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1.
Eur J Neurosci ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38722153

ABSTRACT

The presence of neurofibrillary tangles containing hyper-phosphorylated tau is a characteristic of Alzheimer's disease (AD) pathology. The positron emission tomography (PET) radioligand sensitive to tau neurofibrillary tangles (18F-AV1451) also binds with iron. This off-target binding effect may be enhanced in older adults on the AD spectrum, particularly those with amyloid-positive biomarkers. Here, we examined group differences in 18F-AV1451 PET after controlling for iron-sensitive measures from magnetic resonance imaging (MRI) and its relationships to tissue microstructure and cognition in 40 amyloid beta positive (Aß+) individuals, 20 amyloid beta negative (Aß-) with MCI and 31 Aß- control participants. After controlling for iron, increased 18F-AV1451 PET uptake was found in the temporal lobe and hippocampus of Aß+ participants compared to Aß- MCI and control participants. Within the Aß+ group, significant correlations were seen between 18F-AV1451 PET uptake and tissue microstructure and these correlations remained significant after controlling for iron. These findings indicate that off-target binding of iron to the 18F-AV1451 ligand may not affect its sensitivity to Aß status or cognition in early-stage AD.

2.
PLoS One ; 19(5): e0298651, 2024.
Article in English | MEDLINE | ID: mdl-38753655

ABSTRACT

Dynamic functional connectivity investigates how the interactions among brain regions vary over the course of an fMRI experiment. Such transitions between different individual connectivity states can be modulated by changes in underlying physiological mechanisms that drive functional network dynamics, e.g., changes in attention or cognitive effort. In this paper, we develop a multi-subject Bayesian framework where the estimation of dynamic functional networks is informed by time-varying exogenous physiological covariates that are simultaneously recorded in each subject during the fMRI experiment. More specifically, we consider a dynamic Gaussian graphical model approach where a non-homogeneous hidden Markov model is employed to classify the fMRI time series into latent neurological states. We assume the state-transition probabilities to vary over time and across subjects as a function of the underlying covariates, allowing for the estimation of recurrent connectivity patterns and the sharing of networks among the subjects. We further assume sparsity in the network structures via shrinkage priors, and achieve edge selection in the estimated graph structures by introducing a multi-comparison procedure for shrinkage-based inferences with Bayesian false discovery rate control. We evaluate the performances of our method vs alternative approaches on synthetic data. We apply our modeling framework on a resting-state experiment where fMRI data have been collected concurrently with pupillometry measurements, as a proxy of cognitive processing, and assess the heterogeneity of the effects of changes in pupil dilation on the subjects' propensity to change connectivity states. The heterogeneity of state occupancy across subjects provides an understanding of the relationship between increased pupil dilation and transitions toward different cognitive states.


Subject(s)
Bayes Theorem , Brain , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/methods , Brain/physiology , Brain/diagnostic imaging , Nerve Net/physiology , Nerve Net/diagnostic imaging , Models, Neurological , Markov Chains , Connectome/methods , Brain Mapping/methods
3.
Int Immunopharmacol ; 133: 112102, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38652971

ABSTRACT

Anaplastic thyroid carcinoma (ATC) is the most aggressive subtype of thyroid cancer with few effective therapies. Though immunotherapies such as targeting PD-1/PD-L1 axis have benefited patients with solid tumor, the druggable immune checkpoints are quite limited in ATC. In our study, we focused on the anti-tumor potential of sialic acid-binding Ig-like lectins (Siglecs) in ATC. Through screening by integrating microarray datasets including 216 thyroid-cancer tissues and single-cell RNA-sequencing, SIGLEC family members CD33, SIGLEC1, SIGLEC10 and SIGLEC15 were significantly overexpressed in ATC, among which SIGLEC15 increased highest and mainly expressed on cancer cells. SIGLEC15high ATC cells are characterized by high expression of serine protease PRSS23 and cancer stem cell marker CD44. Compared with SIGLEC15low cancer cells, SIGLEC15high ATC cells exhibited higher interaction frequency with tumor microenvironment cells. Further study showed that SIGLEC15high cancer cells mainly interacted with T cells by immunosuppressive signals such as MIF-TNFRSF14 and CXCL12-CXCR4. Notably, treatment of anti-SIGLEC15 antibody profoundly increased the cytotoxic ability of CD8+ T cells in a co-culture model and zebrafish-derived ATC xenografts. Consistently, administration of anti-SIGLEC15 antibody significantly inhibited tumor growth and prolonged mouse survival in an immunocompetent model of murine ATC, which was associated with increase of M1/M2, natural killer (NK) cells and CD8+ T cells, and decrease of myeloid-derived suppressor cells (MDSCs). SIGLEC15 inhibited T cell activation by reducing NFAT1, NFAT2, and NF-κB signals. Blocking SIGLEC15 increased the secretion of IFN-γ and IL-2 in vitro and in vivo. In conclusion, our finding demonstrates that SIGLEC15 is an emerging and promising target for immunotherapy in ATC.


