MoErv14 mediates the intracellular transport of cell membrane receptors to govern the appressorial formation and pathogenicity of Magnaporthe oryzae.

Magnaporthe oryzae causes rice blasts posing serious threats to food security worldwide. During infection, M. oryzae utilizes several transmembrane receptor proteins that sense cell surface cues to induce highly specialized infectious structures called appressoria. However, little is known about the mechanisms of intracellular receptor tracking and their function. Here, we described that disrupting the coat protein complex II (COPII) cargo protein MoErv14 severely affects appressorium formation and pathogenicity as the ΔMoerv14 mutant is defective not only in cAMP production but also in the phosphorylation of the mitogen-activated protein kinase (MAPK) MoPmk1. Studies also showed that either externally supplementing cAMP or maintaining MoPmk1 phosphorylation suppresses the observed defects in the ΔMoerv14 strain. Importantly, MoErv14 is found to regulate the transport of MoPth11, a membrane receptor functioning upstream of G-protein/cAMP signaling, and MoWish and MoSho1 function upstream of the Pmk1-MAPK pathway. In summary, our studies elucidate the mechanism by which the COPII protein MoErv14 plays an important function in regulating the transport of receptors involved in the appressorium formation and virulence of the blast fungus.

Macrophage diversity in cancer revisited in the era of single-cell omics.

Tumor-associated macrophages (TAMs) have multiple potent functions in cancer and, thus, represent important therapeutic targets. These diverse functions highlight the heterogenous nature of TAMs. Recent single cell omics technologies have significantly advanced our understanding of the molecular diversity of TAMs. However, a unifying nomenclature of TAM diversity and annotation of their molecular signatures is lacking. Here, we review recent major studies of single cell transcriptome, epigenome, metabolome, and spatial omics of cancer with a specific focus on TAMs. We also propose a consensus model of TAM diversity and present avenues for future research.

Macrophage diversity enhances tumor progression and metastasis.

There is persuasive clinical and experimental evidence that macrophages promote cancer initiation and malignant progression. During tumor initiation, they create an inflammatory environment that is mutagenic and promotes growth. As tumors progress to malignancy, macrophages stimulate angiogenesis, enhance tumor cell migration and invasion, and suppress antitumor immunity. At metastatic sites, macrophages prepare the target tissue for arrival of tumor cells, and then a different subpopulation of macrophages promotes tumor cell extravasation, survival, and subsequent growth. Specialized subpopulations of macrophages may represent important new therapeutic targets.

Influence of different baking temperatures of red kojic rice on the physicochemical properties, antioxidant capacity, and functional components of red starter wine.

BACKGROUND: To improve the quality of red starter wine, this study explored the effects of baking red kojic rice at varying temperatures on the physicochemical characteristics of red starter wine. Baking was predicated on understanding crucial enzyme activities and starch granule structure of red kojic rice at 75, 95, and 105 °C, leading to the production of three red starter wine variants (BHQW1, BHQW2, and BHQW3). RESULTS: The results revealed an increased alcohol (increase 0.50%), total sugar (increase 0.14 g L-1 ), and total acid (increase 0.54 g L-1 ) content in red starter wine fermented using baked red kojic rice compared with the control group (wine fermented with unbaked rice, HQW). Furthermore, both the 105 °C baked red kojic rice and its resulting BHQW3 demonstrated significantly higher red color values than HQW (increase 2.03 U g-1 and 0.15 U mL-1 respectively). The highest lovastatin content was presented in red kojic rice baked at 105 °C and its corresponding fermented wine (1420.63 ± 507.9 µg g-1 and 3368.87 ± 228.16 µg L-1 respectively). Additionally, BHQW groups displayed higher total flavonoids and phenols content than HQW. Regarding antioxidant capacity, all BHQW groups showed stronger overall antioxidant capacity than HQW. The determination of volatile components revealed the highest content of volatile compounds in BHQW2 (2621.19 ± 548.24 µg L-1 ) and significantly higher volatile esters in BHQW1 (254.46 ± 16.63 µg L-1 ). Moreover, 16 volatile compounds were identified only in BHQW groups, including isoamyl caprylate, 2-ethylhexyl alcohol, and benzaldehyde. CONCLUSION: Our findings suggested that the baking technique of red kojic rice could enhance the quality of red starter wine through enhancing antioxidant properties, increasing functional components, and enriching volatile flavor compounds, thus providing a foundation for new techniques in red starter wine production. © 2023 Society of Chemical Industry.

