Search

A series of 3-phenyl benzo[d][1,2,3]triazin-4( 3H)-one derivatives were synthesized through the condensation of phenol E and alkyl (alkenyl, alkynyl) chlorides (bromides, iodide) or alkyl chloroacetates or N-alkyl chloroacetamides using K2CO3 as the acid acceptor in N, N-dimethylformamide. Phenol E was prepared from starting material, 5-amino-2-chloro-4-fluorophenyl ethyl carbonate, in four steps involving in , reduction, , and deprotecting-group reaction. The herbicidal activities of the title compounds were tested against two dicotyledonous plants and two monocotyledonous plants, in which some of them exhibited high herbicidal activities against two dicotyledonous plants in preemergence and postemergence treatments. Moreover, when the dosage was decreased to 180 and 90 g/ha, compounds F1, F8, and F9 showed highly selective inhibitory activities against amaranth pigweed, alfalfa, asteraceae, field sowthistle, morning glory, purslane, and velvetleaf in postemergence treatment but had no herbicidal efficacy on rape except F1, suggesting that it be possible to find a kind of herbicides to inhibit dicotyledonous weeds in the field of dicotyledonous crops with the same genus as aforementioned weeds. [ABSTRACT FROM AUTHOR]

Morphological transition and iron metabolism are closely relevant to Candida albicans pathogenicity and virulence. In our previous study, we demonstrated that C. albicans Aft2 plays an important role in ferric reductase activity and virulence. Here, we further explored the roles of C. albicans Aft2 in numerous cellular processes. We found that C. albicans Aft2 exhibited an important role in iron metabolism through bi-directional regulation effects on iron-regulon expression. Deletion of AFT2 reduced cellular iron accumulation under iron-deficient conditions. Furthermore, both reactive oxygen species (ROS) generation and superoxide dismutase (SOD) activity were remarkably increased in the aft2Δ/Δ mutant, which were thought to be responsible for the defective responses to oxidative stress. However, we found that over-expression of C. albicans AFT2 under the regulation of the strong PGK1 promoter could not effectively rescue Saccharomyces cerevisiae aft1Δ mutant defects in some cellular processes, such as cell-wall assembly, ion homeostasis and alkaline resistance, suggesting a possibility that C. albicans Aft2 weakened its functional role of regulating some cellular metabolism during the evolutionary process. Interestingly, deletion of AFT2 in C. albicans increased cell surface hydrophobicity, cell flocculation and the ability of adhesion to polystyrene surfaces. In addition, our results also revealed that C. albicans Aft2 played a dual role in regulating hypha-specific genes under solid and liquid hyphal inducing conditions. Deletion of AFT2 caused an impaired invasive growth in solid medium, but an increased filamentous aggregation and growth in liquid conditions. Moreover, iron deficiency and environmental cues induced nuclear import of Aft2, providing additional evidence for the roles of Aft2 in transcriptional regulation. [ABSTRACT FROM AUTHOR]

Morphological transition and iron metabolism are closely relevant to Candida albicans pathogenicity and virulence. In our previous study, we demonstrated that C. albicans Aft2 plays an important role in ferric reductase activity and virulence. Here, we further explored the roles of C. albicans Aft2 in numerous cellular processes. We found that C. albicans Aft2 exhibited an important role in iron metabolism through bi-directional regulation effects on iron-regulon expression. Deletion of AFT2 reduced cellular iron accumulation under iron-deficient conditions. Furthermore, both reactive oxygen species (ROS) generation and superoxide dismutase (SOD) activity were remarkably increased in the aft2Δ/Δ mutant, which were thought to be responsible for the defective responses to oxidative stress. However, we found that over-expression of C. albicans AFT2 under the regulation of the strong PGK1 promoter could not effectively rescue Saccharomyces cerevisiae aft1Δ mutant defects in some cellular processes, such as cell-wall assembly, ion homeostasis and alkaline resistance, suggesting a possibility that C. albicans Aft2 weakened its functional role of regulating some cellular metabolism during the evolutionary process. Interestingly, deletion of AFT2 in C. albicans increased cell surface hydrophobicity, cell flocculation and the ability of adhesion to polystyrene surfaces. In addition, our results also revealed that C. albicans Aft2 played a dual role in regulating hypha-specific genes under solid and liquid hyphal inducing conditions. Deletion of AFT2 caused an impaired invasive growth in solid medium, but an increased filamentous aggregation and growth in liquid conditions. Moreover, iron deficiency and environmental cues induced nuclear import of Aft2, providing additional evidence for the roles of Aft2 in transcriptional regulation. [ABSTRACT FROM AUTHOR]

