Cr (VI)-induced ribosomal DNA copy number variation is associated with semen quality impairment: Evidence from human to animal study.

OBJECTIVES: This study aimed to analyze the possible role of rDNA copy number variation in the association between hexavalent chromium [Cr (VI)] exposure and semen quality in semen donors and further confirm this association in mice. METHODS: In this cross-sectional study, whole blood and semen samples were collected from 155 semen donors in the Zhejiang Human Sperm Bank from January 1st to April 31st, 2021. Adult C57BL/6 J male mice were treated with different doses of Cr (VI) (0, 10, or 15 mg/kg b.w./day). Semen quality, including semen volume, total spermatozoa count, sperm concentration, progressive motility, and total motility, were analyzed according to the WHO laboratory manual. Cr concentration was detected using inductively coupled plasma mass spectrometry. The rDNA copy number was measured using qPCR. RESULTS: In semen donors, whole blood Cr concentration was negatively associated with semen concentration and total sperm counts. Semen 5 S and 45 S rDNA copy numbers were negatively associated with whole blood Cr concentration and whole blood 5.8 S rDNA copy number was negatively associated with semen Cr concentration. In mice, Cr (VI) damaged testicular tissue, decreased semen quality, and caused rDNA copy number variation. Semen quality was related to the rDNA copy number in whole blood, testicular tissue, and semen samples in mice. CONCLUSION: Cr (VI) was associated with decreased semen quality in semen donors and mice. Our findings suggest an in-depth analysis of the role of the rDNA copy number variation in the Cr (VI)-induced impairment of semen quality.

Trends in research on cochlear implantation with inner ear malformation: a bibliometric and visualization analysis from 1986 to 2024.

OBJECTIVE: The aim of this study was to conduct a bibliometric and visualization analysis of research on cochlear implantation (CI) for inner ear malformations (IEMs) from 1986 to 2024. METHODS: A comprehensive literature search was performed using the Web of Science Core Collection Database, resulting in the identification of 431 relevant publications. Various data analysis and visualization tools, including VOSviewer, CiteSpace, and Bibliometrix, were utilized to analyze annual publication outputs, countries/regions and institutions, authors, journals and studies, keywords, and theme evolution. RESULTS: The study revealed an overall increasing trend in research output on CI for IEMs, with significant contributions from countries such as the United States, China, Turkey, Germany, and Italy. The analysis also identified key authors, research teams, journals, and studies that have made substantial contributions to the field. Furthermore, the study highlighted important research hotspots and trends, such as the classification of IEMs, outcomes of CI for IEMs, and the management of pediatric patients with IEMs. CONCLUSION: The findings of this study provide a comprehensive overview of the research landscape surrounding CI for IEMs. The results serve as a basis for future research topic selection and emphasize the need for enhanced international collaboration and the publication of high-impact research to further advance this field.

[Effects of cochlear implantation on tinnitus in patients with single-sided deafness and asymmetrical hearing loss].

Objective:To evaluate the effects of cochlear implantation in patients with single-sided deafness（SSD） and asymmetrical hearing loss（AHL）. Methods:Seventeen Mandarin-speaking CI patients diagnosed as SSD/AHL were recruited in our study. The Tinnitus Handicap Inventory（THI） and the Visual Analogue Scale（VAS） were used to assess changes in tinnitus distress and tinnitus loudness in SSD patients at each time point（pre-operation and post-operation）. Results:The THI score and all 3 dimensions were significant decreased with CI-on than pre-operation（P<0.05）. Tinnitus VAS scores were also decreased, and VAS scores were lower with CI-on than with CI-off, and were both significantly different at each time point after CI switch-on（P<0.05）. Conclusion:CI could help SSD/AHL patients to suppress tinnitus and reduce the loudness of tinnitus. However, CI should not be a treatment of tinnitus.

[Research status and progress of bilateral cochlear implantation].

