The substantial increase in fungal diseases, the limited availability of antifungal drugs, and rising resistance to existing treatments highlight the urgent need for developing novel antifungal drugs. Natural products, known for their diverse bioactivities and unique structures, remain critical sources for antifungal drug discovery. In this study, we aimed to identify novel antifungal compounds from soil microbes and isolated a novel 28-membered polyene macrolide, compound 1, from Kitasatospora melanogena. This compound demonstrated potent antifungal activity, with MICs of 4-16 μg/mL against Aspergillus fumigatus, Aspergillus flavus, Candida albicans, and Cryptococcus neoformans. Treatment with compound 1 led to significant growth reduction and disruption of the cell wall and membrane in A. fumigatus compared to the wild-type. To understand the underlying mechanism, we performed a transcriptomic analysis of A. fumigatus exposed to compound 1, revealing a substantial downregulation of genes involved in cell wall and membrane biogenesis, as well as those encoding integral membrane proteins and multidrug transporters. Additionally, compound 1 induced oxidative stress, leading to elevated reactive oxygen species levels. These multifaceted mechanisms highlight the potential of K. melanogena natural products in the development of novel antifungal agents. IMPORTANCE:Fungal infections cause substantial morbidity and mortality worldwide, yet current treatments are limited and increasingly undermined by resistance. Natural products remain a proven source of antifungal agents, but few new scaffolds have been introduced in recent decades. We identified a novel polyene macrolide from Kitasatospora melanogena with potent activity against major fungal pathogens. This compound disrupts both the fungal cell wall and membrane while inducing oxidative stress, revealing a multifaceted mechanism of action. Our findings highlight soil microbes as valuable reservoirs for antifungal discovery and provide a promising lead for the development of next-generation therapies against life-threatening fungal diseases.

BrlA is a multifunctional transcription factor identified in specific clades of filamentous fungi, notably within the Hyphomycetes. It is widely involved in sporulation, cell wall stress response and pathogenicity, and plays an important role in fungal growth and development. To investigate the biological function of the FsbrlA in Fusarium solani, this study employed a split-marker homologous recombination strategy to directionally construct FsbrlA knockout and complementation strains. Through analyses of growth and development phenotypes, determination of cell wall components and trehalose content, abiotic stress treatments, and pathogenicity assays, the biological functions of the FsbrlA were systematically elucidated. The study findings indicate that FsbrlA deletion down-regulates the expression of key sporulation genes in F. solani, resulting in a 93.9% reduction in spore production and a 96.4% decrease in spore germination rate. It also leads to increased aerial mycelium length and reduced surface hydrophilicity. The deletion of FsbrlA also disrupts cell membrane structure, reduces the content of key cell wall components chitin, cellulose, and β-1, 3-glucan, and inhibits the biosynthesis of the stress response compound trehalose. This leads to increased susceptibility of the mutant strain to various stresses, particularly cell wall stress. In addition, ΔFsbrlA mutant also showed significantly reduced pathogenicity on wolfberry plants. In summary, loss of FsbrlA leads to impaired sporulation, altered stress sensitivity, and reduced pathogenicity, suggesting its involvement in these biological processes in F. solani. This study provides preliminary evidence for understanding the biological functions of the FsBrlA protein in F. solani and for exploring the potential mechanisms regulating its growth, development, and pathogenicity.

Influenza virus outbreaks remain a persistent public health concern, yet traditional metabolomics methods are inadequate for addressing key analytical challenges of "dark matter" in influenza research. By integrating quantitative MS1 data, MS2-derived fragmentation trees and molecular fingerprints, structure-based comparative metabolomics enhances predictive capability for chemical structures, and enables the discovery of candidate metabolic markers without the need for database spectra. In this study, we established a C57BL/6J mouse model of H1N1 infection (with PBS as control) and performed structure-based comparative metabolomics on fecal samples using liquid chromatography-mass spectrometry (LC-MS). Quantitative analysis of MS1 data identified 40 differential metabolites, while qualitative analysis of MS2 data enabled their structural annotation. A candidate metabolite marker, LysoPE 15:0, along with other potential metabolic markers, was annotated and validated using Mirror plot, CFM-ID, and sim-Rank-Network. Our findings demonstrate that structure-based comparative metabolomics enables library spectra-free annotation of metabolomic "dark matter" and provides a methodological workflow for discovering candidate metabolite markers in other diseases.

