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1.
Bioorg Med Chem Lett ; : 129822, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38823728

ABSTRACT

The quest for novel antibacterial agents is imperative in the face of escalating antibiotic resistance. Naturally occurring tetrahydro-ß-carboline (THßC) alkaloids have been highlighted due to their significant biological derivatives. However, these structures have been little explored for antibacterial drugs development. In this study, a series of 1,2,3,4-THßC derivatives were synthesized and assessed for their antibacterial prowess against both gram-positive and gram-negative bacteria. The compounds exhibited moderate to good antibacterial activity, with some compounds showing superior efficacy against gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), to that of Gentamicin. Among these analogs, compound 3k emerged as a hit compound, demonstrating rapid bactericidal action and a significant post-antibacterial effect, with significant cytotoxicity towards human LO2 and HepG2 cells. In addition, compound 3k (10 mg/kg) showed comparable anti-MRSA efficacy to Ciprofloxacin (2 mg/kg) in a mouse model of abdominal infection. Overall, the present findings suggested that THßC derivatives based on the title compounds hold promising applications in the development of antibacterial drugs.

2.
Chaos ; 34(6)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38838105

ABSTRACT

This study examines the role of periodic information, the mechanism of influence, stochastic resonance, and its controllable analysis in complex corporate financial systems. A stochastic predator-prey complex corporate financial system model driven by periodic information is proposed. Additionally, we introduce signal power amplification to quantify the stochastic resonance phenomenon and develop a method for analyzing stochastic resonance in financial predator-prey dynamics within complex corporate financial systems. We optimize a simplified integral calculation method to enhance the proposed model's performance, which demonstrates superiority over benchmark models based on empirical evidence. Based on stochastic simulations and numerical calculations, we can observe multiple stochastic and multiple inverse stochastic resonances. Furthermore, variations in initial financial information, periodic information frequency, and corporate growth capacity induced stochastic resonance and inverse stochastic resonance. These variations also led to state transitions between the two resonance behaviors, indicating transition phenomena. These findings suggest the potential for regulating and controlling stochastic and inverse stochastic resonance in complex corporate finance, enabling controllable stochastic resonance behaviors.

3.
Theor Appl Genet ; 137(7): 147, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834870

ABSTRACT

KEY MESSAGE: Major QTL for grain number per spike were identified on chromosomes 2B and 2D. Haplotypes and candidate genes of QGns.cib-2B.1 were analyzed. Grain number per spike (GNS) is one of the main components of wheat yield. Genetic dissection of their regulatory factors is essential to improve the yield potential. In present study, a recombinant inbred line population comprising 180 lines developed from the cross between a high GNS line W7268 and a cultivar Chuanyu12 was employed to identify quantitative trait loci (QTL) associated with GNS across six environments. Two major QTL, QGns.cib-2B.1 and QGns.cib-2D.1, were detected in at least four environments with the phenotypic variations of 12.99-27.07% and 8.50-13.79%, respectively. And significant interactions were observed between the two major QTL. In addition, QGns.cib-2B.1 is a QTL cluster for GNS, grain number per spikelet and fertile tiller number, and they were validated in different genetic backgrounds using Kompetitive Allele Specific PCR (KASP) markers. QGns.cib-2B.1 showed pleotropic effects on other yield-related traits including plant height, spike length, and spikelet number per spike, but did not significantly affect thousand grain weight which suggested that it might be potentially applicable in breeding program. Comparison analysis suggested that QGns.cib-2B.1 might be a novel QTL. Furthermore, haplotype analysis of QGns.cib-2B.1 indicated that it is a hot spot of artificial selection during wheat improvement. Based on the expression patterns, gene annotation, orthologs analysis and sequence variations, the candidate genes of QGns.cib-2B.1 were predicted. Collectively, the major QTL and KASP markers reported here provided a wealth of information for the genetic basis of GNS and grain yield improvement.