With the development of social economic and technology, Cochlear Implantation has became an effective therapy for patients who suffered from severe or profound hearing impairment. In the meantime, patients' demands for sound and auditory quality are also increasing. In terms of speech recognition, localization, and auditory quality, bilateral hearing is closer to the auditory experience of normal individuals, so bilateral cochlear implantation（BCI） emerged as the times require. In this article, we will introduce the status and progress of bimodal regarding to the following aspects: the brief history, the advantages of BCI, different methods for BCI, and the problems encountered in BCI.

SERS and electrochemical dual-mode detection of miRNA-141 by using single Au@Ag nanowire as a new platform.

As biomarkers of cancer, the accurate and sensitive detection of microRNAs is of great significance. Therefore, we proposed a surface-enhanced Raman scattering (SERS)/electrochemical (EC) dual-mode nanosensor for sensitively detecting miRNA-141. The nanosensor uses Au@Ag nanowires as a novel SERS/EC sensing platform, which has the advantages of good biocompatibility, fast response, and high sensitivity. The dual-mode nanosensor can not only effectively overcome the problem of insufficient reliability of single signal, but also realize the amplification and stable output of the detection signal, to ensure the reliability and repeatability of miRNA detection. With this sensing strategy, the target miRNA-141 can be detected over a wide linear range (100 fM to 50 nM) (LOD of 18.4 fM for SERS and 16.0 fM for electrochemical methods). In addition, the process shows good selectivity and can distinguish miRNA-141 from other interfering miRNAs. The actual analysis of human serum samples also proves that our strategy has good reliability, repeatability, and has broad application prospects in the field of analysis and detection.

The Novel Fusion Protein Melittin-MIL-2 Exhibits Strong Antitumor Immune Effect in Lung Adenocarcinoma Cell A549.

In previous studies, we developed a novel fusion protein named "melittin-MIL-2" which exhibited more anti-tumor activity. However, it remains unclear whether melittin-MIL-2 possesses antitumor immune effect on lung adenocarcinoma. In this study, the immune effect and mechanism of melittin-MIL-2 inhibiting the growth and invasion of lung adenocarcinoma will be investigated, in order to provide novel perspectives for the immunotherapy of lung cancer. The results indicated that melittin-MIL-2 promoted T cell proliferation, enhanced NK cell cytotoxicity, and boosted IFN-γ secretion in PBMCs. After melittin-MIL-2 stimulation, perforin expression and LAK/NK-like killing activities of human PBMCs and NK cells were significantly enhanced. Melittin-MIL-2 is capable of hampering the development and proliferation of lung adenocarcinoma cell A549. ICAM-1 and Fas expression in A549 cells exposed to melittin-MIL-2 rose significantly. The expression levels of TLR8 and VEGF in A549 cells decreased significantly after melittin-MIL-2 stimulation. In vivo, melittin-MIL-2 substantially impeded the growth of lung adenocarcinoma and formed an immune-stimulating microenvironment locally in tumor tissues. In conclusion, the novel fusion protein melittin-MIL-2 exhibits strong anti-tumor immune effect in lung adenocarcinoma cell A549 via activating the LFA-1/ICAM-1 and Fas/FasL pathways to enhance cytolytic activity, upregulating the secretion of IFN-γ and perforin, and boosting LAK/NK-like killing activities. Immuno-effector cells and their secreted cytokines can form immune stimulation microenvironment locally in lung adenocarcinoma Lewis mice tissue.

Mechanochemical synthesis of corannulene flanked N-heterocyclic carbene (NHC) precursors and preparation of their metal complexes.

The synthesis of new compounds is an important pillar for the advancement of the field of chemistry and adjacent fields. In this regard, over the last decades huge efforts have been made to not only develop new molecular entities but also more efficient sustainable synthetic methodologies due to the increasing concerns over environmental sustainability. In this context, we have developed synthetic routes to novel corannulene flanked imidazolium bromide NHC precursors both in the solid state and solution phases. Our work presents a comprehensive comparative study of mechanochemical routes and conventional solution-based methods. Green metrics and energy consumption comparison were performed for both routes reveal ball-milling generation of these compounds to be an environmentally greener technique to produce such precursors compared to conventional solvent-based methods. In addition, we have demonstrated proof-of-concept of the herein reported corannulene flanked NHCs to be robust ligands to transition metals and their ligand substitution reactions.