Accurate chromosome segregation during meiosis depends on precise homolog pairing. This process is driven by a series of specialized proteins that link chromosomes to cytoskeletal motors and coordinate chromosome movement for homolog recognition and alignment. Here, we identified RBPL-1, the Caenorhabditis elegans homolog of RBBP6, as a germline-expressed regulator essential for proper homolog pairing and associated nuclear reorganization. Depletion of RBPL-1 impaired the formation of clusters of the LINC complex and CHK-2 kinase within the nuclear periphery. Furthermore, we showed that RBPL-1 regulates the protein abundance of ZIM/HIM-8-family proteins and PLK-2 kinase, two critical mediators of homolog pairing. Notably, RBPL-1's role in homolog pairing is independent of the RING finger domain and Zn knuckle motif, which are proposed to mediate ubiquitination and alternative polyadenylation (APA)/mRNA processing respectively. Instead, we reveal that the evolutionarily conserved yet functionally enigmatic DWNN domain is essential for RBPL-1's function in homolog pairing. In summary, our findings demonstrate that RBPL-1 contributes to meiotic homolog pairing through its DWNN domain, by mediating nuclear reorganization and controlling the abundance of essential pairing factors.

Crossover (CO) formation ensures accurate segregation of homologous chromosomes during the first meiotic division. The pro-crossover proteins are essential for crossover formation and undergo dynamic changes during meiotic prophase I, although the underlying regulatory mechanism is largely unknown. Here, we found that the ubiquitin-proteasome system (UPS) plays a pivotal role in orchestrating pro-crossover protein dynamics and crossover patterning during meiosis in Caenorhabditis elegans. Knockdown of either the ubiquitin-activating enzyme E1 or the proteasome resulted in elevated pro-crossover protein levels and crossover designation. Impairing ubiquitination, but not proteasome activity, led to persistent association of pro-crossover proteins on meiotic chromosomes, a process mediated by the CDC-48UFD-1/NPL-4 segregase. Utilizing a hypomorphic allele of cosa-1, a well-characterized pro-crossover protein-encoding gene, we further demonstrate that the UPS restricts crossover formation. Collectively, our findings reveal a multilayered UPS-mediated regulatory network that maintains proper pro-crossover protein dynamics, thereby coordinating crossover formation with meiotic chromosome segregation.

Aspergillus flavus is a ubiquitous filamentous fungus that poses significant threats as both a causative agent of invasive aspergillosis and a major source of crop contamination due to production of aflatoxin B1 (AFB1). Sugars are essential for fungal metabolism, cell wall biosynthesis, and virulence, yet sugar transporters (STPs) in A. flavus remain largely uncharacterized. In this study, we systematically investigated three putative STP genes (G4B84_001982, G4B84_005374, and G4B84_009351) by comprehensive functional characterization of gene deletion mutants. Growth assays revealed that G4B84_001982 and G4B84_005374 mediate uptake of diverse sugar substrates, while G4B84_009351 appeared to be non-essential under tested conditions. Heterologous expressions in the hexose transport-deficient Saccharomyces cerevisiae strain confirmed their sugar transporter activity. Phenotypic analysis revealed that the Δ1982 and Δ5374 mutants showed pleiotropic defects, including impaired growth, reduced sporulation, delayed germination, increased sensitivity to cell wall stressors, and completely abolished sclerotium formation. Pathogenicity assays demonstrated that the two mutants exhibited attenuated virulence in both plants (crop seeds) and animal (Galleria mellonella) infection model. Our findings highlight the essential of two STPs in A. flavus development, stress tolerance, and pathogenicity, offering insights into sugar-mediated pathogenicity in this economically and medically important fungus.

