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1.
Blood Cancer J ; 13(1): 178, 2023 12 05.
Article in English | MEDLINE | ID: mdl-38052803

ABSTRACT

Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.


Subject(s)
Arsenic , Leukemia, Promyelocytic, Acute , Child , Humans , Arsenic/adverse effects , Arsenic Trioxide/adverse effects , Arsenicals/adverse effects , Leukemia, Promyelocytic, Acute/drug therapy , Treatment Outcome , Tretinoin/therapeutic use
2.
Front Physiol ; 14: 1187743, 2023.
Article in English | MEDLINE | ID: mdl-37389122

ABSTRACT

Encarsia formosa is a natural enemy of the invasive pest Bemisia tabaci and is known to be a dominant parasitic. The frequency and magnitude of climate extremes, particularly temperature extremes, have increased, which has put insect populations at risk. However, the effects of temperature extremes on E. formosa are not well understood. To examine the impact of short-term extreme temperature exposure on the development and reproduction of E. formosa, eggs, larvae, pupae, and adults were exposed to high/low temperature treatments (HLT25, HLT50, LLT25, and LLT50). Our findings indicate that the pupal stage of E. formosa exhibited the strongest tolerance to both heat and cold, while adults exhibited a weaker tolerance. The shortest egg-to-adult development period of 12.65 days was observed in E. formosa exposed to HLT50 treatment during the egg-larval stage. The parasitism peak of the adult stage was delayed by 1-6 days after exposure to extreme temperatures during the egg-larval stage. Conversely, the parasitism peak was advanced by 1-3 days after exposure to extreme temperatures during the pupal and adult stages. The eclosion rate, total parasitism, eclosion rate of the F1 generation, and adult longevity of the F1 generation were lower in the treatment groups than in the control groups. The F1 generation's development period was prolonged to 15.49 and 15.19 days after exposure to HLT25 and HLT50 treatments, respectively, during the egg-larval stage. The F1 generation's development period was shortened to 13.33 days after exposure to LLT50 treatment during the pupal stage. Male individuals appeared in the F1 generation after exposure to HLT50 treatment during the pupal stage, with females accounting for only 56.38%. Our results demonstrate that short-term exposure to extreme temperatures has detrimental effects on the growth and reproduction of E. formosa. In field biocontrol against E. formosa, the release of E. formosa should be avoided as much as possible when the ambient temperature is higher than 35°C or lower than 0°C. During extreme temperature conditions, timely supplementation and release of E. formosa population, along with ventilation and cooling in greenhouse facilities during summer, are necessary for better pest control efficacy.

3.
Ann Hematol ; 102(7): 1713-1721, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37199788

ABSTRACT

Realgar-Indigo naturalis formula (RIF), with A4S4 as a major ingredient, is an oral arsenic used in China to treat pediatric acute promyelocytic leukemia (APL). The efficacy of RIF is similar to that of arsenic trioxide (ATO). However, the effects of these two arsenicals on differentiation syndrome (DS) and coagulation disorders, the two main life-threatening events in children with APL, remain unclear. We retrospectively analyzed 68 consecutive children with APL from South China Children Leukemia Group-APL (SCCLG-APL) study. Patients received all-trans retinoic acid (ATRA) on day 1 of induction therapy. ATO 0.16 mg/kg day or RIF 135 mg/kg·day was administrated on day 5, while mitoxantrone was administered on day 3 (non-high-risk) or days 2-4 (high-risk). The incidences of DS were 3.0% and 5.7% in ATO (n = 33) and RIF (n = 35) arms (p = 0.590), and 10.3% and 0% in patients with and without differentiation-related hyperleukocytosis (p = 0.04), respectively. Moreover, in patients with differentiation-related hyperleukocytosis, the incidence of DS was not significantly different between ATO and RIF arms. The dynamic changes of leukocyte count between arms were not statistically different. However, patients with leukocyte count > 2.61 × 109/L or percentage of promyelocytes in peripheral blood > 26.5% tended to develop hyperleukocytosis. The improvement of coagulation indexes in ATO and RIF arms was similar, with fibrinogen and prothrombin time having the quickest recovery rate. This study showed that the incidence of DS and recovery of coagulopathy are similar when treating pediatric APL with RIF or ATO.


