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1.
Plant Cell Environ ; 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39360571

ABSTRACT

Alfalfa (Medicago sativa L.) is an important and widely cultivated forage legume, yet its yield is constrained by salinity stress. In this study, we characterized an R2R3-MYB transcription factor MsEOBI in alfalfa. Its salt tolerance function and regulatory pathways were investigated. The nuclear-localized MsEOBI functions as a transcriptional activator, enhancing salinity tolerance by promoting the biosynthesis of flavonoids and lignin, as well as facilitating the scavenging of reactive oxygen species (ROS). Additionally, MsEOBI promotes pollinator attraction and increases seed yield by activating the biosynthesis of volatile phenylpropanoids. Yeast one-hybrid (Y1H), dual-luciferase reporter and chromatin immunoprecipitation coupled with quantitative PCR (ChIP-qPCR) assays demonstrated that MsEOBI directly binds to the promoter regions of MsPAL1, a key gene in the phenylpropanoid pathway, thereby activating its expression. Overexpression of MsPAL1 enhances salinity tolerance in alfalfa. These findings elucidate the role of the MsEOBI-MsPAL1 regulatory module and provide valuable genetic resources for the future breeding of salt-tolerant alfalfa varieties.

2.
Structure ; 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39368462

ABSTRACT

Human papillomavirus (HPV), known for its oncogenic properties, is the primary cause of cervical cancer and significantly contributes to mortality rates. It also plays a considerable role in the globally rising incidences of head and neck cancers. These cancers pose a substantial health burden worldwide. Current limitations in diagnostic and treatment strategies, along with inadequate coverage of preventive vaccines in low- and middle-income countries, hinder the progress toward the World Health Organization (WHO) HPV prevention and control targets set for 2030. In response to these challenges, extensive research in structural virology has explored the properties of HPV proteins, yielding crucial insights into the mechanisms of HPV infection that are important for the development of prevention and therapeutic strategies. This review highlights recent advances in understanding the structures of HPV proteins and discusses achievements and future opportunities for HPV vaccine development.

3.
J Neurosci ; 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39261008

ABSTRACT

Perivascular mural cells including vascular smooth cells (VSMCs) and pericytes are integral components of the vascular system. In the central nervous system (CNS), pericytes are also indispensable for the blood-brain barrier (BBB), blood-spinal cord barrier and blood-retinal barrier, and play key roles in maintaining cerebrovascular and neuronal functions. However, the functional specifications of pericytes between CNS and peripheral organs have not been resolved at the genetic and molecular levels. Hence, the generation of reliable CNS pericyte-specific models and genetic tools remains very challenging. Here, we report a new CNS pericyte marker in mice. This putative cation-transporting ATPase 13A5 (Atp13a5) marker was identified through single cell transcriptomics, based on its specificity to brain pericytes. We further generated a knock-in model with both tdTomato reporter and Cre recombinase. Using this model to trace the distribution of Atp13a5-positive pericytes in mice, we found that the tdTomato reporter reliably labels the CNS pericytes, including the ones in spinal cord and retina but not peripheral organs. Interestingly, brain pericytes are likely shaped by the developing neural environment, as Atp13a5-positive pericytes start to appear around murine embryonic day 15 (E15) and expand along the cerebrovasculature. Thus, Atp13a5 is a specific marker of CNS pericyte lineage, and this Atp13a5-based model is a reliable tool to explore the heterogeneity of pericytes and BBB functions in health and diseases.Significance Statement Pericyte is a key component of the blood-brain barrier (BBB) and highly implicated in neurological and neurodegenerative diseases. However, current genetic tools for brain pericytes often come with limitations, due to the lack of specificity to the pericytes in the brain or central nervous system (CNS), as well as the overlap with other cell types, particularly vascular smooth muscle cells. Here, we identified that Atp13a5 is a CNS-specific pericyte marker based on mouse single-cell transcriptomics, and further validate it using a knock-in model carrying Atp13a5-driven tdTomato reporter and Cre recombinase. The success of the Atp13a5-based model opens new possibility of genetic manipulations targeting only CNS pericytes in vivo and studying their biology and functions in health and diseases more specifically.

