ABSTRACT
This study aimed to examine the effect of venetoclax coupled with azacytidine in treating older adults with relapsed and refractory (R/R) acute myeloid leukemia (AML). The clinical data of 10 senior patients with AML over 65 years old who were treated with venetoclax and azacytidine, including six patients with R/R AML, were retrospectively evaluated. This study comprised seven males and three females with a median age of 71 years. Five patients had at least one relapse, and one patient did not achieve remission after four cycles of azacytidine monotherapy, considering it resistant. AML with myelodysplasia-related changes was found in four cases. One of the 10 patients died early after 1-13 cycles of venetoclax plus azacytidine treatment due to a protracted period of neutropenia and severe lung infection induced by medications. Six of the remaining nine patients, including six R/R patients, achieved a complete remission (CR) or a CR with incomplete hematologic recovery (CRi). After two cycles of therapy, one patient did not react. Neutropenia lasted an average of 10.5 (6-15) days in all patients, with the most severe cases occurring in the second and third weeks of therapy. Three patients who tested positive for the TP53 gene mutation had the following outcomes: One relapsed patient has been in progression-free remission (PFS) for the past 24 months, whereas another has been in full remission but relapsed 2 months later. Another patient experienced complete remission in myelology for 4 months, but the variable allele fraction (VAF) value steadily rose, suggesting that the illness was on the verge of progressing. IDH2 gene alterations were found in three of four patients who obtained maintained CR for more than 18 months following recurrence. Venetoclax in combination with azacytidine is a successful and well-tolerated therapy for R/R AML in the elderly. Venetoclax and azacytidine may help patients with TP53 mutations and reduce VAF. The IDH2 mutation might be a good predictor of veneclax sensitivity. A notable adverse response in the treatment phase of the regimen is severe infection induced by neutropenia.
Subject(s)
Leukemia, Myeloid, Acute , Neutropenia , Male , Female , Humans , Aged , Azacitidine/adverse effects , Retrospective Studies , Leukemia, Myeloid, Acute/drug therapy , Bridged Bicyclo Compounds, Heterocyclic , Neutropenia/chemically induced , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
Two oleanane-type triterpenoid saponins named pedunsaponin D (1) and pedunsaponin E (2) were isolated from the roots of Pueraria peduncularis. The structures of the new compounds were elucidated based on chemical and physicochemical evidence as follows: pedunsaponin D, 3-O-ß-glucopyranosyl-(1-3)-ß-glucuronopyranosyl-3ß,15α,23α-trihydroxy-11,13(18)-oleanadien-16-one (1); pedunsaponin E, 3-O-ß-glucopyranosyl-(1-2)-ß-glucopy ranosyl(1-2)[ß-glucopyranosyl(1-3)-ß-glucuronopyranosyl]-3ß-hydroxy-16-oxoolean-12-en-30-oic acid (2). The two compounds showed moderate molluscicidal activity.[Formula: see text].
Subject(s)
Pueraria , Saponins , Triterpenes , Molecular Structure , Plant RootsABSTRACT
Ionotropic γ-aminobutyric acid (GABA) receptors (GABARs) mediate rapid inhibitory neurotransmission in both vertebrates and invertebrates, and are important molecular targets of insecticides. However, components of insect GABARs remain elusive. In addition to CsRDL1 and CsRDL2, the complementary DNAs (cDNAs) of another two GABA receptor-like subunits, CsLCCH3 and Cs8916, were identified from the rice striped stem borer, Chilo suppressalis Walker in the present study. Both CsLCCH3 and Cs8916 subunits shared common structural features, such as a highly-conserved Cys-loop structure, six distinct regions involved in ligand binding (loops A-F), and four transmembrane domains (TM 1-4). Transcript analysis demonstrated that the relative mRNA expression levels of both CsLCCH3 and Cs8916 subunits were the highest in the ventral nerve cord. Regarding developmental stage, transcript levels of both subunits were highest in eggs. Injections of double-stranded RNAs (dsRNAs), including dsRDL1, dsRDL2, dsLCCH3, or ds8916, significantly reduced mRNA abundance after 24 and 48â¯h. However, no observable effects on the development of C. suppressalis were observed. Injection of dsRDL1 or dsRDL2 did significantly reduce the mortality of C. suppressalis treated with fluralaner. Our results indicated that CsRDLs mediated the susceptibility of C. suppressalis to fluralaner, whereas CsLCCH3 and CsL8916 did not. The current investigation enhances our knowledge of Lepidopteran GABARs and offers a molecular basis for the development of novel insecticides to control C. suppressalis.
