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1.
J Agric Food Chem ; 72(19): 10828-10841, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38691839

ABSTRACT

Chemosensory proteins (CSPs) constitute a class of olfactory proteins localized in insect sensory organs that serve a crucial function in decoding external chemical stimuli. This study aims to elucidate the involvement of CrufCSP3 in olfactory perception within the context of Cotesia ruficrus, an indigenous endoparasitoid targeting the invasive pest Spodoptera frugiperda. Through fluorescence-competitive binding assays and site-directed mutagenesis, we pinpointed four amino acids as pivotal residues involved in the interaction between CrufCSP3 and five host-related compounds. Subsequent RNA interference experiments targeting CrufCSP3 unveiled a reduced sensitivity to specific host-related compounds and a decline in the parasitism rate of the FAW larvae. These findings unequivocally indicate the essential role of CrufCSP3 in the chemoreception process of C. ruficrus. Consequently, our study not only sheds light on the functional importance of CSPs in parasitic wasp behavior but also contributes to the development of eco-friendly and efficacious wasp behavior modifiers for effectively mitigating pest population surges.


Subject(s)
Insect Proteins , Spodoptera , Wasps , Animals , Wasps/chemistry , Wasps/physiology , Insect Proteins/genetics , Insect Proteins/metabolism , Insect Proteins/chemistry , Larva/growth & development , Host-Parasite Interactions , Olfactory Perception
2.
Article in English | MEDLINE | ID: mdl-38761998

ABSTRACT

BACKGROUND: Previous study implied that local M2 polarization of macrophage promoted mucosal edema and exacerbates Th2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. OBJECTIVE: We thought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. METHODS: RT-qPCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5 knockout mice were used to establish nasal polyp model with Th2 inflammation and investigate the effects of SIRT5 in macrophages on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophages markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5 deficiency mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages through promoting glutaminolysis. CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting the alternative polarization of macrophage and thus provides a potential target for CRSwNP interventions.

3.
Molecules ; 29(9)2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38731482

ABSTRACT

An efficient palladium-catalyzed carbonylation of aryl fluorosulfates with aryl formates for the facile synthesis of esters was developed. The cross-coupling reactions proceeded effectively in the presence of a palladium catalyst, phosphine ligand, and triethylamine in DMF to produce the corresponding esters in moderate to good yields. Of note, functionalities or substituents, such as nitro, cyano, methoxycarbonyl, trifluoromethyl, methylsulfonyl, trifluoromethoxy, fluoro, chloro, bromo, methyl, methoxy, N,N-dimethyl, and [1,3]dioxolyl, were well-tolerated in the reactions, which could be kept for late-stage modification. The reactions employing readily available and relatively robust aryl fluorosulfates as coupling electrophiles could potentially serve as an attractive alternative to traditional cross-couplings with the use of aryl halides and pseudohalides as substrates.

4.
BMC Biol ; 22(1): 54, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38448930

ABSTRACT

BACKGROUND: Gut bacteria are beneficial to the host, many of which must be passed on to host offspring. During metamorphosis, the midgut of holometabolous insects undergoes histolysis and remodeling, and thus risks losing gut bacteria. Strategies employed by holometabolous insects to minimize this risk are obscure. How gut bacteria affect host insects after entering the hemocoel and causing opportunistic infections remains largely elusive. RESULTS: We used holometabolous Helicoverpa armigera as a model and found low Lactobacillus load, high level of a C-type lectin (CTL) gene CD209 antigen-like protein 2 (CD209) and its downstream lysozyme 1 (Lys1) in the midgut of the wandering stage. CD209 or Lys1 depletion increased the load of midgut Lactobacillus, which further translocate to the hemocoel. In particular, CD209 or Lys1 depletion, injection of Lactobacillus plantarum, or translocation of midgut L. plantarum into the hemocoel suppressed 20-hydroxyecdysone (20E) signaling and delayed pupariation. Injection of L. plantarum decreased triacylglycerol and cholesterol storage, which may result in insufficient energy and 20E available for pupariation. Further, Lysine-type peptidoglycan, the major component of gram-positive bacterial cell wall, contributed to delayed pupariation and decreased levels of triacylglycerols, cholesterols, and 20E, in both H. armigera and Drosophila melanogaster. CONCLUSIONS: A mechanism by which (Lactobacillus-induced) opportunistic infections delay insect metamorphosis was found, namely by disturbing the homeostasis of lipid metabolism and reducing 20E production. Moreover, the immune function of CTL - Lys was characterized for insect metamorphosis by maintaining gut homeostasis and limiting the opportunistic infections.


