Lighting up endogenous H2O2 in the tumor microenvironment using a dual-mode nanoprobe for long afterglow and MR bioimaging.

Persistent luminescent nanoparticles (PLNPs) are excellent luminescent materials, and near-infrared PLNPs are efficiently applied for biosensing and bioimaging due to their advantages of no excitation, excellent light stability and long afterglow. However, due to interference from the complex environment within organisms, single-mode imaging methods often face limitations in selectivity, sensitivity, and accuracy. Therefore, it is desirable to construct a dual-mode imaging probe strategy with higher specificity and sensitivity for bioimaging. Magnetic resonance imaging (MRI) has been widely used in the field of bioimaging due to its advantages of high resolution, non-radiation and non-invasiveness. Here, by combining near-infrared PLNPs and manganese dioxide (MnO2) nanosheets, a sensitive and convenient dual-mode "turn on" bioimaging nanoprobe ZGC@MnO2 has been developed for long afterglow imaging and MRI of endogenous hydrogen peroxide (H2O2) in the tumor microenvironment (TME). The monitoring of H2O2 has garnered significant attention due to its crucial role in human pathologies. For the dual-mode "turn on" bioimaging nanoprobe, the near-infrared PLNPs of quasi-spherical ZnGa2O4:Cr (ZGC) nanoparticles were synthesized as luminophores, and MnO2 nanosheets were utilized as a fluorescence quencher, carrier and H2O2 recognizer. H2O2 in the TME could reduce MnO2 nanosheets to Mn2+ for MRI, and ZGC nanoparticles were released for long afterglow imaging. Finally, the ZGC@MnO2 nanoprobe exhibited a rapid response, an excellent signal-to-noise ratio and a limit of detection of 3.67 nM for endogenous H2O2 in the TME. This dual-mode approach enhances the detection sensitivity for endogenous H2O2, thereby facilitating the research of endogenous H2O2-associated diseases and clinical diagnostics.

Asprosin promotes vascular inflammation via TLR4-NFκB-mediated NLRP3 inflammasome activation in hypertension.

Objective: and design Mild vascular inflammation promotes the pathogenesis of hypertension. Asprosin, a newly discovered adipokine, is closely associated with metabolic diseases. We hypothesized that asprosin might led to vascular inflammation in hypertension via NLRP3 inflammasome formation. This study shows the importance of asprosin in the vascular inflammation of hypertension. Methods: Primary vascular smooth muscle cells (VSMCs) were obtained from the aorta of animals, including spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), NLRP3-/- and wild-type mice. Studies were performed in VSMCs in vitro, as well as WKY and SHR in vivo. Results: Asprosin expressions were up-regulated in VSMCs and media of arteries in SHR. Asprosin overexpression promoted NLRP3 inflammasome activation via Toll-like receptor 4 (TLR4), accompanied with activation of NFκB signaling pathway in VSMCs. Exogenous asprosin protein showed similar roles in promoting NLRP3 inflammasome activation. Knockdown of asprosin restrained NLRP3 inflammasome and p65-NFκB activation in VSMCs of SHR. NLRP3 inhibitor MCC950 or NFκB inhibitor BAY11-7082 attenuated asprosin-caused VSMC proliferation and migration. Asprosin-induced interleukin-1ß production, proliferation and migration were attenuated in NLRP3-/- VSMCs. Local asprosin knockdown in common carotid artery of SHR attenuated inflammation and vascular remodeling. Conclusions: Asprosin promoted NLRP3 inflammasome activation in VSMCs by TLR4-NFκB pathway, and thereby stimulates VSMCs proliferation, migration, and vascular remodeling of SHR.

Discovery and biological evaluation of biaryl acetamide derivatives as selective and in vivo active sphingosine kinase-2 inhibitors.