Subject(s)
Lepidoptera/metabolism , Receptors, GABA/metabolism , Animals , DNA, Complementary/metabolism , Moths , RNA, Messenger/metabolismABSTRACT
Botrytis cinerea (anamorph of Botryotinia fuckeliana) causes gray mold on numerous plants, including kiwifruit. The primary aim of this study was to investigate the phenotypic and genetic characteristics of the Botrytis cinerea population from kiwifruit in Sichuan Province, China. In all, 176 isolates were collected from kiwifruit orchards from eight geographic regions in Sichuan. All isolates were identified as B. cinerea sensu stricto based on the combined datasets, including morphological criteria, determination of the Bc-hch allele, and phylogenetic analysis of the genes RPB2, G3PDH, and HSP60. Three colony types (i.e., sclerotial, mycelial, and conidial) were observed on potato dextrose agar after 2 weeks, with sclerotial isolates, the predominant category, accounting for 40.91%. No obvious differences in microscopic characteristics were observed among the three types. Three genotypes of transposable elements were identified in the B. cinerea population: boty, flipper, and transposa types. The most prevalent genotype from different geographic populations of B. cinerea was transposa; in contrast, the flipper genotype accounted for only 3.98% of the total population, whereas the vacuma genotype was absent. According to MAT locus amplification, 87 and 89 isolates are MAT1-1 and MAT1-2 type, respectively, and the two mating types were found to be balanced overall in the population. Forty-eight representative isolates were all able to cause gray mold to some extent, and disease severities were significantly different between the cultivars Hongyang and Hort16A (P < 0.01). Disease severity was significantly greater on young leaves than on mature leaves (P < 0.01). No significant relationship was found between pathogenicity and geographical region, colony type, or transposon distribution. The results obtained in the present study suggest a relatively uniform species diversity of Botrytis but rich phenotypic and genetic differentiation within the B. cinerea population on kiwifruit in China. Utilizing resistant cultivars and rain-shelter cultivation instead of fungicides may be an effective approach to delaying pathogen variability.
Subject(s)
Actinidia , Botrytis , Actinidia/microbiology , Botrytis/classification , Botrytis/genetics , China , Phylogeny , Plant Diseases/microbiologyABSTRACT
OBJECTIVE: To explore the chemical constituents of Salix microstachya var. bordensis and their antioxidant activities. METHODS: Column chromatography was used for separation, NMR, UV and MS spectroscopic methods were used for structure identification. Using Vc and BHT as positive controls, free radical scavenging ability of eight components from Salix microstachya var. bordensis was determined by DPPH · method and IC50 of each compound was calculated. RESULTS: Eight compounds were isolated and identified as kaempferol (1), quercetin-3-o-ß-D-glucoside (2), rhamnetin (3), kaemferol-4'-methylether (4), ferulic acid methyl ester (5), myricarin A (6), kaempferol-7,4'-dimethylether (7) and quercetin (8). Scavenging ability of eight compounds had dose-effect relationship with concentration in a certain concentration range; Scavenging ability on DPPH · radical of myricarin A, kaempferol, quercetin and quercetin-3-O-ß-D-glucoside were equal, lower to Vc, but slightly stronger than BHT. Others were lower than BHT, and ferulic acid methyl ester was the lowest deriving from the IC50. CONCLUSION: Compounds 1-8 are all isolated from Salix microstachya var. bordensis for the first time. Myricarin A, kaempferol, quercetin and quercetin-3-O-ß-D-glucoside, having strong antioxidant activities, can be used as effective natural free radical scavenger and have great prospects for development and utilization.
