ABSTRACT
Pelodiscus sinensis meat is a nutritional food and tonic with angiotensin-converting enzyme (ACE) inhibitory activities. To identify the bioactive substances responsible, several bioinformatics methods were integrated to enable a virtual screening for bioactive peptides in proteins identified within a water-soluble protein fraction of Pelodiscus sinensis meat by Shotgun proteomics. The peptides were generated from the identified proteins by in silico proteolysis using six proteases. A comparison of the numbers of proteins suitable for digestion with each enzyme and the iBAQ (intensity-based absolute quantification) values for these proteins revealed that bromelain and papain were the most suitable proteases for this sample. Next, the water solubility, toxicity, and ADMET (absorption/distribution/metabolism/excretion/toxicity) properties of these peptides were evaluated in silico. Finally, a novel ACE inhibitory peptide IEWEF with an IC50 value of 41.33 µM was identified. The activity of the synthesized peptide was verified in vitro, and it was shown to be a non-competitive ACE inhibitor. Molecular docking revealed that IEWEF could tightly bind to C-ACE, and N-ACE with energies less than 0 kJ mol-1, and the peptide IEWEF can form hydrogen bonds with C-ACE and N-ACE respectively. These results provide evidence that bioactive peptides in the water-soluble protein fraction account for (at least) some of the ACE inhibitory activities observed in Pelodiscus sinensis meat. Furthermore, our research provides a workflow for the efficient identification of novel ACE inhibitory peptides from complex protein mixtures.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors , Molecular Docking Simulation , Peptides , Protein Hydrolysates , Solubility , Angiotensin-Converting Enzyme Inhibitors/chemistry , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/metabolism , Protein Hydrolysates/chemistry , Protein Hydrolysates/metabolism , Animals , Peptides/chemistry , Peptides/pharmacology , Peptides/metabolism , Water/chemistry , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/metabolism , Papain/metabolism , Papain/antagonists & inhibitors , Papain/chemistry , Fish Proteins/chemistry , Fish Proteins/metabolismABSTRACT
Radiotherapy-induced muscle injury (RIMI) is a major complication of radiotherapy for nasopharyngeal carcinoma. Transcription factor (TF) expression and alternative splicing are crucial events in transcriptional and posttranscriptional regulation, respectively, and are known to be involved in key signaling pathways contributing to a variety of human disorders, including radiation injury. To investigate the TFs and alternative splicing events involved in RIMI, we constructed a tree shrew model as described previously in which the RIMI group received 20 Gy of irradiation on the tensor veli palatini (TVP) muscles. The irradiated muscles were evaluated by RNA sequencing (RNA-seq) 6 months later, and the results compared with those for normal TVP muscles. The alt5p and alt3p events were the two main types of differentially regulated alternative splicing events (RASEs) identified via the Splice sites Usage Variation Analysis (SUVA) software, and these RASEs were highly conserved in RIMI. According to functional enrichment analysis, the differentially RASEs were primarily enriched in pathways related to transcriptional regulation. Furthermore, we identified 16 alternative splicing TFs (ASTFs) in ASTF-differentially expressed gene (DEG) networks based on co-expression analysis, and the regulatory networks were chiefly enriched in pathways linked to cell proliferation and differentiation. This study revealed that RASEs and ASTF-DEG networks may both play important regulatory roles in gene expression network alteration in RIMI. Future studies on the targeting mechanisms and early interventions directed at RASEs and ASTF-DEG networks may aid in the treatment of RIMI.
Subject(s)
Transcription Factors , Tupaiidae , Animals , Humans , Transcription Factors/genetics , Transcription Factors/metabolism , Tupaiidae/metabolism , RNA Splicing , Alternative Splicing , Muscles/metabolism , Gene Expression ProfilingABSTRACT
A high power single-frequency operation at 1112â nm with novel insertable monolithic planar ring oscillator based on a Nd:YAG/YAG bonded crystal is proposed. In a proof-of-principle experiment, a finely designed coating on the output surface is carried out to ensure single-wavelength oscillation at 1112â nm, together with a half-wave plate and a Tb3Ga5O12 crystal inserted in the open space of the bonded block to realize the unidirectional operation with power scalability. Consequently, the single-frequency laser delivers an output power of 3.9 W at 1112.3â nm with a slope efficiency of 58.6% and an optical-to-optical efficiency of 17.7%. The power fluctuation is measured to be within ± 0.26% over 20 min, and the laser linewidth is estimated to be 4.15â MHz (Δλ = 0.017 pm).