Sphingosine kinase 2 (SphK2) has emerged as a promising target for cancer therapy due to its critical role in tumor growth. However, the lack of potent and selective inhibitors has hindered its clinical application. Herein, we report the design and synthesis of a series of novel SphK2 inhibitors, culminating in the identification of compound 12q as a highly selective and potent inhibitor of SphK2. Molecular dynamics simulations suggest that the incorporation of larger substitution groups facilitates a more effective occupation of the binding site, thereby stabilizing the complex. Compared to the widely used inhibitor ABC294640, compound 12q exhibits superior anti-proliferative activity against various cancer cells, inducing G2 phase arrest and apoptosis in liver cancer cells HepG2. Notably, 12q inhibited migration and colony formation in HepG2 and altered intracellular sphingolipid content. Moreover, intraperitoneal administration of 12q in mice resulted in decreased levels of S1P. 12q provides a valuable tool compound for exploring the therapeutic potential of targeting SphK2 in cancer.

Direct Synthesis of C4-Acyl Indoles via C-H Acylation.

The direct synthesis of C4-acyl indoles deprived of C2 and C3 substituents has proven to be challenging, with scarce efficient synthetic routes being reported. Herein, we disclose a highly site-selective palladium-catalyzed C-H acylation for the construction of C4-acyl indoles via a Catellani-Lautens cyclization strategy. In addition, we systematically studied the ortho C-H acylation mechanism of iodoaniline through density functional theory (DFT) calculations and combined experimental results to elucidate the principle of high chemoselectivity brought by triazine benzoate as an acylation reagent.

Multi-omics analysis of Streptomyces djakartensis strain MEPS155 reveal a molecular response strategy combating Ceratocystis fimbriata causing sweet potato black rot.

To investigate the potential antifungal mechanisms of rhizosphere Actinobacteria against Ceratocystis fimbriata in sweet potato, a comprehensive approach combining biochemical analyses and multi-omics techniques was employed in this study. A total of 163 bacterial strains were isolated from the rhizosphere soil of sweet potato. Among them, strain MEPS155, identified as Streptomyces djakartensis, exhibited robust and consistent inhibition of C. fimbriata mycelial growth in in vitro dual culture assays, attributed to both cell-free supernatant and volatile organic compounds. Moreover, strain MEPS155 demonstrated diverse plant growth-promoting attributes, including the production of indole-3-acetic acid, 1-aminocyclopropane-1-carboxylate deaminase, phosphorus solubilization, nitrogen fixation, and enzymatic activities such as cellulase, chitinase, and protease. Notably, strain MEPS155 exhibited efficacy against various sweet potato pathogenic fungi. Following the inoculation of strain MEPS155, a significant reduction (P < 0.05) in malondialdehyde content was observed in sweet potato slices, indicating a potential protective effect. The whole genome of MEPS155 was characterized by a size of 8,030,375 bp, encompassing 7234 coding DNA sequences and 32 secondary metabolite biosynthetic gene clusters. Transcriptomic analysis revealed 1869 differentially expressed genes in the treated group that cultured with C. fimbriata, notably influencing pathways associated with porphyrin metabolism, fatty acid biosynthesis, and biosynthesis of type II polyketide products. These alterations in gene expression are hypothesized to be linked to the production of secondary metabolites contributing to the inhibition of C. fimbriata. Metabolomic analysis identified 1469 potential differently accumulated metabolites (PDAMs) when comparing MEPS155 and the control group. The up-regulated PDAMs were predominantly associated with the biosynthesis of various secondary metabolites, including vanillin, myristic acid, and protocatechuic acid, suggesting potential inhibitory effects on plant pathogenic fungi. Our study underscores the ability of strain S. djakartensis MEPS155 to inhibit C. fimbriata growth through the production of secretory enzymes or secondary metabolites. The findings contribute to a theoretical foundation for future investigations into the role of MEPS155 in postharvest black rot prevention in sweet potato.

Portable Triboelectric Electrostatic Tweezer for External Manipulation of Droplets within a Closed Femtosecond Laser-Treated Superhydrophobic System.