Iron is an essential nutrient required for the growth and metabolism in Candida albicans. Here, we for the first time identified Mrs4 as a new member of mitochondrial carrier family in C. albicans. Our experiments revealed that C. albicans Mrs4 (CaMrs4) is localized to the mitochondria and required for mitochondrial morphology. We found that CaMrs4 is required for cell growth, and the mrs4△/△ mutant showed a more severe growth defect in iron deficiency. Deletion of MRS4 affected cellular iron content by altering the expression of iron regulon genes in C. albicans, such as AFT2, SMF3, FTR1 and ISU1. Candida albicans Aft2 factor functions as a negative regulator of MRS4 expression through the CACCC Aft-type sequence in a gene dose-dependent fashion. In addition, the mrs4△/△ mutant exhibited hypersensitivity to oxidants and most metal ions, but decreased sensitivity to cobalt. Exogenous iron could suppress the sensitivity of the mrs4△/△ mutant to oxidants and most metal ions, suggesting that the role of CaMrs4 is partially mediated by iron availability. Furthermore, deletion of MRS4 resulted in delayed filamentation under tested conditions. Taken together, these findings characterize a new mito-chondrial carrier and provide a novel insight into the role of CaMrs4 in mitochondrial function. [ABSTRACT FROM AUTHOR]

Background: The metastatic cascade, a multifaceted and highly aggressive process, is the primary cause of mortality. The survival of quiescent cancer cells in circulatory system during metastasis is crucial, yet our comprehension is constrained by the absence of universally accepted quiescent cancer models., Method: We developed a quiescent cancer cell model using high-density cultivation. Based on the scRNA-seq analysis, IP-MS, metabolomics, mouse lung metastasis models, cholesterol assay, PLA and other molecular experiments, we explored the molecular mechanism. Immunofluorescence, atomic force microscope, FluidFM, and shear stress stimulation were used to analyze the cytoskeleton and membrane properties contributing to mechanical force resistance., Result: We established a quiescent cancer cell model induced by high-density cultivation. Single-cell RNA sequencing (scRNA-seq) analysis reveals that CDC25A plays a crucial role in the transition to quiescence, with its expression significantly elevated in the quiescent state. Depletion of CDC25A leads to an increased proliferative capacity, and reduced metastasis under high-density conditions. Mechanistically, upregulated CDC25A in quiescent cells enhances cholesterol metabolism via endosome pathways, leading to cell cycle arrest. This increase in cholesterol reinforces the cytoskeleton, alters membrane properties, and improves resistance to mechanical forces in circulatory system., Conclusion: CDC25A significantly increased the cholesterol metabolism through endosome pathway in quiescent cancer cells, leading to the significant changes in cytoskeleton and membrane properties so as to enhance the resistance of mechanical force in circulatory system, facilitating lung metastasis. In high-density cultivation, quiescent cancer cells, up-regulate cholesterol metabolism by CDC25A through endosome pathway, enhancing the resistance to mechanical force in circulatory system, facilitating lung metastasis., (© 2024. The Author(s).)