Subject(s)
Arsenic , Arsenicals , Blood Coagulation Disorders , Leukemia, Promyelocytic, Acute , Child , Humans , Leukemia, Promyelocytic, Acute/drug therapy , Arsenic/therapeutic use , Retrospective Studies , Arsenic Trioxide , Tretinoin , Antineoplastic Combined Chemotherapy Protocols , Oxides , Treatment Outcome
4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(2): 293-297, 2023 Mar.
Article in Chinese | MEDLINE | ID: mdl-36949688

ABSTRACT

Objective: To analyze the electroencephalogram (EEG) features of anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) and to study the clinical assessment value of the degree of EEG background slowing and the presence of δ brush. Methods: We enrolled 52 patients with anti-NMDARE and collected their clinical data, including age, sex, form of disease onset, status of tumor comorbidity, auxiliary examination findings (cerebrospinal fluid [CSF] anti-methyl-D-aspartate receptor antibody titers, magnetic resonance imaging [MRI] reports, and EEG results), treatment status, and follow-up after discharge. The degree of EEG background abnormality and the presence of δ brush in the EEG of patients with different clinical features were analyzed. Results: Among the 52 patients, 7 (14%) had normal EEG, and 45 (87%), abnormal EEG, including 25 (48%) with mild abnormalities, 11 (21%) with moderate abnormalities, and 9 (17%) with severe abnormalities. δ brush was seen in 6 (12%) patients. At the time of EEG, 32 (62%) patients were in the mild condition group and 20 (38%) patients were in the severe condition group. After 1 year of follow-up, there were 45 (86%) patients in the good prognosis group and 7 (14%) patients in the poor prognosis group. The exacerbation of EEG background abnormalities and the presence of δ brush were indications for an increase in the proportion of patients who were in severe condition, who needed ICU admission, and who had poor prognosis ( P<0.01). The worse the EEG background abnormalities, the higher the proportion of CSF antibody titers>1∶10 ( P=0.035), and the higher the proportion of patients initiating second-line immunotherapy ( P=0.008). The δ brush was seen a higher proportion in patients with comorbid tumors ( P=0.012). The probability of δ brush presence was higher in the first-time diagnosis cases than that in recurrent cases ( P=0.023). Conclusions: The degree of EEG slowing and the presence of δ brush have shown consistent performance in assessing patients' condition and predicting prognosis. The slower the EEG, the more severe the disease, and the worse the prognosis. The presence of δ brush indicates severe disease and poor prognosis. EEG slowing is correlated with the immune status of patients with anti-NMDARE. The slower the EEG, the more severe the immune abnormalities. In clinical practice, patient EEG should be under dynamic monitoring in order to evaluate the effect of immunotherapy. If EEG slowing is not improved, enhanced immunotherapy should be considered as early as possible. The δ brush is seen at a higher proportion in patients with comorbid tumors. Therefore, active efforts should be made to screen for tumors when δ brush is present.


Subject(s)
Anti-N-Methyl-D-Aspartate Receptor Encephalitis , Humans , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/diagnosis , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/cerebrospinal fluid , Electroencephalography/methods , Hospitalization
5.
Front Physiol ; 14: 1036397, 2023.
Article in English | MEDLINE | ID: mdl-36846336

ABSTRACT

Zeugodacus tau is an economically important invasive pest of various vegetables and fruits. In this study, we evaluated the effects of short-term (12 h) exposure to high temperatures on the reproductive behaviors and physiological enzyme activities of adult Z. tau flies. When compared to the control group, the mating rate in the treated group increased significantly after exposure to 34°C and 38°C. After 34°C exposure, the mating rate of the control♀-treated♂ mating was the highest (60.0%). The use of high temperatures for a short period reduced the pre-mating period and lengthened the duration of copulation. After 38°C exposure, the mating between treated♀ and treated♂ had the shortest pre-mating period of 39.0 min and the longest copulation duration of 67.8 min. Mating after a brief exposure to high temperatures had a negative impact on female reproduction, whereas mating with males who previously had a brief exposure to 34°C and 38°C significantly increased female fecundity. After 40 °C exposure, the mating between treated♀ and control♂ showed the lowest fecundity and hatching rate of 293.25 eggs and 25.71%, respectively. The mating between control♀ and treated♂ showed the highest fecundity of 1,016.75 eggs after exposure to 38°C. The SOD, POD, and CAT activities exhibited significant changes (increase or decrease) after the short-term exposure of Z. tau adults to high temperatures. After being exposed to 38°C, SOD activity increased by 2.64 and 2.10 times in females and males in the treated group, respectively, compared to the SOD activity in the control group. The AchE, CarE, and GST activities first increased and then decreased with the increase in temperature. CarE activity changed the most after exposure to 38°C, with females and males in the treated group increasing by 7.81 and 1.69 times, respectively, compared to the activity in the control group. In conclusion, mating strategy and physiological stress are important adaptive mechanisms of Z. tau for adapting to short-term heat stress in a sex-specific manner.

