ABSTRACT
Many filamentous fungi produce plant-polysaccharide-degrading enzymes (PPDE); however, the regulatory mechanism of this process is poorly understood. A Gal4-like transcription factor, CxrA, is essential for mycelial growth and PPDE production in Penicillium oxalicum. Its N-terminal region, CxrAΔ207-733 is required for the regulatory functions of whole CxrA, and contains a DNA-binding domain (CxrAΔ1-16&Δ59-733) and a methylated arginine (R) 94. Methylation of R94 is mediated by an arginine N-methyltransferase, PRMT2 and appears to induce dimerization of CxrAΔ1-60. Overexpression of prmt2 in P. oxalicum increases PPDE production by 41.4-95.1% during growth on Avicel, compared with the background strain Δku70;hphR+. Another arginine N-methyltransferase, PRMT3, appears to assist entry of CxrA into the nucleus, and interacts with CxrAΔ1-60 in vitro under Avicel induction. Deletion of prmt3 resulted in 67.0-149.7% enhanced PPDE production by P. oxalicum. These findings provide novel insights into the regulatory mechanism of fungal PPDE production.
Subject(s)
Penicillium , Protein-Arginine N-Methyltransferases , Protein-Arginine N-Methyltransferases/genetics , Penicillium/genetics , Cellulose , ArginineABSTRACT
BACKGROUND: Extremely preterm infants (EPIs) are at high-risk of white matter injury (WMI), leading to long-term neurodevelopmental impairments. We aimed to develop nomograms for WMI. METHODS: The study included patients from 31 provinces, spanning ten years. 6074 patients before 2018 were randomly divided into a training and internal validation group (7:3). The external validation group comprised 1492 patients from 2019. Predictors were identified using the least absolute shrinkage and selection operator (LASSO) and multivariable logistic regression and nomograms were constructed. Models' performance was evaluated using receiver operating characteristic (ROC), decision curve analysis (DCA) and calibration curves. RESULTS: The prenatal nomogram included multiple gestation, premature rupture of membranes (PROM), chorioamnionitis, prenatal glucocorticoids, hypertensive disorder complicating pregnancy (HDCP) and Apgar 1 min, with area under the curve (AUC) of 0.805, 0.816 and 0.799 in the training, internal validation and external validation group, respectively. Days of mechanical ventilation (MV), shock, patent ductus arteriosus (PDA) ligation, intraventricular hemorrhage (IVH) grade III-IV, septicemia, hypothermia and necrotizing enterocolitis (NEC) stage II-III were identified as postpartum predictors. The AUCs were 0.791, 0.813 and 0.823 in the three groups, respectively. DCA and calibration curves showed good clinical utility and consistency. CONCLUSION: The two nomograms provide clinicians with precise and efficient tools for prediction of WMI. IMPACT: This study is a large-sample multicenter study, spanning 10 years. The two nomograms are convenient for identifying high-risk infants early, allowing for reducing poor prognosis.