Background: Current diagnostic methods cannot effectively distinguish between latent tuberculosis infection (LTBI) and active tuberculosis (ATB). This study aims to explore novel non-invasive diagnostic biomarkers for LTBI and to elucidate possible molecular mechanisms of LTBI pathogenesis., Methods: Three GEO datasets (GSE19439, GSE19444, and GSE62525) were utilized to analyze the differentially expressed genes (DEGs). Functional enrichment studies were then performed on these DEGs. To ascertain potential diagnostic biomarkers, we utilized two different machine learning techniques: LASSO and RF. ROC curves were constructed in both the training and validation datasets to assess the diagnostic efficacy. The expression of identified biomarkers was verified by RT-qPCR in our own Chinese cohort. Using CIBERSORT, we estimated the abundances of 22 immune cell types in LTBI group, and subsequently analyzed the relationship between biomarker expression and immune cell infiltration., Results: 166 DEGs were identified between ATB and LTBI groups, which are primarily associated with immune responses, inflammatory signaling pathways, and infection factors. Following that, 22 candidate diagnostic biomarkers for LTBI were selected in the machine learning process. Three up-regulated genes, MORN3 , LLGL2 , and IFT140 , whose expression levels were not previously reported in TB, were validated using the training and validation cohort datasets. In our own Chinese cohort, we also found that MORN3 and LLGL2 showed good diagnostic effect using RT-qPCR method. Finally, we revealed the specific infiltration features of immune cells in LTBI and observed a notable correlation between potential marker expression and immune cells., Conclusions: MORN3 and LLGL2 emerged as candidate diagnostic biomarkers for LTBI, following the elucidation of the key immune cell types involved. Our findings will contribute to providing a potential target for early noninvasive diagnosis of LTBI patients.

Background: Motor imagery therapy (MIT) showed positive effects on upper limbs motor function. However, the mechanism by which MIT improves upper limb motor function is not fully understood. Therefore, our purpose was to investigate the changes in functional connectivity (FC) within and outside the sensorimotor network (SMN) induced by MIT associated with improvement in upper limb motor function in stroke patients., Methods: A total of 26 hemiplegic stroke patients were randomly divided into MIT ( n = 13) and control ( n = 13) groups. Fugl-Meyer Assessment Upper Extremity Scale (FMA-UL), Modified Barthel Index (MBI) and resting-state functional magnetic resonance imaging (rs-fMRI) were evaluated in the two groups before treatment and 4 weeks after treatment. The efficacy of MIT on motor function improvement in stroke patients with hemiplegia was evaluated by comparing the FMA-UL and MBI scores before and after treatment in the two groups. Furthermore, the FC within the SMN and between the SMN and the whole brain was measured and compared before and after different treatment methods in stroke patients. The correlation analysis between the improvement of upper limbs motor function and changes in FC within the SMN and between the SMN and the whole brain was examined., Results: The FCs between ipsilesional primary motor cortex (M1.I) and contralateral supplementary motor area (SMA.C), M1.I and ipsilesional SMA (SMA.I), and SMA.C and contralateral dorsolateral premotor cortex (DLPM.C) significantly increased in the control group but decreased in the MIT group; while the FC between SMA.C and contralateral primary somatosensory cortex (S1.C) significantly increased in the control group but showed no significant difference in the MIT group. The FCs between M1.I and the ipsilesional hippocampal gyrus and ipsilesional middle frontal gyrus significantly decreased in the control group but increased in the MIT group; while the FC in the contralateral anterior cingulate cortex significantly increased in the MIT group but there was no significant difference in the control group. The results of the correlation analysis showed that the differences in abnormal intra-FCs within the SMN negatively correlated with the differences in FMA and MBI, and the difference in abnormal inter-FCs of the SMN positively correlated with the differences in FMA and MBI., Conclusions: MIT can improve upper limb motor function and daily activities of stroke patients, and the improvement effect of conventional rehabilitation therapy (CRT) combined with MIT is significantly higher than that of CRT alone. CRT may improve the upper limb motor function of stroke patients with hemiplegia mainly through the functional reorganization between SMN, while MIT may mainly increase the interaction between SMN and other brain networks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer YS declared a shared parent affiliation with the authors to the handling editor at the time of review., (Copyright © 2024 Liu, Cheng, Rao, Yu, Lin, Wang, Wang, Li, Liu and Gao.)