6.
Int J Immunopathol Pharmacol ; 37: 3946320231161174, 2023.
Article in English | MEDLINE | ID: mdl-36848930

ABSTRACT

Apigenin is a kind of flavonoid with many beneficial biological effects. It not only has direct cytotoxicity to tumor cells, but also can boost the antitumor effect of immune cells by modulating immune system. The purpose of this study was to investigate the proliferation of NK cells treated with apigenin and its cytotoxicity to pancreatic cancer cells in vitro, and explore its potential molecular mechanism. In this study, the effect of apigenin on NK cell proliferation and killing pancreatic cancer cells were measured by CCK-8 assay. Perforin, granzyme B (Gran B), CD107a, and NKG2D expressions of NK cells induced with apigenin were detected by flow cytometry (FCM). The mRNA expression of Bcl-2, Bax and protein expression of Bcl-2, Bax, p-ERK, and p-JNK in NK cells were evaluated by qRT-PCR and western blotting analysis, respectively. The results showed that appropriate concentration of apigenin could significantly promote the proliferation of NK cells in vitro and enhance the killing activity of NK cells against pancreatic cancer cells. The expressions of surface antigen NKG2D and intracellular antigen perforin and Gran B of NK cells were upregulated after treating with apigenin. Bcl-2 mRNA expression was increased, while Bax mRNA expression was decreased. Similarly, the expression of Bcl-2, p-JNK, and p-ERK protein was upregulated, and the expression of Bax protein was downregulated. The molecular mechanism of the immunopotentiation effects of apigenin may be that it up-regulates Bcl-2 and down-regulates Bax expression at the gene and protein levels to facilitate NK cell proliferation, and up-regulates the expression of perforin, Gran B, and NKG2D through the activation of JNK and ERK pathways to enhance NK cell cytotoxicity.


Subject(s)
Apigenin , Pancreatic Neoplasms , Humans , Apigenin/pharmacology , bcl-2-Associated X Protein , Cell Proliferation , NK Cell Lectin-Like Receptor Subfamily K , Pancreatic Neoplasms/drug therapy , Perforin , Proto-Oncogene Proteins c-bcl-2 , RNA, Messenger , Natural Killer T-Cells/immunology , Pancreatic Neoplasms
7.
Sci Rep ; 12(1): 18664, 2022 11 04.
Article in English | MEDLINE | ID: mdl-36333318

ABSTRACT

Mosquito transmit numbers of parasites and pathogens resulting in fatal diseases. Species identification is a prerequisite for effective mosquito control. Existing morphological and molecular classification methods have evitable disadvantages. Here we introduced Deep learning techniques for mosquito species identification. A balanced, high-definition mosquito dataset with 9900 original images covering 17 species was constructed. After three rounds of screening and adjustment-testing (first round among 3 convolutional neural networks and 3 Transformer models, second round among 3 Swin Transformer variants, and third round between 2 images sizes), we proposed the first Swin Transformer-based mosquito species identification model (Swin MSI) with 99.04% accuracy and 99.16% F1-score. By visualizing the identification process, the morphological keys used in Swin MSI were similar but not the same as those used by humans. Swin MSI realized 100% subspecies-level identification in Culex pipiens Complex and 96.26% accuracy for novel species categorization. It presents a promising approach for mosquito identification and mosquito borne diseases control.