A double S shape provides the structural basis for the extraordinary binding specificity of Dscam isoforms.

Drosophila Dscam encodes a vast family of immunoglobulin (Ig)-containing proteins that exhibit isoform-specific homophilic binding. This diversity is essential for cell recognition events required for wiring the brain. Each isoform binds to itself but rarely to other isoforms. Specificity is determined by "matching" of three variable Ig domains within an approximately 220 kD ectodomain. Here, we present the structure of the homophilic binding region of Dscam, comprising the eight N-terminal Ig domains (Dscam(1-8)). Dscam(1-8) forms a symmetric homodimer of S-shaped molecules. This conformation, comprising two reverse turns, allows each pair of the three variable domains to "match" in an antiparallel fashion. Structural, genetic, and biochemical studies demonstrate that, in addition to variable domain "matching," intramolecular interactions between constant domains promote homophilic binding. These studies provide insight into how "matching" at all three pairs of variable domains in Dscam mediates isoform-specific recognition.

Comparison on the Effect and Complications of VATS and Radical Thoracotomy for Lung Cancer in the Treatment of Stages IIB-IIIA Non-Small Cell Lung Cancer.

Objective: Lung adenocarcinoma (NSCLC) is a common subtype of lung cancer, and its prevalence has gradually increased in recent years. There are various treatment methods for NSCLC, and surgical resection, as one of the important treatments, is crucial to improving the survival rate and quality of life of patients. To explore the effect and complications of video-assisted thoracic surgery (VATS) and radical thoracotomy for lung cancer (RTLC) in the treatment of stages IIB-IIIA non-small cell lung cancer (NSCLC). Methods: A total of 80 patients with NSCLC admitted to the hospital were enrolled between June 2019 and January 2021. According to the random number table method, they were divided into the VATS group (40 cases, VATS) and RTLC group (40 cases, RTLC). The operation time, intraoperative blood loss, postoperative drainage time, number of lymph node dissections, score of visual analogue scale (VAS) at 24 h after surgery, and hospitalization time were compared between the two groups. We chose specific inclusion criteria, including patients diagnosed with non-small cell lung cancer (NSCLC) who did not receive radiation therapy or chemotherapy before surgery, to ensure consistency and comparability across studies. We focused on indicators related to lung function and immune system, such as CD3+, CD4+ and CD8+ levels, as well as FEV1, FVC and MVV, to evaluate the impact of surgery on lung function and immune status. The levels of CD3+, CD4+, and CD8+ in both groups were detected by flow cytometry at 1 d before surgery and 3 d after surgery. The forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and maximal voluntary ventilation (MVV) in both groups were detected by spirometry before and at 1 month after surgery. The occurrence of postoperative complications in both groups was recorded. After 12 months of follow-up, survival rates in both groups were statistically analyzed. The progression-free survival (PFS) and 12-month overall survival (OS) in both groups were analyzed by the Kaplan-Meier method. Results: The incision length, operation time, intraoperative blood loss, postoperative drainage time, VAS score at 24 h after surgery, and hospitalization time in VATS group were significantly lower than those in RTLC group (P < .05). The two groups had no significant difference in the number of lymph node dissections (P > .05). At 3 d after surgery, levels of CD3+, CD4+ and CD8+ in VATS group were significantly higher than those in RTLC group (P < .05). At 1 month after surgery, FEV1, FVC, and MVV in VATS group operation were significantly higher than those in RTLC group (P < .05). The incidence of postoperative complications in VATS group was lower than that in RTLC group (5.00% vs. 20.00%) (P < .05). Kaplan-Meier survival analysis showed that there was no significant difference in 12-month OS or PFS between the two groups (P > .05). Conclusions: The long-term curative effect of VATS and RTLC is comparable on patients with stages IIB-IIIA NSCLC. The former has advantages such as less surgical injury, faster postoperative recovery, and higher safety, which can reduce the incidence of postoperative complications. This study provides clinicians with important information about the treatment of stage IIb ~ IIIa NSCLC and helps them choose surgical methods more wisely. These results also alert physicians to focus on operative time, blood loss, and complication risk to maximize patient outcomes.