Subject(s)
Immunotherapy , Lectins , Thyroid Carcinoma, Anaplastic , Humans , Animals , Thyroid Carcinoma, Anaplastic/therapy , Thyroid Carcinoma, Anaplastic/immunology , Thyroid Carcinoma, Anaplastic/genetics , Immunotherapy/methods , Mice , Cell Line, Tumor , Lectins/genetics , Lectins/metabolism , Thyroid Neoplasms/therapy , Thyroid Neoplasms/immunology , Thyroid Neoplasms/genetics , Tumor Microenvironment/immunology , CD8-Positive T-Lymphocytes/immunology , Xenograft Model Antitumor Assays , Antineoplastic Agents, Immunological/pharmacology , Antineoplastic Agents, Immunological/therapeutic use , Immunoglobulins , Membrane Proteins
4.
Adv Sci (Weinh) ; : e2306671, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38639383

ABSTRACT

Cancer metastasis is the leading cause of mortality in patients with hepatocellular carcinoma (HCC). To meet the rapid malignant growth and transformation, tumor cells dramatically increase the consumption of nutrients, such as amino acids. Peptide transporter 1 (PEPT1), a key transporter for small peptides, has been found to be an effective and energy-saving intracellular source of amino acids that are required for the growth of tumor cells. Here, the role of PEPT1 in HCC metastasis and its underlying mechanisms is explored. PEPT1 is upregulated in HCC cells and tissues, and high PEPT1 expression is associated with poor prognosis in patients with HCC. PEPT1 overexpression dramatically promoted HCC cell migration, invasion, and lung metastasis, whereas its knockdown abolished these effects both in vitro and in vivo. Mechanistic analysis revealed that high PEPT1 expression increased cellular dipeptides in HCC cells that are responsible for activating the MAP4K4/G3BP2 signaling pathway, ultimately facilitating the phosphorylation of G3BP2 at Thr227 and enhancing HCC metastasis. Taken together, these findings suggest that PEPT1 acts as an oncogene in promoting HCC metastasis through dipeptide-induced MAP4K4/G3BP2 signaling and that the PEPT1/MAP4K4/G3BP2 axis can serve as a promising therapeutic target for metastatic HCC.

5.
J Am Chem Soc ; 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38597345

ABSTRACT

Deubiquitinase-targeting chimeras (DUBTACs) have been recently developed to stabilize proteins of interest, which is in contrast to targeted protein degradation (TPD) approaches that degrade disease-causing proteins. However, to date, only the OTUB1 deubiquitinase has been utilized to develop DUBTACs via an OTUB1 covalent ligand, which could unexpectedly compromise the endogenous function of OTUB1 owing to its covalent nature. Here, we show for the first time that deubiquitinase USP7 can be harnessed for DUBTAC development. Based on a noncovalent ligand of USP7, we developed USP7-based DUBTACs that stabilized the ΔF508-CFTR mutant protein as effectively as the previously reported OTUB1-based DUBTAC. Importantly, using two different noncovalent ligands of USP7, we developed the first AMPK DUBTACs that appear to selectively stabilize different isoforms of AMPKß, leading to elevated AMPK signaling. Overall, these results highlight that, in addition to OTUB1, USP7 can be leveraged to develop DUBTACs, thus significantly expanding the limited toolbox for targeted protein stabilization and the development of novel AMPK DUBTACs as potential therapeutics.