Subject(s)
Chromosome Mapping , Chromosomes, Plant , Haplotypes , Phenotype , Quantitative Trait Loci , Triticum , Triticum/genetics , Triticum/growth & development , Chromosomes, Plant/genetics , Chromosome Mapping/methods , Genetic Markers , Edible Grain/genetics , Edible Grain/growth & development , Seeds/growth & development , Seeds/genetics , Plant Breeding , Alleles , Genes, Plant
4.
Plant Cell Environ ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847345

ABSTRACT

Shoot branching from axillary bud (AB) directly determines plant architecture. However, the mechanism through which AB remains dormant or emerges to form branches as plants grow remains largely unknown. Here, the auxin-strigolactone (IAA-SL) pathway was first shown to regulate shoot branching in poplar, and we found that PagKNAT2/6b could modulate this pathway. PagKNAT2/6b was expressed mainly in the shoot apical meristem and AB and was induced by shoot apex damage. PagKNAT2/6b overexpressing poplar plants (PagKNAT2/6b OE) exhibited multiple branches that mimicked the branching phenotype of nontransgenic plants after decapitation treatment, while compared with nontransgenic controls, PagKNAT2/6b antisense transgenic poplar and Pagknat2/6b mutant lines exhibited a significantly decreased number of branches after shoot apex damage treatment. In addition, we found that PagKNAT2/6b directly inhibits the expression of the key IAA synthesis gene PagYUC6a, which is specifically expressed in the shoot apex. Moreover, overexpression of PagYUC6a in the PagKNAT2/6b OE background reduced the number of branches after shoot apex damage treatment. Overall, we conclude that PagKNAT2/6b responds to shoot apical injury and regulates shoot branching through the IAA-SL pathway. These findings may provide a theoretical basis and candidate genes for genetic engineering to create new forest tree species with different crown types.

5.
One Health ; 18: 100743, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38725962

ABSTRACT

Background: In December 2015, the World Health Organization, the World Animal Health Organization, and the Food and Agriculture Organization of the United Nations convened the International Congress on the elimination of rabies in Geneva. How to use epidemiological factors of post-exposure prophylaxis to prevent rabies has become the focus of attention. Objective: To analyze the epidemiological characteristics of 9772 patients with rabies in a four-year period in one hospital, to clarify the outbreak law of rabies and to explore the corresponding prevention and control strategies. Methods: The epidemiological data of rabies patients were collected from the infectious disease reporting information management system of the hospital from July 2018 to June 2022. The distributional characteristics of 13 influencing factors were analyzed using the chi-square test and linear regression. Results: There was a significant correlation between the number of wounds and age, and the numbers of female and male patients were close. People over the age of 44 were more likely to get bites or scratches on their lower extremity (P<0.0001). There was a greater possibility for elderly people to be bitten by dogs (P<0.0001). Dogs preferred to bite or scratch lower limbs (P<0.0001), while cats upper limbs (P<0.0001). Upper limbs were more possibly attacked by animals at home (P<0.0001). There were significant correlations among exposure grade, wound treatment and number of wounds. Conclusions: Lower extremity protection is needed for the elderly and when encountering dogs, and more attention needs to be paid to the upper extremities when encountering cats and household pets, as well as pets that are cute but need to be protected from bites or scratches.

