ABSTRACT
Pyridazine, as a privileged scaffold, has been extensively utilized in drug development due to its multiple biological activities. Especially around its distinctive anticancer property, a massive number of pyridazine-containing compounds have been synthesized and evaluated that target a diverse array of biological processes involved in cancer onset and progression. These include glutaminase 1 (GLS1) inhibitors, tropomyosin receptor kinase (TRK) inhibitors, and bromodomain containing protein (BRD) inhibitors, targeting aberrant tumor metabolism, cell signal transduction and epigenetic modifications, respectively. Pyridazine moieties functioned as either core frameworks or warheads in the above agents, exhibiting promising potential in cancer treatment. Therefore, the review aims to summarize the recent contributions of pyridazine derivatives as potent anticancer agents between 2020 and 2024, focusing mainly on their structure-activity relationships (SARs) and development strategies, with a view to show that the application of the pyridazine scaffold by different medicinal chemists provides new insights into the rational design of anticancer drugs.
Subject(s)
Antineoplastic Agents , Pyridazines , Pyridazines/chemistry , Pyridazines/pharmacology , Pyridazines/chemical synthesis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Humans , Structure-Activity Relationship , Chemistry, Pharmaceutical , Molecular Structure , Neoplasms/drug therapy , Cell Proliferation/drug effects , Drug Screening Assays, AntitumorABSTRACT
INTRODUCTION: The aim of the study was to conduct a systematic review to explore the therapeutic effect of transcatheter arterial chemoembolization (TACE) combined with portal vein embolization (PVE) for patients with hepatocellular carcinoma (HCC). METHODS: Chinese and English databases (PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang database, and VIP database) were searched from database inception to August 15, 2023. Studies comparing TACE combined with PVE versus TACE alone for patients with HCC were included. The degree of heterogeneity was assessed using I2 statistics and a Q test. The effect size was represented by risk ratio and mean difference (MD), and the effect size range was estimated using a 95% confidence interval (CI). RESULTS: Eight eligible studies were included in the systematic review, involving 689 participants. The results showed that the future liver residual (FLR) of patients treated with TACE combined with PVE was significantly higher than that of those treated with PVE alone (MD = 3.99%; 95% CI: 1.03-6.94). Furthermore, compared with PVE alone, TACE combined with PVE had a positive effect on disease-free survival (odds ratio [OR] = 2.16; 95% CI: 1.20-3.88), recurrence rate (OR = 0.79; 95% CI: 0.07-9.42), and complications (OR = 0.53; 95% CI: 0.30-0.96). There was no statistically significant impact on mortality with TACE combined with PVE treatment. CONCLUSION: The combination of TACE with PVE can significantly reduce the FLR of patients with HCC, with higher disease-free survival, lower recurrence rate, and fewer complications.
ABSTRACT
BACKGROUND: Myopia is the most prevalent refractive error and a growing global health concern that significantly affects visual function. Researchers have recently emphasized considerably on the influence of lifestyle on myopia incidence and development. This study investigates the relationship between leisure sedentary behaviors (LSB)/physical activity (PA)/sleep traits and myopia. METHODS: LSB, PA, and sleep trait-associated genetic variants were used as instrument variables in a Mendelian randomization (MR) study to examine their causal effects on myopia. Summary genome-wide association studies (GWASs) statistical data for LSB and PA were obtained from UK Biobank, and the data of sleep traits was obtained from UK Biobank, UK Biobank and 23andMe, and FinnGen. We used summary statistics data for myopia from MRC IEU. The MR analyses was performed using the inverse variance-weighted (IVW), MR-Egger, weighted median, and MR Pleiotropy RESidual Sum and Outlier methods. RESULTS: Computer use was genetically predicted to increase the myopia risk [IVW odds ratio (OR) = 1.057; 95% confidence interval (CI), 1.038-1.078; P = 7.04 × 10- 9]. The self-reported moderate-to-vigorous physical activity (MVPA) (IVW OR = 0.962; 95% CI, 0.932-0.993; P = 1.57 × 10- 2) and television watching (IVW OR = 0.973; 95% CI, 0.961-0.985, P = 1.93 × 10- 5) were significantly associated with a lower myopia risk. However, genetically predicted sleep traits or accelerometer-measured physical activity had no significant associations with myopia. CONCLUSION: Our results indicated that computer use is a risk factor for myopia, whereas television watching and MVPA may protect against myopia. These findings shed new light on possible strategies for reducing the prevalence of myopia.