ABSTRACT
Objective: Epstein-Barr virus (EBV) is a common virus that infects a large portion of the world's population, with most people becoming infected during childhood or adolescence. The objective of this article is to analyze the clinical and laboratory examination results of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in children, summarize its characteristics, identify critically ill children as soon as possible, and provide a basis for diagnosis and treatment. Method: The retrospective analysis in this study involved collecting data from 34 cases of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) admitted to Hebei Children's Hospital from January 2019 to December 2022. The inclusion criteria for the cases studied likely included confirmed diagnosis of EBV-HLH based on clinical symptoms, laboratory findings, and possibly viral testing results. Key parameters analyzed in the study may have included clinical manifestations, laboratory test results (e.g., levels of lactate dehydrogenase, sCD25, IL-10, calcium ions, glutathione aminotransferase, ferritin, alanine aminotransferase, D-dimer), survival rates, and other relevant indicators. Additionally, the cases were likely divided into high-risk groups (with multiple organ dysfunction or requiring ventilator-assisted ventilation) and non-risk groups for comparative analysis. Results: The results showed that 34 cases (100%) of EBV-HLH had elevated levels of lactate dehydrogenase, sCD25, IL-10, and decreased levels of calcium ions. 97.1% of the children had a fever and elevated levels of glutathione aminotransferase and ferritin, with an 8-week survival rate of 91.2%. The levels of alanine aminotransferase, alanine aminotransferase, lactate dehydrogenase, ferritin, D-dimer, and sCD25 in critically ill children were significantly higher than those in the non-critically ill group, with statistical significance (P < .05). The decreased levels of calcium ions in EBV-HLH patients suggest potential tissue damage and disruption of calcium homeostasis, contributing to the systemic manifestations of the disease. Compared with non-critical recombinant albumin, the decrease in critical recombinant albumin was statistically significant (P < .05). Conclusion: Significant changes in laboratory results can contribute to the early diagnosis and targeted treatment of EBV-HLH, especially for critically ill children. We should pay timely attention to laboratory examinations, diagnosis and treatment, and avoid or reduce the occurrence of adverse consequences. Based on the results of the study on Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in children, specific strategies and criteria can be proposed to aid in the early identification of critically ill children with this condition in clinical practice: Clinical Screening, Risk Stratification, Early Intervention, Multidisciplinary Management and Educational Measures.
Subject(s)
Epstein-Barr Virus Infections , Lymphohistiocytosis, Hemophagocytic , Humans , Lymphohistiocytosis, Hemophagocytic/virology , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/blood , Female , Male , Retrospective Studies , Child , Child, Preschool , Epstein-Barr Virus Infections/complications , Infant , Herpesvirus 4, Human , AdolescentABSTRACT
BACKGROUND: Knee osteoarthropathy is one of the most common degenerative joint diseases in the elderly, total knee arthroplasty (TKA) is the most commonly used treatment for end-stage knee osteoarthropathy. Negative emotions such as anxiety have been extensively documented in knee osteoarthropathy patients. AIM: This study aimed to investigate the Emotional Contagion during hospitalization in patients undergoing TKA. METHODS: Eligible subjects were divided into three case groups according to their anxiety states and bed arrangement. All subjects underwent a unilateral, cemented TKA under general anesthesia. Post-operative recovery outcomes including pain, pain behavior and physical function were recorded pre-operation, 1-day, 1 week, 2-weeks, 1-month and 3-months post-operation. RESULTS: A total of 38 subjects were included in the final analysis. Subjects with anxiety had higher Visual Analogue Scale pain scores, PROMIS-Pain Behavior scores than subjects without anxiety in the Contagion Group preoperation (p ≤ .05). Non-anxiety subjects hospitalized in beds physically adjacent to anxiety subjects experienced more severe pain and poorer function (p ≤ .05). After discharge, all clinical outcomes gradually became lower than anxiety subjects in the Contagion Group, reaching levels similar to non-anxiety subjects in the No Contagion Group within 1 month (p>.05). CONCLUSIONS: This study showed that patients with anxiety may have an "Adjacent Bed Effect" on patients with TKA in the adjacent bed, which may be associated with poorer postoperative recovery, including pain and physical function. We speculate this phenomenon can be effectively avoided by the nursing team through accurately assessing psychological status and reasonable bed arrangements in the inpatient assessment phase.
Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis, Knee , Humans , Aged , Treatment Outcome , Postoperative Period , Pain/complicationsABSTRACT
γ-Lactams are valuable heterocycles in synthetic chemistry and drug development. Here, we report a reductive aza-Pauson-Khand reaction (aza-PKR) of an alkyne, a nitrile, and Co2(CO)8. A wide array of bicyclic α,ß-unsaturated γ-lactams containing two adjacent stereocenters, including an all-carbon quaternary center, from alkyne-tethered malononitriles are efficiently accessed in high diastereoselectivity. Preliminary mechanistic investigations by experiments and DFT calculations reveal that the reaction undergoes an aza-PKR process followed by a in situ reduction. The reducing reagent generated in situ from water also provides a practical tool for deuterium incorporation into the γ-position of lactams using D2O as the deuterium source. This study represents a new mode for [2 + 2 + 1] cycloaddition that enables the direct use of nitrile in aza-heterocycle synthesis.