The photon spectrum from free-electron laser (FEL) light sources offers valuable information in time-resolved experiments and machine optimization in the spectral and temporal domains. We have developed a compact single-shot photon spectrometer to diagnose soft X-ray spectra. The spectrometer consists of an array of off-axis Fresnel zone plates (FZP) that act as transmission-imaging gratings, a Ce:YAG scintillator, and a microscope objective to image the scintillation target onto a two-dimensional imaging detector. This spectrometer operates in segmented energy ranges which covers tens of electronvolts for each absorption edge associated with several atomic constituents: carbon, nitrogen, oxygen, and neon. The spectrometer's performance is demonstrated at a repetition rate of 120 Hz, but our detection scheme can be easily extended to 200 kHz spectral collection by employing a fast complementary metal oxide semiconductor (CMOS) line-scan camera to detect the light from the scintillator. This compact photon spectrometer provides an opportunity for monitoring the spectrum downstream of an endstation in a limited space environment with sub-electronvolt energy resolution.

Directly imaging structural dynamics involving hydrogen atoms by ultrafast diffraction methods is complicated by their low scattering cross sections. Here we demonstrate that megaelectronvolt ultrafast electron diffraction is sufficiently sensitive to follow hydrogen dynamics in isolated molecules. In a study of the photodissociation of gas phase ammonia, we simultaneously observe signatures of the nuclear and corresponding electronic structure changes resulting from the dissociation dynamics in the time-dependent diffraction. Both assignments are confirmed by ab initio simulations of the photochemical dynamics and the resulting diffraction observable. While the temporal resolution of the experiment is insufficient to resolve the dissociation in time, our results represent an important step towards the observation of proton dynamics in real space and time.

Zinc homeostasis has been known to play a role in myocardial ischemia/reperfusion (I/R) injury, but the precise molecular mechanisms regulating the expression of ZIP transporters during reperfusion are still unclear. The aim of this study was to determine whether ER Stress/CaMKII/STAT3 pathway plays a role in the regulation of cellular zinc homeostasis. Zinc deficiency increased mRNA and protein expressions of the ER stress relevant markers Chop and Bip, and STAT3 phosphorylation in H9c2 or HL-1 cells, an effect that was abolished by ZnCl 2 . ER calcium concentration [(Ca 2+ ) ER ] was decreased and cytosolic calcium concentration [(Ca 2+ ) I ] was increased at the condition of normoxia or ischemia/reperfusion, indicating that zinc deficiency triggers ER stress and Ca 2+ leak. Further studies showed that upregulation of STAT3 phosphorylation was reversed by Ca 2+ chelator, indicating that intracellular Ca 2+ is important for zinc deficiency-induced STAT3 activation. In support, zinc deficiency enhanced ryanodine receptors (RyR), a channel in the ER that mediate Ca 2+ release, and Ca 2+ -calmodulin-dependent protein kinase (CaMKII) phosphorylation, implying that zinc deficiency provoked Ca 2+ leak from ER via RyR and p-CaMKII is involved in STAT3 activation. Moreover, inhibition of STAT3 activation blocked zinc deficiency induced ZIP9 expression, and resulted in increased Zn 2+ loss in cardiomyocytes, further confirming that STAT3 activation during reperfusion promotes the expression of ZIP9 zinc transporter to correct the imbalance in zinc homeostasis. In addition, suppressed STAT3 activation aggravated reperfusion injury. These data suggest that the ER Stress/CaMKII/STAT3 axis may be an endogenous protective mechanism, which increases the resistance of the heart to I/R., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Liu, Yan, Bian, Yu, Wang, Cheng and Xu.)