6.
Curr Microbiol ; 81(7): 168, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38733376

ABSTRACT

In 2018, Nouioui et al. proposed that Bifidobacterium coryneforme was a later synonym of Bifidobacterium indicum on the basis of the digital DNA-DNA hybridization (dDDH) value (85.0%) between B. coryneforme LMG 18911T and B. indicum LMG 11587T. However, in the study of Scardovi et al. (1970), the type strains of B. indicum and B. coryneforme only exhibited 60% DNA-DNA hybridization value. In the present study, the genomes of B. coryneforme CGMCC 1.2279T, B. coryneforme JCM 5819T, B. indicum JCM 1302T, B. indicum CGMCC 1.2275T, B. indicum DSM 20214T, B. indicum LMG 27437T, B. indicum ATCC 25912T, B. indicum KCTC 3230T, B. indicum CCUG 34985T, were sequenced, and the taxonomic relationship between B. coryneforme and B. indicum was re-evaluated. On the basis of the results presented here, (i) ATCC 25912 and DSM 20214 deposited by Vittorio Scardovi are two different strains; (ii) the type strain of B. indicum is ATCC 25912T (= JCM 1302T = LMG 27437T = CGMCC 1.2275T = KCTC 3230T), and not DSM 20214 (= BCRC 14674 = CCUG 34985 = LMG 11587); (iii) B. coryneforme and B. indicum represent two different species of the genus Bifidobacterium; (iv) strain DSM 20214 (= BCRC 14674 = CCUG 34985 = LMG 11587) belongs to B. coryneforme.


Subject(s)
Bifidobacterium , DNA, Bacterial , Genome, Bacterial , Phylogeny , Bifidobacterium/genetics , Bifidobacterium/classification , Bifidobacterium/isolation & purification , DNA, Bacterial/genetics , Nucleic Acid Hybridization , Bacterial Typing Techniques , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA
7.
Burns Trauma ; 12: tkae006, 2024.
Article in English | MEDLINE | ID: mdl-38716051

ABSTRACT

Septic shock is a severe form of sepsis characterized by high global mortality rates and significant heritability. Clinicians have long been perplexed by the differential expression of genes, which poses challenges for early diagnosis and prompt treatment of septic shock. Genetic polymorphisms play crucial roles in determining susceptibility to, mortality from, and the prognosis of septic shock. Research indicates that pathogenic genes are known to cause septic shock through specific alleles, and protective genes have been shown to confer beneficial effects on affected individuals. Despite the existence of many biomarkers linked to septic shock, their clinical use remains limited. Therefore, further investigation is needed to identify specific biomarkers that can facilitate early prevention, diagnosis and risk stratification. Septic shock is closely associated with multiple signaling pathways, including the toll-like receptor 2/toll-like receptor 4, tumor necrosis factor-α, phosphatidylinositol 3-kinase/protein kinase B, mitogen-activated protein kinase, nuclear factor κB, Janus kinase/signal transducer and activator of transcription, mammalian target of rapamycin, NOD-like receptor thermal protein domain-associated protein 3 and hypoxia-induced-factor-1 pathways. Understanding the regulation of these signaling pathways may lead to the identification of therapeutic targets for the development of novel drugs to treat sepsis or septic shock. In conclusion, identifying differential gene expression during the development of septic shock allows physicians to stratify patients according to risk at an early stage. Furthermore, auxiliary examinations can assist physicians in identifying therapeutic targets within relevant signaling pathways, facilitating early diagnosis and treatment, reducing mortality and improving the prognosis of septic shock patients. Although there has been significant progress in studying the genetic polymorphisms, specific biomarkers and signaling pathways involved in septic shock, the journey toward their clinical application and widespread implementation still lies ahead.

8.
IEEE Trans Pattern Anal Mach Intell ; 46(6): 4129-4146, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38713562

ABSTRACT

Visual object tracking often employs a multi-stage pipeline of feature extraction, target information integration, and bounding box estimation. To simplify this pipeline and unify the process of feature extraction and target information integration, in this paper, we present a compact tracking framework, termed as MixFormer, built upon transformers. Our core design is to utilize the flexibility of attention operations, and we propose a Mixed Attention Module (MAM) for simultaneous feature extraction and target information integration. This synchronous modeling scheme allows us to extract target-specific discriminative features and perform extensive communication between target and search area. Based on MAM, we build our MixFormer trackers simply by stacking multiple MAMs and placing a localization head on top. Specifically, we instantiate two types of MixFormer trackers, a hierarchical tracker MixCvT, and a non-hierarchical simple tracker MixViT. For these two trackers, we investigate a series of pre-training methods and uncover the different behaviors between supervised pre-training and self-supervised pre-training in our MixFormer trackers. We also extend the masked autoencoder pre-training to our MixFormer trackers and design the new competitive TrackMAE pre-training technique. Finally, to handle multiple target templates during online tracking, we devise an asymmetric attention scheme in MAM to reduce computational cost, and propose an effective score prediction module to select high-quality templates. Our MixFormer trackers set a new state-of-the-art performance on seven tracking benchmarks, including LaSOT, TrackingNet, VOT2020, GOT-10 k, OTB100, TOTB and UAV123. In particular, our MixViT-L achieves AUC scores of 73.3% on LaSOT, 86.1% on TrackingNet and 82.8% on TOTB.