4.
Rev Clin Esp (Barc) ; 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39122177

ABSTRACT

AIMS: Coronary heart disease (CHD) patients with changed serum soluble receptor for advanced glycation end products (sRAGE) will experience microalbuminuria and even kidney dysfunction. However, the role of sRAGE for microalbuminuria in CHD is still not established. This study aimed to evaluate the association between sRAGE and early kidney dysfunction in CHD patients. MATERIALS AND METHODS: In this cross-sectional study, sRAGE and urinary albumin-to-creatinine ratio (uACR) were measured in hospitalized CHD patients who have undergone coronary arteriography to evaluate the distinction and correlation between sRAGE and uACR. RESULTS: There were 127 CHD patients (mean age: 63.06 ± 10.93 years, 93 males) in the study, whose sRAGE were 1.83 ± 0.64 µg/L. The sRAGE level was higher in kidney injury group (uACR ≥ 30 mg/g) compared with no kidney injury group (uACR < 30 mg/g) [(2.08 ± 0.70 vs. 1.75 ± 0.61) µg/L, P < 0.05]. Moreover, the positive correlation between serum sRAGE and uACR was significant in CHD patients (r = 0.196, P < 0.05). Binary logistic regression suggests sRAGE as a predictor for microalbuminuria in CHD patients [Odd Ratio = 2.62 (1.12-6.15), P < 0.05)]. The area under the receiver operating characteristic curve (AUC) of sRAGE is higher than that of the traditional indicators of renal function such as creatinine and estimated glomerular filtration rate, indicating sRAGE might have a good performance in evaluating early kidney injury in CHD patients [AUC is 0.660 (0.543-0.778), P < 0.01)]. CONCLUSIONS: Serum sRAGE was positively correlated to uACR and might serve as a potential marker to predict early kidney injury in CHD patients.

5.
Neurotherapeutics ; 21(5): e00383, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38955643

ABSTRACT

Neuropathic pain (NP), a severe chronic pain condition, remains a substantial clinical challenge due to its complex pathophysiology and limited effective treatments. An association between the members of the Fibroblast Growth Factors (FGFs), particularly Fgf3, and the development of NP has become evident. In this study, utilizing a mouse model of NP, we observed a time-dependent increase in Fgf3 expression at both mRNA and protein levels within the dorsal root ganglia (DRG). Functional studies revealed that blocking Fgf3 expression mitigated nerve injury induced nociceptive hypersensitivity, suggesting its pivotal role in pain modulation. Moreover, our findings elucidate that Fgf3 contributes to pain hypersensitivity through the activation of the Akt/mTOR signaling in injured DRG neurons. These results not only shed light on the involvement of Fgf3 in nerve injury-induced NP but also highlight its potential as a promising therapeutic target for pain management. This study thereby advances our understanding of the molecular mechanisms underlying NP and opens new avenues for the development of effective treatment strategies.


Subject(s)
Ganglia, Spinal , Neuralgia , Proto-Oncogene Proteins c-akt , Sensory Receptor Cells , Signal Transduction , TOR Serine-Threonine Kinases , Animals , Neuralgia/metabolism , Mice , TOR Serine-Threonine Kinases/metabolism , Signal Transduction/physiology , Ganglia, Spinal/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Sensory Receptor Cells/metabolism , Male , Mice, Inbred C57BL , Cells, Cultured
6.
J Hazard Mater ; 472: 134519, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38733790

ABSTRACT

Emerging contaminants (ECs) are increasingly recognized as a global threat to biodiversity and ecosystem health. However, the cumulative risks posed by ECs to aquatic organisms and ecosystems, as well as the influence of anthropogenic activities and natural factors on these risks, remain poorly understood. This study assessed the mixed risks of ECs in Dongting Lake, a Ramsar Convention-classified Typically Changing Wetland, to elucidate the major EC classes, key risk drivers, and magnitude of anthropogenic and natural impacts. Results revealed that ECs pose non-negligible acute (30% probability) and chronic (70% probability) mixed risks to aquatic organisms in the freshwater lake ecosystem, with imidacloprid identified as the primary pollutant stressor. Redundancy analysis (RDA) and structural equation modeling (SEM) indicated that cropland and precipitation were major drivers of EC contamination levels and ecological risk. Cropland was positively associated with EC concentrations, while precipitation exhibited a dilution effect. These findings provide critical insights into the ecological risk status and key risk drivers in a typical freshwater lake ecosystem, offering data-driven support for the control and management of ECs in China.