ABSTRACT
In this work, we present a new time-bin phase-encoding quantum key distribution (QKD), where the transmitter utilizes an inherently stable Sagnac-type interferometer, and has comparable electrical requirements to existing polarization or phase encoding schemes. This approach does not require intensity calibration and is insensitive to environmental disturbances, making it both flexible and high-performing. We conducted experiments with a compact QKD system to demonstrate the stability and secure key rate performance of the presented scheme. The results show a typical secure key rate of 6.2 kbps@20â dB and 0.4 kbps@30â dB with channel loss emulated by variable optical attenuators. A continuous test of 120-km fiber spool shows a stable quantum bit error rate of the time-bin basis within 0.4%â¼0.6% over a consecutive 9-day period without any adjustment. This intrinsically stable and compatible scheme of time-bin phase encoding is extensively applicable in various QKD experiments, including BB84 and measurement-device-independent QKD.
ABSTRACT
Traditional hydrogels with a single-crosslinked network structure suffer from poor stretchability, low sensitivity, and easy contamination, which seriously affect their practical application in the strain sensor field. To overcome these shortcomings, herein, a multiphysical crosslinking strategy (ionic crosslinking and hydrogen bonding) was designed to prepare a hydrogel strain sensor based on chitosan quaternary ammonium salt (HACC)-modified P(AM-co-AA) (acrylamide-co-acrylic acid copolymer) hydrogels. The ionic crosslinking for the double-network P(AM-co-AA)/HACC hydrogels was achieved by an immersion method with Fe3+ as crosslinking sites, which crosslinked with the amino group (-NH2) on HACC and the carboxyl group (-COOH) on P(AM-co-AA) and enabled the hydrogels to recover and reorganize rapidly, resulting in a hydrogel-based strain sensor with excellent tensile stress (3 MPa), elongation (1390%), elastic modulus (0.42 MPa), and toughness (25 MJ/m3). In addition, the prepared hydrogel exhibited high electrical conductivity (21.6 mS/cm) and sensitivity (GF = 5.02 at 0-20% strain, GF = 6.84 at 20-100% strain, and GF = 10.27 at 100-480% strain). Furthermore, the introduction of HACC endowed the hydrogel with excellent antibacterial properties (up to 99.5%) and excellent antibacterial activity against bacteria of three forms, bacilli, cocci, and spores. The flexible, conductive, and antibacterial hydrogel can be applied as a strain sensor for real-time detection of human motions such as joint movement, speech, and respiration, which exhibits a promising application prospect in wearable devices, soft robotic systems, and other fields.
ABSTRACT
Soft, conductive, and stretchable sensors are highly desirable in many applications, including artificial skin, biomonitoring patches, and so on. Recently, a combination of good electrical and mechanical properties was regarded as the most important evaluation criterion for judging whether hydrogel sensors are suitable for practical applications. Herein, we demonstrate a novel carboxylated carbon nanotube (MWCNT-COOH)-embedded P(AM/LMA)/SiO2@PANI hydrogel. The hydrogel benefits from a double-network structure (hydrogen bond cross-linking and hydrophobic connectivity network) due to the role of MWCNT-COOH and SiO2@PANI as cross-linkers, thus resulting in tough composite hydrogels. The obtained P(AM/LMA)/SiO2@PANI/MWCNT-COOH hydrogels exhibited high tensile strength (1939 kPa), super stretchability (3948.37%), and excellent strain sensitivity (gauge factor = 11.566 at 100-1100% strain). Obviously, MWCNT-COOH not only improved the electrical conductivity but also enhanced the mechanical properties of the hydrogel. Therefore, the integration of MWCNT-COOH and SiO2@PANI-based hydrogel strain sensors will display broad application in sophisticated intelligence, soft robotics, bionic prosthetics, personal health care, and other fields using inexpensive, green, and easily available biomass.
