Mitophagy selectively eliminates damaged or dysfunctional mitochondria, playing a crucial role in maintaining mitochondrial quality control. However, it remains unclear whether mitophagy can be fully activated and how it evolves after SCI. Our RNA-seq analysis of animal samples from sham and 1, 3, 5, and 7 days post-SCI indicated that mitophagy was indeed inhibited during the acute and subacute early stages. In vitro experiments showed that this inhibition was closely related to excessive production of reactive oxygen species (ROS) and the downregulation of BNIP3. Excessive ROS led to the blockage of mitophagy flux, accompanied by further mitochondrial dysfunction and increased neuronal apoptosis. Fortunately, ligustilide (LIG) was found to have the ability to reverse the oxidative stress-induced downregulation of BNIP3 and enhance mitophagy through BNIP3-LC3 interaction, alleviating mitochondrial dysfunction and ultimately reducing neuronal apoptosis. Further animal experiments demonstrated that LIG alleviated oxidative stress and mitophagy inhibition, rescued neuronal apoptosis, and promoted tissue repair, ultimately leading to improved motor function. In summary, this study elucidated the state of mitophagy inhibition following SCI and its potential mechanisms, and confirmed the effects of LIG-enhanced mitophagy through BNIP3-LC3, providing new therapeutic targets and strategies for repairing SCI.

Natural products are a valuable resource for the discovery of novel crop protection agents. A series of γ-butyrolactone derivatives, derived from the simplification of podophyllotoxin\'s structure, were synthesized and assessed for their efficacy against tobacco mosaic virus (TMV). Several derivatives exhibited notable antiviral properties, with compound 3g demonstrating the most potent in vivo anti-TMV activity. At 500 μg/mL, compound 3g achieved an inactivation effect of 87.8%, a protective effect of 71.7%, and a curative effect of 67.7%, surpassing the effectiveness of the commercial plant virucides ningnanmycin and ribavirin. Notably, the syn-diastereomer (syn-3g) exhibited superior antiviral activity compared to the anti-diastereomer (anti-3g). Mechanistic studies revealed that syn-3g could bind to the TMV coat protein and interfere with the self-assembly process of TMV particles. These findings indicate that compound 3g, with its simple chemical structure, could be a potential candidate for the development of novel antiviral agents for crop protection.

Ralstonia solanacearum species complex (RSSC) includes soilborne bacterial plant pathogens with worldwide distribution and wide host ranges. Virulence factors are regulated via four hierarchically organized cell-cell contact independent quorum-sensing (QS) signalling systems: the Phc, which uses as signals (R)-methyl 3-hydroxypalmitate [(R)-3-OH PAME] or (R)-methyl 3-hydroxymyristate [(R)-3-OH MAME], the N-acyl homoserine lactone (AHL)-dependent RasI/R and SolI/R systems, and the recently identified anthranilic acid-dependent system. The unique Phc QS system has been extensively studied; however, the role of the two AHL QS systems has only recently been addressed. In this microreview, we present and discuss current data of the SolI/R and RasI/R QS systems in the RSSC. We also present the distribution and frequency of these AHL QS systems in the RSSC, discuss possible ecological roles and evolutive implications. The complex QS hierarchical networks emphasizes the crucial role of cell-cell signalling in the virulence of the RSSC.

Overexpression of carboxyl/cholinesterase (CCE) genes has been reported to be associated with many cases of pesticide resistance in arthropods. However, it has been rarely documented that CCE genes participate in spirodiclofen resistance in Panonychus citri. In previous research, we found that spirodiclofen resistance is related to increased P450 and CCE enzyme activities in P. citri. In this study, we identified two CCE genes, PcCCE3 and PcCCE5, which were significantly upregulated in spirodiclofen-resistant strain and after exposure to spirodiclofen. RNA interference of PcCCE3 and PcCCE5 increased the spirodiclofen susceptibility in P. citri. In vitro metabolism indicated that PcCCE3 and PcCCE5 could interact with spirodiclofen, but metabolites were detected only in the PcCCE3 treatment. Our results indicated that PcCCE3 participates in spirodiclofen resistance through direct metabolism, and PcCCE5 may be involved in the spirodiclofen resistance by passive binding and sequestration, which provides new insights into spirodiclofen resistance in P. citri.

Pseudomonas aeruginosa (P. aeruginosa) biofilm formation is a crucial cause of enhanced antibiotic resistance. Quorum sensing (QS) is involved in regulating biofilm formation; QS inhibitors block the QS signaling pathway as a new strategy to address bacterial resistance. This study investigated the potential and mechanism of L-HSL (N-(3-cyclic butyrolactone)-4-trifluorophenylacetamide) as a QS inhibitor for P. aeruginosa. The results showed that L-HSL effectively inhibited the biofilm formation and dispersed the pre-formed biofilm of P. aeruginosa. The production of extracellular polysaccharides and the motility ability of P. aeruginosa were suppressed by L-HSL. C. elegans infection experiment showed that L-HSL was non-toxic and provided protection to C. elegans against P. aeruginosa infection. Transcriptomic analysis revealed that L-HSL downregulated genes related to QS pathways and biofilm formation. L-HSL exhibits a promising potential as a therapeutic drug for P. aeruginosa infection. KEY POINTS: • Chemical synthesis of N-(3-cyclic butyrolactone)-4-trifluorophenylacetamide, named L-HSL. • L-HSL does not generate survival pressure on the growth of P. aeruginosa and can inhibit the QS system. • KEGG enrichment analysis found that after L-HSL treatment, QS-related genes were downregulated.