Subject(s)
Lakes , Water Pollutants, Chemical , China , Water Pollutants, Chemical/analysis , Risk Assessment , Rivers/chemistry , Environmental Monitoring , Neonicotinoids/analysis , Neonicotinoids/toxicity , Ecosystem , Nitro Compounds/analysis , Aquatic Organisms
7.
ACS Synth Biol ; 13(7): 2081-2090, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-38607270

ABSTRACT

Ectoine is a compatible solute that functions as a cell protector from various stresses, protecting cells and stabilizing biomolecules, and is widely used in medicine, cosmetics, and biotechnology. Microbial fermentation has been widely used for the large-scale production of ectoine, and a number of fermentation strategies have been developed to increase the ectoine yield, reduce production costs, and simplify the production process. Here, Corynebacterium glutamicum was engineered for ectoine production by heterologous expression of the ectoine biosynthesis operon ectBAC gene from Halomonas elongata, and a series of genetic modifications were implemented. This included introducing the de3 gene from Escherichia coli BL21 (DE3) to express the T7 promoter, eliminating the lysine transporter protein lysE to limit lysine production, and performing a targeted mutation lysCS301Y on aspartate kinase to alleviate feedback inhibition of lysine. The new engineered strain Ect10 obtained an ectoine titer of 115.87 g/L in an optimized fed-batch fermentation, representing the highest ectoine production level in C. glutamicum and achieving the efficient production of ectoine in a low-salt environment.


Subject(s)
Amino Acids, Diamino , Corynebacterium glutamicum , Escherichia coli , Fermentation , Halomonas , Metabolic Engineering , Amino Acids, Diamino/biosynthesis , Amino Acids, Diamino/metabolism , Amino Acids, Diamino/genetics , Corynebacterium glutamicum/genetics , Corynebacterium glutamicum/metabolism , Metabolic Engineering/methods , Halomonas/genetics , Halomonas/metabolism , Escherichia coli/genetics , Escherichia coli/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Lysine/metabolism , Lysine/biosynthesis , Promoter Regions, Genetic , Operon/genetics , Aspartate Kinase/genetics , Aspartate Kinase/metabolism , Amino Acid Transport Systems, Basic
10.
IEEE Trans Pattern Anal Mach Intell ; 46(6): 4115-4128, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38285589

ABSTRACT

Human motion modeling is important for many modern graphics applications, which typically require professional skills. In order to remove the skill barriers for laymen, recent motion generation methods can directly generate human motions conditioned on natural languages. However, it remains challenging to achieve diverse and fine-grained motion generation with various text inputs. To address this problem, we propose MotionDiffuse, one of the first diffusion model-based text-driven motion generation frameworks, which demonstrates several desired properties over existing methods. 1) Probabilistic Mapping. Instead of a deterministic language-motion mapping, MotionDiffuse generates motions through a series of denoising steps in which variations are injected. 2) Realistic Synthesis. MotionDiffuse excels at modeling complicated data distribution and generating vivid motion sequences. 3) Multi-Level Manipulation. MotionDiffuse responds to fine-grained instructions on body parts, and arbitrary-length motion synthesis with time-varied text prompts. Our experiments show MotionDiffuse outperforms existing SoTA methods by convincing margins on text-driven motion generation and action-conditioned motion generation. A qualitative analysis further demonstrates MotionDiffuse's controllability for comprehensive motion generation.