ABSTRACT
The central nervous system (CNS) consists of neuron and non-neuron cells including neural stem/precursor cells (NSPCs), neuroblasts, glia cells (mainly astrocyte, oligodendroglia and microglia), which thereby form a precise and complicated network and exert diverse functions through interactions of numerous bioactive ingredients. MicroRNAs (miRNAs), with small size approximately ~ 21nt and as well-documented post-transcriptional key regulators of gene expression, are a cluster of evolutionarily conserved endogenous non-coding RNAs. More than 2000 different miRNAs has been discovered till now. MicroRNA-124(miR-124), the most brain-rich microRNA, has been validated to possess important functions in the central nervous system, including neural stem cell proliferation and differentiation, cell fate determination, neuron migration, synapse plasticity and cognition, cell apoptosis etc. According to recent studies, herein, we provide a review of this conversant miR-124 to further understand the potential functions and therapeutic and clinical value in brain diseases.
Subject(s)
Central Nervous System Diseases , MicroRNAs , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Central Nervous System Diseases/metabolism , Central Nervous System , Neuroglia , Cell Differentiation/geneticsABSTRACT
BACKGROUND: L-Asparaginase (L-asp), the unconjugated form of polyethylene glycol-conjugated L-asparaginase (PEG-asp), regulates T cell stimulation, antibody production, and lysosomal protease activity to mediate PEG-asp-related anaphylaxis. This study aimed to investigate the relation of L-asp activity and anti-L-asp antibody with anaphylaxis risk and non-anaphylaxis adverse reaction risk in childhood acute lymphoblastic leukemia (ALL) patients who underwent PEG-asp contained therapy. METHODS: In total, 170 childhood ALL patients underwent PEG-asp-contained treatment and their L-asp activity and anti-L-asp antibody were detected on the 7th day after treatment initiation. RESULTS: There were 27 (15.9%) patients who had PEG-asp-related adverse reaction: 17 (10.0%) patients experienced PEG-asp-related anaphylaxis and 14 (8.2%) patients experienced PEG- asp-related non-anaphylaxis adverse reaction. Moreover, L-asp activity was negatively related to anti-L-asp antibody in childhood ALL patients (P<0.001). Elevated L-asp activity was associated with the absence of PEG-asp-related anaphylaxis (P<0.001), PEG-asp-related non-anaphylaxis adverse reaction (P=0.004), and PEG-asp-related adverse reaction (P<0.001). However, the anti- L-asp antibody displayed opposite trend similar to L-asp activity. Receiver operating characteristic (ROC) curve analyses exhibited L-asp activity and anti-L-asp antibody exhibited superior predictive values in estimating PEG-asp-related anaphylaxis risk with area under curve (AUC) of 0.955 and 0.905, respectively compared to PEG-asp-related non-anaphylaxis adverse reaction risk with AUC of 0.730 and 0.675, respectively. Besides, patients with de novo disease, higher risk stratification, and allergic history showed trends linked with PEG-asp-related anaphylaxis risk. CONCLUSION: The monitoring of L-asp activity and anti-L-asp antibody maybe useful for early estimation and prevention of PEG-asp-related anaphylaxis in childhood ALL management.