Aspergillus fumigatus, a saprophytic mold, demonstrates metabolic versatility by utilizing diverse carbon sources to sustain its growth and pathogenic potential. While N-acetylglucosamine (GlcNAc), an ubiquitous amino sugar, serves as a vital nutrient, its catabolic pathway in A. fumigatus remains unexplored. Here, we identified core components of this pathway, including GlcNAc-6-phosphate deacetylase (DacA), glucosamine-6-phosphate deaminase (NagA), and the transcription factor RonA. The expressions of dacA, nagA, and ronA were strongly induced when GlcNAc was the sole carbon source. Both ΔdacA and ΔnagA mutants exhibited abolished growth under GlcNAc condition, whereas the ΔronA mutant exhibited pleiotropic defects, including severe growth defects, impaired polarity, delayed development, reduced cell wall integrity, and decreased virulence in a Galleria mellonella infection model. The deletion of ronA resulted in enhanced immune clearance and exacerbated inflammatory responses. Conidial cell wall analysis revealed that ΔronA conidia displayed aberrant cell wall architecture, primarily characterized by increased surface protein exposure and significantly reduced melanin. Collectively, our findings highlight RonA’s critical role in GlcNAc catabolism, conidial cell wall integrity, and the pathogenesis of A. fumigatus, providing novel insights into antifungal drug development.IMPORTANCEAspergillus fumigatus is a major human fungal pathogen known for its ability to cause a wide range of diseases, primarily due to its exceptional adaptability to diverse environments. This study identifies DacA and NagA as key enzymes in GlcNAc catabolism, while the transcription factor RonA is essential for growth, sporulation, and cell wall stress response on GlcNAc. Beyond regulating GlcNAc catabolism, RonA was found to play a pivotal role in modifying the conidial cell wall structure, influencing host-pathogen interactions, including immune modulation and pathogenicity. These findings highlight RonA as a potential therapeutic target for treating A. fumigatus infections.

Aspergillus fumigatus, the primary etiological agent of invasive aspergillosis, causes over 1.8 million deaths annually. Targeting cell wall biosynthetic pathways offers a promising antifungal strategy. Gfa1, a rate-limiting enzyme in UDP-GlcNAc synthesis, plays a pivotal role in the hexosamine biosynthetic pathway (HBP). Deletion of gfa1 (Δgfa1) results in auxotrophy for glucosamine (GlcN) or N-acetylglucosamine (GlcNAc). Under full recovery (FR) conditions, where minimal medium is supplemented with 5 mM GlcN as the sole carbon source, the Δgfa1 mutant shows growth comparable to the wild-type (WT). However, when supplemented with 5 mM GlcN and 55 mM glucose, growth is partially repressed, likely due to carbon catabolite repression, a condition termed partial repression (PR). Under PR conditions, Δgfa1 exhibits compromised growth, reduced conidiation, defective germination, impaired cell wall integrity, and increased sensitivity to endoplasmic reticulum (ER) stress and high temperatures. Additionally, Δgfa1 demonstrates disruptions in protein homeostasis and iron metabolism. Transcriptomic analysis of the mutant under PR conditions reveals significant alterations in carbohydrate and amino acid metabolism, unfolded protein response (UPR) processes, and iron assimilation. Importantly, Gfa1 is essential for A. fumigatus virulence, as demonstrated in Caenorhabditis elegans and Galleria mellonella infection models. These findings underscore the critical role of Gfa1 in fungal pathogenicity and suggest its potential as a therapeutic target for combating A. fumigatus infections.

Copper carbon dots (CuCDs) have garnered extensive research interest. However, their environmental persistence raises concerns about multigenerational ecotoxicological risks. Synchronized L1 larvae were exposed to CuCDs at concentrations of 0, 2, 6, and 10 mg mL-1 in 24-well plates for 72 h. Here, we systematically evaluated six-generation (F0-F5) toxicological endpoints in Caenorhabditis elegans, including lethality, locomotor activity, reproductive output, developmental parameters, and lifespan. CuCD exposure induced dose-dependent phenotypic aberrations in the F1 generation: high lethality (42.22% increase vs. control group), impaired motility (37.7% reduction in lifespan; 22.69% reduction in body bends; 14.98% fewer head swings), reproductive failure (22.83% decreased egg-laying; 40% "bag of worms" incidence, 10% "fewer eggs" incidence), and developmental stunting (14.63% shorter body length) at high concentration. Across chronic CuCD exposure nematodes exhibited increasing tolerance to CuCDs in the F5 generation, with lethality significantly decreasing over time-a pattern aligning with known transgenerational adaptive responses. Notably, reproductive dysfunction was exacerbated, manifesting as a 29.74% reduction in egg-laying capacity and a 40% incidence of oviposition-deficient phenotypes ("fewer eggs"). Integrative transcriptomics and qRT-PCR validation revealed dysregulation of two core pathways: Skp1/Cullin 1/F box (SCF) ubiquitin ligase complex and Wnt/beta-catenin signaling. Longitudinal tracking of Skr-8::mCherry fluorescence intensity revealed progressive transcriptional silencing, correlating with phenotypic penetrance. Crucially, SCF complex-mediated ubiquitination and Wnt signaling dyshomeostasis emerged as the central node to transgenerational reproductive and developmental toxicity.