Controllable droplet manipulation has diverse applications; however, limited methods exist for externally manipulating droplets in confined spaces. Herein, we propose a portable triboelectric electrostatic tweezer (TET) by integrating electrostatic forces with a superhydrophobic surface that can even manipulate droplets in an enclosed space. Electrostatic induction causes the droplet to be subjected to an electrostatic force in an electrostatic field so that the droplet can be moved freely with the TET on a superhydrophobic platform. Characterized by its high precision, flexibility, and robust binding strength, TET can manipulate droplets under various conditions and achieve a wide range of representative fluid applications such as droplet microreactors, precise self-cleaning, cargo transportation, the targeted delivery of chemicals, liquid sorting, soft droplet robotics, and cell labeling. Specifically, TET demonstrated the ability to manipulate internal droplets from the outside of a closed system, such as performing cell labeling experiments within a sealed Petri dish without opening the culture system.

Localized self-assembly of macroscopically structured supramolecular hydrogels through reaction-diffusion.

Localized molecular self-assembly has been developed as an effective approach for the fabrication of spatially resolved supramolecular hydrogels, showing great potential for many high-tech applications. However, the fabrication of macroscopically structured supramolecular hydrogels through molecular self-assembly remains a challenge. Herein, we report on localized self-assembly of low molecular weight hydrogelators through a simple reaction-diffusion approach, giving rise to various macroscopically patterned supramolecular hydrogels. This is achieved on the basis of an acid-catalyzed hydrazone supramolecular hydrogelator system. The acid was pre-loaded in a polydimethylsiloxane (PDMS) substrate, generating a proton gradient in the vicinity of the PDMS surface after immersing the PDMS in the aqueous solution of the hydrogelator precursors. The acid dramatically accelerates the in situ formation and self-assembly of the hydrazone hydrogelators, leading to localized formation of supramolecular hydrogels. The growth rate of the supramolecular hydrogels can be easily tuned through controlling the concentrations of the hydrogelator precursors and HCl. Importantly, differently shaped supramolecular hydrogel objects can be obtained by simply changing the shapes of PDMS. This work suggests that reaction-diffusion-mediated localized hydrogelation can serve as an approach towards macroscopically structuralized supramolecular hydrogels, which may find potential applications ranging from tissue engineering to biosensors.

Neural activation signatures in individuals with subclinical depression: A task-fMRI meta-analysis.

BACKGROUND: Previous task-related functional magnetic resonance imaging (task-fMRI) investigations have documented abnormal brain activation associated with subclinical depression (SD), defined as a clinically relevant level of depressive symptoms that does not meet the diagnostic criteria for major depressive disorder. However, these task-fMRI studies have not reported consistent conclusions. Performing a voxel-based meta-analysis of task-fMRI studies may yield reliable findings. METHODS: We extracted the peak coordinates and t values of included studies and analyzed brain activation between individuals with SD and healthy controls (HCs) using anisotropic effect-size signed differential mapping (AES-SDM). RESULTS: A systematic literature search identified eight studies, including 266 individuals with SD and 281 HCs (aged 14 to 25). The meta-analysis showed that individuals with SD exhibited significantly greater activation in the right lenticular nucleus and putamen according to task-fMRI. The meta-regression analysis revealed a negative correlation between the proportion of females in a group and activation in the right striatum. LIMITATIONS: The recruitment criteria for individuals with SD, type of tasks and MRI acquisition parameters of included studies were heterogeneous. The results should be interpreted cautiously due to insufficient included studies. CONCLUSION: Our findings suggest that individuals with SD exhibit increased activation in the right lenticular nucleus, putamen and striatum, which may indicate a compensatory increase in response to an impairment of insular and striatal function caused by depression. These results provide valuable insights into the potential pathophysiology of brain dysfunction in SD.

Ecological effect of microplastics on soil microbe-driven carbon circulation and greenhouse gas emission: A review.