Ω-Shaped fiber optic LSPR coated with hybridized nanolayers for tumor cell sensing and photothermal treatment.

Circulating tumor cell (CTC) in the blood is the main cause of cancer metastasis for death in cancer patients. It is extremely important for cancer diagnosis at an early stage and treatment to simultaneously detect and kill the CTCs. In this work, a new hybridized nanolayer, namely gold nanoparticle/gold nanorods@ Polydopamine (AuNPs/AuNRs@PDA), was coated on the Ω-shaped fiber optics (Ω-FO) for localized surface plasmonic resonance (LSPR) to perform tumor cell sensing and photothermal treatment (PTT). The PDA nanolayer was formed on a bare fiber optic through the self-polymerization of dopamine under mild conditions. The AuNRs and AuNPs were absorbed on the surface of the PDA nanolayer to form a hybridized nanolayer. The hybridized nanolayer-modified Ω-FO LSPR exhibited a high refractive index sensitivity (RIS) of 37.59 (a.u/RIU) and photothermal conversion efficiency. After being modified with the recognition element of aptamer, the Ω-FO LSPR was used to develop a sensitive and specifical tumor cell sensing. Under the irradiation of near-infrared light (NIR) laser, the Ω-FO LSPR can kill the captured tumor cells with the apoptotic/necrotic rate of 62.6 % and low side-effect for the nontarget cells. The FO LSPR sensor realized the dual functions of CTC sensing and PTT, which provided a new idea for the early diagnosis and treatment of cancer.

5(S)-5-carboxystrictosidine from the root of Mappianthus iodoides ameliorates H2O2-induced apoptosis in H9c2 cardiomyocytes via PI3K/AKT and ERK pathways.

5(S)-5-carboxystrictosidine (5-CS) is a compound found in the root of Mappianthus iodoides, a traditional Chinese medicine used for the treatment of coronary artery disease. The aim of the present study was to investigate the protective effect of 5-CS against oxidative stress-induced apoptosis in H9c2 cardiomyocytes and the underlying mechanisms. 5-CS pretreatment significantly protected against H2O2-induced cell death, LDH leakage and malondialdehyde (MDA) production which are indicators for oxidative stress injury. 5-CS also enhanced the activity of SOD and CAT. In addition, 5-CS pretreatment significantly inhibited H2O2-induced apoptosis, as determined by flow cytometer, suppressed the activity of caspase-3 and caspase-9 and attenuated the activation of cleaved caspase-3 and caspase-9. 5-CS also increased Akt and ERK activation altered by H2O2 using Western blot analysis. The PI3K-specific inhibitor LY294002 abolished 5-CS-induced Akt activation. The ERK-specific inhibitor PD98059 abolished 5-CS-induced ERK activation. Both LY294002 and PD98059 attenuated the protective effect of 5-CS on H9c2 cardiomyocytes against H2O2-induced apoptosis and cell death. Taken together, these results demonstrate that 5-CS prevents H2O2-induced oxidative stress injury in H9c2 cells by enhancing the activity of the endogenous antioxidant enzymes, inhibiting apoptosis, and modulating PI3K/Akt and ERK signaling pathways.

Sliced chaotic encrypted transmission scheme based on key masked distribution in a W-band millimeter-wave system.