Subject(s)
Free Radical Scavengers/chemistry , Phytochemicals/chemistry , Salix/chemistry , Free Radical Scavengers/isolation & purification , Glucosides/chemistry , Glucosides/isolation & purification , Phytochemicals/isolation & purificationABSTRACT
OBJECTIVE: To study whether electroacupuncture (EA) of "Zusanli" (ST36) combined with "Tianshu" (ST25) has a synergistic effect in regulating the colonic function and autonomic nerve balance in rats with irritable bowel syndrome (IBS). METHODS: Male Wistar rats were randomly divided into control, model, EA-ST36, and EA-ST36+ST25 groups, with 14 rats in each group. The IBS model was established by using water avoidance stress method. The visceral hypersensitivity was measured using the abdominal wall retraction reflex (AWR). The rectus abdominis electromyogram (EMG), intestinal electrical activity, and electrocardiogram (ECG) were recorded using a PowerLab data acquisition and analysis system. The contents of serum cAMP and cGMP were determined by ELISA, the expression levels of colonic tyrosine hydroxylase (TH) and choline acetyl-transferase (ChAT) proteins were determined by immunofluorescence staining and Western blot, respectively. RESULTS: Compared with the control group, the model group had an evident increase in the levels of AWR, LF, LF/HF, ChAT protein expression, cAMP and cGMP contents and cAMP/cGMP ratio (P<0.001, P<0.05), and a marked decrease in the levels of HF, frequency of slow waves of intestinal EMG, visceral pain threshold (PT), immunoactivity and expression of TH protein (P<0.05, P<0.001). In contrast to the model group, the levels of AWR, LF, LF/HF, ChAT protein expression and immunoactivity, cAMP and cGMP contents and ratio of cAMP/cGMP were significantly reduced (P<0.001, P<0.05, P<0.01), whereas the levels of frequency of slow waves of intestinal EMG, PT, and the immunoactivity and expression of TH were considerably increased (P<0.001, P<0.05) in both EA-ST36 and EA-ST36+ST25 groups. CONCLUSION: EA of both ST36 and ST36+ST25 can relieve visceral pain, and reduce sympathetic activity to improve autonomic nerve balance, but without apparent synergistic effect between EA-ST36 and EA-ST25 in rats with IBS.
Subject(s)
Electroacupuncture , Irritable Bowel Syndrome , Male , Rats , Animals , Rats, Wistar , Defecation , Autonomic Pathways , Cyclic GMPABSTRACT
OBJECTIVE: To study the chemical constituents of Buddleja davidii. METHODS: The constituents were isolated and purified by silica gel column chromatography, polyamide column chromatography and macroporous adsorption resin and their structures were identified by spectroscopic analysis. RESULTS: Eight compounds were elucidated as : Cranioside A (1), Eutigoside A (2), 1-O-4-Dimethoxyphenylethyl-4-O-3,4-dimethoxyphenylethy-beta-D-glucopyranoside (3), Isomartynoside (4'), 4"-O-Acetylmartynoside (5), Stigmasterol glueoside (6), beta-Sitosterol (7), Daucosterol (8). CONCLUSION: All these compounds are obtained from this plant for the first time.
Subject(s)
Buddleja/chemistry , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Coumarins/chemistry , Coumarins/isolation & purification , Glucosides/chemistry , Glucosides/isolation & purification , Magnetic Resonance Spectroscopy , Plant Components, Aerial/chemistry , Sitosterols/chemistry , Sitosterols/isolation & purification , SolventsABSTRACT
The ecology of soil fungi is poorly understood, and recent comprehensive reports on Trichoderma are unavailable for any region, including the Zoige alpine wetland ecological region in China. One hundred soil samples were collected from different soil types and soil layers in Zoige alpine wetland ecological regions. Using the traditional suspension plating method, 80 Trichoderma strains were chosen to analyze species diversity. After a preliminary classification of morphological characteristics and the genes glyceraldehyde-3-phosphate dehydrogenase (gpd), 57 representative strains were selected and eventually identified as seven species via phylogenetic analyses of multilocus sequences based on the genes transcription elongation factor 1 alpha (tef1), encoding RNA polymerase II subunit B (rpb2) and ATP citrate lyase (acl1). Among them, T. harzianum was the dominant species isolated from five soil layers and four soil types, and had the highest isolation frequency (23%) in this zone, while T. polysporum and T. pyramidale were rare species, with isolation frequencies of less than 1%. Our detailed morphological observation and molecular phylogenetic analyses support the recognition of Trichoderma zoigense was described for the first time as a new species, while T. atrobrunneum as a new record for China was found. Our results will be used as a reference for a greater understanding of soil microbial resources, ecological rehabilitation and reconstructions in the Zoige alpine wetland.