Four undescribed polyketides, beshanzones A (1) and B (2) as well as beshanhexanols A (3) and B (4), along with three known ones (5-7) were isolated from the rice fermentation of two endophytic fungi associated with the critically endangered Chinese endemic conifer Abies beshanzuensis. γ-Butyrolactone derivatives 1, 2, and 5 were isolated from Phomopsis sp. BSZ-AZ-2, an interesting strain that drawn our attention this time. The cyclohexanol derivatives 3, 4, 6, and 7 were obtained during a follow-up investigation on Penicillium commune BSZ-P-4-1. The chemical structures including absolute configurations of compounds 1-4 were determined by spectroscopic methods, Mo2(OAc)4 induced electronic circular dichroism (IECD), GIAO NMR calculations and DP4+ probability analyses. In particular, compound 2 contains a novel 5/5 bicyclic ring system, which might be biogenetically derived from the known compound 5 through hydrolysis followed by an Aldol reaction. All isolates were evaluated for their antimicrobial activities against a small panel of bacterial and fungal pathogens. Compounds 6 and 7 showed moderate inhibitory activities against Candida albicans, with MIC values of 16 and 32 μg/mL, respectively.

Corn ear rot and fumonisin caused by Fusarium verticillioides pose a serious threat to food security. To find more highly active fungicidal and antitoxic candidates with structure diversity based on naturally occurring lead xanthatin, a series of novel spiropiperidinyl-α-methylene-γ-butyrolactones were rationally designed and synthesized. The in vitro bioassay results indicated that compound 7c showed broad-spectrum in vitro activity with EC50 values falling from 3.51 to 24.10 μg/mL against Rhizoctonia solani and Alternaria solani, which was more active than the positive controls xanthatin and oxathiapiprolin. In addition, compound 7c also showed good antitoxic efficacy against fumonisin with a 48% inhibition rate even at a concentration of 20 μg/mL. Fluorescence quenching and the molecular docking validated both 7c and oxathiapiprolin targeting at FvoshC. RNA sequencing analysis discovered that FUM gene cluster and protein processing in endoplasmic reticulum were downregulated. Our studies have discovered spiropiperidinyl-α-methylene-γ-butyrolactone as a novel FvoshC target-based scaffold for fungicide lead with antitoxin activity.

Oxidative stress plays a pivotal role in various neurological disorders, encompassing both neurodegenerative diseases such as Alzheimer\'s and Parkinson\'s, and mood disorders like depression. The balance between the generation of reactive oxygen species (ROS) and the cell\'s antioxidant defenses, when disrupted, can lead to neuronal damage and neurologic dysfunction. In this study, we focused on the pathogenic role of oxidative stress in various neurologic disease models in vitro and investigated the neuroprotective capabilities of some novel bicyclic γ-butyrolactone compounds, with particular emphasis on the compound designated as \'bd\'. Our investigation leveraged the HT22 and SH-SY5Y cells to model oxidative stress induced by H2O2 or corticosterone (CORT), common triggers of neuronal damage in neurodegenerative and mood disorders. We discovered that compound bd robustly reduced ROS production and suppressed neuronal apoptosis, suggesting its potential in treating a wider array of neurological conditions influenced by oxidative stress. In conclusion, our research underscores the importance of addressing oxidative stress in the context of diverse neurological disorders. The identification of compound bd as a neuroprotective agent with potential efficacy against ROS-induced apoptosis in neural cells opens new horizons for therapeutic development, offering hope for patients suffering from neurodegenerative diseases, depression, and other stress-related neurological conditions.

Human intestinal microbiota plays a crucial role in converting secoisolariciresinol diglucoside, a lignan found in flaxseed, to enterodiol, which has a range of health benefits: antioxidative, antitumor, and estrogenic/anti-estrogenic effects. Given the high secoisolariciresinol diglucoside content in flaxseed cake, this study investigated the potential of co-fermenting flaxseed cake with fermented soybean product to isolate bacterial strains that effectively convert secoisolariciresinol diglucoside to enterodiol in a controlled environment (in vitro). The co-fermentation process with stinky tofu microbiota significantly altered the lignan, generating 12 intermediate lignan metabolites as identified by targeted metabolomics. One particular promising strain, ZB26, demonstrated an impressive ability to convert secoisolariciresinol diglucoside. It achieved a conversion rate of 87.42 ± 0.33%, with secoisolariciresinol and enterodiol generation rates of 94.22 ± 0.51% and 2.91 ± 0.03%, respectively. Further optimization revealed, under specific conditions (0.5 mM secoisolariciresinol diglucoside, pH 8, 30 °C for 3 days), ZB26 could convert an even higher percentage (97.75 ± 0.05%) of the secoisolariciresinol diglucoside to generate secoisolariciresinol (103.02 ± 0.16%) and enterodiol (3.18 ± 0.31%). These findings suggest that the identified strains ZB26 have promising potential for developing functional foods and ingredients enriched with lignans.

The citrus red mite, Panonychus citri, is one of the most notorious and devastating citrus pests around the world that has developed resistance to multiple chemical acaricides. In previous research, we found that spirodiclofen-resistant is related to overexpression of P450, CCE, and ABC transporter genes in P. citri. However, the regulatory mechanisms of these detoxification genes are still elusive. This study identified all hormone receptor 96 genes of P. citri. 8 PcHR96 genes contained highly conserved domains. The expression profiles showed that PcHR96h was significantly upregulated in spirodiclofen resistant strain and after exposure to spirodiclofen. RNA interference of PcHR96h decreased expression of detoxification genes and increased spirodiclofen susceptibility in P. citri. Furthermore, molecular docking, heterologous expression, and drug affinity responsive target stability demonstrated that PcHR96h can interact with spirodiclofen in vitro. Our research results indicate that PcHR96h plays an important role in regulating spirodiclofen susceptibility and provides theoretical support for the resistance management of P. citri.