ABSTRACT
This paper formulates a mathematical framework to describe the dynamics of SIS-type infectious diseases with resource constraints. We first define the basic reproduction number that determines disease prevalence and analyze the existence and local stability of the equilibria. Subsequently, we analyze the global dynamics of the model, excluding periodic solutions and heteroclinic orbits, using the compound matrix approach. The analysis implies that the model can undergo forward and backward bifurcations depending on critical parameters. In the former scenario, the disease persists when the basic reproduction number under resource constraints exceeds one. In the latter scenario, the backward bifurcation creates bistability dynamics in which the disease may persist or become extinct depending on the initial level of infected individuals and the resource abundance.
ABSTRACT
A compact 200 W level diode-side-pumped microsecond (µs) pulse linearly polarized rod Nd:YAG laser oscillator was demonstrated with nearly diffraction-limited beam quality. The oscillator was based on a thermally near-unstable cavity design with two concave lenses in the cavity to enlarge the volume of the fundamental mode, leading to improvement of the laser efficiency and beam quality. Consequently, a record-high average power of 222 W was obtained at a repetition rate of 400 Hz with a 180 µs pulse width, corresponding to an optical-to-optical (o-o) conversion efficiency of 37%. The average beam quality factor was measured to be M2=1.32, resulting in a brightness value as high as of 11.25GW/srâ cm2. To the best of our knowledge, this represented the highest average power, the highest o-o efficiency, and the highest brightness for a µs pulse 1064 nm rod Nd:YAG laser oscillator.
ABSTRACT
BACKGROUND: Calcium (Ca2+) plays an important role in plant growth and development, and the maintenance of calcium homeostasis is necessary for the survival of all plant species. Ca2+/H+ exchangers (CAXs) are a subgroup of the CaCA (Ca2+/cation antiporter) superfamily. In general, CAX proteins mediate cytosolic Ca2+ entry into vacuoles to prevent excessive accumulation of Ca2+ in the cytosol. The CaCA superfamily has been identified and characterised in many plant species; however, characterisation of the CaCA superfamily and functional study of apple CAX proteins have yet to be conducted in apple (Malus × domestica Borkh.). RESULTS: Here, we identified 21 CaCA family proteins in apple for the first time. Phylogenetic and gene structure analysis, as well as prediction of conserved motifs, suggested that these proteins could be classified into four groups: CAX, CCX, NCL, and MHX. Expression analysis showed that the 10 MdCAX genes we cloned strongly responded to calcium and abiotic stress treatments. Collinearity analysis and characterisation of calcium transport capacity resulted in the identification of a pair of segmental duplication genes: MdCAX3L-1 and MdCAX3L-2; MdCAX3L-2 showed strong calcium transport capacity, whereas MdCAX3L-1 showed no calcium transport capacity. Yeast two-hybrid (Y2H) assays showed that these two proteins could interact with each other. The high sequence similarity (94.6%) makes them a good model for studying the crucial residues and structural basis of the calcium transport of CAX proteins. Prediction of the protein interaction network revealed several proteins that may interact with CAX proteins and play important roles in plant stress responses, such as SOS2, CXIP1, MHX, NRAMP3, and MTP8. CONCLUSIONS: Our analysis indicated that MdCAX proteins have strong calcium transport capacity and are involved in the abiotic stress response in apple. These findings provide new insight and rich resources for future studies of MdCAX proteins in apple.
Subject(s)
Calcium/metabolism , Ion Transport/genetics , Malus/genetics , Malus/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Stress, Physiological/genetics , Gene Expression Regulation, Plant , Genome, Plant , Genome-Wide Association Study , Multigene FamilyABSTRACT
Abiotic stresses are increasingly harmful to crop yield and quality. Calcium and its signaling pathway play an important role in modulating plant stress tolerance. As specific Ca2+ sensors, calcineurin B-like (CBL) proteins play vital roles in plant stress response and calcium signaling. The CBL family has been identified in many plant species; however, the characterization of the CBL family and the functional study of apple MdCBL proteins in salt response have yet to be conducted in apple. In this study, 11 MdCBL genes were identified from the apple genome. The coding sequences of these MdCBL genes were cloned, and the gene structure and conserved motifs were analyzed in detail. The phylogenetic analysis indicated that these MdCBL proteins could be divided into four groups. The functional identification in Na+-sensitive yeast mutant showed that the overexpression of seven MdCBL genes could confer enhanced salt stress resistance in transgenic yeast. The function of MdCBL10.1 in regulating salt tolerance was also verified in cisgenic apple calli and apple plants. These results provided valuable insights for future research examining the function and mechanism of CBL proteins in regulating apple salt tolerance.