Subject(s)
Myopia , Sedentary Behavior , Humans , Genome-Wide Association Study , Mendelian Randomization Analysis , Myopia/epidemiology , Myopia/genetics , Exercise , Sleep , Leisure ActivitiesABSTRACT
Plants are highly susceptible to abiotic stresses, particularly heat stress during the reproductive stage. However, the specific molecular mechanisms underlying this sensitivity remain largely unknown. In the current study, we demonstrate that the Nuclear Transcription Factor, X-box Binding Protein 1-Like 1 (NFXL1), directly regulates the expression of DEHYDRATION-RESPONSIVE ELEMENT-BINDING PROTEIN 2A (DREB2A), which is crucial for reproductive thermotolerance in Arabidopsis. NFXL1 is upregulated by heat stress, and its mutation leads to a reduction in silique length (seed number) under heat stress conditions. RNA-Seq analysis reveals that NFXL1 has a global impact on the expression of heat stress responsive genes, including DREB2A, Heat Shock Factor A3 (HSFA3) and Heat Shock Protein 17.6 (HSP17.6) in flower buds. Interestingly, NFXL1 is enriched in the promoter region of DREB2A, but not of either HSFA3 or HSP17.6. Further experiments using electrophoretic mobility shift assay have confirmed that NFXL1 directly binds to the DNA fragment derived from the DREB2A promoter. Moreover, effector-reporter assays have shown that NFXL1 activates the DREB2A promoter. The DREB2A mutants are also heat stress sensitive at the reproductive stage, and DEREB2A is epistatic to NFXL1 in regulating thermotolerance in flower buds. It is known that HSFA3, a direct target of DREB2A, regulates the expression of heat shock proteins genes under heat stress conditions. Thus, our findings establish NFXL1 as a critical upstream regulator of DREB2A in the transcriptional cassette responsible for heat stress responses required for reproductive thermotolerance in Arabidopsis.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Thermotolerance , Arabidopsis/metabolism , Thermotolerance/genetics , Arabidopsis Proteins/metabolism , Transcription Factors/metabolism , Heat-Shock Response/genetics , Gene Expression Regulation, Plant/genetics , Plants, Genetically Modified/metabolismABSTRACT
Anti-PD-1 monotherapy had limited clinical efficacy in relapsed/refractory (r/r) AML patients with higher PD-1 and PD-L1 expression. Hence, we investigated the efficacy and safety of PD-1 inhibitor with DNA hypomethylating agent (HMA) + CAG regimen in patients who had failed prior AML therapy. In this phase 2, single-arm study, r/r AML patients received azacitidine or decitabine plus CAG regimen with tislelizumab. Primary endpoints were efficacy (objective response rate [ORR]) and safety. Secondary endpoints included overall survival (OS), event-free survival (EFS) and duration of response (DOR). Statistical analyses were performed using Stata 14.0 and SPSS 20.0 software where P < 0.05 denoted significance. Twenty-seven patients were enrolled patients and completed 1 cycle, and 14 (51.9%) and 4 (14.8%) patients completed 2 and 3 cycles, respectively. ORR was 63% (14: complete remission [CR]/CR with incomplete hematologic recovery [CRi], 3: partial remission (PR), 10: no response [NR]). Median OS (mOS) and EFS were 9.7 and 9.2 months, respectively. With a median follow-up of 8.2 months (1.1-26.9), the mOS was not reached in responders (CR/CRi/PR) while it was 2.4 months (0.0-5.4) in nonresponders (P = 0.002). Grade 2-3 immune-related adverse events (irAEs) were observed in 4 (14.8%) patients and 3 nonresponders died of lung infection after treatment. Tislelizumab + HMA + CAG regimen showed improved outcomes in r/r AML patients with lower pretherapy leukemia burden. irAEs were mild and low-grade and higher pretherapy bone marrow CD4+ CD127+ PD-1+ T cells might serve as a predictor of treatment response.ClinicalTrials.gov identifier NCT04541277.