Subject(s)
Culex , Mosquito Vectors , Animals , Humans , Neural Networks, Computer
8.
Front Plant Sci ; 13: 928634, 2022.
Article in English | MEDLINE | ID: mdl-36119612

ABSTRACT

Bemisia tabaci is the main pest of agriculture in many regions of the world. The resistance of whitefly to pesticides has increased as a consequence of the continuous irrational use of wide-spectrum pesticides. Thus, pesticides are no longer always effective as a long-term control method. The agricultural landscape can affect the occurrence of an insect population. The objective of this study was to clarify the occurrence of whitefly and its predators in tomato fields in different agricultural landscapes. Different landscapes are classified into urban, flower, water, and mountain landscapes by the principal component analysis method. In 2018-2019, whitefly had the longest main activity period and the lowest density in the flower landscape. The water landscape helped to maintain the highest densities of whitefly during the main activity period. Nine species of predators were sampled, and Nesidiocoris tenuis, Chrysoperla sinica, Menochilus sexmaculata, and Harmonia axyridis were the dominant species throughout the sampling season in both years. During the main activity period, N. tenuis had the highest density in all sampled landscapes. The density of the dominant predators was the highest in the flower landscape, and each natural predator had the largest temporal niche width in the 2-year sampling period. Bemisia tabaci, N. tenuis, and M. sexmaculata were highly synchronized temporally. The flower landscape showed satisfactory results in suppressing whitefly. Increasing the proportion of flowering plants and increasing the diversity of plant crops in the agricultural landscape can effectively reduce the densities of whitefly during an outbreak.

9.
Front Oncol ; 12: 943761, 2022.
Article in English | MEDLINE | ID: mdl-36033509

ABSTRACT

Objectives: The prognostic significance of acute lymphoblastic leukemia (ALL) patients with central nervous system leukemia (CNSL) at diagnosis is controversial. We aimed to determine the impact of CNSL at diagnosis on the clinical outcomes of childhood B-cell ALL in the South China Children's Leukemia Group (SCCLG). Methods: A total of 1,872 childhood patients were recruited for the study between October 2016 and July 2021. The diagnosis of CNSL depends on primary cytological examination of cerebrospinal fluid, clinical manifestations, and imaging manifestations. Patients with CNSL at diagnosis received two additional courses of intrathecal triple injections during induction. Results: The frequency of CNLS at the diagnosis of B-cell ALL was 3.6%. Patients with CNSL at diagnosis had a significantly higher mean presenting leukocyte count (P = 0.002) and poorer treatment response (P <0.05) compared with non-CNSL patients. Moreover, CNSL status was associated with worse 3-year event-free survival (P = 0.030) and a higher risk of 3-year cumulative incidence of relapse (P = 0.008), while no impact was observed on 3-year overall survival (P = 0.837). Multivariate analysis revealed that CNSL status at diagnosis was an independent predictor with a higher cumulative incidence of relapse (hazard ratio = 2.809, P = 0.016). Conclusion: CNSL status remains an adverse prognostic factor in childhood B-cell ALL, indicating that additional augmentation of CNS-directed therapy is warranted for patients with CNSL at diagnosis.

10.
Front Oncol ; 12: 854798, 2022.
Article in English | MEDLINE | ID: mdl-35425700

ABSTRACT

Objective: Even though childhood acute lymphoblastic leukemia (ALL) has an encouraging survival rate in recent years, some patients are still at risk of relapse or even death. Therefore, we aimed to construct a nomogram to predict event-free survival (EFS) in patients with ALL. Method: Children with newly diagnosed ALL between October 2016 and July 2021 from 18 hospitals participating in the South China children's leukemia Group (SCCLG) were recruited and randomly classified into two subsets in a 7:3 ratio (training set, n=1187; validation set, n=506). Least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were adopted to screen independent prognostic factors. Then, a nomogram can be build based on these prognostic factors to predict 1-, 2-, and 3-year EFS. Concordance index (C-index), area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance and clinical utility of nomogram. Result: The parameters that predicted EFS were age at diagnosis, white blood cell at diagnosis, immunophenotype, ETV6-RUNX1/TEL-AML1 gene fusion, bone marrow remission at day 15, and minimal residual disease at day 15. The nomogram incorporated the six factors and provided C-index values of 0.811 [95% confidence interval (CI) = 0.792-0.830] and 0.797 (95% CI = 0.769-0.825) in the training and validation set, respectively. The calibration curve and AUC revealed that the nomogram had good ability to predict 1-, 2-, and 3-year EFS. DCA also indicated that our nomogram had good clinical utility. Kaplan-Meier analysis showed that EFS in the different risk groups stratified by the nomogram scores was significant differentiated. Conclusion: The nomogram for predicting EFS of children with ALL has good performance and clinical utility. The model could help clinical decision-making.