Soil organic carbon (SOC) pool, the largest part of terrestrial ecosystem, controls global terrestrial carbon balance and consequently presented carbon cycle-climate feedback in climate projections. Microplastics, (MPs, <5 mm) as common pollutants in soil ecosystems, have an obvious impact on soil-borne carbon circulation by affecting soil microbial processes, which play a central role in regulating SOC conversion. In this review, we initially presented the sources, properties and ecological risks of MPs in soil ecosystem, and then the differentiated effects of MPs on the component of SOC, including dissolved organic carbon, soil microbial biomass carbon and easily oxidized organic carbon varying with the types and concentrations of MPs, the soil types, etc. As research turns into a broader perspective, greenhouse gas emissions dominated by the mineralization of SOC coming into view since it can be significantly affected by MPs and is closely associated with soil microbial respiration. The pathways of MPs impacting soil microbes-driven carbon conversion include changing microbial community structure and composition, the functional enzyme's activity and the abundance and expression of functional genes. However, numerous uncertainties still exist regarding the microbial mechanisms in the deeper biochemical process. More comprehensive studies are necessary to explore the affected footprint and provide guidance for finding the evaluation criterion of MPs affecting climate change.

Mechanism Analysis of OsZF8-Mediated Regulation of Rice Resistance to Sheath Blight.

Transcription factors are key molecules involved in transcriptional and post-transcriptional regulation in plants and play an important regulatory role in resisting biological stress. In this study, we identified a regulatory factor, OsZF8, mediating rice response to Rhizoctonia solani (R. solani) AG1-IA infection. The expression of OsZF8 affects R. solani rice infection. OsZF8 knockout and overexpressed rice plants were constructed, and the phenotypes of mutant and wild-type (WT) plants showed that OsZF8 negatively regulated rice resistance to rice sheath blight. However, it was speculated that OsZF8 plays a regulatory role at the protein level. The interacting protein PRB1 of OsZF8 was screened using the yeast two-hybrid and bimolecular fluorescence complementation test. The results showed that OsZF8 effectively inhibited PRB1-induced cell death in tobacco cells, and molecular docking results showed that PRB1 had a strong binding effect with OsZF8. Further, the binding ability of OsZF8-PRB1 to ergosterol was significantly reduced when compared with the PRB1 protein. These findings provide new insights into elucidating the mechanism of rice resistance to rice sheath blight.

Tumor-resident microbiota contributes to colorectal cancer liver metastasis by lactylation and immune modulation.

The role of tumor-resident microbiota in modulating tumor immunity remains unclear. Here, we discovered an abundance of intra-tumoral bacteria, such us E.coli, residing and resulting in Colorectal cancer liver metastasis (CRLM). E.coli enhanced lactate production, which mediated M2 macrophage polarization by suppressing nuclear factor-κB -gene binding (NF-κB) signaling through retinoic acid-inducible gene 1 (RIG-I) lactylation. Lactylation of RIG-I suppressed recruitment of NF-κB to the Nlrp3 promoter in macrophages, thereby reducing its transcription. This loss of Nlrp3 affected the immunosuppressive activities of regulatory T cells (Tregs) and the antitumor activities of and CD8+ T cells. Small-molecule compound screening identified a RIG-I lactylation inhibitor that suppressed M2 polarization and sensitized CRLM to 5-fluorouracil (5-FU). Our findings suggest that tumor-resident microbiota may be a potential target for preventing and treating CRLM.

Intestinal persistence of Bifidobacterium infantis is determined by interaction of host genetics and antibiotic exposure.

Probiotics have gained significant attention as a potential strategy to improve health by modulating host-microbe interactions, particularly in situations where the normal microbiota has been disrupted. However, evidence regarding their efficacy has been inconsistent, with considerable inter-individual variability in response. We aimed to explore whether a common genetic variant that affects the production of mucosal α(1,2)-fucosylated glycans, present in around 20% of the population, could explain the observed interpersonal differences in the persistence of commonly used probiotics. Using a mouse model with varying α(1,2)-fucosylated glycans secretion (Fut2WT or Fut2KO), we examined the abundance and persistence of Bifidobacterium strains (infantis, breve, and bifidum). We observed significant differences in baseline gut microbiota characteristics between Fut2WT and Fut2KO littermates, with Fut2WT mice exhibiting enrichment of species able to utilise α(1,2)-fucosylated glycans. Following antibiotic exposure, only Fut2WT animals showed persistent engraftment of Bifidobacterium infantis, a strain able to internalise α(1,2)-fucosylated glycans, whereas B. breve and Bifidobacterium bifidum, which cannot internalise α(1,2)-fucosylated glycans, did not exhibit this difference. In mice with an intact commensal microbiota, the relationship between secretor status and B. infantis persistence was reversed, with Fut2KO animals showing greater persistence compared to Fut2WT. Our findings suggest that the interplay between a common genetic variation and antibiotic exposure plays a crucial role in determining the dynamics of B. infantis in the recipient gut, which could potentially contribute to the observed variation in response to this commonly used probiotic species.