Subject(s)
Immune Checkpoint Inhibitors , Leukemia, Myeloid, Acute , Humans , Decitabine , Immune Checkpoint Inhibitors/therapeutic use , Cytarabine/therapeutic use , Treatment Outcome , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Myeloid, Acute/drug therapyABSTRACT
Global warming has profound impact on growth and development, and plants constantly adjust their internal circadian clock to cope with external environment. However, how clock-associated genes fine-tune thermoresponsive growth in plants is little understood. We found that loss-of-function mutation of REVEILLE5 (RVE5) reduces the expression of circadian gene EARLY FLOWERING 4 (ELF4) in Arabidopsis, and confers accelerated hypocotyl growth under warm-temperature conditions. Both RVE5 and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) accumulate at warm temperatures and bind to the same EE cis-element presented on ELF4 promoter, but the transcriptional repression activity of RVE5 is weaker than that of CCA1. The binding of CCA1 to ELF4 promoter is enhanced in the rve5-2 mutant at warm temperatures, and overexpression of ELF4 in the rve5-2 mutant background suppresses the rve5-2 mutant phenotype at warm temperatures. Therefore, the transcriptional repressor RVE5 finetunes ELF4 expression via competing at a cis-element with the stronger transcriptional repressor CCA1 at warm temperatures. Such a competition-attenuation mechanism provides a balancing system for modulating the level of ELF4 and thermoresponsive hypocotyl growth under warm-temperature conditions.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Circadian Clocks , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Temperature , Gene Expression Regulation, Plant , Arabidopsis/metabolism , Hypocotyl , Circadian Clocks/genetics , Circadian Rhythm/geneticsABSTRACT
BACKGROUND: Autistic traits (ATs) are frequently reported in children with Attention-Deficit/Hyperactivity Disorder (ADHD). This study aimed to examine ATs in children with ADHD from both behavioral and neuroimaging perspectives. METHODS: We used the Autism Spectrum Screening Questionnaire (ASSQ) to assess and define subjects with and without ATs. For behavioral analyses, 67 children with ADHD and ATs (ADHD + ATs), 105 children with ADHD but without ATs (ADHD - ATs), and 44 typically developing healthy controls without ATs (HC - ATs) were recruited. We collected resting-state functional magnetic resonance imaging (rs-fMRI) data and analyzed the mean amplitude of low-frequency fluctuation (mALFF) values (an approach used to depict different spontaneous brain activities) in a sub-sample. The imaging features that were shared between ATs and ADHD symptoms or that were unique to one or the other set of symptoms were illustrated as a way to explore the "brain-behavior" relationship. RESULTS: Compared to ADHD-ATs, the ADHD + ATs group showed more global impairment in all aspects of autistic symptoms and higher hyperactivity/impulsivity (HI). Partial-correlation analysis indicated that HI was significantly positively correlated with all aspects of ATs in ADHD. Imaging analyses indicated that mALFF values in the left middle occipital gyrus (MOG), left parietal lobe (PL)/precuneus, and left middle temporal gyrus (MTG) might be specifically related to ADHD, while those in the right MTG might be more closely associated with ATs. Furthermore, altered mALFF in the right PL/precuneus correlated with both ADHD and ATs, albeit in diverse directions. CONCLUSIONS: The co-occurrence of ATs in children with ADHD manifested as different behavioral characteristics and specific brain functional alterations. Assessing ATs in children with ADHD could help us understand the heterogeneity of ADHD, further explore its pathogenesis, and promote clinical interventions.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Autistic Disorder , Humans , Child , Attention Deficit Disorder with Hyperactivity/diagnostic imaging , Autistic Disorder/diagnostic imaging , Autistic Disorder/complications , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , NeuroimagingABSTRACT
BACKGROUND: A high prevalence of nasopharyngeal carcinoma (NPC) has been found in China, but it rarely occurs with syncope. Studies have demonstrated that syncope due to NPC may be related to carotid sinus syndrome, glossopharyngeal irritation, and parapharyngeal and retropharyngeal space lesions. Such patients require evaluation by nasopharyngoscopy and head magnetic resonance imaging/computed tomography. There is no known single effective treatment for these patients. Various interventions may be considered in an effort to relieve syncope, including vasoconstrictive drugs, cardiac pacemaker implantation, radiotherapy and chemotherapy, and surgical resection. CASE PRESENTATION: This case report describes a 56-year-old man who developed recurrent syncope with atrial fibrillation, a long RR interval, and hypotension. A single chamber pacemaker was fitted, but it failed to relieve the symptom. Cranial magnetic resonance imaging and pathological tests led to a final diagnosis of NPC. After six courses of chemotherapy and 35 sessions of radiotherapy, the patient became asymptomatic. However, he died from a massive uncontrolled hemorrhage in the nasopharynx two years later. CONCLUSIONS: This case brings attention to the fact that syncope can be a symptom of NPC. Due to the insidiously malignant nature of this cancer, when a patient presents with syncope, clinicians should bear in mind this connection, albeit a rare one. There are at least two ways of treating NPC-associated syncope, but there is disagreement about which is the most effective.