In order to guarantee the information of the W-band wireless communication system from the physical layer, this paper proposes the sliced chaotic encrypted (SCE) transmission scheme based on key masked distribution (KMD). The scheme improves the security of free space communication in the W-band millimeter-wave wireless data transmission system. In this scheme, the key information is embedded into the random position of the ciphertext information, and then the ciphertext carrying the key information is encrypted by multi-dimensional chaos. Chaotic system 1 constructs a three-dimensional discrete chaotic map for implementing KMD. Chaotic system 2 constructs complex nonlinear dynamic behavior through the coupling of two neurons, and the masking factor generated is used to realize SCE. In this paper, the transmission of 16QAM signals in a 4.5 m W-band millimeter-wave wireless communication system with a rate of 40 Gb/s is proved by experiments, and the performance of the system is analyzed. When the input optical power is 5 dBm, the bit error rate (BER) of the legitimate encrypted receiver is 1.23 × 10-3. When the offset of chaotic sequence x and chaotic sequence y is 100, their BERs are more than 0.21. The key space of the chaotic system reaches 10192, which can effectively prevent illegal attacks and improve the security performance of the system. The experimental results show that the scheme can effectively distribute the keys and improve the security of the system. It has great application potential in the future of W-band millimeter-wave wireless secure communication.

A chaotic map with two-dimensional offset boosting.

A chaotic map with two-dimensional offset boosting is exhaustively studied, which is derived from the Lozi map and shows the controllability of amplitude control. The mechanism of two-dimensional offset boosting is revealed based on the cancelation of offset-involved feedback terms. Furthermore, the coexistence of homogeneous multistability and heterogeneous multistability is disclosed when the offset boosting turns to the initial condition. It is also found that the independent constant term rescales the amplitude of all the sequences without changing the Lyapunov exponents. More strikingly, the parameters for amplitude control and offset boosting are bound together introducing hybrid control. The circuit implementation based on the microcontroller unit is used to validate the theoretical analysis and numerical simulations. This chaotic map is applied for particle swarm optimization showing its stronger performance and robustness in solving optimization problems.

Rule-based omics mining reveals antimicrobial macrocyclic peptides against drug-resistant clinical isolates.

Antimicrobial resistance remains a significant global threat, driving up mortality rates worldwide. Ribosomally synthesized and post-translationally modified peptides have emerged as a promising source of novel peptide antibiotics due to their diverse chemical structures. Here, we report the discovery of new aminovinyl-(methyl)cysteine (Avi(Me)Cys)-containing peptide antibiotics through a synergistic approach combining biosynthetic rule-based omics mining and heterologous expression. We first bioinformatically identify 1172 RiPP biosynthetic gene clusters (BGCs) responsible for Avi(Me)Cys-containing peptides formation from a vast pool of over 50,000 bacterial genomes. Subsequently, we successfully establish the connection between three identified BGCs and the biosynthesis of five peptide antibiotics via biosynthetic rule-guided metabolic analysis. Notably, we discover a class V lanthipeptide, massatide A, which displays excellent activity against gram-positive pathogens, including drug-resistant clinical isolates like linezolid-resistant S. aureus and methicillin-resistant S. aureus, with a minimum inhibitory concentration of 0.25 µg/mL. The remarkable performance of massatide A in an animal infection model, coupled with a relatively low risk of resistance and favorable safety profile, positions it as a promising candidate for antibiotic development. Our study highlights the potential of Avi(Me)Cys-containing peptides in expanding the arsenal of antibiotics against multi-drug-resistant bacteria, offering promising drug leads in the ongoing battle against infectious diseases.

The safety and feasibility of mini-invasive Bentall surgery via right anterior mini-thoracotomy.

Background: The right anterior mini-thoracotomy (RAMT) approach has become a popular technique in cardiac surgery and applied in valve surgery. However, there is very limited evidence on the application of RAMT in the Bentall surgery. In the present study, we aimed to evaluate the safety and feasibility of the RAMT approach in Bentall surgery. Methods: A retrospective analysis was performed on 27 patients who underwent Bentall surgery between September 2020 and April 2022 in the First Affiliated Hospital of Xi'an Jiaotong University. Follow-ups were undertaken 1 and 6 months after their operations. The baseline, perioperative, and follow-up results were retrospectively analyzed. Results: A total of 27 male patients aged 48-61 years were included in the study. The operation time ranged from 4.0 to 5.0 hours, with a median of 4.5 hours. The median aortic cross-clamping time was 122 minutes [interquartile range (IQR): 109-145 minutes], and the median cardiopulmonary bypass (CPB) time was 156 minutes (IQR: 143-183 minutes). The median intensive care unit stay was 3 days (IQR: 1.75-4.25 days). The ventilation time ranged from 6.5 to 22.0 hours, with a median of 13.0 hours. The median drainage volume in the first 24 hours was 210 mL. In the following-up data, no deaths or severe complications were observed. Conclusions: The mini-Bentall procedure through an RAMT approach is a feasible and safe approach with few wounds and good clinical results in patients undergoing aortic root replacement.