Subject(s)
Calcium-Binding Proteins/genetics , Gene Expression Regulation, Plant , Genome, Plant , Malus/genetics , Plant Proteins/genetics , Salt Tolerance/genetics , Amino Acid Sequence , Arabidopsis/classification , Arabidopsis/drug effects , Arabidopsis/genetics , Arabidopsis/metabolism , Calcium/metabolism , Calcium-Binding Proteins/metabolism , Cloning, Molecular , Genetic Vectors/chemistry , Genetic Vectors/metabolism , Malus/classification , Malus/drug effects , Malus/metabolism , Multigene Family , Phylogeny , Plant Proteins/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Salt Stress , Sequence Alignment , Sequence Homology, Amino Acid , Signal Transduction , Sodium/metabolism , Sodium Chloride/pharmacology , Stress, PhysiologicalABSTRACT
In recent years, several studies have found that the disruption of type IA receptor of bone morphogenetic proteins (BMPR1A) could increase bone mass. However, whether disruption of BMPR1A could have an effect on bone quality and bone strength is currently unknown. Osteoblast-targeted conditional knockout (cKO) of BMPRIA by crossing 3.2-kb Col1-CreER™ mice with BMPR1A fx +/+ mice was conducted. Then, in vitro and in vivo studies were employed to examine the effect of BMPR1A knockout on bone quality and bone strength. It was found that the ultimate force and stiffness of the femora decreased significantly in cKO mice when compared to control mice. The content of collagen and mineralization level decreased as the structure of the collagen became disorganized. The morphology of osteocytes in cKO mice was abnormal as well. The expression level of osteocalcin, a marker for the terminal differentiation of osteoblasts, decreased in cKO mice. This data indicated that the differentiation of osteoblasts in cKO mice was impaired. Immunohistochemistry examination revealed deregulated expression of dickkopf 1(DKK1) in osteocytes in cKO mice. Adding DKK1 to the culture medium reversed these effects. In conclusion, even though disruption of BMPR1A could increase bone mass, it also impairs bone quality and bone strength.
Subject(s)
Bone Morphogenetic Protein Receptors, Type I/metabolism , Bone and Bones/physiology , Osteoblasts/metabolism , Osteoclasts/metabolism , Animals , Biomarkers/metabolism , Biomechanical Phenomena , Cell Count , Cell Differentiation , Collagen/metabolism , Male , Mice, Knockout , Osteoblasts/cytology , Osteoblasts/ultrastructure , Osteocytes/metabolism , Osteocytes/ultrastructure , Tibia/physiologyABSTRACT
This work is motivated by a desire to quantify relationships between two time series of pulsing hormone concentrations. The locations of pulses are not directly observed and may be considered latent event processes. The latent event processes of pulsing hormones are often associated. It is this joint relationship we model. Current approaches to jointly modeling pulsing hormone data generally assume that a pulse in one hormone is coupled with a pulse in another hormone (one-to-one association). However, pulse coupling is often imperfect. Existing joint models are not flexible enough for imperfect systems. In this article, we develop a more flexible class of pulse association models that incorporate parameters quantifying imperfect pulse associations. We propose a novel use of the Cox process model as a model of how pulse events co-occur in time. We embed the Cox process model into a hormone concentration model. Hormone concentration is the observed data. Spatial birth and death Markov chain Monte Carlo is used for estimation. Simulations show the joint model works well for quantifying both perfect and imperfect associations and offers estimation improvements over single hormone analyses. We apply this model to luteinizing hormone (LH) and follicle stimulating hormone (FSH), two reproductive hormones. Use of our joint model results in an ability to investigate novel hypotheses regarding associations between LH and FSH secretion in obese and non-obese women.