A C-H functionalization approach to diverse nitrogenous scaffolds through conjugate addition of catalytic allyliron nucleophiles.

Cyclopentadienyliron(ii) dicarbonyl complexes capable of coordinating to and enhancing the acidity of a range of unsaturated substrates have emerged as a new class of base-metal derived catalysts for C-H functionalization. In this manuscript, the iron-catalyzed C-H functionalization of allylic C(sp3)-H bonds using nitrogen containing α,ß-unsaturated carbonyl compounds as coupling partners is reported. Employing a cationic cyclopentadienyliron dicarbonyl complex, this redox neutral process converts simple alkenes into allylic anion equivalents for 1,4-addition into maleimides, acyclic α,ß-unsaturated imides, and vinylogous amides. The judicious pairing of pyridine and alkylamine bases with Lewis acid additives allowed each of these classes of substrates to be successfully employed, allowing for the formation of a diverse collection of cyclic and acyclic nitrogen-containing compounds featuring C-C unsaturation. The resulting Michael adducts can be further transformed into a variety of useful scaffolds such as allylated pyrroles, pyrrolidines, and carbocyclic acids.

Elucidating the association of obstructive sleep apnea with brain structure and cognitive performance.

BACKGROUND: Obstructive sleep apnea (OSA) is a pervasive, chronic sleep-related respiratory condition that causes brain structural alterations and cognitive impairments. However, the causal association of OSA with brain morphology and cognitive performance has not been determined. METHODS: We conducted a two-sample bidirectional Mendelian randomization (MR) analysis to investigate the causal relationship between OSA and a range of neurocognitive characteristics, including brain cortical structure, brain subcortical structure, brain structural change across the lifespan, and cognitive performance. Summary-level GWAS data for OSA from the FinnGen consortium was used to identify genetically predicted OSA. Data regarding neurocognitive characteristics were obtained from published meta-analysis studies. Linkage disequilibrium score regression analysis was employed to reveal genetic correlations between OSA and related traits. RESULTS: Our MR study provided evidence that OSA was found to significantly increase the volume of the hippocampus (IVW ß (95% CI) = 158.997 (76.768 to 241.227), P = 1.51e-04), with no heterogeneity and pleiotropy detected. Nominally causal effects of OSA on brain structures, such as the thickness of the temporal pole with or without global weighted, amygdala structure change, and cerebellum white matter change covering lifespan, were observed. Bidirectional causal links were also detected between brain cortical structure, brain subcortical, cognitive performance, and OSA risk. LDSC regression analysis showed no significant correlation between OSA and hippocampus volume. CONCLUSIONS: Overall, we observed a positive association between genetically predicted OSA and hippocampus volume. These findings may provide new insights into the bidirectional links between OSA and neurocognitive features, including brain morphology and cognitive performance.

Inkjet printing quality improvement research progress: A review.

Inkjet printing is a prevalent printing technology that finds extensive applications in diverse fields, including mechanical manufacturing and flexible electronics. Enhancing the quality of inkjet printing has consistently piqued significant interest, with the goal of attaining superior printing resolution, precise color reproduction, and finer image details. This article begins with an overview of the current advancements in inkjet printing, elaborating on four key principles and technologies of inkjet printing. Subsequently, the article delves into the application and research progress related to enhancing inkjet printing quality across various fields. This exploration is structured around four perspectives: printing equipment, substrates, ink properties, and emerging printing technologies. Significant enhancements in inkjet printing quality, resulting in improved image details and color reproduction effects, can be attained by optimizing ink formulations, refining inkjet head design, and selecting suitable substrates and surface treatment methods. To conclude, this article addresses and summarizes future technological advancements aimed at enhancing inkjet printing quality.

A Current Understanding of FXR in NAFLD: The multifaceted regulatory role of FXR and novel lead discovery for drug development.