Exosomal proteomics and cytokine analysis distinguish silicosis cases from controls.

Occupational silica exposure caused a serious disease burden of silicosis. There is currently a lack of sensitive and effective biomarkers for silicosis, and the pathogenesis of silicosis is unclear. Exosomes were significant in the pathogenesis of silicosis, and our study was carried out from exosomal proteomics and cytokine analysis. Firstly, the plasma levels of cytokines were detected using a Luminex multiplex assay, and the results indicated that the plasma levels of TNF-α, IL-6, CCL2, CXCL10, and PDGF-AB were significantly higher in silicosis patients than in silica-exposed workers and controls (p < 0.05). After correlation analysis, the plasma levels of cytokines were positively correlated with exosomal protein concentration. Secondly, data-independent acquisition (DIA) was performed on plasma-derived exosomes in the screening population, which identified 88, 151, 293, and 53 differentially expressed proteins (DEPs) in exposure/control, silicosis/control, silicosis/exposure, and silicosis stage Ⅲ/silicosis stage Ⅰ groups respectively. After parallel reaction monitoring (PRM) in an independent verification population, the results indicated that the changing trend of 15 DEPs was coincident in screening and verification results. The result of correlation analysis indicated that the plasma level of TNF-α was negatively correlated with the expression of exosomal DSP, KRT78, SERPINB12, and CALML5. The AUC of combined determination of TNF-α and CALML5 reached 0.900, with a sensitivity of 0.714 and a specificity of 0.933. Overall, our study revealed the exosomal proteomic profiling of silicosis patients, silica-exposed workers, and controls, indicating that exosomes were significant in the pathogenesis of silicosis. It also revealed that the combined of the plasma levels of cytokines and the expression of exosomal DEPs could increase determination efficiency. This study provided directions for the development of silicosis biomarkers and a scientific basis for the pathogenesis research of silicosis in the future.

Photonic crystal-enhanced fluorescence biosensor with logic gate operation based on one-pot cascade amplification DNA circuit for enzyme-free and ultrasensitive analysis of two microRNAs.

The development of sensitive and efficient analytical methods for multiple biomarkers is crucial for cancer screening at early stage. MicroRNAs (miRNAs) are a kind of biomarkers with diagnostic potential for cancer. However, the ultrasensitive and logical analysis of multiple miRNAs with simple operation still faces some challenges. Herein, a photonic crystal (PC)-enhanced fluorescence biosensor with logic gate operation based on one-pot cascade amplification DNA circuit was developed for enzyme-free and ultrasensitive analysis of two cancer-related miRNAs. The fluorescence biosensor was performed by biochemical recognition amplification module (BCRAM) and physical enhancement module (PEM) to achieve logical and sensitive detection. In the BCRAM, one-pot cascade amplification circuit consisted of the upstream parallel entropy-driven circuit (EDC) and the downstream shared catalytic hairpin assembly (CHA). The input of target miRNA would trigger each corresponding EDC, and the parallel EDCs released the same R strand for triggering subsequent CHA; thus, the OR logic gate was obtained with minimization of design and operation. In the PEM, photonic crystal (PC) array was prepared easily for specifically enhancing the fluorescence output from BCRAM by the optical modulation capabilities; meanwhile, the high-throughput signal readout was achieved by microplate analyzer. Benefiting from the integrated advantages of two modules, the proposed biosensor achieved ultrasensitive detection of two miRNAs with easy logic gate operation, obtaining the LODs of 8.6 fM and 6.7 fM under isothermal and enzyme-free conditions. Hence, the biosensor has the advantages of high sensitivity, easy operation, multiplex and high-throughput analysis, showing great potential for cancer screening at early stage.