Subject(s)
Biometry/methods , Hormones/analysis , Proportional Hazards Models , Adult , Female , Follicle Stimulating Hormone/metabolism , Humans , Luteinizing Hormone/metabolism , Markov Chains , Monte Carlo Method , Obesity , Time FactorsABSTRACT
Accumulating evidence suggests that Wnt/ß-catenin signaling plays a central role in controlling bone mass. We previously reported that constitutive activation of ß-catenin (CA-ß-catenin) in osteoblasts potentially has side effects on the bone growth and bone remodeling process, although it could increase bone mass. The present study aimed to observe the effects of osteoblastic CA-ß-catenin on bone quality and to investigate possible mechanisms of these effects. It was found that CA-ß-catenin mice exhibited lower mineralization levels and disorganized collagen in long bones as confirmed by von Kossa staining and sirius red staining, respectively. Also, bone strength decreased significantly in CA-ß-catenin mice. Then the effect of CA-ß-catenin on biological functions of osteoblasts were investigated and it was found that the expression levels of osteocalcin, a marker for the late differentiation of osteoblasts, decreased in CA-ß-catenin mice, while the expression levels of osterix and alkaline phosphatase, two markers for the early differentiation of osteoblasts, increased in CA-ß-catenin mice. Furthermore, higher proliferation rate were revealed in osteoblasts that were isolated from CA-ß-catenin mice. The Real-time PCR and western blot examination found that the expression level of c-myc and cyclin D1, two G1 progression-related molecules, increased in osteoblasts that were isolated from the CA-ß-catenin mice, and the expression levels of CDK14 and cyclin Y, two mitotic-related molecules that can accelerate cells entering into S and G2/M phases, increased in osteoblasts that were isolated from the CA-ß-catenin mice. In summary, osteoblastic CA-ß-catenin kept osteoblasts in high proliferative state and impaired the terminal osteoblast differentiation, and this led to changed bone structure and decreased bone strength.
Subject(s)
Bone and Bones/metabolism , Cell Differentiation/physiology , Cell Proliferation/physiology , Osteoblasts/metabolism , beta Catenin/metabolism , Animals , Bone Development , Bone and Bones/cytology , Cell Differentiation/genetics , Cell Line , Mice , Osteoblasts/cytology , Wnt Proteins/metabolism , Wnt Signaling Pathway/physiologyABSTRACT
UNLABELLED: Sodium bisulfite conversion followed by sequencing (BS-Seq, such as whole genome bisulfite sequencing or reduced representation bisulfite sequencing) has become popular for studying human epigenetic profiles. Identifying single nucleotide polymorphisms (SNPs) is important for quantification of methylation levels and for study of allele-specific epigenetic events such as imprinting. However, SNP calling in such data is complex and time consuming. Here, we present an ultrafast and memory-efficient package named BS-SNPer for the exploration of SNP sites from BS-Seq data. Compared with Bis-SNP, a popular BS-Seq specific SNP caller, BS-SNPer is over 100 times faster and uses less memory. BS-SNPer also offers higher sensitivity and specificity compared with existing methods. AVAILABILITY AND IMPLEMENTATION: BS-SNPer is written in C++ and Perl, and is freely available at https://github.com/hellbelly/BS-Snper.
Subject(s)
DNA Methylation , Polymorphism, Single Nucleotide , Sequence Analysis, DNA/methods , Software , Sulfites , Alleles , HumansABSTRACT
PURPOSE: To enhance the awareness of rare complications of pelvic fracture and describe the correct diagnosis and effective treatment. METHODS: A total of 188 cases of pelvic fractures were retrospectively reviewed, and four patients who suffered from four types of rare pelvic fracture complications were described, namely ureteral obstruction caused by retroperitoneal hematoma-induced abdominal compartment syndrome (ACS), bowel entrapment, external iliac artery injury, and open scrotal sac injury. RESULTS: We demonstrated that combined measures should be employed to prevent the occurrence of ACS following major pelvic fractures. Ureteral catheter support may be a good option at an early stage when ACS occurred. Contrasted computed tomography examination and sufficient awareness are keys to a correct diagnosis of bowel entrapment following pelvic fractures. Recognition of risk factors, early diagnosis, and prompt treatment of suspected injury of the external iliac artery are keys to patient survival and to avoid limb loss. Scrotal and/or testicular injury complicated by pelvic fractures should be carefully treated to maintain normal gonad function. Additionally, establishment of a sophisticated trauma care system and multi-disciplinary coordination are important for correct diagnosis and treat- ment of rare complications in pelvic fractures. CONCLUSIONS: Rare complications of pelvic fractures are difficult to diagnose and negatively impact outcome. Recognition of risk factors and sufficient awareness are essential for correct diagnosis and prompt treatment.