9.
J Hazard Mater ; 473: 134587, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38772107

ABSTRACT

One of the factors influencing the behavior of arsenic (As) in environment is microbial-mediated As transformation. However, the detailed regulatory role of gene expression on the changes of root exudation, rhizosphere microorganisms, and soil As occurrence forms remains unclear. In this study, we evidence that loss-of-function of OsSAUR2 gene, a member of the SMALL AUXIN-UP RNA family in rice, results in significantly higher As uptake in roots but greatly lower As accumulation in grains via affecting the expression of OsLsi1, OsLsi2 in roots and OsABCC1 in stems. Further, the alteration of OsSAUR2 expression extensively affects the metabolomic of root exudation, and thereby leading to the variations in the composition of rhizosphere microbial communities in rice. The microbial community in the rhizosphere of Ossaur2 plants strongly immobilizes the occurrence forms of As in soil. Interestingly, Homovanillic acid (HA) and 3-Coumaric acid (CA), two differential metabolites screened from root exudation, can facilitate soil iron reduction, enhance As bioavailability, and stimulate As uptake and accumulation in rice. These findings add our further understanding in the relationship of OsSAUR2 expression with the release of root exudation and rhizosphere microbial assembly under As stress in rice, and provide potential rice genetic resources and root exudation in phytoremediation of As-contaminated paddy soil.

10.
Ecotoxicol Environ Saf ; 278: 116417, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38701655

ABSTRACT

Cadmium (Cd) pollutes 7.0 % of China's land area. This study examined the potential of Houttuynia cordata for Cd phytoremediation because of its ability to accumulate Cd in its growth matrix. H. cordata were planted in plastic pots filled with paddy field soils having low (LCd), medium (MCd), and high (HCd) Cd levels of 0.19, 0.69, and 2.91 mg/kg, respectively. After six months of growth, harvested plant parts were evaluated for Cd uptake and tolerance mechanisms. Metabolomics and metagenomics approaches were employed to investigate the soil rhizosphere mechanism. Results showed that the average plant biomass increased as soil Cd increased. The biomass Cd contents surpassed the allowable Cd limits for food (≤ 0.2 mg/kg) and medicinal uses (≤ 0.3 mg/kg). Cd contents were higher in H. cordata roots (30.59-86.27 mg/kg) than in other plant parts (0.63-2.90 mg/kg), with significantly increasing values as Cd soil level increased. Phenolic acids, lipids, amino acids and derivatives, organic acids, and alkaloids comprised the majority (69 in MCd vs HCd and 73 % in LCd vs HCd) of the shared upregulated metabolites. In addition, 13 metabolites specific to H. cordata root exudates were significantly increased. The top two principal metabolic pathways were arginine and proline metabolism, and beta-alanine metabolism. H. cordata increased the abundance of Firmicutes and Glomeromycota across all three Cd levels, and also stimulated the growth of Patescibacteria, Rozellomycota, and Claroideoglomus in HCd. Accordingly, H. cordata demonstrated potential for remediation of Cd-contaminated soils, and safety measures for its production and food use must be highly considered.