Subject(s)
Gastrointestinal Microbiome , Lysine , Animals , Drosophila melanogaster , Dysbiosis , Bacteria , Immunity
5.
World J Clin Cases ; 12(5): 995-1003, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38414609

ABSTRACT

BACKGROUND: A solitary fibrous tumor (SFT) is often located in the pleura, while SFT of the pancreas is extremely rare. Here, we report a case of SFT of the pancreas and discuss imaging, histopathology, and immunohistochemistry for accurate diagnosis and treatment. CASE SUMMARY: A 54-year-old man presented to our hospital with pancreatic occupancy for over a month. There were no previous complaints of discomfort. His blood pressure was normal. Blood glucose, tumor markers, and enhanced computed tomography (CT) suggested a malignant tumor. Because the CT appearance of pancreatic cancer varies, we could not confirm the diagnosis; therefore, we performed endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). Pathology and immunohistochemistry were consistent with SFT of the pancreas. The postoperative pathology and immunohistochemistry were consistent with the puncture results. The patient presented for a follow-up examination one month after discharge with no adverse effects. CONCLUSION: Other diseases must be excluded in patients with a pancreatic mass that cannot be diagnosed. CT and pathological histology have diagnostic value for pancreatic tumors. Endoscopic puncture biopsy under ultrasound can help diagnose pancreatic masses that cannot be diagnosed preoperatively. Surgery is an effective treatment for SFT of the pancreas; however, long-term follow-up is strongly recommended because of the possibility of malignant transformation of the tumor.

6.
Insects ; 14(12)2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38132594

ABSTRACT

Chemosensory proteins (CSPs) are a class of soluble proteins that facilitate the recognition of chemical signals in insects. While CSP genes have been identified in many insect species, studies investigating their function remain limited. Cotesia ruficrus (Hymenoptera: Braconidae) holds promise as an indigenous biological control agent for managing the invasive pest Spodoptera frugiperda (Lepidoptera: Noctuidae) in China. This study aimed to shed light on the gene expression, ligand binding, and molecular docking of CrufCSP1 in C. ruficrus. A RT-qPCR analysis revealed that the expression of CrufCSP1 was higher in the wings, with male adults exhibiting significantly higher relative expression levels than other developmental stages. A fluorescence competitive binding analysis further demonstrated that CrufCSP1 has a high binding ability with several host-related volatiles, with trans-2-hexenal, octanal, and benzaldehyde showing the strongest affinity to CrufCSP1. A molecular docking analysis indicated that specific amino acid residues (Phe24, Asp25, Thr53, and Lys81) of CrufCSP1 can bind to these specific ligands. Together, these findings suggest that CrufCSP1 may play a crucial role in the process of C. ruficrus locating hosts. This knowledge can contribute to the development of more efficient and eco-friendly strategies for protecting crops and managing pests.

7.
Ear Nose Throat J ; : 1455613231198986, 2023 Sep 16.
Article in English | MEDLINE | ID: mdl-37715691

ABSTRACT

Rhabdomyosarcoma (RMS) is a rare and aggressive cancerous tumor that arises from embryonal mesenchymal cells with skeletal muscle differentiation, and it is exceedingly rare that occurs specifically in the larynx. To date, only 22 instances of laryngeal pleomorphic RMSs have been documented in adults. Consequently, there is limited information available to assist healthcare professionals in effectively handling RMS in the larynx of adult patients. Here, we present an uncommon occurrence involving a 45-year-old man who experienced progressive hoarseness and received a diagnosis of pleomorphic RMS affecting the larynx. Pleomorphic RMS had been pathologically diagnosed after a vertical hemilaryngectomy. Following the surgical intervention, the patient underwent chemotherapy and radiation therapy. As of now, there have been no indications of tumor recurrence.

8.
World J Gastroenterol ; 29(30): 4616-4627, 2023 Aug 14.
Article in English | MEDLINE | ID: mdl-37662858

ABSTRACT

After being ingested and entering the human stomach, Helicobacter pylori (H. pylori) adopts several effective strategies to adhere to and colonize the gastric mucosa and move to different regions of the stomach to obtain more nutrients and escape from the harsher environments of the stomach, leading to acute infection and chronic gastritis, which is the basis of malignant gastric tumors. The endoscopic manifestations and pathological features of H. pylori infection are diverse and vary with the duration of infection. In this review, we describe the endoscopic manifestations of each stage of H. pylori gastritis and then reveal the potential mechanisms of bacterial intragastric colonization and migration from the perspective of endoscopists to provide direction for future research on the effective therapy and management of H. pylori infection.