Due to the increase in aging populations and the prevalence of aging-associated diseases, there is a growing interest in finding therapeutic interventions. Antioxidants play a vital role in mitigating the adverse conditions associated with aging. In this study, we investigated the impact of Dendrobium officinale alkaloids (DOA) cultivated in diverse environments on antioxidative and anti-aging responses in Caenorhabditis elegans. Three distinct sources of DOA, represented as tree (TR)-DOA, greenhouse (GH)-DOA, and rock (RK)-DOA, were examined. Following initial testing of three DOA concentrations, 10 µg/mL was selected, which increased the TJ1060 lifespan by 23%, and exhibited no toxicity. TR-DOA, GH-DOA, and RK-DOA exhibited robust antioxidative effects, significantly reducing reactive oxygen species levels by 37%, 54%, and 60%, respectively on day 1, and 68%, 73%, and 75% on day 5, respectively. On day 4, TR-DOA, GH-DOA, and RK-DOA significantly reduced lipofuscin levels by 36%, 51%, and 39%, respectively (P < 0.000 1). On day 8, lipofuscin levels were significantly reduced by 34% (P < 0.01), 32% (P < 0.05), and 33% (P < 0.05), respectively. TR-DOA, GH-DOA, and RK-DOA, likewise, reduced the level of the endoplasmic reticulum stress marker, HSP-4::GFP, by 36%, 37%, and 35%, respectively (P < 0.000 1) on day 1, and by 38%, 40%, and 45%, respectively (P < 0.000 1) on day 8. Compared to the control, RK-DOA, GH-DOA, and TR-DOA significantly upregulated HSP-6::GFP (P < 0.0001, P < 0.001, and P < 0.05, respectively), and enhanced heat stress resistance (P < 0.0001, P < 0.001, and P < 0.01, respectively). RK-DOA, GH-DOA, and TR-DOA significantly reduced α-synuclein aggregation by 31%, 25%, and 18% respectively on day 1 (P < 0.0001, P < 0.0001, and P < 0.01, respectively), and by 32%, 27%, and 12% on day 3 (P < 0.01, P < 0.01, and P > 0.05, respectively). RK-DOA, GH-DOA, and TR-DOA delayed paralysis (P < 0.0001, in all cases) and significantly increased worm activity (P < 0.001, P < 0.001, and P < 0.01, respectively). RK-DOA, GH-DOA, and TR-DOA also significantly increased the rate of body bend on day 5 (P < 0.001, P < 0.01, P < 0.0001) and day 10 (P < 0.001, P < 0.0001, P < 0.01). Our findings suggest that DOA, particularly RK-DOA, offers promising antioxidative and anti-aging benefits in C. elegans. The differential responses among DOA variants highlight the importance of the cultivation environment in shaping the bioactivity of natural compounds.

The SMC-5/6 complex safeguards genome stability through the coordinated action of its core SMC proteins and associated NSE subunits. NSE-1 is a key component of the complex and is essential for DNA repair, yet it remains poorly characterized in Caenorhabditis elegans. To further elucidate the functional mechanisms of NSE-1, we performed an EMS-based forward genetic screen in an nse-1::gfp(wsh1) reporter strain to identify mutants with defective NSE-1 expression or nuclear localization. We isolated three mutants; smc-5(wsh31), smc-5(wsh32), and smc-5(wsh33), that display impaired NSE-1::GFP nuclear localization. SNP mapping and whole-genome sequencing revealed three novel smc-5 alleles: two truncations, alleles smc-5(wsh31) (C587*) and smc-5(wsh32) (Q655*), and one missense variant, smc-5(wsh33) (Y975D), each altering a highly conserved residue in the SMC domain. All three mutants exhibited significantly reduced brood size, progeny viability, and slightly elevated male percentages. Phenotypic characterization revealed that the truncations completely abrogate NSE-1::GFP nuclear localization, whereas the missense allele causes stage-dependent, partial mislocalization. Functional assays further demonstrated allele-specific and developmental stage-dependent hypersensitivities to DNA-damaging agents (MMS, HU, and cisplatin). These separation-of-function smc-5 alleles underscore the importance of domains and conserved residues in complex integrity and genome maintenance, and provide powerful genetic tools to dissect SMC-5/6 functions in vivo.