Online-Dynamic-Clustering-Based Soft Sensor for Industrial Semi-Supervised Data Streams.

In the era of big data, industrial process data are often generated rapidly in the form of streams. Thus, how to process such sequential and high-speed stream data in real time and provide critical quality variable predictions has become a critical issue for facilitating efficient process control and monitoring in the process industry. Traditionally, soft sensor models are usually built through offline batch learning, which remain unchanged during the online implementation phase. Once the process state changes, soft sensors built from historical data cannot provide accurate predictions. In practice, industrial process data streams often exhibit characteristics such as nonlinearity, time-varying behavior, and label scarcity, which pose great challenges for building high-performance soft sensor models. To address this issue, an online-dynamic-clustering-based soft sensor (ODCSS) is proposed for industrial semi-supervised data streams. The method achieves automatic generation and update of clusters and samples deletion through online dynamic clustering, thus enabling online dynamic identification of process states. Meanwhile, selective ensemble learning and just-in-time learning (JITL) are employed through an adaptive switching prediction strategy, which enables dealing with gradual and abrupt changes in process characteristics and thus alleviates model performance degradation caused by concept drift. In addition, semi-supervised learning is introduced to exploit the information of unlabeled samples and obtain high-confidence pseudo-labeled samples to expand the labeled training set. The proposed method can effectively deal with nonlinearity, time-variability, and label scarcity issues in the process data stream environment and thus enable reliable target variable predictions. The application results from two case studies show that the proposed ODCSS soft sensor approach is superior to conventional soft sensors in a semi-supervised data stream environment.

MoErv29 promotes apoplastic effector secretion contributing to virulence of the rice blast fungus Magnaporthe oryzae.

During plant-pathogenic fungi and host plants interactions, numerous pathogen-derived proteins are secreted resulting in the activation of the unfolded protein response (UPR) pathway. For efficient trafficking of secretory proteins, including those important in disease progression, the cytoplasmic coat protein complex II (COPII) exhibits a multifunctional role whose elucidation remains limited. Here, we discovered that the COPII cargo receptor MoErv29 functions as a target of MoHac1, a previously identified transcription factor of the UPR pathway. In Magnaporthe oryzae, deletion of MoERV29 severely affected the vegetative growth, conidiation and biotrophic invasion of the fungus in susceptible rice hosts. We demonstrated that MoErv29 is required for the delivery of secreted proteins through recognition and binding of the amino-terminal tripeptide motifs following the signal peptide. By using bioinformatics analysis, we predicted a cargo spectrum of MoErv29 and found that MoErv29 is required for the secretion of many proteins, including extracellular laccases and apoplastic effectors. This secretion is mediated through the conventional endoplasmic reticulum-Golgi secretion pathway and is important for conferring host recognition and disease resistance. Taken together, our results revealed how MoErv29 operates on effector secretion, and our findings provided a critical link between COPII vesicle trafficking and the UPR pathway.

Preparation, Identification, Molecular Docking Study and Protective Function on HUVECs of Novel ACE Inhibitory Peptides from Protein Hydrolysate of Skipjack Tuna Muscle.