Subject(s)
Trichoderma , Wetlands , Soil , Phylogeny , Soil Microbiology , ChinaABSTRACT
BACKGROUND: Verrucous epidermal nevus (VEN) are keratinocytic epidermal nevus that appear at birth or in early childhood. They exhibit a range of manifestations, depending on the patient's age. VEN are rarely encountered in clinical practice, and the systemic and comprehensive clinical characteristics of VEN have not been well investigated. Furthermore, the association between tandem mass tag (TMT)-based quantitative proteomics and the VEN phenotype is still unclear. OBJECTIVES: This study investigated the differences in the clinical characteristics and lesion proteomics between inflammatory linear VEN (ILVEN) and local VEN. METHODS: This retrospective study enrolled 125 patients with histopathologically diagnosed VEN who presented to our hospital between 2019 and 2021. We collected the clinical data of all patients with VEN using a self-designed questionnaire. The expression of proteins in VEN lesions was analyzed using TMT proteomics technology. RESULTS: In total, there were 125 patients with VEN that were evaluated, including 67 (53.60%) patients with local VEN and 58 (46.40%) with ILVEN. No significant differences were found in sex, onset age, and lesion location between patients with local VEN and those with ILVEN (all P > 0.05). Significant differences were found in the onset site and pruritus scores between patients with ILVEN and those with local VEN (all P < 0.05). According to the TMT proteomics results, 89 proteins were up or downregulated with at least 1.3-fold (upregulated: 38, downregulated: 51; P < 0.05) in ILVEN lesions relative to VEN lesions. The top 10 differentially expressed proteins between ILVEN and local VEN lesions were OGN, NT5C3A, ADD1, OLFML1, DHRS1, CALML5, SAMHD1, SFRP2, SPRR1B, and SERPINB13. The upregulated proteins are mainly involved in neutrophil activation, neutrophil-mediated immunity, and p53 signaling pathway (hsa04115). The downregulated proteins are mainly involved in cellular response to cytokine stimulus, cell adhesion, Th1 and Th2 cell differentiation. In total, based on the differentially expressed proteins between ILVEN and local VEN, five pathways that may be associated with the pathogenesis of inflammation, including CAMs (P = 0.006), Th1 and Th2 cell differentiation (P = 0.017), PPAR signaling pathway (P = 0.023), Th17 cell differentiation (P = 0.024), and p53 signaling pathway (P = 0.041). CONCLUSIONS: Clinical data of the patients revealed that ILVEN lesions presented with intense pruritus and inflammatory change. Differentially expressed proteins between ILVEN and local VEN are mainly involved in multiple inflammation related pathways associated with the pathogenesis mechanisms of pruritus. LIMITATIONS: The small sample size in clinical characteristic and proteomics study is one of the most significant limitations in our study. The inflammation associated proteins and signal pathways in the pathogenesis of pruritus in ILVEN is not explored. SIGNIFICANCE: In this study, we found the lesions of ILVEN patients presented with intense pruritus and inflammational change. A total of 89 proteins were up or downregulated with at least 1.3-fold (upregulated: 38, downregulated: 51; P < 0.05) in ILVEN lesions relative to VEN lesions. On the other hand, the etiology of itch in ILVEN mainly associated with inflammation, but the exact mechanisms was still unclear. We found the differentially expressed proteins between ILVEN and local VEN enriched five pathways that may be associated with the pathogenesis of inflammation and pruritus.
