ABSTRACT
Objective: To investigate the incidence and influencing factors of hypogammaglobulinemia (HGG) in children with steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS) treated with rituximab (RTX), and its relationship with the risk of severe infections. Methods: The clinical data of children with SDNS/FRNS treated with RTX at the Department of Pediatrics of the First Affiliated Hospital of Zhengzhou University from December 2020 to January 2023 were retrospectively analyzed. RTX treatment was performed using a B-cell-guided regimen (a single dose of 375 mg/m2, a maximum of 500 mg/dose, and an additional one dose when reassessment of peripheral blood CD19+B cells≥1%). Patients were divided into HGG and non-HGG groups according to the presence or absence of HGG during the follow-up period. A multivariate logistic regression model was used to analyze the influencing factors of HGG, and the predictive value of each influencing factor on HGG was assessed by plotting the receiver operating characteristic (ROC) curve. Results: A total of 59 SDNS/FRNS children (48 males and 11 females) were included, and aged [M (Q1, Q3)] 9.4 (6.5, 12.2) years at the time of the first RTX treatment, with a median application of 3 (2, 4) doses of RTX. During the follow-up period of 15.5 (9.9, 22.8) months, the HGG was present in 16 (27.1%) children, of which seven persisted for more than 1 year. Compared with non-HGG group, HGG group had a shorter duration of the disease [3.3 (2.1, 3.6) vs 4.6 (2.4, 8.0) years, P=0.030], younger age at the time of the first RTX treatment [6.2 (5.6, 7.4) vs 11.3 (8.8, 13.3) years, P<0.001], and lower serum IgG levels [5.9 (4.9, 6.4) vs 7.5 (6.1, 8.2) g/L, P<0.001]. Multivariate logistic regression analysis showed that young age at the time of the first RTX treatment (OR=0.52, 95%CI: 0.35-0.78, P=0.002) was an influencing factor of HGG. The area under the curve (AUC) for age at first RTX treatment to predict HGG was 0.887 (95%CI: 0.778-0.955, P<0.001), with an optimal cut-off value of 8.3 years. During the follow-up period, six children (10.2%) developed severe infectious, and there was no statistically significant difference in the incidence of serious infections between the HGG and non-HGG groups [12.5% (2/16) vs 9.3% (4/43), P=1.000]. Conclusions: HGG is frequent in children with SDNS/FRNS treated with RTX, and nearly half of HGG persists for more than 1 year. The possibility of HGG is greater in those≤8.3 years at the first RTX treatment, but HGG does not increase the risk of severe infections in children.
Subject(s)
Agammaglobulinemia , Nephrotic Syndrome , Male , Female , Humans , Child , Aged , Rituximab/therapeutic use , Nephrotic Syndrome/drug therapy , Agammaglobulinemia/drug therapy , Incidence , Retrospective Studies , Steroids/therapeutic use , Recurrence , Immunosuppressive Agents/therapeutic use , Treatment OutcomeABSTRACT
AIM: To evaluate whole-node histogram parameters of blood flow (BF) maps derived from three-dimensional pseudo-continuous arterial spin-labelled (3D pCASL) imaging in discriminating metastatic from benign upper cervical lymph nodes (UCLNs) for nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS: Eighty NPC patients with a total of 170 histologically confirmed UCLNs (67 benign and 103 metastatic) were included retrospectively. Pre-treatment 3D pCASL imaging was performed and whole-node histogram analysis was then applied. Histogram parameters and morphological features, such as minimum axis diameter (MinAD), maximum axis diameter (MaxAD), and location of UCLNs, were assessed and compared between benign and metastatic lesions. Predictors were identified and further applied to establish a combined model by multivariate logistic regression in predicting the probability of metastatic UCLNs. Receiver operating characteristic (ROC) curves were used to analyse the diagnostic performance. RESULTS: Metastatic UCLNs had larger MinAD and MinAD/MaxAD ratio, greater energy and entropy values, and higher incidence of level II (upper jugular group), but lower BF10th value than benign nodes (all p<0.05). MinAD, BF10th, energy, and entropy were validated as independent predictors in diagnosing metastatic UCLNs. The combined model yielded an area under the curve (AUC) of 0.932, accuracy of 84.42 %, sensitivity of 80.6 %, and specificity of 90.29 %. CONCLUSIONS: Whole-node histogram analysis on BF maps is a feasible tool to differentiate metastatic from benign UCLNs in NPC patients, and the combined model can further improve the diagnostic efficacy.