Subject(s)
Gastritis , Helicobacter pylori , Humans , Gastric Mucosa , Endoscopy
9.
Curr Med Sci ; 43(4): 794-802, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37498408

ABSTRACT

OBJECTIVE: Histone modification has a significant effect on gene expression. Enhancer of zeste homolog 2 (EZH2) contributes to the epigenetic silencing of target chromatin through its roles as a histone-lysine N-methyltransferase enzyme. The development of anoikis resistance in tumor cells is considered to be a critical step in the metastatic process of primary malignant tumors. The purpose of this study was to investigate the effect and mechanism of anoikis resistance in ovarian adenocarcinoma peritoneal metastasis. METHODS: In addition to examining EZH2 protein expression in ovarian cancer omental metastatic tissues, we established a model of ovarian cancer cell anoikis and a xenograft tumor model in nude mice. Anoikis resistance and ovarian cancer progression were tested after EZH2 and N6-methyladenosine (m6A) levels were modified. RESULTS: EZH2 expression was significantly higher in ovarian cancer omental metastatic tissues than in normal ovarian tissues. Reducing the level of EZH2 decreased the level of m6A and ovarian cancer cell anoikis resistance in vitro and inhibited ovarian cancer progression in vivo. M6a regulation altered the effect of EZH2 on anoikis resistance. CONCLUSION: Our results indicate that EZH2 contributes to anoikis resistance and promotes ovarian adenocarcinoma abdominal metastasis by m6A modification. Our findings imply the potential of the clinical application of m6A and EZH2 for patients with ovarian cancer.


Subject(s)
Adenocarcinoma , Ovarian Neoplasms , Peritoneal Neoplasms , Animals , Female , Humans , Mice , Adenocarcinoma/pathology , Anoikis/genetics , Carcinoma, Ovarian Epithelial/genetics , Cell Line, Tumor , Enhancer of Zeste Homolog 2 Protein/genetics , Enhancer of Zeste Homolog 2 Protein/metabolism , Mice, Nude , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/genetics , Peritoneal Neoplasms/secondary
11.
J Econ Entomol ; 116(3): 790-797, 2023 06 13.
Article in English | MEDLINE | ID: mdl-37085154

ABSTRACT

The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith), is a significant invasive pest identified as a serious threat to global agricultural production and food security. However, its ovipositional preference, larval feeding selectivity, and nutritional indices are less studied. Here, we investigated these traits of FAW when fed on maize, wheat, soybean, tomato, cotton, and Chinese cabbage, and analyzed the correlation between its nutritional indices and the nutritional contents of crops. The results showed that the highest number of eggs were laid on maize and the lowest number were laid on tomato. The highest feeding choice rate of third instar larvae was on maize, and the lowest was on Chinese cabbage. The fifth instar larvae showed the highest feeding choice rate on maize, but no significant differences were found among other crop species. The food consumption (FC), the relative growth rate (RGR), and the approximate digestibility (AD) were significantly higher on maize and wheat, while the efficiency of conversion of ingested food (ECI) and the efficiency of conversion of digested food (ECD) were significantly higher when fed on cotton and Chinese cabbage. The FC, the relative consumption rate (RCR), RGR, and AD were significantly and positively correlated with soluble sugar and protein contents of host plants, while the ECI and ECD were significantly and negatively correlated with the soluble sugar content. The present study indicates that FAW may cause potential economic losses to these crops besides maize, and these findings are valuable in managing and controlling this pest.


Subject(s)
Brassica , Moths , Solanum lycopersicum , Animals , Spodoptera , Larva , Nutrition Assessment , Crops, Agricultural , Zea mays , Sugars
12.
Curr Med Sci ; 43(3): 551-559, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37115398