Subject(s)
Movement , Humans , Movement/physiology , Algorithms , Image Processing, Computer-Assisted/methods , Computer Graphics , Motion
11.
Retina ; 44(2): 333-344, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37831943

ABSTRACT

PURPOSE: To quantify associations between various retinal microvascular changes and the risk of the development of coronary heart disease (CHD). METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were searched for cohort studies on the association between retinal microvascular changes and incident CHD up to July 31, 2023. The summary risk estimates were estimated using the random-effects model. Subgroup and sensitivity analyses were performed to investigate the potential source of heterogeneity. RESULTS: The authors identified 21 studies that met the inclusion criteria of this meta-analysis through database searching. This study yielded significant associations between retinal microvascular changes, including arteriolar narrowing, venular widening, vessel occlusion, and other retinal vascular signs, and the risk of CHD, with pooled adjusted hazard ratios of 1.20 (95% confidence interval: 1.13-1.27). In sex- and age-stratified analyses, retinal microvascular changes were associated with a greater risk of developing CHD in female patients and younger adults. CONCLUSION: A range of retinal microvascular changes was associated with the risk of CHD, particularly in female patients and younger ages. The results of this study support the concept that retinal microvascular abnormalities may be markers for future CHD. Noninvasive retinal microvascular assessments may be helpful in screening patients with increased CHD risk.


Subject(s)
Coronary Disease , Retinal Vessels , Adult , Female , Humans , Cohort Studies , Coronary Disease/diagnosis , Coronary Disease/epidemiology , Retina , Retinal Vessels/pathology , Risk Factors , Venules/pathology
12.
Bioelectrochemistry ; 156: 108628, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38104457

ABSTRACT

To enhance the sensitivity of flexible glucose sensors made with 3-aminophenylboronic acid and pyrrole as functional molecules and a carbon tri-electrode as substrate, graphene sponge (GS) and Prussian blue (PB) were used to enhance the charge transfer between the molecularly imprinted cavities and the electrodes. Electrochemical impedance spectroscopy and cyclic voltammetry showed that modifying the electrode with GS and PB significantly reduced the charge transfer impedance and increased the redox current of the sensor. The sensor has a sensitivity of up to 25.81 µA⋅loge (µM)-1⋅cm-2 for the detection of glucose using differential pulse voltammetry in the range of 7.78 to 600 µM, with a low detection limit of 1.08 µM (S/N = 3). When the pH varies in the range of 5.5 to 7.5, the sensor maintains a certain level of stability for glucose detection. The presence of lactic acid, urea, and ascorbic acid had minimal impact on glucose detection by the sensor. After 20 days of storage at room temperature, the sensor maintains 80 % efficiency. This study supports the development of wearable glucose sensors with high sensitivity, specificity, and stability through molecular imprinting.


Subject(s)
Graphite , Molecular Imprinting , Graphite/chemistry , Carbon/chemistry , Ferrocyanides/chemistry , Molecular Imprinting/methods , Electrodes , Glucose , Electrochemical Techniques/methods , Limit of Detection
13.
Front Cardiovasc Med ; 10: 1234325, 2023.
Article in English | MEDLINE | ID: mdl-37868781

ABSTRACT

Background: This study aims to investigate the association between an elevated bilateral pulse wave velocity difference (BPWVD) and cardiovascular diseases (CVDs) and all-cause mortality. Methods: This study included a total of 38,356 participants. A multivariable Cox proportional hazards regression was used to assess the association between high BPWVD and the increased risk of CVDs and all-cause mortality by calculating hazard ratios (HRs) with 95% confidence intervals. Results: A total of 1,213 cases of CVDs were identified over a mean duration of 6.19 years, including 886 cases of cerebral infarction (CI), 105 cases of intracerebral hemorrhage (ICH), and 222 cases of myocardial infarction (MI), along with 1,182 cases of all-cause mortality. The median BPWVD was 42 cm/s (19-80 cm/s). After adjusting for all confounders and baseline brachial-ankle PWV (baPWV), our analysis revealed a significant correlation between a higher risk of CVDs, MI, and all-cause mortality with an increase in BPWVD per standard deviation. HRs (95% confidence interval) were found to be 1.06 (1.01-1.11), 1.11 (1.02-1.21), and 1.07 (1.04-1.10), respectively. Among the participants with higher baPWV on the left side, the HRs (95% confidence interval) were 1.08 (1.02-1.14) for CVDs, 1.27 (1.10-1.46) for incident ICH, 1.16 (1.00-1.24) for incident MI, and 1.10 (1.07-1.15) for all-cause mortality, for per standard deviation increase in BPWVD. Conclusions: Our findings reveal a significant correlation between elevated BPWVD and the risks of developing CVDs and all-cause mortality. This highlights the importance of thoroughly evaluating BPWVD as a means of detecting individuals at risk for CVDs and mortality.