Subject(s)
Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/diagnostic imaging , Nasopharyngeal Carcinoma/pathology , Lymphatic Metastasis/diagnostic imaging , Lymphatic Metastasis/pathology , Retrospective Studies , Nasopharyngeal Neoplasms/pathology , Perfusion Imaging , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathologyABSTRACT
The Rare-RI Ring (R3) is a recently commissioned cyclotronlike storage ring mass spectrometer dedicated to mass measurements of exotic nuclei far from stability at Radioactive Isotope Beam Factory (RIBF) in RIKEN. The first application of mass measurement using the R3 mass spectrometer at RIBF is reported. Rare isotopes produced at RIBF-^{127}Sn, ^{126}In, ^{125}Cd, ^{124}Ag, ^{123}Pd-were injected in R3. Masses of ^{126}In, ^{125}Cd, and ^{123}Pd were measured whereby the mass uncertainty of ^{123}Pd was improved. This is the first reported measurement with a new storage ring mass spectrometry technique realized at a heavy-ion cyclotron and employing individual injection of the preidentified rare nuclei. The latter is essential for the future mass measurements of the rarest isotopes produced at RIBF. The impact of the new ^{123}Pd result on the solar r-process abundances in a neutron star merger event is investigated by performing reaction network calculations of 20 trajectories with varying electron fraction Y_{e}. It is found that the neutron capture cross section on ^{123}Pd increases by a factor of 2.2 and ß-delayed neutron emission probability, P_{1 n}, of ^{123}Rh increases by 14%. The neutron capture cross section on ^{122}Pd decreases by a factor of 2.6 leading to pileup of material at A=122, thus reproducing the trend of the solar r-process abundances. The trend of the two-neutron separation energies (S_{2n}) was investigated for the Pd isotopic chain. The new mass measurement with improved uncertainty excludes large changes of the S_{2n} value at N=77. Such large increase of the S_{2n} values before N=82 was proposed as an alternative to the quenching of the N=82 shell gap to reproduce r-process abundances in the mass region of A=112-124.
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Objective: To investigate the clinicopathological features, surgical methods and prognosis of primary appendiceal neoplasms. Methods: A descriptive case series study was performed. Clinical data of patients diagnosed with primary appendiceal neoplasms in Peking University First Hospital from 2006 to 2017 were retrospectively analyzed. Patients who underwent surgery and were confirmed as appendiceal neoplasms by postoperative pathology were included. Cases of cecal tumor invading the appendix and other organ tumors implanting in the appendix and cases of recurrent appendix tumors were excluded Pathological classification was based on the 4th edition of the WHO classification of digestive tract tumors (2010 edition), and the efficacy of operation methods of low grade appendiceal mucinous neoplasm (LAMN) were analyzed. Results: A total of 115 patients were enrolled, including 52 males and 63 females with a median age of 59 (51, 71) years. Clinical symptoms usually manifested as dormant pain in the right lower quadrant, migrating right lower abdominal pain, fever and bloating. Twenty-four cases were accidentally discovered during surgery, and 21 cases were found by physical examination. The preoperative diagnosis rate of CT and ultrasound was 40.2% (43/107) and 25.5% (24/94) respectively. The postoperative pathological types contained 83 cases of LAMN, 12 cases of mucinous adenocarcinoma, 9 cases of appendiceal neuroendocrine neoplasms (aNEN), 2 cases of mucinous adenocarcinoma with signet ring cells, 3 cases of serrated adenoma, 2 cases of goblet cell carcinoid, 2 cases of lymphoma, 1 case of leiomyoma and 1 case of schwannomas. All the patients underwent surgical resection, including 41 cases of appendectomy, 21 cases of partial cecectomy, 48 cases of right hemicolectomy, and 5 cases of combined organ resection due to appendiceal tumor infiltration or dissemination. Eighteen cases were diagnosed with pseudomyxoma peritonei (PMP) during operation. A total of 98 patients were enrolled for follow-up. The median follow-up time was 58 (5-172) months. The 5-year disease-free survival (DFS) rate was 84.5% and 5-year overall survival (OS) was 88.2%. Multivariate analysis revealed that high-grade malignancy tumors (HR=25.881, 95% CI: 2.827-236.935, P=0.004) and PMP formation (HR=42.166, 95% CI: 3.470-512.439,P=0.003) were independent risk factors for prognosis. Patients undergoing right hemicolectomy presented longer operation time, more blood loss and higher morbidity of complication as compared to those undergoing appendectomy and partial cecectomy (all P<0.05), while no significant differences in 5-year DFS (P=0.627) and 5-year OS (P=0.718) were found. Conclusions: Primary appendiceal neoplasms usually have no typical features, accompanied with low preoperative diagnosis rate. The common pathological types are LAMN, mucinous adenocarcinoma and aNEN. Appendectomy or partial cecectomy for LAMN may achieve satisfactory prognosis. High-grade malignancy tumors and PMP formation are independent risk factors for prognosis.