Subject(s)
Anaphylaxis , Asparaginase , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Anaphylaxis/chemically induced , Asparaginase/adverse effects , Asparaginase/therapeutic use , Biomarkers , Polyethylene Glycols/adverse effects , Polyethylene Glycols/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/chemically induced , ChildABSTRACT
OBJECTIVES: To investigate the expression and significance of jumonji domain-containing protein 2B (JMJD2B) and hypoxia-inducible factor-1α (HIF-1α) in non-Hodgkin's lymphoma (NHL) tissues in children. METHODS: Immunohistochemistry was used to detect the expression of JMJD2B and HIF-1α in lymph node tissue specimens from 46 children with NHL (observation group) and 24 children with reactive hyperplasia (control group). The relationship between JMJD2B and HIF-1α expression with clinicopathological characteristics and prognosis in children with NHL, as well as the correlation between JMJD2B and HIF-1α expression in NHL tissues, were analyzed. RESULTS: The positive expression rates of JMJD2B (87% vs 21%) and HIF-1α (83% vs 42%) in the observation group were higher than those in the control group (P<0.05). The expression of JMJD2B and HIF-1α was correlated with serum lactate dehydrogenase levels and the risk of international prognostic index in children with NHL (P<0.05). The expression of JMJD2B was positively correlated with the HIF-1α expression in children with NHL (rs=0.333, P=0.024). CONCLUSIONS: JMJD2B and HIF-1α are upregulated in children with NHL, and they may play a synergistic role in the development of pediatric NHL. JMJD2B can serve as a novel indicator for auxiliary diagnosis, evaluation of the severity, treatment guidance, and prognosis assessment in pediatric NHL.
Subject(s)
Hypoxia-Inducible Factor 1, alpha Subunit , Lymphoma, Non-Hodgkin , Humans , Child , Prognosis , HypoxiaABSTRACT
Bronchopulmonary dysplasia (BPD) is an inflammation-related respiratory disorder in infants. MiR-382-5p has displayed low expression in developing lungs with BPD, while the effect of miR-382-5p on BPD remains elusive. Here, a hyperoxia (85% oxygen)-induced BPD model in neonatal mice was established. On postnatal days 10 and 15, hyperoxia reduced miR-382-5p expression in lungs of mice. Besides, CDK8, CD68 and CD86 levels were elevated on day 15 after birth, implying the involvement of CDK8 in M1 macrophage polarization. In addition, in vitro injury in RAW264.7 macrophages was induced by IFN-γ and LPS stimulation. Lentivirus-encoding miR-382-5p decreased CDK8 expression, alleviated the production of inflammatory cytokines TNF-α, IL-1ß and IL-6, and restricted the levels of CD40 and CD86 in response to IFN-γ and LPS. Moreover, miR-382-5p inhibited the phosphorylation of STAT1. Luciferase reporter assay verified that miR-382-5p might target the 3'UTR of CDK8. Rescue assays revealed that CDK8 reversed the mitigating roles of miR-382-5p in inflammatory response and M1 macrophage polarization, as reflected by increased IL-6 and CD40 levels. Taken together, these findings indicate that miR-382-5p may suppress M1 macrophage activation and inflammatory response via inhibiting CDK8, thereby regulating the development of BPD, which is possibly mediated by STAT1 signaling.
Subject(s)
Bronchopulmonary Dysplasia , Cyclin-Dependent Kinase 8/metabolism , MicroRNAs/metabolism , 3' Untranslated Regions , Animals , Bronchopulmonary Dysplasia/genetics , Disease Models, Animal , Humans , Infant, Newborn , Macrophage Activation , Macrophages , Mice , MicroRNAs/genetics , STAT1 Transcription Factor/geneticsABSTRACT
INTRODUCTION: Solitary pulmonary nodules (SPNs) are commonly found in imaging technologies, but are plagued by high false-positive rates. OBJECTIVE: We aimed to identify metabolic alterations in SPN etiology and diagnosis using less invasive plasma metabolomics and lipidomics. METHODS: In total, 1160 plasma samples were obtained from healthy volunteers (n = 280), benign SPNs (n = 157) and malignant SPNs (stage I, n = 723) patients enrolled from 5 independent centers. Gas chromatography-triple quadrupole mass spectrometry (GCâMS) and liquid chromatography-Q Exactive Hybrid Quadrupole-Orbitrap mass spectrometry (LCâMS) were used to analyze the samples for untargeted metabolomics and lipidomics. RESULTS AND CONCLUSION: GCâMS-based metabolomics revealed 1336 metabolic features, while LCâMS-based lipidomics revealed 6088 and 2542 lipid features in the positive and negative ion modes, respectively. The metabolic and lipidic characteristics of healthy vs. benign or malignant SPNs exhibited substantial pattern differences. Of note, benign and malignant SPNs had no significant variations in circulating metabolic and lipidic markers and were validated in four other centers. This study demonstrates evidence of early metabolic alterations that can possibly distinguish SPNs from healthy controls, but not between benign and malignant SPNs.