ABSTRACT

OBJECTIVE: To compare survival outcomes between primary radical surgery and primary radiation in early cervical cancer. METHODS: Patient information was extracted from the Surveillance, Epidemiology, and Results database. Patients diagnosed with early cervical cancer of stage T1a, T1b, and T2a (American Joint Committee on Cancer, 7th edition) from 1998 to 2015 were included in this study after propensity score matching. Overall survival (OS) was analyzed using the Kaplan-Meier method. RESULTS: Among the 4964 patients included in the study, 1080 patients were identified as having positive lymph nodes (N1), and 3884 patients were identified as having negative lymph nodes (N0). Patients with primary surgery had significantly longer 5-year OS than those with primary radiotherapy in both the N1 group (P<0.001) and N0 group (P<0.001). In the subgroup analysis, similar results were found in patients with positive lymph nodes of stage T1a (100.0% vs. 61.1%), T1b (84.1% vs. 64.3%), and T2a (74.4% vs. 63.8%). In patients with T1b1 and T2a1, primary surgery resulted in longer OS than primary radiation, but not in patients with T1b2 and T2a2. In multivariate analysis, the primary treatment was identified as an independent prognostic factor in both N1 and N0 patients (HRN1=2.522, 95% CI=1.919-3.054, PN1<0.001; HRN0=1.895, 95% CI=1.689-2.126, PN0<0.001). CONCLUSION: In early cervical cancer stage T1a, T1b1, and T2a1, primary surgery may result in longer OS than primary radiation for patients with and without lymph node metastasis.


Subject(s)
Lymph Nodes , Uterine Cervical Neoplasms , Female , Humans , Lymph Nodes/surgery , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Neoplasm Staging , Uterine Cervical Neoplasms/radiotherapy , Uterine Cervical Neoplasms/surgery , Uterine Cervical Neoplasms/pathology
13.
BMC Plant Biol ; 23(1): 134, 2023 Mar 08.
Article in English | MEDLINE | ID: mdl-36882703

ABSTRACT

BACKGROUND: Calcium ions (Ca2+), secondary messengers, are crucial for the signal transduction process of the interaction between plants and pathogens. Ca2+ signaling also regulates autophagy. As plant calcium signal-decoding proteins, calcium-dependent protein kinases (CDPKs) have been found to be involved in biotic and abiotic stress responses. However, information on their functions in response to powdery mildew attack in wheat crops is limited. RESULT: In the present study, the expression levels of TaCDPK27, four essential autophagy-related genes (ATGs) (TaATG5, TaATG7, TaATG8, and TaATG10), and two major metacaspase genes, namely, TaMCA1 and TaMCA9, were increased by powdery mildew (Blumeria graminis f. sp. tritici, Bgt) infection in wheat seedling leaves. Silencing TaCDPK27 improves wheat seedling resistance to powdery mildew, with fewer Bgt hyphae occurring on TaCDPK27-silenced wheat seedling leaves than on normal seedlings. In wheat seedling leaves under powdery mildew infection, silencing TaCDPK27 induced excess contents of reactive oxygen species (ROS); decreased the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT); and led to an increase in programmed cell death (PCD). Silencing TaCDPK27 also inhibited autophagy in wheat seedling leaves, and silencing TaATG7 also enhanced wheat seedling resistance to powdery mildew infection. TaCDPK27-mCherry and GFP-TaATG8h colocalized in wheat protoplasts. Overexpressed TaCDPK27-mCherry fusions required enhanced autophagy activity in wheat protoplast under carbon starvation. CONCLUSION: These results suggested that TaCDPK27 negatively regulates wheat resistance to PW infection, and functionally links with autophagy in wheat.


Subject(s)
Calcium , Disease Resistance , Plant Diseases , Triticum , Amino Acids , Erysiphe , Protein Kinases , Seedlings , Triticum/genetics , Triticum/microbiology , Disease Resistance/genetics , Plant Diseases/genetics , Plant Diseases/microbiology , Genes, Plant
14.
iScience ; 26(3): 106119, 2023 Mar 17.
Article in English | MEDLINE | ID: mdl-36852268

ABSTRACT

Long-read sequencing (LRS) facilitates both the genome assembly and the discovery of structural variants (SVs). Here, we built a graph-based pig pangenome by incorporating 11 LRS genomes with an average of 94.01% BUSCO completeness score, revealing 206-Mb novel sequences. We discovered 183,352 nonredundant SVs (63% novel), representing 12.12% of the reference genome. By genotyping SVs in an additional 196 short-read sequencing samples, we identified thousands of population stratified SVs. Particularly, we detected 7,568 Tibetan specific SVs, some of which demonstrate significant population differentiation between Tibetan and low-altitude pigs, which might be associated with the high-altitude hypoxia adaptation in Tibetan pigs. Further integrating functional genomic data, the most promising candidate genes within the SVs that might contribute to the high-altitude hypoxia adaptation were discovered. Overall, our study generates a benchmark pangenome resource for illustrating the important roles of SVs in adaptive evolution, domestication, and genetic improvement of agronomic traits in pigs.