Subject(s)
Adenocarcinoma, Mucinous , Appendiceal Neoplasms , Adenocarcinoma, Mucinous/surgery , Appendectomy , Appendiceal Neoplasms/surgery , Humans , Male , Neoplasm Recurrence, Local , Retrospective StudiesABSTRACT
Objective: To explore the clinical effects of follicle unit extraction (FUE) transplantation combined with recombinant bovine basic fibroblast growth factor (rb-bFGF) gel and minoxidil tincture in treating secondary cicatricial alopecia (hereinafter referred to as cicatricial alopecia). Methods: A retrospective observational study was conducted. According to the different treatment methods, 50 cicatricial alopecia patients who met the inclusion criteria and only underwent FUE transplantation in the First Affiliated Hospital of Air Force Medical University from March 2013 to April 2017 were recruited into FUE alone group (26 males and 24 females, aged (28±13) years), and 50 cicatricial alopecia patients who met the inclusion criteria and underwent FUE transplantation+rb-bFGF gel during 1 to 14 days after surgery+minoxidil tincture during 15 to 180 days after surgery in this hospital from May 2017 to April 2020 were recruited into FUE+rb-bFGF+minoxidil group (32 males and 18 females, aged (27±9) years). Hair loss rates in post surgery month (PSM) 3 and 6, hair survival rates and satisfaction rates of patients in PSM 12, and the adverse effect rates of patients in the 2 groups within PSM 12 were observed and calculated. Data were statistically analyzed with chi-square test, Fisher's exact probability test, and independent sample t test. Results: In PSM 3 and 6, the hair loss rates of patients in FUE alone group were significantly higher than those in FUE+rb-bFGF+minoxidil group, respectively (t=70.850, 42.610, P<0.01). In PSM 12, the hair survival rate of patients in FUE+rb-bFGF+minoxidil group was (91.0±2.8)%, which was significantly higher than (80.9±6.9)% in FUE alone group (t=9.665, P<0.01). In PSM 12, 25 patients were very satisfied, 12 patients were fairly satisfied, 10 patients were slightly satisfied, 2 patients were not satisfied, and 1 patient was very unsatisfied in FUE alone group; 42 patients were very satisfied, 5 patients were fairly satisfied, and 3 patients were slightly satisfied in FUE+rb-bFGF+minoxidil group. The satisfaction rate of patients in FUE alone group was 74% (37/50), which was significantly lower than 94% (47/50) in FUE+rb-bFGF+minoxidil group (P<0.01). Within PSM 12, compared with those in FUE+rb-bFGF+minoxidil group, the incidence rates of folliculitis, abnormal growth direction, and skin necrosis in transplant site were not obviously changed in FUE alone group (P>0.05), while the incidence of scar in donor site was significantly higher (P<0.05). Conclusions: Compared with FUE transplantation alone, FUE transplantation combined with rb-bFGF and minoxidil can reduce the hair loss rate, improve the hair survival rate and the satisfaction rate of patients with cicatricial alopecia after FUE transplantation, with less adverse effects, thus are good for cicatricial alopecia treatment.