Subject(s)
Biodegradation, Environmental , Cadmium , Houttuynia , Rhizosphere , Soil Pollutants , Cadmium/metabolism , Cadmium/analysis , Soil Pollutants/metabolism , China , Plant Roots/metabolism , Soil/chemistry , Biomass
11.
Article in English | MEDLINE | ID: mdl-38805027

ABSTRACT

Strain S30A2T, isolated from the acid mine drainage sediment of Mengzi Copper Mine, Yunnan, is proposed to represent a novel species of the sulphur-oxidizing genus Acidithiobacillus. Cells were Gram-stain-negative, non-endospore forming, highly motile with one or two monopolar flagella and rod-shaped. The strain was mesophilic, growing at 30-50 °C (optimum, 38 °C), acidophilic, growing at pH 2.0-4.5 (optimum, pH 2.5), and tolerant of 0-4 % (w/v; 684 mol l-1) NaCl. The 16S rRNA gene-based sequence analysis showed that strain S30A2T belongs to the genus Acidithiobacillus and shows the largest similarity of 96.6 % to the type strain Acidithiobacillus caldus KUT. The genomic DNA G+C content of strain S30A2T was 59.25 mol%. The average nucleotide identity ANIb and ANIm values between strain S30A2T and A. caldus KUT were 70.95 and 89.78 %, respectively and the digital DNA-DNA hybridization value was 24.9 %. Strain S30A2T was strictly aerobic and could utilize elementary sulphur and tetrathionate to support chemolithotrophic growth. The major cellular fatty acid of S30A2T was C19 : 1ω7c. The respiratory quinones were ubiquinone-8 and ubiquinone-7. Based upon its phylogenetic, genetic, phenotypic, physiologic and chemotaxonomic characteristics, strain S30A2T is considered to represent a novel species of the genus Acidithiobacillus, for which the name Acidithiobacillus acidisediminis sp. nov. is proposed. The type strain is S30A2T (=CGMCC 1.17059T=KCTC 72580T).


Subject(s)
Acidithiobacillus , Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Fatty Acids , Geologic Sediments , Mining , Nucleic Acid Hybridization , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Sulfur , RNA, Ribosomal, 16S/genetics , Sulfur/metabolism , DNA, Bacterial/genetics , Fatty Acids/analysis , Geologic Sediments/microbiology , Acidithiobacillus/classification , Acidithiobacillus/genetics , Acidithiobacillus/isolation & purification , China , Oxidation-Reduction , Chemoautotrophic Growth , Ubiquinone , Copper/metabolism
12.
Sci Rep ; 14(1): 11388, 2024 05 18.
Article in English | MEDLINE | ID: mdl-38762672

ABSTRACT

Capmatinib is a potent selective mesenchymal-epithelial transition inhibitor approved in 2020 for the treatment of metastatic non-small cell lung cancer. As real-world evidence is very limited, this study evaluated capmatinib-induced adverse events through data mining of the FDA Adverse Event Reporting System database. Four disproportionality analysis methods were employed to quantify the signals of capmatinib-related adverse events. The difference in capmatinib-associated adverse event signals was further investigated with respect to sex, age, weight, dose, onset time, continent, and concomitant drug. A total of 1518 reports and 4278 adverse events induced by capmatinib were identified. New significant adverse event signals emerged, such as dysphagia, dehydration, deafness, vocal cord paralysis, muscle disorder, and oesophageal stenosis. Notably, higher risk of alanine aminotransferase and aspartate aminotransferase increases were observed in females, especially when capmatinib was combined with immune checkpoint inhibitors. Compared with Europeans and Asians, Americans were more likely to experience peripheral swelling, especially in people > 65 years of age. Renal impairment and increased blood creatinine were more likely to occur with single doses above 400 mg and in Asians. This study improves the understanding of safety profile of capmatinib.