Subject(s)
Hypotension , Nasopharyngeal Neoplasms , Male , Humans , Middle Aged , Nasopharyngeal Carcinoma/complications , Nasopharyngeal Carcinoma/therapy , Syncope , Hypotension/etiology , Magnetic Resonance Imaging/adverse effects , Nasopharyngeal Neoplasms/complications , Nasopharyngeal Neoplasms/therapyABSTRACT
An effective portfolio selection model is constructed on the premise of measuring accurately the risk and return on assets. According to the reality that asset returns obey the asymmetric power-law distribution, this paper first builds two fractal statistical measures, fractal expectation and fractal variance to measure the asset returns and risks, inspired by the method of measuring the curve length in the fractal theory. Then, by incorporating the fractal statistical measure into the return-risk criterion, a portfolio selection model based on the fractal statistical measure is established, namely, the fractal portfolio selection model, and the closed-form solution of the model is given. Finally, through empirical analysis, it is found that under the constraints of typical factual characteristics that the asset returns obey the asymmetric power-law distribution, the fractal portfolio is better than the traditional portfolio as a whole, which not only can improve the investment performance but also has better robustness. The validity of the fractal investment portfolio is experimentally tested.
ABSTRACT
Brachybotrys paridiformis Maxim. ex Oliv. (Boraginaceae) is a perennial medicinal plant and vegetable that is cultivated commercially in China. Anthracnose is a devastating disease of B. paridiformis, with annual production losses exceeding 33% based on our survey. In July 2021, anthracnose of B. paridiformis was observed on 2-year-old plants in Shenyang city, Northeast China, which is the most important region for B. paridiformis cultivation. Round or irregular-shaped black spots were exhibited on leaves, with the leaf edges most commonly infected. As the necrosis expanded, the leaves withered and dropped; young leaves were generally not infected (Fig. 1). More than 40% of the plants in a 21-ha sampling field were infected in 2021. Symptomatic leaves (n = 20) were collected and the diseased tissue was cut into small pieces, immersed in 1% NaOCl for 2 min, rinsed three times with sterile water, and placed on acidified potato dextrose agar (PDA) in Petri dishes. After a 3-day incubation in darkness at 25 °C, 18 suspected single-pure morphologically identical Colletotrichum isolates were obtained and sequenced. Isolate SQZ9 was randomly selected and identified. Colonies on PDA were initially white, but gradually became pale brownish with a reverse side that was pale yellowish to pinkish. Aerial mycelia were grayish-white, dense, and cottony, with microsclerotia detected on some aging mycelia. The detected single-celled conidia (11.65-17.25 × 4.25-6.15 µm; n = 50) were fusiform to cylindrical with obtuse to slightly rounded ends. Appressoria were ovoid to clavate and medium brown. Setae were not observed. The morphological characteristics were similar to those of Colletotrichum spp. (Prihastuti et al. 2009; Weir et al. 2012). Initial BLAST searches of the GenBank database revealed the SQZ9 rDNA internal transcribed spacer region (OP389109, 566 bp), glyceraldehyde-3-phosphate dehydrogenase (OP407730, 260 bp), chitin synthase (OP407731, 301 bp), calmodulin (OP407732, 712 bp), actin (OP407733, 282 bp), glutamine synthetase (OP407734, 909 bp), ß-tublin (OP407735, 498 bp), and superoxide dismutase (OP407736, 396 bp) sequences were respectively 99%-100% similar to the C. siamense type strain JX010278, JX010019, JX009709, GQ856775, GQ856730, JX010100, JX010410, and JX010332 sequences (Carbone & Kohn 1999; Moriwaki & Tsukiboshi 2009; Stephenson et al. 1997). The SQZ9 identity was confirmed by constructing a phylogenetic tree combining all loci, which grouped the isolate and the C. siamense type strain in the same clade (Fig. 2). For pathogenicity tests, 15 healthy 2-year-old plants (3 plants per pot) were spray-inoculated with SQZ9 conidial suspension (1 × 105 conidia/mL) at 2 mL per plant. Same number of plants sprayed with water were used as control. This experiment was repeated twice. All plants were covered with clear plastic bags for 72 h to maintain high humidity and then placed in a greenhouse (29 °C, natural light, and 85% relative humidity). After six days, the inoculated leaves exhibited symptoms that were similar to those observed in the field, but the controls were symptomless. The same fungus was recovered from inoculated symptomatic leaves, and its identity was confirmed by sequencing and a phylogenetic analysis. This is the first report of C. siamense causing anthracnose on B. paridiformis in China. Future studies should assess the effectiveness of chemical and biological control measures for managing this disease.