6.
Mol Plant Pathol ; 25(2): e13431, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38353627

ABSTRACT

Feruloyl esterase (ferulic acid esterase, FAE) is an essential component of many biological processes in both eukaryotes and prokaryotes. This research aimed to investigate the role of FAE and its regulation mechanism in plant immunity. We identified a secreted feruloyl esterase VdFAE from the hemibiotrophic plant pathogen Verticillium dahliae. VdFAE acted as an important virulence factor during V. dahliae infection, and triggered plant defence responses, including cell death in Nicotiana benthamiana. Deletion of VdFAE led to a decrease in the degradation of ethyl ferulate. VdFAE interacted with Gossypium hirsutum protein dihydroflavanol 4-reductase (GhDFR), a positive regulator in plant innate immunity, and promoted the degradation of GhDFR. Furthermore, silencing of GhDFR led to reduced resistance of cotton plants against V. dahliae. The results suggested a fungal virulence strategy in which a fungal pathogen secretes FAE to interact with host DFR and interfere with plant immunity, thereby promoting infection.


Subject(s)
Acremonium , Alcohol Oxidoreductases , Ascomycota , Carboxylic Ester Hydrolases , Gossypium , Verticillium
7.
Phytopathology ; 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38330212

ABSTRACT

Stripe rust, caused Puccinia striiformis f. sp. tritici (Pst), is one of the main diseases of wheat worldwide. Mianyang of Sichuan province in southwest in China is one of main regions for winter Pst inoculum production and spring epidemic, and provides urediniospores for infecting wheat in the surrounding regions. Understanding the urediniospore dynamics is important to predict and manage stripe rust. In this study, spore trapping coupled with a TaqMan real-time quantitative PCR (TaqMan-qPCR) method was used to monitor airborne Pst urediniospores from December 2019 to December 2022 in Mianyang. Weather conditions (temperature, relative humidity, daily sunshine duration and precipitation) were collected for the same period. These data were used to study the relationship of airborne urediniospore density with climatic conditions. The results showed that Pst urediniospores were captured all year round, and the annual peak of urediniospore densities occurred in the period from March to April in which the urediniospores accounted for the largest proportion of the annual total urediniospores. The density of urediniospores in the period of March to April was linearly related to the average sunshine duration of 20 days and average temperature of 15 days prior to the final day of a 7-day trapping period. This relationship needs to be tested in other regions where Pst can sporulate during the winter before it can be integrated with Pst infection conditions to predict rust development.

8.
Eur J Pediatr ; 183(3): 1233-1244, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38091068

ABSTRACT

This study aims to examine the clinical characteristics and outcomes of clinical myocarditis in pediatric patients in China. This is a multicenter retrospective study. Children diagnosed with clinical myocarditis from 20 hospitals in China and admitted between January 1, 2015, and December 30, 2021, were enrolled. The clinical myocarditis was diagnosed based on the "Diagnostic Recommendation for Myocarditis in Children (Version 2018)". The clinical data were collected from their medical records. A total of 1210 patients were finally enrolled in this study. Among them, 45.6% had a history of respiratory tract infection. An abnormal electrocardiogram was observed in 74.2% of patients. Echocardiography revealed that 32.3% of patients had a left ventricular ejection fraction of less than 50%. Cardiac MRI was performed in 4.9% of children with clinical myocarditis, of which 61% showed localized or diffuse hypersignal on T2-weighted images. Serum levels of cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and N-terminal B-type natriuretic peptide (NT-proBNP) were higher in patients with fulminant myocarditis than in patients with myocarditis, making them potential risk factors for fulminant myocarditis. Following active treatment, 12.1% of patients were cured, and 79.1% were discharged with improvement. CONCLUSION: Clinical myocarditis in children often presents with symptoms outside the cardiovascular system. CK-MB, cTnI, and NT-proBNP are important indicators for assessing clinical myocarditis. The electrocardiogram and echocardiogram findings in children with clinical myocarditis exhibit significant variability but lack specificity. Cardiac MRI can be a useful tool for screening clinical myocarditis. Most children with clinical myocarditis have a favorable prognosis. WHAT IS KNOWN: • Pediatric myocarditis presents complex clinical manifestations and exhibits varying degrees of severity. Children with mild myocarditis generally have a favorable prognosis, while a small number of children with critically ill myocarditis experience sudden onset, hemodynamic disorders, and fatal arrhythmias. Therefore, early diagnosis and timely treatment of myocarditis are imperative. WHAT IS NEW: • To the best of our knowledge, this multicenter retrospective study is the largest ever reported in China, aiming to reveal the clinical characteristics and outcomes of pediatric clinical myocarditis in China. We provided an extensive analysis of the clinical characteristics, diagnosis, treatment, prognosis, and factors impacting disease severity in pediatric clinical myocarditis in China, which provides insights into the epidemiological characteristics of pediatric clinical myocarditis.