11.
Pest Manag Sci ; 78(1): 329-335, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34523221

ABSTRACT

BACKGROUND: The use of chemical insecticides to control Bemisia tabaci Gennadius (Hemiptera: Aleyrodidae) is widespread, although it might exert a sublethal effect on its dominant parasitoid, Encarsia formosa Gahan (Hymenoptera: Aphelinidae). To investigate the sublethal effect of spirotetramat on E. formosa, we observed the ability of E. formosa to locate and handle the host, oviposit and preen after exposure to sublethal concentrations of spirotetramat. RESULTS: After exposure to spirotetramat at LC50 , the response time of E. formosa to the volatile reached 223.40 s and was significantly prolonged. Only 56.44% of the wasps were attracted by the volatile and the insect crawled the slowest among all of the treatments. The averages of oviposition posture adopted and host handled by each E. formosa in 1 h decreased significantly to 1.79 and 1.27, respectively. At the sublethal concentration of LC10 , 94.59% of the wasps were attracted by the volatile and the insect crawled the fastest. The average of host handled by each E. formosa was 3.92, and the frequency of drumming while walking and drumming the host was 12.34 times per second and 12.30 times per second, respectively, demonstrating a significant acceleration in these abilities. CONCLUSION: These findings demonstrate that spirotetramat induced hormesis in E. formosa on exposure to its LC10 concentration and accelerated its host locating, host handling and frequency of antennae drumming. These findings could assist in balancing the chemical and biological control of B. tabaci and enhancing the efficacy of E. formosa as a biocontrol agent. © 2021 Society of Chemical Industry.


Subject(s)
Aza Compounds , Hemiptera , Wasps , Animals , Aza Compounds/toxicity , Female , Spiro Compounds , Taiwan
12.
Front Oncol ; 11: 797194, 2021.
Article in English | MEDLINE | ID: mdl-34988026

ABSTRACT

PURPOSE: To analyzed the outcome of ETV6/RUNX1-positive pediatric acute B lymphoblastic leukemia (B-ALL) with the aim of identifying prognostic value. METHOD: A total of 2,530 pediatric patients who were diagnosed with B-ALL were classified into two groups based on the ETV6/RUNX1 status by using a retrospective cohort study method from February 28, 2008, to June 30, 2020, at 22 participating ALL centers. RESULTS: In total, 461 (18.2%) cases were ETV6/RUNX1-positive. The proportion of patients with risk factors (age <1 year or ≥10 years, WB≥50×109/L) in ETV6/RUNX1-positive group was significantly lower than that in negative group (P<0.001), while the proportion of patients with good early response (good response to prednisone, D15 MRD < 0.1%, and D33 MRD < 0.01%) in ETV6/RUNX1-positive group was higher than that in the negative group (P<0.001, 0.788 and 0.004, respectively). Multivariate analysis of 2,530 patients found that age <1 or ≥10 years, SCCLG-ALL-2016 protocol, and MLL were independent predictor of outcome but not ETV6/RUNX1. The EFS and OS of the ETV6/RUNX1-positive group were significantly higher than those of the negative group (3-year EFS: 90.11 ± 4.21% vs 82 ± 2.36%, P<0.0001, 3-year OS: 91.99 ± 3.92% vs 88.79 ± 1.87%, P=0.017). Subgroup analysis showed that chemotherapy protocol, age, prednisone response, and D15 MRD were important factors affecting the prognosis of ETV6/RUNX1-positive children. CONCLUSIONS: ETV6/RUNX1-positive pediatric ALL showed an excellent outcome but lack of independent prognostic significance in South China. However, for older patients who have the ETV6/RUNX1 fusion and slow response to therapy, to opt for more intensive treatment.

13.
Front Physiol ; 9: 1610, 2018.
Article in English | MEDLINE | ID: mdl-30483157

ABSTRACT

Halyomorpha halys is a major herbivore insect in the fruit orchards of China that has become a devastating invasive pest in North America and Europe since its accidental introductions in the 1990s and 2000s, respectively. Like other hemipteran insects, H. halys releases defensive chemicals against natural enemies, including (E)-2-decenal, which is an aldehyde associated with alarm pheromones. In this study, a series of electrophysiological and behavioral tests were conducted to characterize the alarm functions of (E)-2-decenal among H. halys adults and nymphs. An antennal transcriptome was obtained from a Chinese H. halys population, and 44 odorant-binding protein (OBP) genes were annotated. Among them, five putative alarm pheromone-binding proteins were screened and were extremely consistent with their homologs from US populations. These five OBPs were later expressed in a heterologous expression system, harvested, and then challenged with (E)-2-decenal in a binding assay. All five OBPs showed high binding activities to (E)-2-decenal, which demonstrated its behavioral significance as a defensive component in H. halys, as well as being the first report of its olfactory reception. These findings will help develop behavioral-mediating tools as part of integrated pest management approaches to control this invasive pest.