Subject(s)
Fractures, Bone/complications , Intra-Abdominal Hypertension/diagnosis , Pelvic Bones/injuries , Adult , Female , Humans , Iliac Artery/injuries , Intra-Abdominal Hypertension/therapy , Male , Middle Aged , Scrotum/injuries , Testis/injuries , Tomography, X-Ray ComputedABSTRACT
Branch bark extract (BBE) derived from the mulberry cultivar Husang 32 (Morus multicaulis L.) with aqueous alcohol solution has been investigated as an inhibitor of α-glycosidase in vitro. Mulberry BBE was orally administered to STZ-induced diabetic mice for three weeks, and it improved the weight gain and ameliorated the swelling of liver and kidney in diabetic mice. Obviously, mulberry BBE not only can reduce the abnormally elevated levels of serum insulin and ameliorate insulin resistance induced by STZ, but also it regulates dyslipidemia in diabetic mice. To understand this therapeutic effect and the regulatory mechanisms of BBE in diabetic mice, a qRT-PCR experiment was performed, indicating that the mulberry BBE can regulate the mRNA expression of glycometabolism genes in diabetic mice, including glucose-6-phosphatase (G6Pase), glucokinase (GCK), and phosphoenolpyruvate carboxykinase (PEPCK), thereby regulating sugar metabolism and reducing the blood glucose level in diabetic mice. The mulberry BBE can increase the mRNA expression of the genes Ins1, Ins2 and pancreatic duodenal homeobox-1 (PDX-1) and may decrease the insulin resistance in diabetic mice. Those results provide an important basis for making the best use of mulberry branch resources and producing biomedical drugs with added value.
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Drugs, Chinese Herbal/therapeutic use , Morus/chemistry , Animals , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/metabolism , Glucokinase/genetics , Glucokinase/metabolism , Glucose-6-Phosphatase/genetics , Glucose-6-Phosphatase/metabolism , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Insulin/genetics , Insulin/metabolism , Insulin Resistance , Male , Mice , Mice, Inbred ICR , Phosphoenolpyruvate Carboxykinase (ATP)/genetics , Phosphoenolpyruvate Carboxykinase (ATP)/metabolism , Plant Bark/chemistry , RNA, Messenger/genetics , RNA, Messenger/metabolism , Trans-Activators/genetics , Trans-Activators/metabolismABSTRACT
A method for the in vitro isolation, purification, identification, and induced differentiation of satellite cells from adult tree shrew skeletal muscle was established. The mixed enzyme digestion method and differential adhesion method were used to obtain skeletal muscle satellite cells, which were identified and induced to differentiate to verify their pluripotency. The use of a mixture of collagenase II, hyaluronidase IV, and DNase I is an efficient method for isolating adult tree shrew skeletal muscle satellite cells. The P3 generation of cells had good morphology, rapid proliferation, high viability, and an "S"-shaped growth curve. Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence staining indicated that marker genes or proteins were expressed in skeletal muscle satellite cells. After myogenic differentiation was induced, multiple-nucleated myotubes were observed, and the MyHC protein was expressed. The expression of myogenic marker genes changed with the differentiation process. After the induction of adipogenic differentiation, orange-red lipid droplets were observed, and the expression of adipogenic marker genes increased gradually with the differentiation process. In summary, satellite cells from adult tree shrew skeletal muscle were successfully isolated using a mixed enzyme digestion method, and their potential for differentiation into myogenic and adipogenic cells was confirmed, laying a foundation for further in vitro study of tree shrew muscle damage.