To prepare bioactive peptides with high angiotensin-I-converting enzyme (ACE)-inhibitory (ACEi) activity, Alcalase was selected from five kinds of protease for hydrolyzing Skipjack tuna (Katsuwonus pelamis) muscle, and its best hydrolysis conditions were optimized using single factor and response surface experiments. Then, the high ACEi protein hydrolysate (TMPH) of skipjack tuna muscle was prepared using Alcalase under the optimum conditions of enzyme dose 2.3%, enzymolysis temperature 56.2 °C, and pH 9.4, and its ACEi activity reached 72.71% at 1.0 mg/mL. Subsequently, six novel ACEi peptides were prepared from TMPH using ultrafiltration and chromatography methods and were identified as Ser-Pro (SP), Val-Asp-Arg-Tyr-Phe (VDRYF), Val-His-Gly-Val-Val (VHGVV), Tyr-Glu (YE), Phe-Glu-Met (FEM), and Phe-Trp-Arg-Val (FWRV), with molecular weights of 202.3, 698.9, 509.7, 310.4, 425.6, and 606.8 Da, respectively. SP and VDRYF displayed noticeable ACEi activity, with IC50 values of 0.06 ± 0.01 and 0.28 ± 0.03 mg/mL, respectively. Molecular docking analysis illustrated that the high ACEi activity of SP and VDRYF was attributed to effective interaction with the active sites/pockets of ACE by hydrogen bonding, electrostatic force, and hydrophobic interaction. Furthermore, SP and VDRYF could significantly up-regulate nitric oxide (NO) production and down-regulate endothelin-1 (ET-1) secretion in HUVECs after 24 h treatment, but also abolish the negative effect of 0.5 µM norepinephrine (NE) on the generation of NO and ET-1. Therefore, ACEi peptides derived from skipjack tuna (K. pelamis) muscle, especially SP and VDRYF, are beneficial components for functional food against hypertension and cardiovascular diseases.

Plate Load Tests on an Unsaturated Sand-Kaolin Mixture with Varying Water Table.

Clayey sand is widely distributed and commonly encountered in geotechnical engineering practice. To understand its bearing capacity behavior under unsaturated conditions, plate load tests are performed on sand-kaolin mixture samples with varying water tables. The distributions of suction and volumetric water content with depth are measured by vibrating wire piezometers and soil moisture sensors, respectively. It is shown by the test results that the bearing capacity increases when the water table in the soil sample drops. The influence of suction on the bearing capacity is found to be dependent on the height of the water table and the hydraulic loading history of the soil sample. The plate load test results are interpreted using bearing capacity equations. Good agreement is obtained between measured and calculated bearing capacities. This study provides a simple method to estimate the bearing capacity of in situ unsaturated soil foundations.

FedMSA: A Model Selection and Adaptation System for Federated Learning.

Federated Learning (FL) enables multiple clients to train a shared model collaboratively without sharing any personal data. However, selecting a model and adapting it quickly to meet user expectations in a large-scale FL application with heterogeneous devices is challenging. In this paper, we propose a model selection and adaptation system for Federated Learning (FedMSA), which includes a hardware-aware model selection algorithm that trades-off model training efficiency and model performance base on FL developers' expectation. Meanwhile, considering the expected model should be achieved by dynamic model adaptation, FedMSA supports full automation in building and deployment of the FL task to different hardware at scale. Experiments on benchmark and real-world datasets demonstrate the effectiveness of the model selection algorithm of FedMSA in real devices (e.g., Raspberry Pi and Jetson nano).

Genome-wide identification, phylogenetic and expression of MAPKKK gene family in Arabidopsis pumila.

Mitogen-activated protein kinase kinase kinases (MAPKKKs) are important components of the MAPK cascade and play crucial roles in development and stress responses. Arabidopsis pumila is an ephemeral Brassicaceae plant growing in Xinjiang desert regions, which possesses salt tolerance. To explore the evolution and function of the MAPKKK gene family in A. pumila, 143 ApMAPKKK genes were identified from A. pumila genome by genome-wide analysis, which were categorized into three subfamilies: ZIK (20), MEKK (36) and RAF (87). There existed 74 and 72 colinear genes between A. thaliana, A. lyrata and A. pumila, respectively, indicating that this gene family expanded obviously in A. pumila genome. Evolutionary analysis revealed that there were 64 duplicated gene pairs with Ka/Ks less than 1, and purifying selection was dominant. RNA-seq data were used to analyze the expression characteristics of ApMAPKKK genes in response to salt stress and in different tissues. The results showed that most ApMAPKKK genes were up-regulated under 250 mmol/L NaCl stress. For example, ApMAPKKK18-1/2 and ApMAPKKK17-1/2 were substantially up-regulated. Tissue expression profiles showed that ApMAPKKK mainly presented six expression patterns. Some duplicated genes were differentially expressed in response to salt stress and in different tissues. These results lay a foundation for further understanding the complex mechanism of MAPKKK gene family transduction pathway in response to abiotic stresses in A. pumila.