A facile and on-site sensing strategy for phenolic compounds based on a novel nanozyme with high polyphenol oxidase-like activity.

Phenolic compounds (PCs) are diverse in nature and undergo complex migration and transformations in the environment, making it challenging to use techniques such as chromatography and other traditional methods to determine the concentration of PCs by separation, individual monitoring and subsequent addition. To address this issue, a facile and on-site strategy was developed to measure the concentration of PCs using a novel nanozyme with polyphenol oxidase-like activity. First, the nanozyme was designed by coordinating the asymmetric ligand nicotinic acid with copper to mimic the structure of mononuclear and trinuclear copper clusters of natural laccases. Subsequently, by introducing 2-mercaptonicotinic acid to regulate the valence state of copper, the composite nanozyme CuNA10S was obtained with significantly enhanced activity. Interestingly, CuNA10S was shown to have a broad substrate spectrum capable of catalyzing common PCs. Building upon the superior performance of this nanozyme, a method was developed to determine the concentration of PCs. To enable rapid on-site sensing, we designed and prepared CuNA10S-based test strips and developed a tailored smartphone sensing platform. Using paper strip sensors combined with a smartphone sensing platform with RGB streamlined the sensing process, facilitating rapid on-site analysis of PCs within a range of 0-100 µM. Our method offers a solution for the quick screening of phenolic wastewater at contaminated sites, allowing sensitive and quick monitoring of PCs without the need for standard samples. This significantly simplifies the monitoring procedure compared to more cumbersome large-scale instrumental methods.

Prognostic value of pulmonary hypertension with a nomogram in acute myocardial infarction patients with reduced left ventricular function.

Background: Pulmonary hypertension (PH) is a common prognostic factor for acute myocardial infarction (AMI) and its impact may increase when combined with reduced left ventricular function. Methods: This retrospective cohort study enrolled AMI patients with reduced left ventricular function at the First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to January 2022. Basing on the systolic pulmonary artery pressure assessed by echocardiogram, patients were assigned to the PH group and control group. Propensity score matching (PSM) in sex, age and Killip classification was used to match patients between two groups. The primary outcome was defined as 1-year mortality rate, which were obtained from medical records and phone calls. Results: After the PSM, a total of 504 patients were enrolled, with 252 in both groups. No significant difference of the adjusted factors was observed between the two groups. The 1-year mortality rate was significantly higher in the PH group compared with the control group (15.5% vs. 5.3%, P < 0.001). In the cox regression analysis, PH (HR: 2.068, 95% CI: 1.028-4.161, P = 0.042) was identified as an independent risk factor, alongside left ventricular ejection fraction (HR: 0.948; 95% CI: 0.919-0.979; P < 0.001), creatine kinase-MB isoenzymes (HR: 1.002; 95% CI: 1.000-1.003; P = 0.010) and pro-brain natriuretic peptide (HR: 1.000; 95% CI: 1.000-1.000; P = 0.018) for the 1-year mortality in AMI patients with reduced left ventricular function. A nomogram was established using the above factors to predict the 1-year mortality risks in these patients. Conclusion: AMI patients with reduced left ventricular function showed higher 1-year mortality rate when concomitant with PH. Four independent risk factors, including PH, were identified and used to establish a nomogram to predict the 1-year mortality risks in these patients. Clinical Trialsgov ID: NCT06186713.

Effect of negative emotion on prospective memory and its different components.