Subject(s)
Satellite Cells, Skeletal Muscle , Tupaia , Animals , Tupaiidae , Cells, Cultured , Cell Differentiation/physiology , Muscle, Skeletal , Muscle Fibers, Skeletal/metabolismABSTRACT
BACKGROUND: The treatment and management of hip fracture poses a great challenge for clinicians in osteology and surgery. The aim of this study is to compare the clinical effectiveness of the percutaneous compression plate (PCCP) versus proximal femoral nail anti-rotation (PFNA) in the treatment of intertrochanteric fractures in elderly patients. METHODS: A prospective randomized study was carried out from January 2008 to October 2011 involving 90 elderly patients with intertrochanteric fractures (90 hips) who underwent minimally invasive surgery using the PCCP or PFNA. Evaluation variables, including operation time, intra- and perioperative blood loss, duration of hospital stay, incidence of postoperative complications, and final clinical outcomes by the end of follow-up, were used to compare the benefits of these two implants. RESULTS: Among 90 subjects, 45 received PCCPs and 45 received PFNAs. The baseline characteristics of the two groups were comparable. The median follow-up time was 16.9 months (12-24 months). In the PCCP group, the mean operative time was 53 min (40-75 min), and the mean intra- and perioperative blood losses were 100.7 ml (60-150 ml) and 916 ml (433-1339 ml), respectively, which were significantly lower than those in the PFNA group. Nevertheless, there was no statistical difference in the incidence of postoperative complications and final clinical outcomes including pain complaints, range of motion of the hip, postoperative hip function at 12 months, and the recovery of walking ability to pre-injury status between these two implants. CONCLUSIONS: Overall, the PCCP and PFNA appear to have similar clinical effects in treating elderly patients with intertrochanteric fractures, although the PCCP provided shorter operation times and less blood loss than PFNA. Both implants discussed were demonstrated to be ideal for the treatment of femoral intertrochanteric fractures in elderly patients.
Subject(s)
Bone Nails , Bone Plates , Fracture Fixation, Internal/instrumentation , Fracture Fixation, Intramedullary/instrumentation , Hip Fractures/surgery , Aged , Aged, 80 and over , Female , Follow-Up Studies , Fracture Fixation, Internal/methods , Fracture Fixation, Intramedullary/methods , Geriatric Assessment , Hip Fractures/diagnostic imaging , Humans , Injury Severity Score , Male , Middle Aged , Minimally Invasive Surgical Procedures/adverse effects , Minimally Invasive Surgical Procedures/methods , Pain Measurement , Pain, Postoperative/physiopathology , Pilot Projects , Postoperative Complications/diagnostic imaging , Postoperative Complications/epidemiology , Postoperative Complications/physiopathology , Prospective Studies , Radiography , Range of Motion, Articular/physiology , Risk Assessment , Time Factors , Treatment OutcomeABSTRACT
The use of information from real world to assess the effectiveness of medical products is becoming increasingly popular and more acceptable by regulatory agencies. According to a strategic real-world evidence framework published by U.S. Food and Drug Administration, a hybrid randomized controlled trial that augments internal control arm with real-world data is a pragmatic approach worth more attention. In this paper, we aim to improve on existing matching designs for such a hybrid randomized controlled trial. In particular, we propose to match the entire concurrent randomized clinical trial (RCT) such that (1) the matched external control subjects used to augment the internal control arm are as comparable as possible to the RCT population, (2) every active treatment arm in an RCT with multiple treatments is compared with the same control group, and (3) matching can be conducted and the matched set locked before treatment unblinding to better maintain the data integrity and increase the credibility of the analysis. Besides a weighted estimator, we also introduce a bootstrap method to obtain its variance estimation. The finite sample performance of the proposed method is evaluated by simulations based on data from a real clinical trial.
Subject(s)
Research Design , Humans , Control GroupsABSTRACT
Cancer stem-like cells (CSCs) identified by self-renewal ability and tumor-initiating potential are responsible for tumor recurrence and metastasis in many cancers. Conventional chemotherapy fails to eradicate CSCs that hold a state of dormancy and possess multi-drug resistance. Spurred by the progress of nanotechnology for drug delivery and biomedical applications, nanomedicine has been increasingly developed to tackle stemness-associated chemotherapeutic resistance for cancer therapy. This review focuses on advances in nanomedicine-mediated therapeutic strategies to overcome chemoresistance by specifically targeting CSCs, the combination of chemotherapeutics with chemopotentiators, and programmable controlled drug release. Perspectives from materials and formulations at the nano-scales are specifically surveyed. Future opportunities and challenges are also discussed.