Prickly pear extract (PPE) exhibits diverse effects, including antioxidative, hypoglycemic, and antiobesity properties. While its role in alcoholic liver disease (ALD) prevention remains understudied, this research unveils PPE's chemical composition (total protein, sugar, phenols, flavonoids, and polyphenols). Employing an ALD animal model, we identified 12 PPE metabolites that directly entered the liver, mitigating alcohol-induced oxidative damage by reducing ALT, AST, and MDA levels, elevating SOD and GSH levels, and enhancing ADH and ALDH enzymatic activity. Examining ethanol-induced HepG2 cells, PPE activated the Fanconi anemia (FA) pathway, upregulating proteins (ub-FANCD2, ub-FANCI, FANCA) involved in antioxidant gene expression and FA complex proteins (ub-FANCM, MHF1, FAAP24) promoting DNA repair. These findings highlight PPE's ability to combat oxidative stress and DNA damage through FA pathway activation, affirming its hepatoprotective potential as a natural product.

Glucoamylase is essential for the hydrolysis of starch to glucose and has broad industrial applications. Although its catalytic domain shares similarities with GH8 family chitosanases, which are known for their bifunctional activity, no bifunctional glucoamylase has been reported to date. In this study, we identify and characterize AfGA, a glucoamylase from the pathogenic fungus Aspergillus fumigatus 293, which exhibits a dual hydrolytic activity toward both starch and chitosan. AfGA demonstrated efficient starch hydrolysis at 70 °C with a specific activity of 503.28 ± 1.3 U/mg and chitosan hydrolysis at 90 °C with a specific activity of 3.67 ± 0.1 U/mg. Molecular docking and dynamics simulations revealed that the enhanced catalytic activity and substrate binding of AfGA for starch are attributed to increased interactions within the substrate-binding pocket. The ΔAfga strain exhibited reduced growth, sporulation, and carbon utilization efficiency as well as hypersensitivity to cell wall-disrupting agents. These results highlight Afga's critical role in maintaining cell wall integrity and carbon metabolism in A. fumigatus. Our findings provide new insights into the substrate promiscuity of glycoside hydrolases and underscore the potential of AfGA in both industrial biocatalysis and fungal biology.

Accurate chromosome segregation during meiosis requires the establishment of at least one crossover (CO) between each pair of homologous chromosomes. CO formation depends on a group of conserved pro-CO proteins, which colocalize at CO-designated sites during late meiotic prophase I. However, it remains unclear whether these pro-CO proteins form a functional complex and how they promote meiotic CO formation in vivo. Here, we show that COSA-1, a key component required for CO formation, interacts with other pro-CO factors, MSH-5 and ZHP-3, via its N-terminal disordered region. Point mutations that impair these interactions do not affect CO designation, but they strongly hinder the accumulation of COSA-1 at CO-designated sites and result in defective CO formation. These defects can be partially bypassed by artificially tethering an interaction-compromised COSA-1 derivate to ZHP-3. Furthermore, we revealed that the accumulation of COSA-1 into distinct foci is required to assemble functional 'recombination nodules'. These prevent early CO-designated recombination intermediates from being dismantled by the RTEL-1 helicase and protect late recombination intermediates, such as Holliday junctions, until they are resolved by CO-specific resolvases. Altogether, our findings provide insight into COSA-1 mediated pro-CO complex assembly and its contribution to CO formation.

COSA-1 is essential for accurate meiosis in C. elegans . Two null mutants ( cosa-1 ( me13 ) and cosa-1 ( tm3298 ) ) have been notably studied. These null mutants exhibit severe meiotic defects, hindering the observation of the subtle or dynamic nature of COSA-1 function. To overcome these limitations, we developed a C. elegans strain with inducible COSA-1 degradation using the Auxin-Inducible Degron (AID) system. This strain exhibits normal fertility and COSA-1::GFP foci. Auxin treatment successfully depletes COSA-1, resulting in a 96% decrease in progeny viability and 12 univalent chromosomes in diakinesis oocytes. This strain serves as a valuable tool for studying the dynamics of COSA-1.