Subject(s)
Fibroblast Growth Factor 2 , Minoxidil , Alopecia , Animals , Cattle , Cicatrix/pathology , Female , Humans , Male , Retrospective StudiesABSTRACT
Objective: To observe the clinical effects of fine follicular unit extraction (FUE) and transplantation in repairing cicatricial eyebrow defects. Methods: The retrospective observational study was conducted. From September 2013 to January 2020, 58 patients (36 males and 22 females, aged 12-40 years) underwent fine FUE and transplantation to treat cicatricial eyebrow defects in the First Affiliated Hospital of Air Force Medical University. The hair survival rate in 10 months post operation was observed and calculated, and the curative effect was graded. Visual Analogue Scale was used to evaluate patients' satisfaction in one year post operation. The adverse reactions during operation and within one year post operation were recorded, and the adverse reaction incidence was calculated. Results: The hair survival rate of 58 patients in 10 months post operation was (84±5)%. Four patients (6.9%) had good curative effect, 54 patients (93.1%) had excellent curative effect in effect evaluation. Four patients (6.90%) were moderately satisfied, 5 patients (8.62%) were fairly satisfied, and 49 patients (84.48%) were very satisfied in satisfaction evaluation. Twelve patients had 14 adverse reactions, with an incidence of 24.14%. Conclusions: Fine FUE and transplantation can provide good cosmetic results for patients with cicatricial eyebrow defects, with high satisfaction of patient and few adverse reactions.
Subject(s)
Eyebrows , Hair Follicle , Female , Hair , Humans , Male , Patient Satisfaction , Retrospective StudiesABSTRACT
BACKGROUND AND PURPOSE: Zero TE-MRA is less sensitive to field heterogeneity, complex flow, and acquisition noise. This study aimed to prospectively validate the feasibility of zero TE-MRA for cerebrovascular diseases assessment, compared with TOF-MRA. MATERIALS AND METHODS: Seventy patients suspected of having cerebrovascular disorders were recruited. Sound levels were estimated for each MRA subjectively and objectively in different modes. MRA image quality was estimated by 2 neuroradiologists. The degree of stenosis (grades 0-4) and the z-diameter of aneurysms (tiny group ≤3 mm and large group >3 mm) were measured for further quantitative analysis. CTA was used as the criterion standard. RESULTS: Zero TE-MRA achieved significantly lower subjective perception and objective noise reduction (37.53%). Zero TE-MRA images showed higher signal homogeneity (3.29 ± 0.59 versus 3.04 ± 0.43) and quality of venous signal suppression (3.67 ± 0.47 versus 2.75 ± 0.46). The intermodality agreement was higher for zero TE-MRA than for TOF-MRA (zero TE, 0.90; TOF, 0.81) in the grading of stenosis. Zero TE-MRA had a higher correlation than TOF-MRA (zero TE, 0.84; TOF, 0.74) in the tiny group and a higher consistency with CTA (intraclass correlation coefficient, 0.83; intercept, -0.5084-1.1794; slope -0.4952 to -0.2093) than TOF-MRA (intraclass correlation coefficient, 0.64; intercept, 0.7000-2.6133; slope -1.0344 to -0.1923). Zero TE-MRA and TOF-MRA were comparable in the large group. Zero TE-MRA had more accurate details than TOF-MRA of AVM and Moyamoya lesions. CONCLUSIONS: Compared with TOF-MRA, zero TE-MRA achieved more robust performance in depicting cerebrovascular diseases. Therefore, zero TE-MRA was shown to be a promising MRA technique for further routine application in the clinic in patients with cerebrovascular diseases.
Subject(s)
Cerebrovascular Disorders/diagnostic imaging , Magnetic Resonance Angiography/methods , Adult , Aged , Aged, 80 and over , Cerebral Angiography , Cohort Studies , Constriction, Pathologic/diagnostic imaging , Feasibility Studies , Female , Humans , Image Processing, Computer-Assisted , Intracranial Arteriovenous Malformations/diagnostic imaging , Male , Middle Aged , Moyamoya Disease/diagnostic imaging , Prospective Studies , Young AdultABSTRACT
One of the main functions of the piwi-interacting RNA pathway is the post-transcriptional silencing of transposable elements in the germline of many species. In insects, proteins belonging to the Tudor superfamily proteins belonging to the Tudor superfamily play an important role in to play an important role in this mechanism. In this study, we identified the tudor gene in the oriental fruit fly, Bactrocera dorsalis, investigated the spatiotemporal expressional profile of the gene, and performed a functional analysis using RNA interference. We identified one transcript for a tudor homologue in the B. dorsalis transcriptome, which encodes a protein containing the typical 10 Tudor domains and an Adenosine triphosphate (ATP) synthase delta subunit signature. Phylogenetic analysis confirmed the identity of this transcript as a tudor homologue in this species. The expression profile indicated a much higher expression in the adult and pupal stages compared to the larval stages (up to a 60-fold increase), and that the gene was mostly expressed in the ovaries, Malpighian tubules and fat body. Finally, gene knockdown of tudor in B. dorsalis led to clearly underdeveloped ovaries in the female adult and reductions in copulation rate and amount of oviposition, indicating its important role in reproduction. The results of this study shed more light on the role of tudor in ovary development and reproduction.