ABSTRACT
The bHLH family, the second largest transcription factor (TF) family in plants, plays a crucial role in regulating plant growth and development processes. However, the biological functions and mechanisms of most bHLH proteins remain unknown, particularly in apples. In this study, we found that MdbHLH4 positively modulates plant growth and development by enhancing cell expansion. Overexpression (OE) of MdbHLH4 resulted in increased biomass, stem and root length, leaf area, and larger areas of pith, xylem, and cortex with greater cell size compared with wild-type apple plants. Conversely, RNA interference (RNAi)-mediated silencing of MdbHLH4 led to reduced xylem and phloem as well as smaller cell size compared to wild-type apple plants. Ectopic expression of MdbHLH4 in tomatoes resulted in enlarged fruits with impaired color appearance, decreased accumulation of soluble solids, and decreased flesh firmness along with larger seeds. Subsequent investigations have shown that MdbHLH4 directly binds to the promoters of MdARF6b and MdPIF4b, enhancing their expression levels. These findings suggest that MdbHLH4 potentially regulates plant cell expansion through auxin and light signaling pathways. These study results not only provide new insights into the roles of bHLH transcription factors in regulating plant growth and development but also contribute to a deeper understanding of their underlying mechanisms.
Subject(s)
Malus , Malus/metabolism , Transcription Factors/genetics , Fruit/metabolism , Cell Enlargement , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolismABSTRACT
Multifunctional architecture with intriguing structural design is highly desired for realizing the promising performances in wearable sensors and flexible energy storage devices. Cellulose nanofiber (CNF) is employed for assisting in building conductive, hyperelastic, and ultralight Ti3C2Tx MXene hybrid aerogels with oriented tracheid-like texture. The biomimetic hybrid aerogels are constructed by a facile bidirectional freezing strategy with CNF, carbon nanotube (CNT), and MXene based on synergistic electrostatic interaction and hydrogen bonding. Entangled CNF and CNT "mortars" bonded with MXene "bricks" of the tracheid structure produce good interfacial binding, and superior mechanical strength (up to 80% compressibility and extraordinary fatigue resistance of 1000 cycles at 50% strain). Benefiting from the biomimetic texture, CNF/CNT/MXene aerogel shows ultralow density of 7.48 mg cm-3 and excellent electrical conductivity (~ 2400 S m-1). Used as pressure sensors, such aerogels exhibit appealing sensitivity performance with the linear sensitivity up to 817.3 kPa-1, which affords their application in monitoring body surface information and detecting human motion. Furthermore, the aerogels can also act as electrode materials of compressive solid-state supercapacitors that reveal satisfactory electrochemical performance (849.2 mF cm-2 at 0.8 mA cm-2) and superior long cycle compression performance (88% after 10,000 cycles at a compressive strain of 30%).
ABSTRACT
Background: Animal models suitable for investigating mechanisms behind radiation-induced muscle injury are lacking. We developed a tree shrew model of such injury and investigated pathological changes and mechanisms. Methods: Animals were divided into control (n = 5), radiation-induced acute injury (n = 5), and radiation-induced chronic injury (n = 5) groups. Tensor veli palatini (TVP) muscles of acute injury and chronic injury groups were dissected under a microscope at 1 and 24 weeks after radiation therapy, respectively. TVP muscles were stained with HE and Masson to visualize pathological changes. ELISA was performed to measure oxidative injury. RT-qPCR and immunohistochemical staining was performed to measure expression levels of miR-206 and histone deacetylase 4 (HDAC4). Results: Compared to the control group, acute injury group showed a significant decrease in miR-206 expression (.061 ± .38, P < .05) and a significant increase in HDAC4 expression (37.05 ± 20.68, P < .05). Chronic injury group showed a significant decrease in miR-206 expression (.23 ± .19, P < .05) and a significant increase in HDAC4 expression (9.66 ± 6.12, P < .05). Discussion: A tree shrew model of radiation-induced muscle injury was established by exposing TVP muscle region to radiation of 20-Gy. Experimental results indicated that injury caused by radiation persisted despite gradual healing of the TVP muscle and miR-206 regulatory pathway plays a key role in regulating radiation-induced muscle injury.