Subject(s)
Myocarditis , Child , Humans , Myocarditis/diagnosis , Myocarditis/therapy , Retrospective Studies , Stroke Volume , Ventricular Function, Left , Creatine Kinase, MB Form , Arrhythmias, Cardiac , China/epidemiology
9.
Sci Transl Med ; 15(725): eadh7668, 2023 12 06.
Article in English | MEDLINE | ID: mdl-38055802

ABSTRACT

Targeting angiotensin-converting enzyme 2 (ACE2) represents a promising and effective approach to combat not only the COVID-19 pandemic but also potential future pandemics arising from coronaviruses that depend on ACE2 for infection. Here, we report ubiquitin specific peptidase 2 (USP2) as a host-directed antiviral target; we further describe the development of MS102, an orally available USP2 inhibitor with viable antiviral activity against ACE2-dependent coronaviruses. Mechanistically, USP2 serves as a physiological deubiquitinase of ACE2, and targeted inhibition with specific small-molecule inhibitor ML364 leads to a marked and reversible reduction in ACE2 protein abundance, thereby blocking various ACE2-dependent coronaviruses tested. Using human ACE2 transgenic mouse models, we further demonstrate that ML364 efficiently controls disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as evidenced by reduced viral loads and ameliorated lung inflammation. Furthermore, we improved the in vivo performance of ML364 in terms of both pharmacokinetics and antiviral activity. The resulting lead compound, MS102, holds promise as an oral therapeutic option for treating infections with coronaviruses that are reliant on ACE2.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Humans , Mice , Angiotensin-Converting Enzyme 2 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Mice, Transgenic , Pandemics , Peptidyl-Dipeptidase A/metabolism , Ubiquitin Thiolesterase
10.
Microsyst Nanoeng ; 9: 138, 2023.
Article in English | MEDLINE | ID: mdl-37941763

ABSTRACT

High-performance micro-electro-mechanical system (MEMS) gyrocompasses for north-finding systems have been very popular for decades. In this paper, a MEMS north-finding system (NFS) based on virtual maytagging (VM) is presented for the first time. In stark contrast to previous schemes of MEMS-based NFSs (e.g., carouseling, maytagging) and the abandoning rate table, we developed a honeycomb disk resonator gyroscope (HDRG) and two commercial accelerometers for azimuth detection. Instead of the physical rotation of the integrated turntable in traditional NFSs, the vibratory working modes of the HDRG are rotated periodically with electronic control to reduce the uncertainty in the azimuth. After systematically analyzing the principle of NFSs with VM, we designed tests to verify the practicability at the sensor level. A bias instability of 0.0078°/h can be obtained during one day with VM in an HDRG. We also implemented comparative north-finding experiments to further check our strategy at the system level. The accuracy in the azimuth can reach 0.204° for 5 min at 28.2° latitude with VM and 0.172° with maytagging. The results show that without any mechanical turning parts, VM technology makes it possible to develop high-precision handheld MEMS NFSs.

11.
J Med Chem ; 66(23): 16168-16186, 2023 12 14.
Article in English | MEDLINE | ID: mdl-38019706

ABSTRACT

As a core chromatin-regulatory scaffolding protein, WDR5 mediates numerous protein-protein interactions (PPIs) with other partner oncoproteins. However, small-molecule inhibitors that block these PPIs exert limited cell-killing effects. Here, we report structure-activity relationship studies in pancreatic ductal adenocarcinoma (PDAC) cells that led to the discovery of several WDR5 proteolysis-targeting chimer (PROTAC) degraders, including 11 (MS132), a highly potent and selective von Hippel-Lindau (VHL)-recruiting WDR5 degrader, which displayed positive binding cooperativity between WDR5 and VHL, effectively inhibited proliferation in PDAC cells, and was bioavailable in mice and 25, a cereblon (CRBN)-recruiting WDR5 degrader, which selectively degraded WDR5 over the CRBN neo-substrate IKZF1. Furthermore, by conducting site-directed mutagenesis studies, we determined that WDR5 K296, but not K32, was involved in the PROTAC-induced WDR5 degradation. Collectively, these studies resulted in a highly effective WDR5 degrader, which could be a potential therapeutic for pancreatic cancer and several potentially useful tool compounds.