ABSTRACT
Ligularia fischeri (Ledeb.) is a perennial herbal plant of Compositae that is cultivated commercially in China as a medicinal, ornamental, and edible plant. Leaf spots were observed in 2-year-old L. fischeri in Benxi County of northeast China, in August 2021. Irregular reddish brown spots ranging from 3 to 11 mm were observed on infected leaves, and each leaf had dozens of spots (Fig. 1). As the disease progressed, the diseased spots withered and the centers fell out, and multiple lesions merge into large diseased spots, causing leaf wilting. The roots and stem bases were not infected during the reproductive stage. More than 37% of the plants in a 18 ha field were infected in 2021. The ten diseased leaves were collected and cut into small (3-5 mm) pieces, which were surface-disinfested by immersing into 1% NaOCl for 2 min and rinsing with sterile distilled water three times. The leaf pieces were then placed on acidified potato dextrose agar (PDA) in petri plates and incubated in the dark at 25°C. Twenty isolates with the same morphological characteristics were obtained. Isolates were further purified by starting a new colony for each isolate from a single spore collected from water agar. Isolate TYTW7 was randomly selected for identification and pathogenicity testing. It grew rapidly and produced profuse aerial mycelia with a carmine red underside. The conidiophores had many fertile branches and formed an elongated stipe with a sphaeropedunculate vesicle at the tip. The one-septate conidia were cylindrical and almost straight with parallel walls and rounded ends. Their sizes ranged from 30.35 to 51.76 × 2.93 to 5.01 µm (n = 100) and the pathogens were initially identified as Calonectria sp. (Crous 2002; Crous et al. 2004; Lombard et al. 2015, 2016). Further confirmation of the identification was determined according to published method (Liu and Chen 2017; Shao and Li 2021). The partial gene regions including the translation elongation factor 1-alpha (GenBank accession no. OP290551), histone H3 (OP290552), calmodulin (OP290553) and ß-tubulin (OP290554) were obtained, and BLAST searches showed 99-100% homology with the ex-type culture CERC 8952 (MF527049, MF527065, MF527081 and MF527107) and phylogenetic analysis combining all loci revealed that the isolate TYTW7 and the type strain of Ca. montana clustered in one group (Fig. 2). Based on morphological characteristics and phylogenetic analysis, isolate TYTW7 was identified as Ca. Montana. Healthy 2-year-old plants were used for the pathogenicity test. A spore suspension (1×105 spores/mL water) was used to inoculate three host plants; sterile water was sprayed on the same number plants serving as a control. The experiment was repeated three times. All plants were incubated at 27±2°C (12h photoperiod) and were evaluated after seven days. The inoculated plants showed lesions on the leaf surface, similar to those in the field, and the control remained symptomless. The pathogens were successfully reisolated and identified by sequencing, and no pathogens were isolated from symptomless control plants. To our knowledge, this is the first report of Ca. montana causing L. fischeri leaf spot. The disease poses a threat to the production and more control strategies are needed on management options to minimize losses.
ABSTRACT
Macleaya cordata (Willd.) R. Br. is a perennial herbaceous medicinal plant (Papaveraceae) commercially cultivated in China which has been studied for detumescence, detoxification, and insecticidal effect (Lin et al. 2018). In August 2021, anthracnose was observed in 2-year-old M. cordata plants in Benxi county, northeast China (41°45'48â³N, 123°69'15â³E). Dozens of irregular reddish-brown spots (3-11 mm) were observed on each diseased leaf. The lesions were covered with a layer of gray-white mycelia. As the disease progressed, the spots became necrosis and perforation or they would merged into large lesions, ultimately resulting in wilted leaves (Fig. 1). More than 33% of the plants in a 16-ha field were infected in 2021. The diseased leaves were collected and cut into 3-8 mm pieces, surface-disinfested by immersing them into 1% NaOCl for 2 min, and rinsed three times with sterile distilled water. They were then dried with sterilized absorbent paper, placed on PDA medium amended with chloramphenicol (40 mg/L), and incubated in darkness at 25°C with a 12-h photoperiod. Twenty isolates (BLH1 to 20) were obtained and purified using a single-spore method. Isolate BLH12 was identified and used for the pathogenicity test. Colonies were sparsely fluffy with smooth edges, and gradually became gray to pale orange from the initial white. The underside of the colonies was pale orange towards the center. Conidia were single-celled, cylindrical, and transparent with broadly blunt ends, measuring (15.13 ± 1.14) × (5.80 ± 0.60) µm (n=50). Appressoria were single-celled, brown-to-dark brown, usually elliptical or irregular, and sometimes lobed. Setae were not observed. The isolate was initially identified as Colletotrichum gloeosporioides complex (Prihastuti et al. 2009). The identification was confirmed as described previously (Weir et al. 2012). The rDNA internal transcribed spacer region (OP415560), the glyceraldehyde-3-phosphate dehydrogenase (OP433642), chitin synthase (OP433643), calmodulin (OP433644), actin (OP433645), glutamine synthetase (OP433646), ß-tubulin (OP433647), and superoxide dismutase (OP433648) gene sequences were obtained (Carbone & Kohn 1999; Weir et al. 2012), and BLAST searches revealed 99-100% homology with the type culture ICMP 18608 (JX010244, JX010044, JX009683, JX009443, JX009744, JX010078, JX010389, and JX010311). A phylogenetic analysis of combining all loci indicated BLH12 and the type strain of C. aenigma were clustered in one group (Fig. 2). Based on the basis of morphological characteristics and phylogenetic relationships, BLH12 was identified as C. aenigma. For the pathogenicity test, healthy 2-year-old plants were sprayed with a BLH12 spore suspension (1 × 105/mL). Control plants were sprayed with sterile water.There were three replicates (five plants each) per treatment. All plants were incubated at 25°C (12-h photoperiod and 86% relative humidity) and examined after 7 days. The experiment was repeated twice. The inoculated plants showed lesions on the leaf surface, similar to those in the field, whereas the control plants were asymptomatic. The pathogen was successfully reisolated and identified as the methods mentioned above. This fungus reportedly infects the leaves of many woody plants in China (Wang et al. 2020; Zhang et al. 2021). This is the first report of C. aenigma causing anthracnose on M. cordata, which will provide an guideline for developing effective field control practices for the disease.