Prospective memory is an important and complex social cognitive ability, which is easily disturbed by negative emotions. According to the relationship between prospective memory cues and ongoing tasks, prospective memory can be divided into focal prospective memory and non-focal prospective memory. This study focuses on the influence of negative emotions on different types of prospective memory. In Experiment 1, 117 participants were recruited, using a 2 (emotion: negative, neutral) × 2 (cue focality: focal, non-focal) between-subjects design to initially explore whether negative emotions can interfere with the prospective memory of both focal cue and non-focal cue. The results show that negative emotions simultaneously reduce both types of prospective memory performance. At the same time, negative emotions occupy additional attention resources and impair the prospective component of prospective memory with non-focal cues. In Experiment 2, 64 participants were recruited to improve the difficulty of the retrospective component of prospective memory with non-focal cues, and the influence of negative emotions on different components of prospective memory with non-focal cues was further explored. The results show that negative emotions can impair both the prospective and retrospective components of prospective memory. In short, the results of this study indicate that negative emotion can impair prospective memory, and the impairment effect is not limited by the cue type of prospective memory. Meanwhile, negative emotion will occupy more attentional resources and simultaneously affect the prospective and retrospective components of prospective memory.

Exploring the roles of ribosomal peptides in prokaryote-phage interactions through deep learning-enabled metagenome mining.

BACKGROUND: Microbial secondary metabolites play a crucial role in the intricate interactions within the natural environment. Among these metabolites, ribosomally synthesized and post-translationally modified peptides (RiPPs) are becoming a promising source of therapeutic agents due to their structural diversity and functional versatility. However, their biosynthetic capacity and ecological functions remain largely underexplored. RESULTS: Here, we aim to explore the biosynthetic profile of RiPPs and their potential roles in the interactions between microbes and viruses in the ocean, which encompasses a vast diversity of unique biomes that are rich in interactions and remains chemically underexplored. We first developed TrRiPP to identify RiPPs from ocean metagenomes, a deep learning method that detects RiPP precursors in a hallmark gene-independent manner to overcome the limitations of classic methods in processing highly fragmented metagenomic data. Applying this method to metagenomes from the global ocean microbiome, we uncover a diverse array of previously uncharacterized putative RiPP families with great novelty and diversity. Through correlation analysis based on metatranscriptomic data, we observed a high prevalence of antiphage defense-related and phage-related protein families that were co-expressed with RiPP families. Based on this putative association between RiPPs and phage infection, we constructed an Ocean Virus Database (OVD) and established a RiPP-involving host-phage interaction network through host prediction and co-expression analysis, revealing complex connectivities linking RiPP-encoding prokaryotes, RiPP families, viral protein families, and phages. These findings highlight the potential of RiPP families involved in prokaryote-phage interactions and coevolution, providing insights into their ecological functions in the ocean microbiome. CONCLUSIONS: This study provides a systematic investigation of the biosynthetic potential of RiPPs from the ocean microbiome at a global scale, shedding light on the essential insights into the ecological functions of RiPPs in prokaryote-phage interactions through the integration of deep learning approaches, metatranscriptomic data, and host-phage connectivity. This study serves as a valuable example of exploring the ecological functions of bacterial secondary metabolites, particularly their associations with unexplored microbial interactions. Video Abstract.

The Autophagy-Related Protein ATG8 Orchestrates Asexual Development and AFB1 Biosynthesis in Aspergillus flavus.

Autophagy, a conserved cellular recycling process, plays a crucial role in maintaining homeostasis under stress conditions. It also regulates the development and virulence of numerous filamentous fungi. In this study, we investigated the specific function of ATG8, a reliable autophagic marker, in the opportunistic pathogen Aspergillus flavus. To investigate the role of atg8 in A. flavus, the deletion and complemented mutants of atg8 were generated according to the homologous recombination principle. Deletion of atg8 showed a significant decrease in conidiation, spore germination, and sclerotia formation compared to the WT and atg8C strains. Additionally, aflatoxin production was found severely impaired in the ∆atg8 mutant. The stress assays demonstrated that ATG8 was important for A. flavus response to oxidative stress. The fluorescence microscopy showed increased levels of reactive oxygen species in the ∆atg8 mutant cells, and the transcriptional result also indicated that genes related to the antioxidant system were significantly reduced in the ∆atg8 mutant. We further found that ATG8 participated in regulating the pathogenicity of A. flavus on crop seeds. These results revealed the biological role of ATG8 in A. flavus, which might provide a potential target for the control of A. flavus and AFB1 biosynthesis.