Subject(s)
Lung Neoplasms , Solitary Pulmonary Nodule , Diagnosis, Differential , Humans , Lipidomics , MetabolomicsABSTRACT
PURPOSE: Focal cortical dysplasia (FCD) is the most common developmental malformation that causes refractory epilepsy. FCD II is a common neuropathological finding in tissues resected therapeutically from patients with drug-resistant epilepsy. However, its molecular genetic etiology remains unclear. This study aimed to identify potential molecular markers of FCD II using bioinformatics analysis. METHODS: We downloaded two datasets for FCD II from the Gene Expression Omnibus data repository. Differentially expressed genes (DEGs) between FCD II and normal brain tissues were identified, and functional enrichment analysis was performed. A protein-protein interaction network was constructed, and hub genes were identified from the DEGs. The hub gene expression was validated using WB in vitro. IHC staining was performed to verify the feasibility of the target molecular markers identified in the bioinformatics analysis. RESULTS: One hundred sixty-seven common DEGs were identified between the datasets. The GO and KEGG analyses showed that variations were prominently enriched in some functions associated with gene expression. Five hub genes (i.e., FANCI, FANCA, BRCA2, RAD18, and KEAP1) were identified. Western blotting confirmed that all hub gene expressions were higher in the FCD II tissue than in the normal brain tissue. IHC staining showed that the FANCI expression significantly increased in the FCD II tissue. CONCLUSION: There are DEGs between FCD II and normal brain tissues, which may be considered biomarkers for FCD II, along with FANCI. The DEGs and hub genes identified in the bioinformatics analysis could serve as candidate targets for diagnosing and treating FCD II.
Subject(s)
Epilepsy , Malformations of Cortical Development, Group I , Biomarkers, Tumor/genetics , Computational Biology , DNA-Binding Proteins/genetics , Gene Expression Profiling , Humans , Kelch-Like ECH-Associated Protein 1/genetics , Malformations of Cortical Development, Group I/genetics , NF-E2-Related Factor 2/genetics , Ubiquitin-Protein LigasesABSTRACT
A new polychiral bisabolane sesquiterpene, bisabolanoic acid A (1), was isolated from the mangrove-derived fungus Colletotrichum sp. SCSIO KcB3-2. Its planar structure was identified on the basis of spectroscopic data analysis (HRESIMS, 1D, and 2D NMR), and the absolute configurations of three chiral carbons were determined by experimental and calculated electronic circular dichroism (ECD) and optical rotatory dispersion (ORD), together with Mo2(OAc)4-induced ECD methods. Bisabolanoic acid A (1) showed moderate inhibitory activity against acetylcholinesterase (AChE) with IC50 value of 2.2 µM, and the in silico molecular docking was also performed.