ABSTRACT
Plants have short-term stress memory that enables them to maintain the expression state of a substantial subset of heat-inducible genes during stress recovery after heat stress. Little is known about the molecular mechanisms controlling stress-responsive gene expression at the recovery stage in plants, however. In this article, we demonstrate that histone H3K4 methyltransferases SDG25 and ATX1 are required for heat-stress tolerance in Arabidopsis. SDG25 and ATX1 are not only important for stress-responsive gene expression during heat stress, but also for maintaining stress-responsive gene expression during stress recovery. A combination of whole-genome bisulfite sequencing, RNA-sequencing and ChIP-qPCR demonstrated that mutations of SDG25 and ATX1 decrease histone H3K4me3 levels, increase DNA cytosine methylation and inhibit the expression of a subset of heat stress-responsive genes during stress recovery in Arabidopsis. ChIP-qPCR results confirm that ATX1 binds to chromatins associated with these target genes. Our results reveal that histone H3K4me3 affects DNA methylation at regions in the loci associated with heat stress-responsive gene expression during stress recovery, providing insights into heat-stress transcriptional memory in plants.
Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/enzymology , Arabidopsis/metabolism , Histone Methyltransferases/metabolism , Arabidopsis/genetics , Arabidopsis Proteins/genetics , DNA Methylation , Gene Expression Regulation, Plant , Histone Methyltransferases/geneticsABSTRACT
OBJECTIVE: To observe the effects of moxibustion on "Shenshu" and "Zusanli" on macrophage polarization and IL-4/STAT6 signaling pathway in rats with rheumatoid arthritis (RA). To further explore the possible anti-inflammatory mechanism of moxibustion in the treatment of RA. METHODS: The rats' right hind paws were injected with freund's complete adjuvant (FCA) to establish the model of RA. Seven days after the injection of FCA, moxibustion therapy was performed on the acupoints of Shenshu (BL23) and Zusanli (ST36) once a day for three weeks. The researchers measured the thickness of the foot pad. ELISA and Histological Analysis were performed to observe the anti-inflammatory effect of moxibustion. Then researchers detected the expression of macrophage phenotype and the expression of IL-4/STAT6 signaling pathway related molecules. RESULTS: It was observed that after the injection of FCA, the rats' feet showed obvious symptoms of redness and swelling. But the symptoms were significantly improved when moxibustion was employed. The study found lower IL-23 and higher IL-4 level in the serum of FCA-injected rats after moxibustion treatment. HE staining showed that the synovium of the RA group was hyperemia and edema, with a large number of inflammatory cells infiltration and vascular dilatation. In the moxibustion group, the degree of synovial hyperemia and edema was improved, and the infiltration of inflammatory cells and vascular dilation were reduced. The study also found that there wer differences among the expressions of macrophage phenotypes in RA, and this was shown by the high expression of CD86 and low expression of CD206. However, the polarization of macrophages in the moxibustion group changed, and that was manifested by enhanced M2-polarized Mφs and inhibited M1-polarized Mφs. Meanwhile, moxibustion suppressed the activation of JAK1, JAK3 and STAT6 in the IL-4/STAT6 signaling pathway, which contributed to the polarization of M2 . CONCLUSION: The results demonstrate that moxibustion not only suppresses the polarization of M1, but also promotes the polarization of M1. The anti-inflammatory effect of moxibustion may be related to the regulation of macrophage polarization through IL-4/STAT6 signaling pathway.