The global prevalence of nonalcoholic fatty liver disease (NAFLD) has reached 30 %, with an annual increase. The incidence of NAFLD-induced cirrhosis is rapidly rising and has become the leading indicator for liver transplantation in the US. However, there are currently no US Food and Drug Administration-approved drugs for NAFLD. Increasing evidence underscores the close association between NAFLD and bile acid metabolism disorder, highlighting the feasibility of targeting the bile acid signaling pathway for NAFLD treatment. The farnesoid X receptor (FXR) is an endogenous receptor for bile acids that exhibits favorable effects in ameliorating the metabolic imbalance of bile acids, lipid disorders, and disruption of intestinal homeostasis, all of which are key characteristics of NAFLD, making FXR a promising therapeutic target for NAFLD. The present review provides a comprehensive overview of the diverse mechanisms through which FXR improves NAFLD, with particular emphasis on its involvement in regulating bile acid homeostasis and the recent advancements in drug development targeting FXR for NAFLD treatment.

Anorexia nervosa and bulimia nervosa: a Mendelian randomization study of gut microbiota.

Background: Anorexia nervosa (AN) and bulimia nervosa (BN) poses a significant challenge to global public health. Despite extensive research, conclusive evidence regarding the association between gut microbes and the risk of AN and BN remains elusive. Mendelian randomization (MR) methods offer a promising avenue for elucidating potential causal relationships. Materials and methods: Genome-wide association studies (GWAS) datasets of AN and BN were retrieved from the OpenGWAS database for analysis. Independent single nucleotide polymorphisms closely associated with 196 gut bacterial taxa from the MiBioGen consortium were identified as instrumental variables. MR analysis was conducted utilizing R software, with outlier exclusion performed using the MR-PRESSO method. Causal effect estimation was undertaken employing four methods, including Inverse variance weighted. Sensitivity analysis, heterogeneity analysis, horizontal multivariate analysis, and assessment of causal directionality were carried out to assess the robustness of the findings. Results: A total of 196 bacterial taxa spanning six taxonomic levels were subjected to analysis. Nine taxa demonstrating potential causal relationships with AN were identified. Among these, five taxa, including Peptostreptococcaceae, were implicated as exerting a causal effect on AN risk, while four taxa, including Gammaproteobacteria, were associated with a reduced risk of AN. Similarly, nine taxa exhibiting potential causal relationships with BN were identified. Of these, six taxa, including Clostridiales, were identified as risk factors for increased BN risk, while three taxa, including Oxalobacteraceae, were deemed protective factors. Lachnospiraceae emerged as a common influence on both AN and BN, albeit with opposing effects. No evidence of heterogeneity or horizontal pleiotropy was detected for significant estimates. Conclusion: Through MR analysis, we revealed the potential causal role of 18 intestinal bacterial taxa in AN and BN, including Lachnospiraceae. It provides new insights into the mechanistic basis and intervention targets of gut microbiota-mediated AN and BN.

A comparative analysis reveals the genomic diversity among eight Muscovy duck populations.

The Muscovy duck (Cairina moschata) is a waterfowl indigenous to the neotropical regions of Central and South America. It has low demand for concentrated feed and strong adaptability to different rearing conditions. After being introduced to China through Eurasian commercial trade, Muscovy ducks have a domestication history of around 300 years in the Fujian Province of China. In the 1990s, the commodity Muscovy duck breed "Crimo", cultivated in Europe, entered the Chinese market for consumption and breeding purposes. Due to the different selective breeding processes, Muscovy ducks have various populational traits and lack transparency of their genetic background. To remove this burden in Muscovy duck breeding process, we analyzed genomic data from 8 populations totaling 83 individuals. We identify 11.24 million single nucleotide polymorphisms (SNPs) and categorized these individuals into the Fujian-bred and the Crimo populations according to phylogenetic analyses. We then delved deeper into their evolutionary relationships through assessing population structure, calculating fixation index (FST) values, as well as measuring genetic distances. Our exploration of runs of homozygosity (ROH) and homozygous-by-descent (HBD) uncovered genomic regions enriched for genes implicated in fatty acid metabolism, development and immunity pathways. Selective sweep analyses further indicated strong selective pressures exerted on genes including TECR, STAT2 and TRAF5. These findings provide insights into genetic variations of Muscovy ducks, thus offering valuable information regarding genetic diversity, population conservation, and genome-associated for the breeding of Muscovy ducks.