Subject(s)
Insect Proteins/genetics , Tephritidae/genetics , Animals , Copulation , Female , Insect Proteins/chemistry , Insect Proteins/metabolism , Male , Ovary/growth & development , Ovary/metabolism , RNA Interference , Tephritidae/growth & development , Tephritidae/metabolism , Tudor DomainABSTRACT
Different materials have been used for vital dental pulp treatment. Preferably a pulp capping agent should show appropriate biological performance, excellent handling properties, and a good imaging contrast. These features can be delivered into a single material through the combination of therapeutic and diagnostic agents (i.e. theranostic). Calcium phosphate based composites (CPCs) are potentially ideal candidate for pulp treatment, although poor imaging contrast and poor dentino-inductive properties are limiting their clinical use. In this study, a theranostic dental pulp capping agent was developed. First, imaging properties of the CPC were improved by using a core-shell structured dual contrast agent (csDCA) consisting of superparamagnetic iron oxide (SPIO) and colloidal gold, as MRI and CT contrast agent respectively. Second, biological properties were implemented by using a dentinogenic factor (i.e. bone morphogenetic protein 2, BMP-2). The obtained CPC/csDCA/BMP-2 composite was tested in vivo, as direct pulp capping agent, in a male Habsi goat incisor model. Our outcomes showed no relevant alteration of the handling and mechanical properties (e.g. setting time, injectability, and compressive strength) by the incorporation of csDCA particles. In vivo results proved MRI contrast enhancement up to 7weeks. Incisors treated with BMP-2 showed improved tertiary dentin deposition as well as faster cement degradation as measured by µCT assessment. In conclusion, the presented theranostic agent matches the imaging and regenerative requirements for pulp capping applications. STATEMENT OF SIGNIFICANCE: In this study, we combined diagnostic and therapeutic agents in order to developed a theranostic pulp capping agent with enhanced MRI and CT contrast and improved dentin regeneration ability. In our study we cover all the steps from material preparation, mechanical and in vitro characterization, to in vivo study in a goat dental model. To the best of our knowledge, this is the first time that a theranostic pulp capping material have been developed and tested in an in vivo animal model. Our promising results in term of imaging contrast enhancement and of induction of new dentin formation, open a new scenario in the development of innovative dental materials.
Subject(s)
Acrylic Resins , Composite Resins , Contrast Media , Incisor , Magnetic Resonance Imaging/methods , Polyurethanes , Pulp Capping and Pulpectomy Agents , Theranostic Nanomedicine/methods , Tomography, X-Ray Computed/methods , Acrylic Resins/chemistry , Acrylic Resins/pharmacokinetics , Acrylic Resins/pharmacology , Animals , Bone Morphogenetic Protein 2/chemistry , Bone Morphogenetic Protein 2/pharmacokinetics , Bone Morphogenetic Protein 2/pharmacology , Composite Resins/chemistry , Composite Resins/pharmacokinetics , Composite Resins/pharmacology , Contrast Media/chemistry , Contrast Media/pharmacokinetics , Contrast Media/pharmacology , Ferric Compounds/chemistry , Ferric Compounds/pharmacokinetics , Ferric Compounds/pharmacology , Goats , Gold Colloid/chemistry , Gold Colloid/pharmacokinetics , Gold Colloid/pharmacology , Humans , Incisor/diagnostic imaging , Incisor/metabolism , Incisor/surgery , Polyurethanes/chemistry , Polyurethanes/pharmacokinetics , Polyurethanes/pharmacology , Pulp Capping and Pulpectomy Agents/chemistry , Pulp Capping and Pulpectomy Agents/pharmacokinetics , Pulp Capping and Pulpectomy Agents/pharmacologyABSTRACT
A Low-Energy intense-highly charged ion Accelerator Facility (LEAF) program has been launched at Institute of Modern Physics. This accelerator facility consists of a superconducting Electron Cyclotron Resonance (ECR) ion source, a Low Energy Beam Transport (LEBT) system, and a Radio Frequency Quadrupole (RFQ). It is especially of interest for the extracted ion beam from the ECR ion source, which is transversely coupled, and this property will significantly affect the beam transmission in the LEBT line and the matching with the downstream RFQ. In the beam transport design of LEAF, beam decoupling in the LEBT is considered to lower down the projection emittances and the feasibility of the design has been verified by beam simulation with a transversely coupled beam from the ECR ion source.