Subject(s)
Arthritis, Rheumatoid , Interleukin-4 , Macrophages , Moxibustion , STAT6 Transcription Factor , Animals , Anti-Inflammatory Agents , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/therapy , Cell Polarity/genetics , Cell Polarity/physiology , Hyperemia , Interleukin-4/metabolism , Macrophages/metabolism , Rats , STAT6 Transcription Factor/metabolismABSTRACT
Electrochemical measurements at the single entity level provide ultra-sensitive tools for the precise diagnosis and understanding of basic biological and chemical processes. By decoding current signatures, single-entity electrochemistry provides abundant information on charges, sizes, shapes, catalytic performances and compositions. The accuracy of single-entity electrochemistry highly relies on advanced instrumentation to achieve the amperometric resolution at the sub-picoampere level and the temporal resolution at the sub-microsecond level. Currently, it is still a challenge for paralleling amplifiers to allow low-noise and high bandwidth single-entity electrochemical measurements. Herein, we developed a low-noise four-channel electrochemical instrumentation that integrates an Au electrode array with amplifiers in the circuit board. With this amplifier array, we achieved a high bandwidth (>100 kHz) electrochemical measurement. The further practical experiments proved the capability of this amplifier array system in acquiring transient signals from both single-molecule detection with an aerolysin nanopore and single Pt nanoparticle catalysis during the dynamic collision process. Paired with appropriate microfluidic array systems, our instrumentation will enable an extraordinarily high-throughput feature for single-entity sensing.
Subject(s)
Nanopores , Catalysis , Electrochemistry , Electrodes , NanotechnologyABSTRACT
Making a hydrogel-based first-aid bandage with green resources, desirable biocompatibility, universal adhesive properties, low cost and simple production is a long-standing research aspiration. Considering this, three naturally existing organic acids, namely tannic acid, thioctic acid and phytic acid, were used to construct a novel adhesive gel (TATAPA hydrogel) for epidermal tissue bandage applications. This hydrogel could be synthesized under mild conditions with no need for a freeze-thawing shaping procedure, and was transparent, moldable and stretchable with good stability under continuous water immersion. In lap-shear tests, the TATAPA hydrogel could adhere to various hydrophilic and hydrophobic surfaces. Moreover, in the case of skin tissue adhesion, the hydrogel could be easily peeled off from the skin, meeting wearability requirements. Rheological tests showed that the hydrogel possessed thermal sensitive properties derived from multi-supramolecular interactions. The methicillin-resistant Staphylococcus aureus (MRSA)-infected burn wound test demonstrated that the hydrogel had desirable antibacterial activity and was beneficial for wound healing. A femoral artery bleeding assay was also used to reveal that the TATAPA hydrogel could be directly pasted onto the bleeding site for hemostasis. Overall, this hydrogel demonstrates potential as a surgical bioadhesive for a broad range of medical applications.
Subject(s)
Bandages , Hydrogels , Methicillin-Resistant Staphylococcus aureus , Adhesives/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Hydrogels/chemistry , Phytic Acid , Tannins , Thioctic AcidABSTRACT
Novel 3D metal formate frameworks {[Ba4Cl][M3(HCO2)13]}n (M = Mn for 1, Co for 2, and Mg for 3) were successfully assembled via microwave-assisted synthesis. The complexes are rare coordination polymers crystallized at space group P4cc with the polar point group C4v. In the structure, the MII ions are bridged by two types of anti-anti formate in forming a 3D pcu framework, and additional formates coordinate to the unsaturated sites of the MII ions in the framework, giving an anionic M-formate net. Ba4Cl clusters take the cavities of the net as charge balance, in which the chloride ion deviates from the center of the barium ions. The asymmetric Ba4Cl structure is transmitted throughout the crystal resulting in polar structure, which is further confirmed by nonlinear optical and piezoelectric test. Nonlinear optical activity tests of 1 and 3 show SHG signals 0.32 and 0.28 times that of KDP, while 2 has a piezoelectric coefficient d33 of 6.8 pC/N along polar axis. Magnetic studies reveal antiferromagnetic coupling between MII ions in 1 and 2. Spin canting was found only in 2 with anisotropic CoII ions, and 2 is a canted antiferromagnetically with TN = 5 K. Further field-induced spin flop was also found in 2 with a critical field 0.9 T.