14.
Biochem Biophys Res Commun ; 505(2): 578-585, 2018 10 28.
Article in English | MEDLINE | ID: mdl-30274775

ABSTRACT

Long noncoding RNA (OGFRP1) has been reported to be involved in the progression of non-small cell lung cancer (NSCLC). However, the expression pattern, functions and molecular mechanisms of OGFRP1 in NSCLC remains unclear. In the present study, we found that OGFRP1 expression was significantly up-regulated in both NSCLC tissues and cell lines, and the upregulation of OGFRP1 expression is a powerful predictor of advanced clinical stage, lymph nodes metastasis and poor prognosis for NSCLC patients. Loss-of-function assay indicated that knockdown of OGFRP1 inhibited proliferation, migration and invasion, and induced apoptosis in vitro. Mechanistically, OGFRP1 could directly bind to miR-124-3p and effectively act as a competing endogenous RNA (ceRNA) for miR-124-3p to promote the expression of the target gene LYPD3. Taken together, OGFRP1 contributed to progression of NSCLC at least partly through upregulating LYPD3 expression by sponging miR-124-3p, indicating that OGFRP1 may be a novel prognostic biomarker and therapeutic target in NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Cell Adhesion Molecules/genetics , Gene Expression Regulation, Neoplastic , Lung Neoplasms/genetics , RNA, Long Noncoding/metabolism , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Cell Adhesion Molecules/metabolism , Cell Line, Tumor , Disease Progression , GPI-Linked Proteins/genetics , GPI-Linked Proteins/metabolism , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/mortality , Lung Neoplasms/pathology , MicroRNAs/metabolism , Prognosis
15.
Am J Hematol ; 93(12): 1467-1473, 2018 12.
Article in English | MEDLINE | ID: mdl-30160789

ABSTRACT

Intravenous arsenic trioxide (ATO) has been adopted as the first-line treatment for acute promyelocytic leukemia (APL). Another arsenic compound named the Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine containing As4 S4 , has been shown to be highly effective in treating adult APL. In the treatment of pediatric APL, the safety and efficacy of RIF remains to be confirmed. This randomized, multicenter, and noninferiority trial was conducted to determine whether intravenous ATO can be substituted by oral RIF in the treatment of pediatric APL. From September 2011 to January 2017, among 92 patients who were 16 years old or younger with newly diagnosed PML-RARa positive APL, 82 met eligible criteria and were randomly assigned to ATO (n = 42) or RIF (n = 40) group. The remaining 10 patients did not fulfilled eligible criteria because five did not accept randomization, four died and one had hemiplegia prior to arsenic randomization due to intracranial hemorrhage or cerebral thrombosis. Induction and consolidation treatment contained ATO or RIF, all-trans-retinoic acid and low intensity chemotherapy. End points included event-free survival (EFS), adverse events and hospital days. After a median 3-year follow-up, the estimated 5-year EFS was 100% in both groups, and adverse events were mild. However, patients in the RIF group had significantly less hospital stay than those in the ATO group. This interim analysis shows that oral RIF is as effective and safe as intravenous ATO for the treatment of pediatric APL, with the advantage of reducing hospital stay. Final trial analysis will reveal mature outcome data.


Subject(s)
Arsenic Trioxide/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Leukemia, Promyelocytic, Acute/drug therapy , Adolescent , Arsenic Trioxide/administration & dosage , Arsenic Trioxide/adverse effects , Child , Child, Preschool , Disease-Free Survival , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/adverse effects , Humans , Infant , Length of Stay , Male , Treatment Outcome , Tretinoin/therapeutic use
16.
Front Immunol ; 9: 1297, 2018.
Article in English | MEDLINE | ID: mdl-29963044