Subject(s)
Adverse Drug Reaction Reporting Systems , Benzamides , Pharmacovigilance , United States Food and Drug Administration , Humans , Male , Female , United States , Middle Aged , Aged , Adverse Drug Reaction Reporting Systems/statistics & numerical data , Benzamides/adverse effects , Benzamides/therapeutic use , Adult , Triazines/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Aged, 80 and over , Young Adult , Lung Neoplasms/drug therapy , Adolescent , Imidazoles
13.
Sci Rep ; 14(1): 8022, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38580659

ABSTRACT

The increasing depth of mine excavation presents greater challenges in mine ventilation and in managing cooling energy consumption. Therefore, there is an urgent need for comprehensive research on jet ventilation influenced by low-speed crossflows. This study investigated the impact of flow velocity ratios (R) and jet exit diameters (d) on flow-field distribution and flow characteristics through velocity measurements and smoke flow visualization experiments. The results of the study revealed two distinct types of air lakes formed by jet ventilation in crossflow (JVIC), with one being wall-attached and the other suspended. Notably, a significant secondary flow phenomenon was observed in the near-field near the upper wall. Additionally, the deflection angle (θj) of JVIC decreases as R and d/D increase, leading to the formation and movement of a semi-confined point (SP) and a confined point (CP) in the -x direction. Moreover, the wall confinement effect diminishes the jet's diffusion and deflection ability in the -z direction, leading to increased penetration in the x direction. Before the formation of the SP, the deflection section of the jet lengthens, followed by a rapid shortening upon its formation. Finally, the study further developed empirical equations for the jet axial trajectory and diffusion width.

14.
RSC Med Chem ; 15(4): 1198-1209, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38665835

ABSTRACT

Ferroptosis is a nonapoptotic, iron-catalyzed form of regulated cell death. It has been shown that high glucose (HG) could induce ferroptosis in vascular endothelial cells (VECs), consequently contributing to the development of various diseases. This study synthesized and evaluated a series of novel ferrostatin-1 (Fer-1) derivatives fused with a benzohydrazide moiety to prevent HG-induced VEC ferroptosis. Several promising compounds showed similar or improved inhibitory effects compared to positive control Fer-1. The most effective candidate 12 exhibited better protection against erastin-induced ferroptosis and high glucose-induced ferroptosis in VECs. Mechanistic studies revealed that compound 12 prevented mitochondrial damage, reduced intracellular ROS accumulation, upregulated the expression of GPX4, and decreased the amounts of ferrous ion, LPO and MDA in VECs. However, compound 12 still exhibited undesirable microsomal stability like Fer-1, suggesting the need for further optimization. Overall, the present findings highlight ferroptosis inhibitor 12 as a potential lead compound for treating ferroptosis-associated vascular diseases.

15.
J Mol Model ; 30(4): 116, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38561503

ABSTRACT

INTRODUCTION: The electronic and optical properties of ß-Ga2O3 have been investigated by CASTEP using first principles. It is found that ß-Ga2O3 has an indirect band gap and the conduction band base is located at the Γ point. The stability of ß-Ga2O3 is demonstrated by the calculation of elastic constants, and the ductility of ß-Ga2O3 is demonstrated by the ratio of Poisson's ratio to shear modulus. The optical property analysis shows that ß-Ga2O3 has a high absorption capacity in the ultraviolet region, but a low absorption capacity in visible and infrared light. CONTEXT: The structure, optical, and electronic properties of ß-Ga2O3 are calculated and analyzed based on first-principles calculation. The optimized structures of ß-Ga2O3 are in good agreement with previously studied. In this paper, the elastic, electronic, and optical properties of ß-Ga2O3 are calculated. METHODS: The CASTEP code was employed to execute these calculations in the present work, where the exchange-correlation interactions were treated in the generalized gradient approximation (GGA) using the Perdew-Burke-Ernzerhof (PBE) functional in the geometry optimizations and electronic and elastic properties.