ABSTRACT
Tribulus terrestris L. is an annual herbaceous medicinal plant of Zygophyllaceae, which is cultivated commercially in China. Subrotund or irregular gray, sunken, necrotic spots ranging from 2 to 9 mm were observed on diseased leaves of T. terrestris landrace in Fushun County, Liaoning Province of northeast China in July 2021, with more than 32% of the plants being infected in a 18-ha field. The symptoms first appeared on older leaves and gradually spread to younger leaves. The lesions developed a white center gradually and became perforated; multiple lesions could coalesce (Fig. 1). Ten symptomatic leaves were collected and the diseased tissues were cut into small pieces, immersed in 1% NaOCl for 2 min, rinsed three times with sterile water, and placed on acidified potato dextrose agar (PDA) in Petri dishes at 25°C in darkness. Fifteen suspected Colletotrichum single-spore fungal isolates (JL1 to JL15) with consistent morphological characteristics were obtained, and isolate JL6 was selected for identification and pathogenicity testing. Colonies on PDA were flat with an entire margin, dense and white at first, then became dark gray with numerous black microsclerotia and formed a concentric circular pattern with aging. Conidia were single-celled, sickle-curved with a tapered tip and truncate base, ranging from 16.46 to 20.26 µm in length and 2.81 to 3.96 µm in width (n=100). Setae were dark brown, septate, straight with a slightly acute tip, 75.45 to 135.63×3.19 to 4.95 µm in size. Appressoria were dark brown, round or irregular, mostly in groups. All characteristics were consistent with the descriptions of C. truncatum (Damm et al. 2009). Further confirmation of the identification was determined according to methods described previously (Damm et al. 2009). The rDNA internal transcribed spacer region (OP364400, 585 bp), and actin (OP380867, 290 bp), beta-tubulin (OP380868, 498 bp), chitin synthase 1 (OP380869, 277 bp), glyceraldehyde-3-phosphate dehydrogenase (OP380870, 280 bp), and histone (OP380871, 411 bp) genes were amplified by PCR and sequenced (Carbone and Kohn 1999; Glass and& Donaldson 1995; Guerber et al. 2003; O'Donnell and Cigelnik 1997). BLAST results showed 98-100% similarity at 85-97% coverage compared to the corresponding sequences of the type strain CBS 151.35 (GU227862, GU227960, GU228156, GU228352, GU228254, and GU228058). Phylogenetic analysis combining all loci revealed that the isolate JL6 and the type strains of C. truncatum clustered in one group (Fig. 2). One-year-old healthy seedlings of T. terrestris (cultivar: landrace) were used for pathogenicity test. Suspension (1×105 conidia/mL) of isolate JL6 was sprayed on ten seedlings, and ten seedlings sprayed with sterilized distilled water were used as the control. Three replicates were performed on each treatment. All plants were kept at 28±1°C (12 h photoperiod), and were evaluated after 7 days. The inoculated plants showed lesions on the leaf surface, similar to those in the field, and the control remained symptomless. The pathogen was successfully reisolated and identified using the methods mentioned above. To our knowledge, this is the first report of C. truncatum causing anthracnose on T. terrestris, which will provide valuable information for designing strategies to manage anthracnose on T. terrestris.
ABSTRACT
Based on the theory of planned behavior, the aim of this study was to describe the influencing factors of patient delay intentions and behaviors in benign prostatic hyperplasia (BPH) patients and to provide a reference for the development of a patient delay intention scale. This study was carried out over 4 months in 2021 in Daqing, Heilongjiang, China. The participants were 20 patients with BPH who were aged 60 to 82 years and experienced patient delay; participants were selected through a purposive sampling method. The data were collected via face-to-face semistructured interviews. Five main themes emerged from the interviews, including an insufficient understanding of symptoms, experiences of coping instead of seeking health care, negative attitudes toward care-seeking, the influence of others on decision-making for care-seeking, and obstacles to seeking health care. In conclusion, the patient delay intentions and behaviors of BPH patients are the result of a combination of many factors.
Subject(s)
Prostatic Hyperplasia , Aged , China , Humans , Male , Patient Acceptance of Health Care , Prostatic Hyperplasia/complications , Prostatic Hyperplasia/therapy , Qualitative ResearchABSTRACT
Lonicerae Japonicae Flos, as common Chinese medicine, has been used for thousands of years in the treatment of inflammation and infectious diseases with definite efficacies. The complex composition of Lonicerae Japonicae Flos results in its extensive pharmacological effects, so the assessment of its quality by only a few index components is not comprehensive. Guided by the quality marker(Q-marker), the present study comprehensively analyzed and predicted the quality connotation of Lonicerae Japonicae Flos based on the chemical composition and component transfer, the phylogenetic relationship, chemical composition effectiveness, measurability, and specificity. Chlorogenic acid, isochlorogenic acids A, B, and C, luteoloside, rutin, sweroside, and secoxyloganin were predicted as candidate Q-markers of Lonicerae Japonicae Flos.