Subject(s)
Nevus, Sebaceous of Jadassohn , Skin Neoplasms , Child, Preschool , Humans , Inflammation , Nevus, Sebaceous of Jadassohn/complications , Oxidoreductases , Proteomics , Pruritus/etiology , Retrospective Studies , Skin Neoplasms/complications , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Tumor Suppressor Protein p53ABSTRACT
BACKGROUND: Two-spotted spider mite (TSSM), Tetranychus urticae Koch, is one of the most serious pests of agricultural crops. Broflanilide exhibits high lethality against various pests and has been marketed worldwide under the Vedira and Tenebenal brands in 2020. Nevertheless, little information has been reported about its effects on agricultural mites. RESULTS: Broflanilide displayed higher toxicity to TSSM eggs (24 h LC50 , 1.015 mg L-1 ) and adult females (24 h LC50 , 2.062 mg L-1 ) than commercial acaricides, including cyflumetofen, bifenazate, and profenofos. In contrast, the adverse effects of broflanilide on the predatory mite, Typhlodromips swirskii Athias-Henriot, was lower than those of fenpyroximate and abamectin. In the sublethal effect study, while adult females were treated with broflanilide, the number of eggs and longevity were reduced in LC10 and LC30 treatments; when eggs were treated with broflanilide, the egg duration and deutonymph duration were prolonged in LC30 treatment. A significant decrease in the total life span and duration and fecundity of adult females was observed in LC10 and LC30 treatments. Furthermore, the number of eggs per adult female was significantly reduced from 103.48 ± 3.69 in the control group to 69.42 ± 2.22 and 48.33 ± 1.75 in LC10 and LC30 treatments, respectively. In the greenhouse bioassay, broflanilide 5% suspension concentrate (MCI-8007) showed excellent acaricidal activity to TSSM, with 99.22% corrected control, compared with the MCI-8007 untreated group. CONCLUSION: Our results indicated that broflanilide has a high acaricidal activity to TSSM and significant inhibition to fecundity of adult female, and could be considered as a potential alternative for TSSM management. © 2021 Society of Chemical Industry.
Subject(s)
Acaricides , Mites , Tetranychidae , Acaricides/pharmacology , Animals , Benzamides , Female , Predatory BehaviorABSTRACT
The cytoskeleton undergoes dramatic reorganization during plant defence. This response is generally interpreted as part of the cellular repolarization establishing physical barriers against the invading pathogen. To gain insight into the functional significance of cytoskeletal responses for defence, two Vitis cell cultures that differ in their microtubular dynamics were used, and the cytoskeletal response to the elicitor Harpin in parallel to alkalinization of the medium as a fast response, and the activation of defence-related genes were followed. In one cell line derived from the grapevine cultivar 'Pinot Noir', microtubules contained mostly tyrosinylated alpha-tubulin, indicating high microtubular turnover, whereas in another cell line derived from the wild grapevine V. rupestris, the alpha-tubulin was strongly detyrosinated, indicating low microtubular turnover. The cortical microtubules were disrupted and actin filaments were bundled in both cell lines, but the responses were elevated in V. rupestris as compared with V. vinifera cv. 'Pinot Noir'. The cytoskeletal responsiveness correlated with elicitor-induced alkalinization and the expression of defence genes. Using resveratrol synthase and stilbene synthase as examples, it could be shown that pharmacological manipulation of microtubules could induce gene expression in the absence of elicitor. These findings are discussed with respect to a role for microtubules as positive regulators of defence-induced gene expression.
Subject(s)
Bacterial Outer Membrane Proteins/pharmacology , Cytoskeleton/ultrastructure , Vitis/genetics , Vitis/ultrastructure , Acyltransferases/genetics , Cytoskeleton/drug effects , Gene Expression/drug effects , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Plant , Microtubules/drug effects , Microtubules/ultrastructure , Tubulin/metabolism , Vitis/metabolismABSTRACT
INTRODUCTION: Many studies have explored the imaging characteristics of patients with neurosyphilis, but no systematic study has been made on the neuroimaging changes after anti-syphilitic treatment. The purpose of this study was to examine neuroimaging differences before and after treatment, comparing patients with asymptomatic and symptomatic neurosyphilis. METHODS: A total of 102 patients with neurosyphilis, including 60 cases of symptomatic neurosyphilis and 42 cases of asymptomatic neurosyphilis, were identified between December 2012 and June 2019. Their demographics, medical histories, serological tests of peripheral blood and cerebrospinal fluid, and especially neuroimaging features before and after anti-syphilitic treatment were collected and analyzed. RESULTS: The patients presented with variable clinical and neuroimaging features, including cerebral infarction or hemorrhage, atrophy, demyelination, arteritis, encephalitis, and hippocampal sclerosis. A total of 29 neuroradiological re-examinations were performed in 19 patients treated with anti-syphilitic medicine. The results indicated that some patients still presented neuroradiological progression after treatment, including 42.1% showing infarction lesions, 47.4% mild to severe brain atrophy, and 15.8% white matter demyelination. CONCLUSION: The clinical and neuroimaging features of neurosyphilis patients are diverse, and their follow-up neuroimaging continued to show progression even with standardized treatment.