Subject(s)
Pancreatic Neoplasms , Proteolysis Targeting Chimera , Animals , Mice , Proteolysis , Structure-Activity Relationship , Pancreatic Neoplasms/drug therapy , Ubiquitin-Protein Ligases/metabolism
12.
Plant Dis ; 2023 Nov 08.
Article in English | MEDLINE | ID: mdl-37938905

ABSTRACT

Aegilops species are wheat relatives that harbor valuable disease resistance genes for wheat breeding. The wheat Yr8 near-isogenic line, AvSYr8NIL, has long been believed to carry only Yr8 for race-specific all-stage resistance to stripe rust, caused by Puccinia striiformis f. sp. tritici, derived from Aegilops comosa. However, AvSYr8NIL has been found to have high-temperature adult-plant (HTAP) resistance in our field and greenhouse tests. To confirm both HTAP and Yr8 resistance, seeds from AvSYr8NIL were treated with ethyl methanesulfonate to generate mutant lines. The mutant lines with only Yr8 (M641) and only HTAP resistance (M488) were crossed with the susceptible recurrent parent, Avocet S (AvS). The F1 and F4 lines of AvS/M641 were phenotyped with Yr8-avirulent races in the seedling stage at the low-temperature (4-20oC) profile, while the F1, F2, F4, and F5 lines of AvS/M488 were phenotyped with Yr8-virulent races in the adult-plant stage at the high-temperature (10-30oC) profile. Both Yr8 and the HTAP resistance gene (YrM488) were recessive. The F4 populations of AvS/M641 and AvS/M488 were genotyped using polymorphic Kompetitive allele-specific PCR markers converted from SNPs. Yr8 was mapped to a 0.66 cM fragment and YrM488 to a 1.22 cM interval on chromosome 2D. The physical distance between the two resistance genes was estimated to be over 500 Mb, indicating their distinct loci. The mutant lines with separated resistance genes would be useful in enhancing our understanding of different types of resistance and in further studying the interactions between wheat and the stripe rust pathogen.

13.
J. physiol. biochem ; 79(4): 757-770, nov. 2023.
Article in English | IBECS | ID: ibc-227550

ABSTRACT

Recent studies suggest that Rab11-family interacting proteins (Rab11-FIPs) play an important role in tumorigenesis and progression. Among the Rab11-FIPs, Rab11-FIP4 has been reported to be significantly upregulated in various cancers, including hepatocellular carcinoma (HCC). However, the possible effect on HCC stemness and the underlying mechanism has never been characterized. Here, we found that Rab11-FIP4 was dramatically increased in HCC cell lines and tissues, and had a positive correlation with cancer stemness. Functional studies revealed that elevated expression of Rab11-FIP4 in HCC cells significantly promoted sphere formation, and enhanced the mRNA and protein levels of stemness-associated markers, ALDH1A1, CD133, NANOG, and OCT4. Conversely, the knockdown of Rab11-FIP4 suppressed the cancer stem cell (CSC)-like characteristics of HCC cells. Moreover, silencing of Rab11-FIP4 obviously increased the sensitivity of HCC cells to sorafenib. Mechanistically, Rab11-FIP4 was shown to interact with ADP-ribosylation factor 5 (ARF5) to influence cell cycle-related proteins, CDK1/cyclin B, thereby promoting HCC stemness. Taken together, our results uncovered an essential role for Rab11-FIP4 in regulating CSC-like features of HCC cells and identified Rab11-FIP4 as a potential target for HCC therapy. (AU)


Subject(s)
Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , ADP-Ribosylation Factors/metabolism , Cell Line, Tumor , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Sorafenib , Carrier Proteins/physiology
14.
Food Res Int ; 173(Pt 1): 113274, 2023 11.
Article in English | MEDLINE | ID: mdl-37803586