Subject(s)
Cholinesterase Inhibitors , Colletotrichum , Rhizophoraceae/microbiology , Sesquiterpenes , Acetylcholinesterase , China , Colletotrichum/chemistry , Molecular Docking Simulation , Molecular Structure , Sesquiterpenes/pharmacologyABSTRACT
OBJECTIVE: This study was performed to investigate the potential key molecules involved in the progression of skeletal muscle atrophy after SCI. METHODS: Based on GSE21497 dataset, the DEmRNAs and DElncRNAs were screened after differentially expressed analysis. Then the enrichment analyses were performed on DEmRNAs. Then the PPI network and ceRNA network were constructed. Finally, the DGIdb was utilized to predict drug-gene interactions. RESULTS: A total of 412 DEmRNAs and 21 DElncRNAs were obtained. The DEmRNAs were significantly enriched in MAPK signaling pathway and FoxO signaling pathway. In addition, UBE2D1, JUN, and FBXO32 had higher node degrees in PPI network, and the top 20 genes with high degree were significantly enriched in FoxO signaling pathway and Endometrial cancer. Moreover, FOXO3 was regulated by hsa-miR-1207-5p and hsa-miR-1207-5p was regulated by lncRNA RP11-253E3.3 in ceRNA network. Finally, 37 drug-gene interactions were obtained based on the 26 genes in ceRNA network. CONCLUSION: UBE2D1, JUN, and FBXO32 are likely to be related to the progression of skeletal muscle atrophy after SCI, and activating of MAPK signaling pathway, Endometrial cancer and FoxO signaling pathway may induce skeletal muscle inflammation, apoptosis, autophagy and atrophy after SCI. Moreover, RP11-253E3.3-hsa-miR-1207-5p-FOXO3 axis may be a promising therapeutic target for skeletal muscle atrophy after SCI.
Subject(s)
MicroRNAs , Muscle, Skeletal/pathology , RNA, Long Noncoding , Spinal Cord Injuries , Atrophy , Forkhead Box Protein O3 , Humans , MicroRNAs/genetics , RNA, Long Noncoding/genetics , RNA, Messenger , Spinal Cord Injuries/complications , Spinal Cord Injuries/geneticsABSTRACT
The plant secondary metabolite 6-methoxybenzoxazolinone (6-MBOA) can stimulate and enhance animal reproduction. This compound has been successfully detected in Leymus chinensis, which is the main diet of Brandt's voles. The aim of this study was to investigate the effect of different 6-MBOA doses on the reproductive physiology of male Brandt's voles under a short photoperiod. The results showed that 6-MBOA administration increased relative testis weight, regardless of the dose, but it had little effect on the body mass. Low and middle doses of 6-MBOA increased the concentrations of luteinizing hormone and testosterone in the serum and the mRNA levels of StAR and CYP11a1 in the testes. However, 6-MBOA did not cause any significant increase in the mRNA levels of KiSS-1, GPR54, and GnRH compared to those in the control group. The mRNA level of KiSS-1 in the arcuate nucleus (ARC) was higher than that in the anteroventral periventricular nucleus (AVPV). Collectively, our results demonstrated that the number of KiSS-1-expressing neurons located in the ARC was the highest, and that 6-MBOA, which might modulate the reproductive activity along the hypothalamic-pituitary-gonadal axis, had a dose-dependent stimulatory effect on the reproductive activity of Brandt's voles under a short photoperiod. Our study provided insights into the mechanism of 6-MBOA action and the factors influencing the onset of reproduction in Brandt's voles.