Terpinen-4-ol from tea tree oil prevents Aspergillus flavus growth in postharvest wheat grain.

Plant volatile organic compounds (PVOCs) have gained increasing attention for their role in preventing fungal spoilage and insect contamination in postharvest agro-products owing to their effectiveness and sustainability. In this study, the essential oil was extracted from fresh M. alternifolia (tea tree) leaves, and the fumigation vapor of tea tree oil (TTO) completely inhibited the growth of Aspergillus flavus on agar plates at a concentration of 1.714 µL/mL. Terpinen-4-ol was identified as the major component (40.76 %) of TTO volatiles analyzed using headspace gas chromatography-mass spectrometry. Terpinen-4-ol vapor completely inhibited the A. flavus growth on agar plates and 20 % moisture wheat grain at 0.556 and 1.579 µL/mL, respectively, indicating that terpinen-4-ol serves as the main antifungal constituent in TTO volatiles. The minimum inhibitory concentration of terpinen-4-ol in liquid-contact culture was 1.6 µL/mL. Terpinen-4-ol treatment caused depressed, wrinkled, and punctured mycelial morphology and destroyed the plasma membrane integrity of A. flavus. Metabolomics analysis identified significant alterations in 93 metabolites, with 79 upregulated and 14 downregulated in A. flavus mycelia exposed to 1.6 µL/mL terpinen-4-ol for 6 h, involved in multiple cellular processes including cell membrane permeability and integrity, the ABC transport system, pentose phosphate pathway, and the tricarboxylic acid cycle. Biochemical analysis and 2,7-dichlorofluorescein diacetate staining showed that terpinen-4-ol induced oxidative stress and mitochondrial dysfunction in A. flavus mycelia. This study provides new insights into the antifungal effects of the main TTO volatile compounds terpinen-4-ol on the growth of A. flavus.

Analysis of functional connectivity changes in attention networks and default mode networks in patients with depression and insomnia.

PURPOSE: Major Depressive Disorder (MDD) and Insomnia Disorder (ID) are prevalent psychiatric conditions often occurring concurrently, leading to substantial impairment in daily functioning. Understanding the neurobiological underpinnings of these disorders and their comorbidity is crucial for developing effective interventions. This study aims to analyze changes in functional connectivity within attention networks and default mode networks in patients with depression and insomnia. METHODS: The functional connectivity alterations in individuals with MDD, ID, comorbid MDD and insomnia (iMDD), and healthy controls (HC) were assessed from a cohort of 174 participants. They underwent rs-fMRI scans, demographic assessments, and scale evaluations for depression and sleep quality. Functional connectivity analysis was conducted using region-of-interest (ROI) and whole-brain methods. RESULTS: The MDD and iMDD groups exhibited higher Hamilton Depression Scale (HAMD) scores compared to HC and ID groups (P < 0.001). Both ID and MDD groups displayed enhanced connectivity between the left and right orbital frontal cortex compared to HC (P < 0.05), while the iMDD group showed reduced connectivity compared to HC and ID groups (P < 0.05). In the left insula, reduced connectivity with the right medial superior frontal gyrus was observed across patient groups compared to HC (P < 0.05), with the iMDD group showing increased connectivity compared to MDD (P < 0.05). Moreover, alterations in functional connectivity between the left thalamus and left temporal pole were found in iMDD compared to HC and MDD (P < 0.05). Correlation analyses revealed associations between abnormal connectivity and symptom severity in MDD and ID groups. CONCLUSIONS: Our findings demonstrate distinct patterns of altered functional connectivity in individuals with MDD, ID, and iMDD compared to healthy controls. These findings contribute to a better understanding of the pathophysiology of depression and insomnia, which could be used as a reference for the diagnosis and treatments of these patients.