16.
J Cell Mol Med ; 28(9): e18339, 2024 May.
Article in English | MEDLINE | ID: mdl-38687049

ABSTRACT

Glioma is the most prevalent malignant brain tumour. Currently, reshaping its tumour microenvironment has emerged as an appealing strategy to enhance therapeutic efficacy. As the largest group of transmembrane transport proteins, solute carrier proteins (SLCs) are responsible for the transmembrane transport of various metabolites and ions. They play a crucial role in regulating the metabolism and functions of malignant cells and immune cells within the tumour microenvironment, making them a promising target in cancer therapy. Through multidimensional data analysis and experimental validation, we investigated the genetic landscape of SLCs in glioma. We established a classification system comprising 7-SLCs to predict the prognosis of glioma patients and their potential responses to immunotherapy and chemotherapy. Our findings unveiled specific SLC expression patterns and their correlation with the immune-suppressive microenvironment and metabolic status. The 7-SLC classification system was validated in distinguishing subgroups within the microenvironment, specifically identifying subsets involving malignant cells and tumour-associated macrophages. Furthermore, the orphan protein SLC43A3, a core member of the 7-SLC classification system, was identified as a key facilitator of tumour cell proliferation and migration, suggesting its potential as a novel target for cancer therapy.


Subject(s)
Brain Neoplasms , Gene Expression Regulation, Neoplastic , Glioma , Solute Carrier Proteins , Tumor Microenvironment , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Humans , Glioma/genetics , Glioma/immunology , Glioma/pathology , Glioma/metabolism , Brain Neoplasms/genetics , Brain Neoplasms/immunology , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Solute Carrier Proteins/genetics , Solute Carrier Proteins/metabolism , Prognosis , Cell Proliferation/genetics , Gene Expression Profiling , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Multiomics
17.
Bioorg Med Chem ; 105: 117716, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38608329

ABSTRACT

In this study, a series of new formylpiperazine-derived ferroptosis inhibitors were designed and synthesized based on the structure of a known ferroptosis inhibitor, ferrostatin-1 (Fer-1). The anti-ferroptosis activity of these synthetic compounds in human umbilical vein endothelial cells (HUVECs) induced by Erastin was evaluated. It was found that some of the new compounds, especially compound 26, showed potent anti-ferroptosis activity, as evidenced by its ability to restore cell viability, reduce iron accumulation, scavenge reactive oxygen species, maintain mitochondrial membrane potential, increase GSH levels, decrease LPO and MDA content, and upregulate GPX4 expression. Moreover, compound 26 exhibited superior microsomal stability than Fer-1. The present results suggest that compound 26 is a promising lead compound for the development of new ferroptosis inhibitors for the treatment of vascular diseases.


Subject(s)
Cell Survival , Cyclohexylamines , Drug Design , Ferroptosis , Human Umbilical Vein Endothelial Cells , Piperazines , Humans , Ferroptosis/drug effects , Piperazines/pharmacology , Piperazines/chemical synthesis , Piperazines/chemistry , Human Umbilical Vein Endothelial Cells/drug effects , Structure-Activity Relationship , Cyclohexylamines/pharmacology , Cyclohexylamines/chemistry , Cyclohexylamines/chemical synthesis , Cell Survival/drug effects , Molecular Structure , Phenylenediamines/pharmacology , Phenylenediamines/chemistry , Phenylenediamines/chemical synthesis , Dose-Response Relationship, Drug , Reactive Oxygen Species/metabolism , Ferrous Compounds/pharmacology , Ferrous Compounds/chemistry , Ferrous Compounds/chemical synthesis , Membrane Potential, Mitochondrial/drug effects
18.
Plant Sci ; 344: 112083, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38588982