ABSTRACT
The testis is a highly specialized tissue that plays a vital role in ensuring fertility by producing spermatozoa, which are transferred to the female during mating. Spermatogenesis is a complex process, resulting in the production of mature sperm, and involves significant structural and biochemical changes in the seminiferous epithelium of the adult testis. The identification of genes involved in spermatogenesis of Bactrocera dorsalis (Hendel) is critical for a better understanding of its reproductive development. In this study, we constructed a cDNA library of testes from male B. dorsalis adults at different ages, and performed de novo transcriptome sequencing to produce a comprehensive transcript data set, using Illumina sequencing technology. The analysis yielded 52 016 732 clean reads, including a total of 4.65 Gb of nucleotides. These reads were assembled into 47 677 contigs (average 443 bp) and then clustered into 30 516 unigenes (average 756 bp). Based on BLAST hits with known proteins in different databases, 20 921 unigenes were annotated with a cut-off E-value of 10(-5). The transcriptome sequences were further annotated using the Clusters of Orthologous Groups, Gene Orthology and the Kyoto Encyclopedia of Genes and Genomes databases. Functional genes involved in spermatogenesis were analysed, including cell cycle proteins, metalloproteins, actin, and ubiquitin and antihyperthermia proteins. Several testis-specific genes were also identified. The transcripts database will help us to understand the molecular mechanisms underlying spermatogenesis in B. dorsalis. Furthermore, 2913 simple sequence repeats and 151 431 single nucleotide polymorphisms were identified, which will be useful for investigating the genetic diversity of B. dorsalis in the future.
Subject(s)
Gene Expression Profiling , Insect Proteins/genetics , Spermatogenesis/genetics , Tephritidae/genetics , Testis/metabolism , Animals , Base Sequence , Gene Library , Insect Proteins/metabolism , Male , Microsatellite Repeats , Molecular Sequence Data , Spermatogenesis/physiology , Tephritidae/metabolismABSTRACT
In eukaryotes, microRNAs (miRNAs) are small, conserved, noncoding RNAs that have emerged as critical regulators of gene expression. The oriental fruit fly Bactrocera dorsalis is one of the most economically important fruit fly pests in East Asia and the Pacific. Although transcriptome analyses have greatly enriched our knowledge of its structural genes, little is known about post-transcriptional regulation by miRNAs in this dipteran species. In this study, small RNA libraries corresponding to four B. dorsalis developmental stages (eggs, larvae, pupae and adults) were constructed and sequenced. Approximately 30.7 million reads of 18-30 nucleotides were obtained, with 123 known miRNAs and 60 novel miRNAs identified amongst these libraries. More than half of the miRNAs were stage-specific during the four developmental stages. A set of miRNAs was found to be up- or down-regulated during development by comparison of their reads at different developmental stages. Moreover, a small part of miRNAs owned both miR-#-3p and miR-#-5p types, with enormously variable miR-#-3p/miR-#-5p ratios in the same library and amongst different developmental stages for each miRNA. Taking these findings together, the current study has uncovered a number of miRNAs and provided insights into their possible involvement in developmental regulation by expression profiling of miRNAs. Further analyses of the expression and function of these miRNAs could increase our understanding of regulatory networks in this insect and lead to novel approaches for its control.
