental materials, this chapter introduces the protein extraction, digestion with filter-aided sample preparation (FASP), eight-plex iTRAQ labeling, TiO2-based enrichment of phosphopeptides, LC-MS/MS analysis, as well as bioinformatic methods and protocols.
Subject(s)
Glycine max , Proteomics , Chromatography, Liquid , Phosphopeptides/metabolism , Phosphoproteins/metabolism , Phosphorylation , Plant Roots , Salinity , Glycine max/metabolism , Tandem Mass SpectrometryABSTRACT
Basic helix-loop-helix proteins (bHLHs) comprise one of the largest families of transcription factors in plants. They have been shown to be involved in responses to various abiotic stresses, such as drought, salinity, chilling, heavy metal toxicity, iron deficiency, and osmotic damages. By specifically binding to cis-elements in the promoter region of stress related genes, bHLHs can regulate their transcriptional expression, thereby regulating the plant's adaptive responses. This review focuses on the structural characteristics of bHLHs, the regulatory mechanism of how bHLHs are involved transcriptional activation, and the mechanism of how bHLHs regulate the transcription of target genes under various stresses. Finally, as increasing research demonstrates that flavonoids are usually induced under fluctuating environments, the latest research progress and future research prospects are described on the mechanisms of how flavonoid biosynthesis is regulated by bHLHs in the regulation of the plant's responses to abiotic stresses.
ABSTRACT
Long non-coding RNAs (lncRNAs) are major components of cellular transcripts that are arising as important players in various biological pathways. They have received extensive attention in recent years, regarded to be involved in both developmental processes and various diseases. Due to their specific expression and functional diversity in a variety of cancers, lncRNAs have promising applications in cancer diagnosis, prognosis and therapy. Studies have shown that lncRNAs with high specificity and accuracy have the potential to become biomarkers in cancers. LncRNAs can be noninvasively extracted from body fluids, tissues and cells, and can be used as independent or auxiliary biomarkers to improve the accuracy of diagnosis or prognosis. Currently, the most well-recognized lncRNA is PCA3, which has been approved for use in the diagnosis of prostate cancer. Moreover, the underlying mechanisms of lncRNAs were explored as therapeutic targets, which have been investigated in clinical trials of several cancers. In this review, we presented a compilation of recent publications, clinical trials and patents, addressing the potential of lncRNAs that could be considered as biomarkers or therapeutic targets, with the hopes of providing promised implications for future cancer therapy.