ABSTRACT

To investigate the changes in phenolics, flavonoids, and their bio-activities of wampee (Clausena lansium (Lour.) Skeels) during digestion, the peel and pulp were subjected to simulated in vitro digestion, encompassing oral, gastric, small intestine, and large intestine digestion stages. The peel exhibited a total release of 91.93 mg GAE/g DW of phenolics and 61.86 mg RE/g DW of flavonoids, whereas the pulp displayed a release of 27.83 mg GAE/g DW of phenolics and 8.94 mg RE/g DW of flavonoids. Notably, the phenolics and flavonoids were mostly released during the oral digestion stage for peel, while they were mostly released during the small intestine digestion stage for pulp. The results of the targeted flavonoids analysis indicated that rutin and l-epicatechin were the two most widely released compounds in each digestion step. Moreover, myricetin has been identified as the best inhibitor against α-glucosidase, probably because it formed the most H-bonds, 8, with 6 catalytic residues, which was the highest number. Furthermore, the soluble substances released from the peel exhibited significantly higher antioxidant activities and inhibitory activity against α-glucosidase (p < 0.05) compared to those from the pulp. Positive correlations were observed between the total phenolic content or total flavonoid content and the antioxidant activities (r > 0.73 (peel), > 0.61 (pulp)), as well as α-glucosidase inhibitory activity (r <  - 0.48 (peel), < -0.64 (pulp)) of peel and pulp. In conclusion, these findings provide valuable insights into the digestive characteristics and health benefits of both wampee peel and pulp.


Subject(s)
Antioxidants , Clausena , Antioxidants/pharmacology , Antioxidants/chemistry , Clausena/chemistry , alpha-Glucosidases , Plant Extracts/pharmacology , Plant Extracts/chemistry , Phenols/chemistry , Flavonoids/chemistry , Digestion
15.
Front Microbiol ; 14: 1205477, 2023.
Article in English | MEDLINE | ID: mdl-37779707

ABSTRACT

Invasive fungal disease (IFD) poses a significant threat to immunocompromised patients and remains a global challenge due to limited treatment options, high mortality and morbidity rates, and the emergence of drug-resistant strains. Despite advancements in antifungal agents and diagnostic techniques, the lack of effective vaccines, standardized diagnostic tools, and efficient antifungal drugs contributes to the ongoing impact of invasive fungal infections (IFI). Recent studies have highlighted the presence of extracellular vesicles (EVs) released by fungi carrying various components such as enzymes, lipids, nucleic acids, and virulence proteins, which play roles in both physiological and pathological processes. These fungal EVs have been shown to interact with the host immune system during the development of fungal infections whereas their functional role and potential application in patients are not yet fully understood. This review summarizes the current understanding of the biologically relevant findings regarding EV in host-pathogen interaction, and aim to describe our knowledge of the roles of EV as diagnostic tools and vaccine vehicles, offering promising prospects for the treatment of IFI patients.

16.
Mol Plant Pathol ; 24(12): 1522-1534, 2023 12.
Article in English | MEDLINE | ID: mdl-37786323

ABSTRACT

Wheat cultivar Xiaoyan 6 (XY6) has high-temperature seedling-plant (HTSP) resistance to Puccinia striiformis f. sp. tritici (Pst). However, the molecular mechanism of Pst effectors involved in HTSP resistance remains unclear. In this study, we determined the interaction between two Pst effectors, PstCEP1 and PSTG_11208, through yeast two-hybrid (Y2H), bimolecular fluorescence complementation (BiFC), and pull-down assays. Transient overexpression of PSTG_11208 enhanced HTSP resistance in different temperature treatments. The interaction between PstCEP1 and PSTG_11208 inhibited the resistance enhancement by PSTG_11208. Furthermore, the wheat apoplastic thaumatin-like protein 1 (TaTLP1) appeared to recognize Pst invasion by interacting with PSTG_11208 and initiate the downstream defence response by the pathogenesis-related protein TaPR1. Silencing of TaTLP1 and TaPR1 separately or simultaneously reduced HTSP resistance to Pst in XY6. Moreover, we found that PstCEP1 targeted wheat ferredoxin 1 (TaFd1), a homologous protein of rice OsFd1. Silencing of TaFd1 affected the stability of photosynthesis in wheat plants, resulting in chlorosis on the leaves and reducing HTSP resistance. Our findings revealed the synergistic mechanism of effector proteins in the process of pathogen infection.