ABSTRACT
Seasonal weather systems that establish prevailing winds and seasonal rainfall on a large scale largely determine insect migration patterns, especially for micro-insects with completely windborne migration. Recent studies indicated that the summer migration of the brown planthopper (BPH, Nilaparvata lugens) in eastern China is related to the strength and position of the Western Pacific Subtropical High-Pressure (WPSH) system and its associated wind and rainfall patterns. Compared with the BPH, the white-backed planthopper (WBPH, Sogatella furcifera) has a similar diet, analogous body size, and strong long-distance migration ability. Thus, the migration pattern for the WBPH can be speculated to be similar to that of the BPH. However, the migration pattern of the WBPH and how this pattern relates to climatic conditions have scarcely been described. Based on almost three decades of data (1977-2003), it was suggested that the WBPH in southern China (south of approximately 27° N) migrates into the middle and lower reaches of the Yangtze River after the abrupt movements of the WPSH in mid-June, similar to the BPH. By contrast, the emigration of the WBPH in southern China begins in late May. Further analysis indicated that the migration of the WBPH in late May and early June was short or unsuccessful due to heavy precipitation during the preflood season in southern China from late May to middle June. The results herein demonstrate the differences in migration patterns between two rice planthoppers in the eastern Asia migration arena. We also provide new information that could assist with forecasting outbreaks and implementing control measures against these migratory pests.
ABSTRACT
OBJECTIVE: To analyze the mutation of TSC gene in two sporadic patients with tuberous sclerosis complex (TSC). METHODS: All the coding exons of TSC1 and TSC2 genes of these two patients, unaffected member in the two families, and 100 unrelated population-matched controls were amplified by polymerase chain reaction. The products were analyzed by direct sequencing. RESULT: Two TSC2 gene mutations (c. 268C > T, c. 5 227C > T) were identified in two patients, but not in their family members and in 100 unrelated population-matched controls. CONCLUSION: These two mutations are the cause of the clinical phenotypes of these two sporadic patients with TSC.
Subject(s)
Tuberous Sclerosis/genetics , Tumor Suppressor Proteins/genetics , Genetic Association Studies , Humans , Mutation , Tuberous Sclerosis Complex 1 Protein , Tuberous Sclerosis Complex 2 ProteinABSTRACT
Continuous rain and an abnormally wet climate during harvest can easily lead to soybean plants being damaged by field mold (FM), which can reduce seed yield and quality. However, to date, the underlying pathogen and its resistance mechanism have remained unclear. The objective of the present study was to investigate the fungal diversity of various soybean varieties and to identify and confirm the FM pathogenic fungi. A total of 62,382 fungal ITS1 sequences clustered into 164 operational taxonomic units (OTUs) with 97% sequence similarity; 69 taxa were recovered from the samples by internal transcribed spacer (ITS) region sequencing. The fungal community compositions differed among the tested soybeans, with 42 OTUs being amplified from all varieties. The quadratic relationships between fungal diversity and organ-specific mildew indexes were analyzed, confirming that mildew on soybean pods can mitigate FM damage to the seeds. In addition, four potentially pathogenic fungi were isolated from FM-damaged soybean fruits; morphological and molecular identification confirmed these fungi as Aspergillus flavus, A. niger, Fusarium moniliforme, and Penicillium chrysogenum. Further re-inoculation experiments demonstrated that F. moniliforme is dominant among these FM pathogenic fungi. These results lay the foundation for future studies on mitigating or preventing FM damage to soybean.