Fusarium head blight (FHB), a fungal disease caused by Fusarium species that produce food toxins, currently devastates wheat production worldwide, yet few resistance resources have been discovered in wheat germplasm. Here, we cloned the FHB resistance gene Fhb7 by assembling the genome of Thinopyrum elongatum , a species used in wheat distant hybridization breeding. Fhb7 encodes a glutathione S-transferase (GST) and confers broad resistance to Fusarium species by detoxifying trichothecenes through de-epoxidation. Fhb7 GST homologs are absent in plants, and our evidence supports that Th. elongatum has gained Fhb7 through horizontal gene transfer (HGT) from an endophytic Epichloë species. Fhb7 introgressions in wheat confers resistance to both FHB and crown rot in diverse wheat backgrounds without yield penalty, providing a solution for Fusarium resistance breeding., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objective: To identify potential mutation of the colony stimulating factor 1 receptor gene (CSF1R) in a large Chinese family affected with hereditary diffuse leukoencephalopathy with spheroids (HDLS) and analyze the genotype-phenotype correlation., Methods: The proband was evaluated physically and radiologically to ascertain the HDLS phenotype. Genomic DNA was extracted from peripheral blood samples from family members. The coding region of the CSF1R gene was amplified with PCR and subjected to direct DNA sequencing., Results: There were 9 affected members (5 alive) in this five-generation family (1 member had died during the follow-up). A missense mutation c.2563C>A (p.P855T) of the CSF1R gene has been identified in the proband. The same mutation was identified in 3 affected and 1 unaffected members of the family., Conclusion: The family was consistent with autosomal dominant inheritance. CSF1R gene mutation is also a disease-causing mutation in Chinese patients.

A convenient base-mediated strategy to synthesize 3-aryol-4-methyl (or benzyl)-2-methylthio furans 2 (trisubstituted furans) has been developed through the domino coupling/annulations between available α-oxo ketene dithioacetals 1 and propargyl alcohols. In this strategy, these types of bases play an important role in driving the domino coupling reaction of propargyl alcohols and further intramolecular annulations to realize the target compounds. The possible mechanism for the formation of the various products is believed to involve the generation of allenes 7, followed by intramolecular annulations.

Objective: Ferric reductases play a central role in iron acquisition and mobilization in C. albicans. This study focuses on stress response strategies exhibited by several ferric reductase genes through function and expression analyses., Methods: Northern blot analysis was used to examine ferric reductase genes expression levels in different iron deficiency. We constructed ferric reductase-null mutants by a PCR-based homologous recombination, and examined the effects of gene deletion on cell-surface ferric reductase activity and growth ability under different conditions. Sub-cellular localization of Frpl-GFP fusion was imaged and analyzed by confocal laser scanning fluorescence microscopy., Results: FRE10 was highly expressed at acidic pH, compared to that at alkaline pH, whereas the expression of FRE2 was just the opposite. Deletion of FRE10 resulted in a significant decreased surface reductase activity at acidic pH, with 75.5% down-regulation compared to wild-type levels. The fre2delta/delta mutant showed significantly attenuated growth ability and cell-surface ferric reductase activity at alkaline pH. Sub-cellular localization revealed that the green fluorescence was accumulated in the vacuoles., Conclusion: The expression of both FRE10 and FRE2 is induced in a pH-dependent manner. FRE2 encodes a major cell surface ferric reductase under alkaline pH condition. Frp1 localizes to the vacuole, and might support mobilization and transport of vacuolar ferric iron stores.