Subject(s)
Gene Expression Regulation, Developmental , Gene Library , MicroRNAs/genetics , Tephritidae/genetics , Animals , High-Throughput Nucleotide Sequencing , Larva/metabolism , MicroRNAs/metabolism , Ovum/metabolism , Pupa/metabolism , Real-Time Polymerase Chain Reaction , Sequence Analysis, RNA , Tephritidae/growth & development , Tephritidae/metabolismABSTRACT
The citrus red mite (Panonychus citri) can feed on more than 112 plant species around the world. Endogenous small RNAs (sRNAs) have proved to be important components of gene regulation in many eukaryotes. Recently, many sRNAs have been shown to be involved in various biological processes, such as development in many animals, including insects; however, to date, no sRNAs have been reported in the citrus red mite. Using Illumina sequencing, several categories of sRNAs were identified, including 594 known microRNAs (miRNAs) grouped into 206 families and 31 novel miRNAs in the four developmental stages of citrus red mite. In addition, according to bioinformatics analysis and S-Poly(T) miRNA assays, the expression level of many miRNAs varied among the developmental stages. Furthermore, the prediction of miRNAs target genes and their functional annotation indicated that miRNAs are involved in the regulation of multiple pathways in the citrus red mite. As the first report of the sRNA world in citrus red mite, the present study furthers our understanding of the roles played by sRNAs in the development of citrus red mite and the data may help to develop methods of controlling the pests in the field.
Subject(s)
MicroRNAs/genetics , Tetranychidae/genetics , Transcriptome , Animals , Female , Larva/genetics , Larva/metabolism , MicroRNAs/metabolism , Molecular Sequence Data , Nymph/genetics , Nymph/metabolism , Ovum/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Tetranychidae/growth & development , Tetranychidae/metabolismABSTRACT
As the second largest organ in insects, the insect midgut is the major tissue involved in the digestion of food and detoxification of xenobiotics, such as insecticides, and the first barrier and target for oral RNA interference (RNAi). In this study, we performed a midgut-specific transcriptome analysis in the oriental fruit fly, Bactrocera dorsalis, an economically important worldwide pest, with many populations showing high levels of insecticide resistance. Using high-throughput sequencing, 52 838 060 short reads were generated and assembled to 25 236 unigenes with a mean length of 758 bp. Interestingly, 34 unique sequences encoding digestion enzymes were newly described and these included aminopeptidase and trypsin, genes associated with Bacillus thuringiensis resistance and fitness cost. Second, 41 transcripts were annotated to particular detoxification genes such as glutathione S-transferases, carboxylesterases and cytochrome P450s, and the subsequent phylogenetic analysis indicated homology with tissue-specific and insecticide resistance-related genes of Drosophila melanogaster. Third, we identified the genes involved in the mechanism of RNAi and the uptake of double-stranded RNA. The sequences encoding Dicer-2, R2D2, AGO2, and Eater were confirmed, but SID and SR-CI were absent in the midgut transcriptome. In conclusion, the results provide basic molecular information to better understand the mechanisms of food digestion, insecticide resistance and oral RNAi in this important pest insect in agriculture. Specific genes in these systems can be used in the future as potential targets for pest control, for instance, with RNAi technology.
Subject(s)
Digestion/genetics , Insecticide Resistance/genetics , RNA Interference , Tephritidae/genetics , Animals , Carboxylesterase/genetics , Computer Simulation , Cytochrome P-450 Enzyme System/genetics , Female , Gastrointestinal Tract/metabolism , Gene Expression Profiling , Glutathione Transferase/genetics , Inactivation, Metabolic , Insect Control , Molecular Sequence Annotation , Tephritidae/enzymologyABSTRACT
Metastasis is a major clinical obstacle in the treatment of gastric cancer (GC) and it accounts for the majority of cancer-related mortality. MicroRNAs have recently emerged as regulators of metastasis by acting on multiple signaling pathways. In this study, we found that miR-7 is significantly downregulated in highly metastatic GC cell lines and metastatic tissues. Both gain-of-function and loss-of-function experiments showed that increased miR-7 expression significantly reduced GC cell migration and invasion, whereas decreased miR-7 expression dramatically enhanced cell migration and invasion. In vivo metastasis assays also demonstrated that overexpression of miR-7 markedly inhibited GC metastasis. Moreover, the insulin-like growth factor-1 receptor (IGF1R) oncogene, which is often mutated or amplified in human cancers and functions as an important regulator of cell growth and tumor invasion, was identified as a direct target of miR-7. Silencing of IGF1R using small interefering RNA (siRNA) recapitulated the anti-metastatic function of miR-7, whereas restoring the IGF1R expression attenuated the function of miR-7 in GC cells. Furthermore, we found that suppression of Snail by miR-7, through targeting IGF1R, increased E-cadherin expression and partially reversed the epithelial-mesenchymal transition (EMT). Finally, analyses of miR-7 and IGF1R levels in human primary GC with matched lymph node metastasis tissue arrays revealed that miR-7 is inversely correlated with IGF1R expression. The present study provides insight into the specific biological behavior of miR-7 in EMT and tumor metastasis. Targeting this novel miR-7/IGF1R/Snail axis would be helpful as a therapeutic approach to block GC metastasis.