ABSTRACT

Activation of the DNA-dependent innate immune pathway plays a pivotal role in the host defense against poxvirus. Cyclic GMP-AMP synthase (cGAS) is a key cytosolic DNA sensor that produces the cyclic dinucleotide cGMP-AMP (cGAMP) upon activation, which triggers stimulator of interferon genes (STING), leading to type I Interferons (IFNs) production and an antiviral response. Ectromelia virus (ECTV) has emerged as a valuable model for investigating the host-Orthopoxvirus relationship. However, the role of cGas-Sting pathway in response to ECTV is not clearly understood. Here, we showed that murine cells (L929 and RAW264.7) mount type I IFN responses to ECTV that are dependent upon cGas, Sting, TANK binding kinase 1 (Tbk1), and interferon regulatory factor 3 (Irf3) signaling. Disruption of cGas or Sting expression in mouse macrophages blocked the type I IFN production and facilitated ECTV replication. Consistently, mice deficient in cGas or Sting exhibited lower type I IFN levels and higher viral loads, and are more susceptible to mousepox. Collectively, our study indicates that the cGas-Sting pathway is critical for sensing of ECTV infection, inducing the type I IFN production, and controlling ECTV replication.


Subject(s)
Ectromelia virus/immunology , Ectromelia, Infectious/immunology , Ectromelia, Infectious/metabolism , Immunity, Innate , Membrane Proteins/metabolism , Nucleotidyltransferases/metabolism , Signal Transduction , Animals , Chlorocebus aethiops , Ectromelia, Infectious/virology , Host-Pathogen Interactions , Humans , Interferon Regulatory Factor-3/metabolism , Interferon Type I/biosynthesis , Macrophages/immunology , Macrophages/metabolism , Mice , Mice, Knockout , Mice, Transgenic , NIH 3T3 Cells , Phosphorylation , Protein Serine-Threonine Kinases/metabolism , RAW 264.7 Cells , Vero Cells , Virus Replication
17.
J Econ Entomol ; 111(3): 1433-1438, 2018 05 28.
Article in English | MEDLINE | ID: mdl-29566182

ABSTRACT

Mayetiola destructor (Say) (Diptera: Cecidomyiidae) is a destructive pest of wheat and is mainly controlled by deploying resistant cultivars. Unfortunately, wheat resistance to Hessian fly is often lost when temperatures rise to a certain level. This study analyzed temperature sensitivity of 20 wheat cultivars that contain different resistance (R) genes. The lowest temperatures at which the percentage of resistant plants fell below 50% in an assay were 18°C for 'D6647 H17' (921680D1-7) (containing the R gene H17), 20°C for 'Redland' (H18), 22°C for '84702B14-1-3-4-3' (H19), 24°C for 'Carol' (H3) and 'Sincape90' (H29), 26°C for 'Erin' (H5), 'Jori 13' (H20), and 'PI59190' (H28), 28°C for 'Joy' (H10), 'KS99WGRC42' (Hdic), 'Karen' (H11), 'Caldwell' (H6), and 'Seneca' (H7H8), 30°C for 'KS85WGRC01' (H22) and 'KS92WGRC20' (H25), 32°C for 'Molly' (H13), and 34°C for 'Iris' (H9). The three cultivars 'H32 Synthetic' (H32), '81602C5-3-3-8-1' (H15), and 'KS93WGRC26' (H26) exhibited the most resistance to temperature increases. The percentages of resistant plants remained above 50% at 36°C for these three cultivars, the highest temperature that can be tested without significantly damaging wheat plant growth. The temperature sensitivity of R gene-mediated fly resistance is also strongly affected by genetic background of wheat cultivars that contain a specific R gene. Our data should provide useful information for breeding wheat resistance to control Hessian fly damage in different regions based on historic temperature data.


Subject(s)
Antibiosis/genetics , Diptera/physiology , Food Chain , Hot Temperature , Triticum/genetics , Animals , Diptera/growth & development , Larva/growth & development , Larva/physiology , Triticum/physiology
18.
Mol Med Rep ; 16(1): 75-86, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28534993