Sugarcane smut, caused by Sporisorium scitamineum, poses a significant global threat, leading to substantial economic losses. The pathogenic process involves haploid spores engaging in sexual mating to produce diploid mycelia, which then initiates the disease by penetrating sugarcane tissues. Targeting the mating process has thus emerged as the Achilles’ heel in controlling sugarcane smut. In this study, we isolated a fungus designated as P-6 from a bryophyte, which impeded the mycelia formation of S. scitamineum. Phylogenetic and morphological analyses classified the strain P-6 within the genus Paramyrothecum. Through ethyl acetate extraction, subsequent separation, and nuclear magnetic resonance (NMR) analysis, we identified the active compound responsible for inhibiting the mating process as verrucarin A (Ver-A). Specifically, Ver-A inhibited the sexual mating of S. scitamineum by modulating the gene expression of loci a and b. Greenhouse pot experiments underscored the efficacy of strain P-6’s fermentation products in reducing the incidence of sugarcane smut. These findings lay a robust groundwork for the development and application of P-6 as a novel biocontrol strain against sugarcane smut.

Passion fruit (Passilora edulis), known as the "king of fruit juices", is popular in southern China (Yuan et al. 2019). Stem base rot is a devastating disease of passion fruit commonly caused by several Fusarium spp. (Zakaria, 2022). In July 2022, typical symptoms of stem base rot were observed in a poorly managed “Qinmi No. 9” Golden passion fruit orchard in Jingxi (23°13'10"N, 106°5'23"E). The disease incidence had reached 40% (n=200) in the survey. Symptoms included ulceration and mutilation at the stem base, making the plants prone to breakage when pulled, wilting and drooping leaves above ground, and severe cases leading to the entire plant withering and dying. Fourteen plants with obvious symptoms were collected. Thin sections of plant tissue were cut from junction of sickness and health of stem, sterilized with ethanol and sodium hypochlorite, and placed on PDA medium at 28°C. Sixty fungal strains were obtained, 90% of which was identified as Fusarium based on morphology. 80% of Fusarium were F. oxysporum species complex (FOSC), but pathogenicity experiment showed all FOSC were weakly pathogenic. However, two severely pathogenic fungi with similar morphology but distinct from Fusarium were identified from the same plant. The representative strain C11 was selected for further study. C11 demonstrated a rapid growth rate, reaching a 90 mm diameter colony on PDA cultured at 25°C for 7 days. The colony displaced a round, flat shape with an overall light brown front, and cottony gray or light brown mycelium, while the reverse side was dark brown. Conidia production was observed as typically occurred in multiple chains after 14 days culture on OA medium, with round, oval or straight rod-like brown conidia ranging in size from 5.74-23.42×14.67-67.22, featuring 1-8 transverse septa and 0-3 mediastinum (Figure S1). For molecular identification, the internal transcribed spacer (ITS, OR616614), translation elongation factor 1-alpha (TEF, OR633298), alternaria major allergen (Alt a1, OR633294) gene, glyceraldehyde 3-phosphate dehydrogenase (GAPDH, OR633295), RNA polymerase subunit II gene (RPB2, OR633297), 18S Small subunit rDNA (SSU, OR616608) , 28S Large Subunit rDNA (LSU, OR616615), the KOG1058 gene regions (OR633296) and an approximately segment of the anonymous noncoding region (OPA10-2, OR633299) were amplified from C11 (Liu et al. 1999, Li et al. 2023, Andrew et al. 2009), and deposited in GenBank with accession number shown in the brackets. Phylogenetic trees were constructed in MEGA11 after splicing by BioEdit (Figure S3). Combining morphology and molecular analyses, C11 was identified as Alternaria gossypina (Woudenberg et al. 2015). To test the pathogenicity, the base of the seedling stem (20cm in height) of 50 healthy “Tainong No. 1” variety of purple passion fruit, which was more susceptible to stem-base rot, was puncture wound with needles, inoculated with 6 mm diameter colonies of fungi, and then wrapped in wet cotton (Ángel et al. 2018). Ten healthy seedlings inoculated with PDA were used as controls. These plants were cultured in an artificial greenhouse at 30±5℃with 80±5% humidity. After 15 days, the plants inoculated with C11 exhibited symptoms similar to those in the field, whereas the controls remained healthy. A. gossypina was reisolated from the diseased plant stems, with the morphology and GAPDH sequence consistent with the inoculated (Figure S1, S2). This is the first report of passion fruit stem rot caused by A. gossypina. This finding will aid in the prevention and control of stem rot in passion fruit.