Objective: To explore the characteristics of cognitive impairment and correlation analysis in patients with chronic renal failure (CRF)., Methods: The Addenbrooke's cognitive examination revised (ACE-R) scale was used to evaluate the cognitive function for 101 cases of chronic renal failure patients (group CRF) receiving outpatient and inpatient treatments and selected 30 individuals with normal renal function as normal controls (group NC) for cross-sectional analysis. T test, receiver operating characteristic (ROC) curve and other statistical methods were adopted for comparing differences., Results: (1) Compared with group NC (83.4 ± 6.5), group CRF (71.9 ± 17.6) showed significantly statistical difference on Addenbrooke's cognitive examination revised (ACE-R) scale scores (P < 0.01); (2)compared with normal controls, the patients with CRF had significantly statistical difference on the scores of visual spatial ability (11.5 ± 3.2, 14.0 ± 3.0 respectively), language fluency (7.0 ± 2.6, 8.7 ± 1.9) (P < 0.01) and memory (18.1 ± 7.0, 21.5 ± 3.6 respectively) (P < 0.05); (3) the cognitive function of patients with CRF were significantly positive correlated with glomerular filtration rate (GFR) (r = 0.614, P < 0.01) and negatively correlated with the duration of illness (r = -0.492, P < 0.01); (4) From ROC curve and the area under curve (AUC), ACE-R scale (AUC = 0.680) showed a higher sensitivity than mini-mental state examination scale (AUC = 0.576) in assessing cognitive function in patients with CRF (P < 0.01)., Conclusion: (1) Under similar basic conditions of age, level of education and background, CRF patients showed significant damage overall cognitive function, cognitive impairment in visual spatial ability, executive function, long-term memory and logical judgment ability was particularly impaired. Immediate and delayed memory, attention, orientation and language ability also manifested different degrees of decline; (2) the severity of cognitive impairment in patients with CFR was closely related with the level of GFR; (3) the ACE-R scale showed a higher sensitivity than mini-mental state examination scale in assessing cognitive function in patients with CRF.

Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is a rare autosomal dominant leukoencephalopathy disease, and colony stimulating factor 1 receptor (CSF1R) is the only gene in which mutations are known to cause HDLS. HDLS should be suspected in individuals with progressive neurological decline, characteristic MR imaging findings, and positive family history. This article reviews recent advance in imaging findings, clinical manifestations, genetic counseling and management in HDLS.

The calcium gate encoded by CCH1 and MID1 genes is the main channel for external calcium absorption. As one of the important secondary messengers, the elevation of calcium concentration could activate some pathways to take part in various cell processes. In this study, we used CCH1 and MID1 mutant strains and also constructed their complementary strains to study the effect of drug tolerance and virulence of Candida albicans after CCH1 or MID1 deletion. By drug plate sensitivity assay and the broth microdilution method, we compared the changes between different strains. Moreover, we added calcium channel blocker and inhibitors to analyze the effect of calcium concentration on drug action. After the deletion of CCH1 or MID1 gene, the strain exhibited an obvious sensitivity to FLUC and ITRA, and the drug action was regulated by the calcium concentration. In a mouse model of intravenous infection, we found that attenuated virulence of cch1delta/delta or mid1delta/delta strain is specifically due to a loss of CCH1 or MID1 gene.

We have investigated the adsorption of hydrophobically end-capped poly(ethylene glycol) (HE-PEG) with carbon number (m) in the hydrocarbon end chain ranging from 0 to 16 onto phospholipid membrane by use of quartz crystal microbalance with dissipation (QCM-D), surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). QCM-D and SPR studies show that the hydrophobic interaction between HE-PEG chains and the lipid membrane increases with the hydrocarbon chain length. At a low HE-PEG concentration, the adsorption cannot induce a vesicle-to-bilayer transition until the carbon number is up to 16. However, at a high HE-PEG concentration, the adsorption results in a vesicle-to-bilayer transition at m > or = 12. ITC measurements demonstrate that enthalpy change (DeltaH) for the mixing of lipid vesicles with HE-PEG chains is too small to be detectable when m is less than 12. However, DeltaH changes from positive to negative as the carbon number increases from 12 to 16, indicating that the HE-PEG insertion increases with its hydrocarbon end-chain length. The present study reveals that the hydrophobic interaction between the lipid membrane and HE-PEG chains as well as the osmotic pressure drive the adsorption and insertion of such polymer chains.