ABSTRACT

The T cell receptor (TCR) is a complex heterodimer that recognizes fragments of antigens as peptides and binds to major histocompatibility complex molecules. The TCR α and ß chains possess three hypervariable regions termed complementarity determining regions (CDR1, 2 and 3). CDR3 is responsible for recognizing processed antigen peptides. Immunoscope spectratyping is a simple technique for analyzing CDR3 polymorphisms and sequence length diversity, in order to investigate T cell function and the pattern of TCR utilization. The present study employed this technique to analyze CDR3 polymorphisms and the sequence length diversity of TCR α and ß chains in porcine CD4+ and CD8+ T cells. Polymerase chain reaction products of 19 TCR α variable regions (AV) and 20 TCR ß variable regions (BV) gene families obtained from the CD4+ and CD8+ T cells revealed a clear band following separation by 1.5% agarose gel electrophoresis, and each family exhibited >8 bands following separation by 6% sequencing gel electrophoresis. CDR3 spectratyping of all identified TCR AV and BV gene families in the sorted CD4+ and CD8+ T cells by GeneScan, demonstrated a standard Gaussian distribution with >8 peaks. CDR3 in CD4+ and CD8+ T cells demonstrated different expression patterns. The majority of CDR3 recombined in frame and the results revealed that there were 10 and 14 amino acid discrepancies between the longest and shortest CDR3 lengths in specific TCR AV and TCR BV gene families, respectively. The results demonstrated that CDR3 polymorphism and length diversity demonstrated different expression and utilization patterns in CD4+ and CD8+ T cells. These results may facilitate future research investigating the porcine TCR CDR3 gene repertoire as well as the functional complexity and specificity of the TCR molecule.


Subject(s)
CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , Complementarity Determining Regions/genetics , Genetic Variation , Receptors, Antigen, T-Cell, alpha-beta/genetics , Animals , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Female , Gene Expression , Gene Frequency , Multigene Family , Sequence Analysis, DNA , Swine
19.
Biomed Res Int ; 2017: 6456180, 2017.
Article in English | MEDLINE | ID: mdl-29430463

ABSTRACT

Ectromelia virus (ECTV), the causative agent of mousepox, has emerged as a valuable model for investigating the host-Orthopoxvirus relationship as it relates to pathogenesis and the immune response. ECTV is a mouse-specific virus and causes high mortality in susceptible mice strains, including BALB/c and C3H, whereas C57BL/6 and 129 strains are resistant to the disease. To understand the host genetic factors in different mouse strains during the ECTV infection, we carried out a microarray analysis of spleen tissues derived from BALB/c and C57BL/6 mice, respectively, at 3 and 10 days after ECTV infection. Differential Expression of Genes (DEGs) analyses revealed distinct differences in the gene profiles of susceptible and resistant mice. The susceptible BALB/c mice generated more DEGs than the resistant C57BL/6 mice. Additionally, gene ontology and KEGG pathway analysis showed the DEGs of susceptible mice were involved in innate immunity, apoptosis, metabolism, and cancer-related pathways, while the DEGs of resistant mice were largely involved in MAPK signaling and leukocyte transendothelial migration. Furthermore, the BALB/c mice showed a strong induction of interferon-induced genes, which, however, were weaker in the C57BL/6 mice. Collectively, the differential transcriptome profiles of susceptible and resistant mouse strains with ECTV infection will be crucial for further uncovering the molecular mechanisms of the host-Orthopoxvirus interaction.


Subject(s)
Disease Resistance/genetics , Ectromelia, Infectious/genetics , Host-Parasite Interactions/genetics , Transcriptome/genetics , Animals , Disease Susceptibility/virology , Ectromelia virus/pathogenicity , Ectromelia, Infectious/pathology , Ectromelia, Infectious/virology , Gene Expression Regulation , Immunity, Innate/genetics , Interferons/genetics , Mice , Spleen/metabolism , Spleen/virology
20.
Inorg Chem ; 55(22): 11979-11986, 2016 Nov 21.
Article in English | MEDLINE | ID: mdl-27934312

ABSTRACT

Low (α)- and high-temperature (ß) forms of BiTaO4 have attracted much attention due to their dielectric and photocatalytic properties. In the present work, a third form, the so-called HP-BiTaO4, was synthesized at high temperature and pressure. The phase evolution, phase transformations, and dielectric properties of α- and ß-BiTaO4 and HP-BiTaO4 ceramics are studied in detail. ß-BiTaO4 ceramics densified at 1300 °C with the microwave permittivity εr ≈ 53, the microwave quality factor Qf ≈ 12070 GHz, and the temperature coefficient of resonant frequency τf ≈ -200 ppm/°C. HP-BiTaO4 ceramics were synthesized at 5 GPa and 1300 °C followed by annealing at 600 °C. In contrast with the α phase, HP-BiTaO4 exhibited εr ≈ 195 at 1 kHz to 10 MHz, accompanied by a low dielectric loss of ∼0.004. The relation between structure and dielectric properties is discussed in the context of Shannon's additive rule and bond theory.

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