14.
Front Plant Sci ; 14: 1209384, 2023.
Article in English | MEDLINE | ID: mdl-37528980

ABSTRACT

Rice (Oryza sativa L.) is a staple food in many countries around the world, particularly in China. The production of rice is seriously affected by the bacterial leaf streak and rice blast, which can reduce rice yield or even cause it to fail to be harvested. In this study, susceptible material 58B was edited by CRISPR/Cas9, targeting a target of the Pi21 gene and a target of the effector-binding element (EBE) of the OsSULTR3;6 gene, and the mutants 58b were obtained by Agrobacterium-mediated method. The editing efficiency of the two targets in the T0 generation was higher than 90.09%, the homozygous mutants were successfully selected in the T0 generation, and the homozygous mutation rate of each target was higher than 26.67%. The expression of the edited pi21 and EBE of Ossultr3;6 was significantly reduced, and the expression of defense responsive genes was significantly upregulated after infected with rice blast. The lesion areas of rice blast and bacterial leaf streak were significantly reduced in 58b, and the resistance of both was effectively improved. Furthermore, the gene editing events did not affect the agronomic traits of rice. In this study, the resistance of 58b to rice blast and bacterial leaf streak was improved simultaneously. This study provides a reference for using Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 (CRISPR/Cas9) to accelerate the improvement of rice varieties and the development of new materials for rice breeding.

15.
Heliyon ; 9(6): e17027, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37342581

ABSTRACT

A novel PANI@CS solid-phase dispersive extractant combined with ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed for the first time, which was used for high-throughput, multi-component, real-time online rapid pretreatment and quantitative classification of 16 mycotoxins from five different medicinal parts of 13 genuine traditional Chinese medicines (TCMs). Ultra performance liquid chromatography combined with triple quadrupole mass spectrometry was used for separation and ESI detection. An internal standard isotope matching calibration was used for quantification purposes to compensate for matrix effects. The limits of detection (LOD) of 16 mycotoxins ranged from 0.1 to 6.0 µg/kg. The linear coefficients (R2) were ≥0.996 in the linear range from 10.0 to 200 µg/L. The recoveries of the 16 mycotoxins ranged from 90.1% to 105.8%, and the relative standard deviations (RSDs) ranged from 1.3% to 4.1%. Thirteen TCMs from five representative medicinal parts were selected and tested under the best sample preparation procedure and chromatographic analysis conditions. The results showed that the method could improve the sensitivity and accuracy of the sample analysis, improve the selectivity and reproducibility of the decolorization and purification of TCMs, which is suitable for the practical application of mycotoxin in trace analysis. This method can also provide a new idea for accurate, efficient, rapid and multi-component online detection of mycotoxins for quality and safety control of TCMs.