Subject(s)
Carcinoma/genetics , Carcinoma/pathology , MicroRNAs/physiology , Receptor, IGF Type 1/genetics , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Animals , Cells, Cultured , Female , Gene Expression Regulation, Neoplastic/drug effects , Gene Targeting , HEK293 Cells , Humans , Mice , Mice, Nude , MicroRNAs/genetics , Molecular Targeted Therapy , Neoplasm Metastasis , RNA, Small Interfering/pharmacology , Receptor, IGF Type 1/antagonists & inhibitors , Xenograft Model Antitumor AssaysABSTRACT
The citrus red mite, Panonychus citri, is known for its ability rapidly to evolve resistance to insecticides/acaricides and to adapt to hosts that produce toxins. In this study, we constructed an unprecedented four gigabase pair transcriptome of P. citri, which was assembled into 64 149 unique transcripts, the functions of which were annotated by five public databases. A total of 116 unique transcripts were identified as representatives of potential involvement in the detoxification of xenobiotics. Genes recorded to encoding insecticide/acaricide target proteins were also obtained from the P. citri transcriptome. In order to explore novel candidate genes potentially involved in the pesticide detoxification of P. citri, we also constructed digital gene expression libraries of short-term transcriptome responses of P. citri to pesticides, which resulted in the identification of 120 unique transcripts potentially associated with insecticide/acaricide detoxification. Our study will facilitate molecular research on pesticide resistance in citrus red mites, as well as in other phytophagous mites.
Subject(s)
Metabolic Networks and Pathways/genetics , Mites/genetics , Tick Control , Acaricides/pharmacology , Animals , Drug Resistance/genetics , Gene Expression/drug effects , Gene Expression Profiling , Gene Library , High-Throughput Nucleotide Sequencing , Mites/drug effects , Organ Specificity , Pyrethrins/pharmacology , Pyridazines/pharmacologyABSTRACT
Gliomatosis cerebri (GC) is a challenging tumor, considered to have a poor prognosis and poor response to treatments. The purpose of this study is to better understand glial tumor metabolism and post chemotherapy, radiotherapy and antiangiogenic variations in a longitudinal study to determine cerebral variation in MRS area, amplitude, and ratios of metabolites and spectral profiles during a five year longitudinal follow-up in 14 patients with gliomatosis without initial hyperperfusion and treated with chemotherapy (Temozolomide (Temodal(®))), radiotherapy and subsequent antiangiogenic therapy. The study also aimed to detect changes in infiltration, proliferation, lipids or glycolytic metabolism, as these changes could be monitored longitudinally in humans with glial brain tumors (low and high grade) after therapy, using conventional magnetic resonance imaging (MRI), spectroscopy (MRS) and MR perfusion. Most patients had first initial clinical and MRS improvement and stable MRI. After 12 to 24 chemotherapy treatment cycles MRS usually showed an increase in the Cho/Cr ratio (proliferation) and sometimes contrast enhancements. Later, the patients showed clinical deterioration and radiotherapy was started. There was an improvement with radiotherapy that lasted nine to 18 months. This was followed by a worsening that led to try antiangiogenic therapy. Later in the evolution for three patients with hyperperfusion this symptom disappeared, but proliferation, infiltration and glycolytic metabolism remained at a high level. Spectroscopic and metabolic changes often occur well before clinical deterioration and sometimes before improvement. Therefore, MRS could be more sensitive and could detect changes earlier than MRI and is sometimes predictive. Despite the difficulty, the variability and unknown factors, these repeated measurements give us a better insight into the nature of the different processes, tumor progression and could lead to better understanding of therapeutic response.
ABSTRACT
In this paper the frequency dependence and focusing performance in focal plane of a diffractive lens is analyzed by FDTD method at millimeter wavelengths. Binary lens and four-level lens are considered. The field distribution on the focal plane of the diffractive lens for the incident wave at different frequency is presented, which shows the frequency dependence and focusing performance of the lens.