Subject(s)
Arvicolinae/physiology , Benzoxazoles/pharmacology , Photoperiod , Reproduction/drug effects , Animals , Gene Expression Regulation/drug effects , Luteinizing Hormone/blood , Male , Neurons/drug effects , Testis/drug effects , Testosterone/bloodABSTRACT
This article focused on the assessment of the potential of Raman spectroscopy for the determination of structural changes in black-bean protein isolate (BBPI) dispersions with low-frequency (20 kHz) ultrasonication applied at various powers (150, 300 or 450 W) and for different durations (12 or 24 min). It also reported on differential scanning calorimetry analyses. A decrease in TD at low- and medium-power ultrasonication confirmed these ultrasonication treatment disrupted internal hydrophobic interactions of protein molecules and broke up unstable aggregates to smaller soluble protein aggregates, while an increase in TD at high-power was attributed to repolymerization of aggregates. Raman spectroscopy analysis revealed a decrease in the α-helix proportion and an increase in ß-sheets after ultrasonic treatment except Sample E (300 W, 24 min). Transformation of aggregation results in a reconstruction in secondary structure of BBPI, especially in ß-sheet structure. Ultrasonic-treatment induced a decrease in the normalized intensity of the Raman band near 760 cm-1 which indicated that Tryptophan residues tended to expose and also indicated protein partially unfolding. No significant difference was found in Tyr doublet ratios between unheated and ultrasound-treated BBPI indicated that ultrasound did not change the microenvironment around tyrosyl residues. While the intensity of 1 450 cm-1 band increased with increasing ultrasonic intensity and treatment time, and then decreased with further increase in power and treatment time. In general, the formation of aggregation transferred g-g-t conformation to t-g-t conformation. Though some mechanism of aggregation-repolymerization of BBPI remains to be clearly defined, Raman spectroscopy provide a feasible tool to study the structural changes of BBPI prepared under different ultrasonic conditions, give a new perspective to elucidation of protein structure.
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PURPOSE: To evaluate the rate of overexpression of matrix metalloproteinase-2 (MMP2), mouse double minute 2 homolog (MDM2) and epidermal growth factor receptor (EGFR) in patients with non-small cell lung cancer (NSCLC), and evaluate their correlation with clinicopathological parameters and prognosis. METHODS: This was a prospective cohort study conducted from 2003 to 2008 among 184 NSCLC patients who underwent tumor resection. Each patient's clinical history and tumor characteristics were obtained from histopathology reports and medical records. EGFR, MDM2 and MMP2 expression were assessed by immunohistochemical (IHC) staining of the tissue specimens. RESULTS: MDM2 overexpression was observed in 70 (38%) of the patients studied, and was significantly higher in younger patients (p=0.01). Only 46 (25%) of patients had overexpression of MMP2. EGFR positive staining occurred in 105 (57%percnt;) of the evaluated tumor specimens and was more frequent in specimens with squamous cell carcinoma (p<0.001), the elderly (p<0.001), and in smokers (p<0.001). Independent risk factors for mortality were older age (adjusted odds ratio/aOR 1.3=), being a smoker (aOR 10), having stage II disease (aOR 10.8) or stage III/IV disease (aOR 28.3), expression of EGFR (aOR 5.9) and MMP2 (aOR 4.1). However, the expression of MDM2 independently predicted a reduced risk of death (aOR 0.3). CONCLUSION: Overexpression of MMP2 and EGFR were independent risk factors for mortality in NSCLC patients, while overexpression of MDM2 independently predicted a reduced risk of death.
Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Non-Small-Cell Lung/chemistry , ErbB Receptors/analysis , Lung Neoplasms/chemistry , Matrix Metalloproteinase 2/analysis , Proto-Oncogene Proteins c-mdm2/analysis , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Chi-Square Distribution , Female , Humans , Immunohistochemistry , Logistic Models , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Predictive Value of Tests , Prognosis , Prospective Studies , Protective Factors , Risk Factors , Up-RegulationABSTRACT
Pro-prostate-specific antigen (proPSA) is the precursor of PSA and a form of free PSA (fPSA). In recent years, a lot of studies have been done on proPSA, the roles of its related indexes in the diagnosis of prostate cancer, and the value of its clinical application. The correlated indexes of proPSA include proPSA, % pPSA, p2PSA, % p2PSA and prostate health index (PHI). They are more effective than total PSA (tPSA) and fPSA in the diagnosis of prostate cancer, especially % p2PSA and PHI, which may significantly increase our ability to detect and identify PCa and lower the rate of unnecessary biopsies. This article presents an overview on the advances in the studies of proPSA and the application of its related indexes in the diagnosis of prostate cancer.