16.
Child Adolesc Psychiatry Ment Health ; 17(1): 82, 2023 Jun 29.
Article in English | MEDLINE | ID: mdl-37386597

ABSTRACT

BACKGROUND: Callous-unemotional traits and emotional lability/negativity of young children have been regarded as the markers of externalizing problem behaviors. Based on the sensitivity to threat and affiliative reward model and the general aggression model, emotional lability/negativity may act as a mediator in the relationship between callous-unemotional traits and externalizing problem behaviors. Additionally, a positive teacher-child relationship could act as a buffer given the parental absence in left-behind children. However, these links remain unexplored in left-behind preschool children. Therefore, this study explored the link between callous-unemotional traits of left-behind preschool children and externalizing problem behaviors, as well as the mediating role of emotional lability/negativity and the moderating role of a positive teacher-child relationship. METHOD: Data were collected on 525 left-behind children aged 3 to 6 years from rural kindergartens in China. Preschool teachers reported all data through an online survey platform. Moderated mediation analysis was performed to examine whether the mediated relation between callous-unemotional traits and externalizing problem behaviors was moderated by a positive teacher-child relationship. RESULTS: The results showed callous-unemotional traits significantly predicted externalizing problem behaviors and lability/negativity acted as a mediator, while a positive teacher-child relationship acted as a protective factor in moderating the relationship between callous-unemotional traits and emotional lability/negativity. This study identified a moderated mediation effect among the four variables in left-behind preschool children in China. CONCLUSION: The findings provide support for the advancement of theoretical foundations, and provide an avenue for further exploration to support the mental health and overall development of left-behind children during early childhood.

17.
Front Immunol ; 14: 1181016, 2023.
Article in English | MEDLINE | ID: mdl-37153544

ABSTRACT

Atypical chemokine receptor-1 (ACKR1), previously known as the Duffy antigen receptor for chemokines, is a widely conserved cell surface protein that is expressed on erythrocytes and the endothelium of post-capillary venules. In addition to being the receptor for the parasite causing malaria, ACKR1 has been postulated to regulate innate immunity by displaying and trafficking chemokines. Intriguingly, a common mutation in its promoter leads to loss of the erythrocyte protein but leaves endothelial expression unaffected. Study of endothelial ACKR1 has been limited by the rapid down-regulation of both transcript and protein when endothelial cells are extracted and cultured from tissue. Thus, to date the study of endothelial ACKR1 has been limited to heterologous over-expression models or the use of transgenic mice. Here we report that exposure to whole blood induces ACKR1 mRNA and protein expression in cultured primary human lung microvascular endothelial cells. We found that contact with neutrophils is required for this effect. We show that NF-κB regulates ACKR1 expression and that upon removal of blood, the protein is rapidly secreted by extracellular vesicles. Finally, we confirm that endogenous ACKR1 does not signal upon stimulation with IL-8 or CXCL1. Our observations define a simple method for inducing endogenous endothelial ACKR1 protein that will facilitate further functional studies.


Subject(s)
Endothelial Cells , Extracellular Vesicles , Animals , Humans , Mice , Chemokines/metabolism , Endothelial Cells/metabolism , Endothelium/metabolism , Extracellular Vesicles/metabolism , Neutrophils/metabolism
18.
Sci Total Environ ; 888: 164174, 2023 Aug 25.
Article in English | MEDLINE | ID: mdl-37201826

ABSTRACT

The effect of different carbon sources on nitrogen (N) transformation and N loss through nitrogenous gas volatilization during composting of manure is not clear. Disaccharides had moderate degradation stability compared to monosaccharides and polysaccharides. Therefore, we investigated the effect of adding sucrose (nonreducing sugar) and maltose (reducing sugar) as carbon sources on volatile N loss and hydrolysable organic nitrogen (HON) transformation. HON is composed of bioavailable organic nitrogen (BON) and hydrolysable unknown nitrogen (HUN). Three laboratory-scale experimental groups were conducted with control (CK), 5 % sucrose (SS), and 5 % maltose (MS) addition. Our findings indicated that, while excluding leaching and surface runoff, adding sucrose and maltose decreased the N loss through gas volatilization by 15.78 % and 9.77 %, respectively. The addition of maltose significantly increased the BON content (P < 0.05), which was 6.35 % higher than in CK. The addition of sucrose led to an increase in HUN content (P < 0.05), which was 22.89 % higher than that in CK. In addition, the core microbial communities associated with HON changed after the addition of disaccharides. The transformation of the HON fractions was facilitated by the succession of microbial communities. Ultimately, variation partition analysis (VPA) and structural equation modeling (SEM) verified that the core microbial communities were the major contributors to promoting HON transformation. In summary, adding disaccharides could promote the different transformations of organic nitrogen (ON) and reduce the volatilization of nitrogenous gases by changing the succession of the core microbial communities during composting. This study provided theoretical and technical support for reducing volatile N loss and promoting ON fraction sequestration during composting. Furthermore, the effect of carbon source addition on the nitrogen cycle was also explored.