ABSTRACT

Due to the extended generation cycle of trees, the breeding process for forest trees tends to be time-consuming. Genetic engineering has emerged as a viable approach to expedite the genetic breeding of forest trees. However, current genetic engineering techniques employed in forest trees often utilize continuous expression promoters such as CaMV 35S, which may result in unintended consequences by introducing genes into non-target tissues. Therefore, it is imperative to develop specific promoters for forest trees to facilitate targeted and precise design and breeding. In this study, we utilized single-cell RNA-Seq data and co-expression network analysis during wood formation to identify three vascular tissue-specific genes in poplar, PP2-A10, PXY, and VNS07, which are expressed in the phloem, cambium/expanding xylem, and mature xylem, respectively. Subsequently, we cloned the promoters of these three genes from '84K' poplar and constructed them into a vector containing the eyGFPuv visual selection marker, along with the 35S mini enhancer to drive GUS gene expression. Transgenic poplars expressing the ProPagPP2-A10::GUS, ProPagPXY::GUS, and ProPagVNS07::GUS constructs were obtained. To further elucidate the tissue specificity of these promoters, we employed qPCR, histochemical staining, and GUS enzyme activity. Our findings not only establish a solid foundation for the future utilization of these promoters to precisely express of specific functional genes in stems but also provide a novel perspective for the modular breeding of forest trees.


Subject(s)
Populus , Promoter Regions, Genetic , Populus/genetics , Populus/metabolism , Promoter Regions, Genetic/genetics , Gene Expression Regulation, Plant , Plants, Genetically Modified/genetics , Xylem/genetics , Xylem/metabolism , Phloem/genetics , Phloem/metabolism , Genes, Plant
19.
Plant Sci ; 344: 112106, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38663480

ABSTRACT

PXY (Phloem intercalated with xylem) is a receptor kinase required for directional cell division during the development of plant vascular tissue. Drought stress usually affects plant stem cell division and differentiation thereby limiting plant growth. However, the role of PXY in cambial activities of woody plants under drought stress is unclear. In this study, we analyzed the biological functions of two PXY genes (PagPXYa and PagPXYb) in poplar growth and development and in response to drought stress in a hybrid poplar (Populus alba × P. glandulosa, '84K'). Expression analysis indicated that PagPXYs, similar to their orthologs PtrPXYs in Populus trichocarpa, are mainly expressed in the stem vascular system, and related to drought. Interestingly, overexpression of PagPXYa and PagPXYb in poplar did not have a significant impact on the growth status of transgenic plants under normal condition. However, when treated with 8 % PEG6000 or 100 mM H2O2, PagPXYa and PagPXYb overexpressing lines consistently exhibited more cambium cell layers, fewer xylem cell layers, and enhanced drought tolerance compared to the non-transgenic control '84K'. In addition, PagPXYs can alleviate the damage caused by H2O2 to the cambium under drought stress, thereby maintaining the cambial division activity of poplar under drought stress, indicating that PagPXYs play an important role in plant resistance to drought stress. This study provides a new insight for further research on the balance of growth and drought tolerance in forest trees.


Subject(s)
Cambium , Droughts , Plant Proteins , Populus , Reactive Oxygen Species , Populus/genetics , Populus/physiology , Populus/metabolism , Populus/growth & development , Cambium/genetics , Cambium/growth & development , Cambium/physiology , Cambium/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Reactive Oxygen Species/metabolism , Plants, Genetically Modified/genetics , Homeostasis , Gene Expression Regulation, Plant , Xylem/metabolism , Xylem/physiology , Xylem/genetics , Stress, Physiological , Drought Resistance
20.
Angew Chem Int Ed Engl ; : e202405838, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38647574

ABSTRACT

Transition-metal-catalyzed [4+4] cycloaddition leading to cyclooctanoids has centered on dimerization between 1,3-diene-type substrates. Herein, we describe a [4σ+4π-1] and [4σ+4π] cycloaddition strategy to access 7/8-membered fused carbocycles through rhodium-catalyzed coupling between the 4σ-donor (benzocyclobutenones) and pendant diene (4π) motifs. The two pathways can be controlled by adjusting the solvated CO concentration. A broad range (>40 examples) of 5-6-7 and 5-6-8 polyfused carbocycles was obtained in good yields (up to 90 %). DFT calculations, kinetic monitoring and 13C-labeling experiments were carried out, suggesting a plausible mechanism. Notably, one 5-6-7 tricycle was found to be a very rare, potent, and selective ligand for the liver X receptor ß (KD=0.64 µM), which is a potential therapeutic target for cholesterol-metabolism-related fatal diseases.

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