15.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(1): 67-72, 2023 Jan 15.
Article in Chinese | MEDLINE | ID: mdl-36655666

ABSTRACT

OBJECTIVES: To study the clinical features of children with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). METHODS: A retrospective analysis was performed on the medical data of 34 children with GFAP-A who attended the Department of Neurology, Children's Hospital of Chongqing Medical University, from January 2020 to February 2022. The medical data included clinical manifestations, cerebrospinal fluid features, imaging examination results, treatment, and prognosis. RESULTS: The median age of onset was 8.4 (range 1.9-14.9) years for the 34 children with GFAP-A. The main clinical manifestations included headache (50%, 17/34), fever (47%, 16/34), visual impairment (47%, 16/34), and disturbance of consciousness (44%, 15/34). Abnormal cerebrospinal fluid results were observed in 19 children (56%, 19/34), among whom 8 children had positive autoantibody. The children with overlap syndrome had significantly higher recurrence rate and rate of use of immunosuppressant than those without overlap syndrome (P<0.05). About 77% (24/31) of the children had good response to immunotherapy, and only 1 child had poor prognosis. CONCLUSIONS: Children with GFAP-A often have non-specific clinical symptoms and show good response to immunotherapy. Children with overlap syndrome have a high recurrence rate, and early application of immunosuppressants may help to prevent recurrence and alleviate symptoms.


Subject(s)
Astrocytes , Autoimmune Diseases , Glial Fibrillary Acidic Protein , Adolescent , Child , Child, Preschool , Humans , Infant , Astrocytes/metabolism , Autoantibodies/metabolism , Glial Fibrillary Acidic Protein/cerebrospinal fluid , Glial Fibrillary Acidic Protein/metabolism , Prognosis , Retrospective Studies , Autoimmune Diseases/diagnosis , Autoimmune Diseases/metabolism
16.
Respir Res ; 23(1): 317, 2022 Nov 19.
Article in English | MEDLINE | ID: mdl-36403022

ABSTRACT

BACKGROUND: Emerging experimental and epidemiological evidence highlights a crucial cross-talk between the intestinal flora and the lungs, termed the "gut-lung axis". However, the function of the gut microbiota in bronchiectasis remains undefined. In this study, we aimed to perform a multi-omics-based approach to identify the gut microbiome and metabolic profiles in patients with bronchiectasis. METHODS: Fecal samples collected from non-CF bronchiectasis patients (BE group, n = 61) and healthy volunteers (HC group, n = 37) were analyzed by 16 S ribosomal RNA (rRNA) sequencing. The BE group was divided into two groups based on their clinical status: acute exacerbation (AE group, n = 31) and stable phase (SP group, n = 30). Further, metabolome (lipid chromatography-mass spectrometry, LC-MS) analyses were conducted in randomly selected patients (n = 29) and healthy volunteers (n = 31). RESULTS: Decreased fecal microbial diversity and differential microbial and metabolic compositions were observed in bronchiectasis patients. Correlation analyses indicated associations between the differential genera and clinical parameters such as bronchiectasis severity index (BSI). Disease-associated gut microbiota was screened out, with eight genera exhibited high accuracy in distinguishing SP patients from HCs in the discovery cohort and validation cohort using a random forest model. Further correlation networks were applied to illustrate the relations connecting disease-associated genera and metabolites. CONCLUSION: The study uncovered the relationships among the decreased fecal microbial diversity, differential microbial and metabolic compositions in bronchiectasis patients by performing a multi-omics-based approach. It is the first study to characterize the gut microbiome and metabolome in bronchiectasis, and to uncover the gut microbiota's potentiality as biomarkers for bronchiectasis. TRIAL REGISTRATION:  This study is registered with ClinicalTrials.gov, number NCT04490447.


Subject(s)
Bronchiectasis , Microbiota , Adult , Humans , Bronchiectasis/diagnosis , Fibrosis , Metabolome , Microbiota/genetics , RNA, Ribosomal, 16S/genetics
17.
Front Plant Sci ; 13: 904933, 2022.
Article in English | MEDLINE | ID: mdl-35812918