Subject(s)
Composting , Nitrogen , Animals , Disaccharides , Manure , Chickens , Maltose , Soil , Carbon , Sucrose
19.
Brain ; 146(9): 3866-3884, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37012681

ABSTRACT

Nerve injury to peripheral somatosensory system causes refractory neuropathic pain. Maladaptive changes of gene expression in primary sensory neurons are considered molecular basis of this disorder. Long non-coding RNAs (lncRNAs) are key regulators of gene transcription; however, their significance in neuropathic pain remains largely elusive.Here, we reported a novel lncRNA, named sensory neuron-specific lncRNA (SS-lncRNA), for its expression exclusively in dorsal root ganglion (DRG) and trigeminal ganglion. SS-lncRNA was predominantly expressed in small DRG neurons and significantly downregulated due to a reduction of early B cell transcription factor 1 in injured DRG after nerve injury. Rescuing this downregulation reversed a decrease of the calcium-activated potassium channel subfamily N member 1 (KCNN1) in injured DRG and alleviated nerve injury-induced nociceptive hypersensitivity. Conversely, DRG downregulation of SS-lncRNA reduced the expression of KCNN1, decreased total potassium currents and afterhyperpolarization currents and increased excitability in DRG neurons and produced neuropathic pain symptoms.Mechanistically, downregulated SS-lncRNA resulted in the reductions of its binding to Kcnn1 promoter and heterogeneous nuclear ribonucleoprotein M (hnRNPM), consequent recruitment of less hnRNPM to the Kcnn1 promoter and silence of Kcnn1 gene transcription in injured DRG.These findings indicate that SS-lncRNA may relieve neuropathic pain through hnRNPM-mediated KCNN1 rescue in injured DRG and offer a novel therapeutic strategy specific for this disorder.


Subject(s)
Neuralgia , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Sensory Receptor Cells/metabolism , Neuralgia/therapy , Small-Conductance Calcium-Activated Potassium Channels/genetics
20.
Pest Manag Sci ; 79(5): 1922-1930, 2023 May.
Article in English | MEDLINE | ID: mdl-36658467

ABSTRACT

BACKGROUND: Succinate dehydrogenase inhibitor (SDHI) fungicides are an important class of agricultural fungicides with the advantages of high efficiency and a broad bactericidal spectrum. To pursue novel SDHIs, a series of N-substituted dithiin tetracarboximide derivatives were designed, synthesized, and characterized by 1 H NMR, 13 C NMR, and high resolution mass spectrum (HRMS). RESULTS: These engineered compounds displayed potent fungicidal activity against phytopathogens, including Sclerotinia sclerotiorum, Botrytis cinerea, and Rhizoctonia solani, comparable with that of the commercial SDHI fungicide boscalid. In particular, compound 18 stood out with prominent activity against S. sclerotiorum with a half-maximal effective concentration (EC50 ) value of 1.37 µg ml-1 . Compound 1 exhibited the most potent antifungal activity against B. cinerea with EC50 values of 5.02 µg ml-1 . As for R. solani, 12 and 13 exhibited remarkably inhibitory activity with EC50 values of 4.26 and 5.76 µg ml-1 , respectively. In the succinate dehydrogenase (SDH) inhibition assay, 13 presented significant inhibitory activity with a half-maximal inhibitory concentration (IC50 ) value of 15.3 µm, which was approximately equivalent to that of boscalid (14.2 µm). Furthermore, molecular docking studies revealed that 13 could anchor in the binding site of SDH. CONCLUSION: Taken together, results suggested that the dithiin tetracarboximide scaffold possessed a huge potential to be developed as novel fungicides and SDHIs. © 2023 Society of Chemical Industry.


Subject(s)
Antifungal Agents , Fungicides, Industrial , Antifungal Agents/chemistry , Fungicides, Industrial/chemistry , Structure-Activity Relationship , Molecular Docking Simulation , Succinate Dehydrogenase
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