Subject(s)
Basidiomycota , Seedlings , Seedlings/metabolism , Triticum/genetics , Triticum/metabolism , Temperature , Puccinia , Basidiomycota/physiology , Plant Diseases
17.
Heliyon ; 9(10): e20094, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37867870

ABSTRACT

Cutaneous endometriosis, characterized by the presence of endometrium or endometrial-like tissue outside of the uterine cavity, is an uncommon and chronic disease. Depending on a patient's history, cutaneous endometriosis is classified as either primary cutaneous endometriosis (PCE) or secondary cutaneous endometriosis (SCE). We report a case of SCE presenting with the classic triad of previous caesarean section, subcutaneous nodules at the site of the scar, and pain associated with menstruation. Considering histopathology as the standard, we confirmed a diagnosis of cutaneous endometriosis by ultrasound and histopathology. Furthermore, we compared and analyzed the clinical characteristics of PCE and SCE, the study included 20 and 14 patients with cutaneous endometriosis diagnosed with PCE and SCE respectively. In the PCE group, the mean age of patients at the onset was 33.7 years, while it was 40.6 years in the SCE group. The mean disease-duration time of PCE was shorter than that of SCE (1.3 vs. 2.8 years, P > 0.05). The most common clinical presentation of PCE and SCE was a nodule (90% vs. 86%). The PCE was mainly bleeding with pain (45%), whereas the SCE of only pain and bleeding with pain accounted for the same proportion (45%). The most common sites of PCE and SCE were in the umbilical region (90% vs. 57%, P < 0.05). In our study, some statistically significant difference was found between different types of CE and it may contribute to improve clinicians' understanding of the disease, and perform early diagnosis and treatment.

18.
Curr Med Chem ; 2023 Oct 24.
Article in English | MEDLINE | ID: mdl-37877505

ABSTRACT

Malignant melanoma (MM) is a highly aggressive cancer with a poor prognosis. Currently, although a variety of therapies are available for treating melanoma, MM is still a serious threat to the patient's life due to numerous factors, such as the recurrence of tumors, the emergence of drug resistance, and the lack of effective therapeutic agents. Exosomes are biologically active lipid-bilayer extracellular vesicles secreted by diverse cell types that mediate intercellular signal communication. Studies found that exosomes are involved in cancer by carrying multiple bioactive molecules, including non-- coding RNAs (ncRNAs). The ncRNAs have been reported to play an important role in regulating proliferation, angiogenesis, immune regulation, invasion, metastasis, and treatment resistance of tumors. However, the functional role of exosomal ncRNAs in MM remains unknown. Therefore, this review summarizes the current state of melanoma diagnosis, treatment, and the application of exosomal ncRNAs in MM patients, which may provide new insights into the mechanisms involved in melanoma progression and serve as biomarkers for diagnosis and therapeutic targets.

19.
Chempluschem ; 88(9): e202300315, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37565738

ABSTRACT

Ni-Fe battery is one of prospective aqueous alkaline batteries due to its high safety, eco-friendliness and cost-effectiveness. However, the electrochemical performance of Fe-based anodes is limited due to the particle aggregation and low electric conductivity. In this work, iron powder is used as a precursor in a chemical bath deposition method. By optimizing the concentration of HNO3 , a balanced dissolution-crystallization process is achieved to obtain uniform Fe2 O3 nanospheres in size between 60 and 90 nm, which are separately anchored on ultrasonically prepared multilayer graphene (MLG). This composite delivers specific discharge capacities of 191.1 and 160.8 mAh g-1 at the current densities of 2 and 10 A g-1 , respectively. A Ni-Fe battery with the as-prepared Fe2 O3 /MLG as anode and Ni(OH)2 /MLG as cathode exhibits an energy density of 69.5 Wh kg-1 at a high power density of 3931.6 W kg-1 .

20.
Food Chem X ; 19: 100835, 2023 Oct 30.
Article in English | MEDLINE | ID: mdl-37636899

ABSTRACT

Wampee is a tropical fruit having high medicinal value. To fully realize the fruit's potential, it is essential to reveal the flavor characteristics. In this study, a comprehensive analysis of the aroma and taste profiles of different parts from the wampee fruit was conducted. The aroma profile was analyzed by E-nose, and 67 volatile components were identified through HS-SPME-GC-MS. Among them, 11 were considered as crucial compounds. Additionally, 42 volatile components were identified by HS-GC-IMS, with 22 compounds showing a variable importance in projection scores greater than 1.0. Moreover, the taste profile and representative compounds were analyzed by E-tongue and HPLC, and 12 compounds were considered as important taste contributors based on taste activity value. These findings shed light on the various compounds responsible for the unique aroma and taste of the wampee fruit, providing theoretical foundation for exploring ways for its comprehensive utilization and development.

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