ABSTRACT

Metacaspases (MCAs), a family of caspase-like proteins, are important regulators of programmed cell death (PCD) in plant defense response. Autophagy is an important regulator of PCD. This study explored the underlying mechanism of the interaction among PCD, MCAs, and autophagy and their impact on wheat response to salt stress. In this study, the wheat salt-responsive gene TaMCA-Id was identified. The open reading frame (ORF) of TaMCA-Id was 1,071 bp, coding 356 amino acids. The predicted molecular weight and isoelectric point were 38,337.03 Da and 8.45, respectively. TaMCA-Id had classic characteristics of type I MCAs domains, a typical N-terminal pro-domain rich in proline. TaMCA-Id was mainly localized in the chloroplast and exhibited nucleocytoplasmictrafficking under NaCl treatment. Increased expression of TaMCA-Id in wheat seedling roots and leaves was triggered by 150 mM NaCl treatment. Silencing of TaMCA-Id enhanced sensitivity of wheat seedlings to NaCl stress. Under NaCl stress, TaMCA-Id-silenced seedlings exhibited a reduction in activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), higher accumulation of H2O2 and O 2 . - , more serious injury to photosystem II (PSII), increase in PCD level, and autophagy activity in leaves of wheat seedlings. These results indicated that TaMCA-Id functioned in PCD through interacting with autophagy under NaCl stress, which could be used to improve the salt tolerance of crop plants.

18.
Int J Mol Sci ; 23(13)2022 Jul 01.
Article in English | MEDLINE | ID: mdl-35806346

ABSTRACT

As essential calcium ion (Ca2+) sensors in plants, calcium-dependent protein kinases (CDPKs) function in regulating the environmental adaptation of plants. However, the response mechanism of CDPKs to salt stress is not well understood. In the current study, the wheat salt-responsive gene TaCDPK27 was identified. The open reading frame (ORF) of TaCDPK27 was 1875 bp, coding 624 amino acids. The predicted molecular weight and isoelectric point were 68.905 kDa and 5.6, respectively. TaCDPK27 has the closest relationship with subgroup III members of the CDPK family of rice. Increased expression of TaCDPK27 in wheat seedling roots and leaves was triggered by 150 mM NaCl treatment. TaCDPK27 was mainly located in the cytoplasm. After NaCl treatment, some of this protein was transferred to the membrane. The inhibitory effect of TaCDPK27 silencing on the growth of wheat seedlings was slight. After exposure to 150 mM NaCl for 6 days, the NaCl stress tolerance of TaCDPK27-silenced wheat seedlings was reduced, with shorter lengths of both roots and leaves compared with those of the control seedlings. Moreover, silencing of TaCDPK27 further promoted the generation of reactive oxygen species (ROS); reduced the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT); aggravated the injury to photosystem II (PS II); and increased programmed cell death (PCD) in wheat leaves under NaCl treatment, confirming that the TaCDPK27-silenced seedlings exhibited more NaCl injury than control seedlings. Taken together, the decrease in NaCl tolerance in TaCDPK27-silenced seedlings was due to excessive ROS accumulation and subsequent aggravation of the NaCl-induced PCD. TaCDPK27 may be essential for positively regulating salt tolerance in wheat seedlings.


Subject(s)
Salt Tolerance , Triticum , Calcium/metabolism , Protein Kinases/genetics , Protein Kinases/metabolism , Reactive Oxygen Species/metabolism , Salt Tolerance/genetics , Seedlings/metabolism , Sodium Chloride/metabolism , Sodium Chloride/pharmacology , Triticum/metabolism
19.
Nat Biomed Eng ; 6(1): 76-93, 2022 01.
Article in English | MEDLINE | ID: mdl-34992270

ABSTRACT

A reduced removal of dysfunctional mitochondria is common to aging and age-related neurodegenerative pathologies such as Alzheimer's disease (AD). Strategies for treating such impaired mitophagy would benefit from the identification of mitophagy modulators. Here we report the combined use of unsupervised machine learning (involving vector representations of molecular structures, pharmacophore fingerprinting and conformer fingerprinting) and a cross-species approach for the screening and experimental validation of new mitophagy-inducing compounds. From a library of naturally occurring compounds, the workflow allowed us to identify 18 small molecules, and among them two potent mitophagy inducers (Kaempferol and Rhapontigenin). In nematode and rodent models of AD, we show that both mitophagy inducers increased the survival and functionality of glutamatergic and cholinergic neurons, abrogated amyloid-ß and tau pathologies, and improved the animals' memory. Our findings suggest the existence of a conserved mechanism of memory loss across the AD models, this mechanism being mediated by defective mitophagy. The computational-experimental screening and validation workflow might help uncover potent mitophagy modulators that stimulate neuronal health and brain homeostasis.


Subject(s)
Alzheimer Disease , Mitophagy , Alzheimer Disease/drug therapy , Alzheimer Disease/pathology , Amyloid beta-Peptides , Animals , Machine Learning , Mitophagy/physiology , Workflow
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