Methyl Ganoderate E (MGE) is a triterpenoid derived from Ganoderma lucidum (Reishi), an edible mushroom, commonly processed into food forms such as soups, drinks, culinary dishes, and supplements. MGE has been shown to inhibit 3T3-L1 murine adipocyte differentiation when combined with other G. lucidum triterpenes. However, the specific effect of MGE on biological processes remains unknown. In this study, we present the first evidence of MGE's anti-aging effect in Caenorhabditis elegans. Through our screening process using the UPRER regulation ability, we evaluated a library of 74 pure compounds isolated from G. lucidum, and MGE exhibited the most promising results. Subsequent experiments demonstrated that MGE extended the lifespan by 26% at 10 μg ml-1 through daf-16, hsf-1, and skn-1-dependent pathways. MGE also enhanced resistance to various molecular stressors, improved healthspan, increased fertility, and reduced the aggregation of alpha-synuclein and amyloid-beta. Transcriptome data revealed that MGE promoted processes associated with proteolysis and neural activity, while not promoting cell death processes. Collectively, our findings suggest that G. lucidum MGE could be considered as a potential anti-aging intervention, adding to the growing list of such interventions.

The Smc5/6 complex is evolutionarily conserved across all eukaryotes and plays a pivotal role in preserving genomic stability. Mutations in genes encoding Smc5/6 complex subunits have been associated with human lung disease, immunodeficiency, and chromosome breakage syndrome. Despite its critical importance, much about the Smc5/6 complex remains to be elucidated. Various evidences have suggested possible role of a subunit of the Smc5/6 complex, Nse1, in chromosome segregation and DNA repair. Current knowledge regarding the role of Nse1 is primarily derived from single-cell-based analyses in yeasts, Arabidopsis thaliana, and human cell lines. However, our understanding of its function is still limited and requires further investigation. This study delves into the role of nse-1 in Caenorhabditis elegans, revealing its involvement in meiotic recombination and DNA repair. nse-1 mutants display reduced fertility, increased male incidence, and increased sensitivity to genotoxic chemicals due to defects in meiotic chromosome segregation and DNA repair. These defects manifest as increased accumulation of RAD-51 foci, increased chromosome fragmentation, and susceptibility to MMS, cisplatin, and HU. Furthermore, nse-1 mutation exacerbates germ cell death by upregulating ced-13 and egl-1 genes involved in the CEP-1/p53-mediated apoptotic pathway. NSE-1 is essential for the proper localization of NSE-4 and MAGE-1 on the chromosomes. Collectively, these findings firmly establish nse-1 as a crucial factor in maintaining genomic stability.

Sugarcane leaves-derived polyphenols (SLP) have been demonstrated to have diverse health-promoting benefits, but the mechanism of action has not been fully elucidated. This study aimed to investigate the anti-metabolic disease effects of SLP and the underlying mechanisms in mice. In the current study, we prepared the SLP mainly consisting of three flavonoid glycosides, three phenol derivatives, and two lignans including one new compound, and further demonstrated that SLP reduced body weight gain and fat accumulation, improved glucose and lipid metabolism disorders, ameliorated hepatic steatosis, and regulated short-chain fatty acids (SCFAs) production and secondary bile acids metabolism in ob/ob mice. Notably, SLP largely altered the gut microbiota composition, especially enriching the commensal bacteria Akkermansia muciniphila and Bacteroides acidifaciens. Oral gavage with the above two strains ameliorated metabolic syndrome (MetS), regulated secondary bile acid metabolism, and increased the production of SCFAs in high-fat diet (HFD)-induced obese mice. These results demonstrated that SLP could be used as a prebiotic to attenuate MetS via regulating gut microbiota composition and further activating the secondary bile acids-mediated gut-adipose axis.