M1 macrophage-derived exosomes impair beta cell insulin secretion via miR-212-5p by targeting SIRT2 and inhibiting Akt/GSK-3ß/ß-catenin pathway in mice.

AIMS/HYPOTHESIS: Macrophage levels are elevated in pancreatic islets, and the resulting inflammatory response is a major contributor to beta cell failure during obesity and type 2 diabetes mellitus. Previous studies by us and others have reported that exosomes released by macrophages play important roles in mediating cell-to-cell communication, and represent a class of inflammatory factors involved in the inflammatory process associated with type 2 diabetes mellitus. However, to date, no reports have demonstrated the effect of macrophage-derived exosomes on beta cells, and little is known regarding their underlying mechanisms in beta cell injury. Thus, we aimed to study the impact of macrophage-derived exosomes on islet beta cell injury in vitro and in vivo. METHODS: The phenotypic profiles of islet-resident macrophages were analysed in C57BL/6J mice fed a high-fat diet (HFD). Exosomes were collected from the medium of cultured bone marrow-derived macrophages (BMDMs) and from isolated islet-resident macrophages of HFD-fed mice (HFD-Exos). The role of exosomes secreted by inflammatory M1 phenotype BMDMs (M1-Exos) and HFD-Exos on beta cell function was assessed. An miRNA microarray and quantitative real-time PCR (qPCR) were conducted to test the level of M1-Exos-derived miR-212-5p in beta cells. Then, miR-212-5p was overexpressed or inhibited in M1-Exos or beta cells to determine its molecular and functional impact. RESULTS: M1-polarised macrophages were enriched in the islets of obese mice. M1 macrophages and islet-resident macrophages of HFD-fed mice impaired beta cell insulin secretion in an exosome-dependent manner. miR-212-5p was notably upregulated in M1-Exos and HFD-Exos. Enhancing the expression of miR-212-5p impaired beta cell insulin secretion. Blocking miR-212-5p elicited a significant improvement in M1-Exos-mediated beta cell insulin secretion during injury. Mechanistically, M1-Exos mediated an intercellular transfer of the miR-212-5p, targeting the sirtuin 2 gene and regulating the Akt/GSK-3ß/ß-catenin pathway in recipient beta cells to restrict insulin secretion. CONCLUSIONS/INTERPRETATION: A novel exosome-modulated mechanism was delineated for macrophage-beta cell crosstalk that drove beta cell dysfunction and should be explored for its therapeutic utility.

KDM5A silencing transcriptionally suppresses the FXYD3-PI3K/AKT axis to inhibit angiogenesis in hepatocellular cancer via miR-433 up-regulation.

Hepatocellular cancer (HCC) has been reported to belong to one of the highly vascularized solid tumours accompanied with angiogenesis of human umbilical vein endothelial cells (HUVECs). KDM5A, an attractive drug target, plays a critical role in diverse physiological processes. Thus, this study aims to investigate its role in angiogenesis and underlying mechanisms in HCC. ChIP-qPCR was utilized to validate enrichment of H3K4me3 and KDM5A on the promotor region of miR-433, while dual luciferase assay was carried out to confirm the targeting relationship between miR-433 and FXYD3. Scratch assay, transwell assay, Edu assay, pseudo-tube formation assay and mice with xenografted tumours were conducted to investigate the physiological function of KDM5A-miR-433-FXYD3-PI3K-AKT axis in the progression of HCC after loss- and gain-function assays. KDM5A p-p85 and p-AKT were highly expressed but miR-433 was down-regulated in HCC tissues and cell lines. Depletion of KDM5A led to reduced migrative, invasive and proliferative capacities in HCC cells, including growth and a lowered HUVEC angiogenic capacity in vitro. Furthermore, KDM5A suppressed the expression of miR-433 by demethylating H3K4me3 on its promoterregion. miR-433 negatively targeted FXYD3. Depleting miR-433 or re-expressing FXYD3 restores the reduced migrative, invasive and proliferative capacities, and lowers the HUVEC angiogenic capacity caused by silencing KDM5A. Therefore, KDM5A silencing significantly suppresses HCC tumorigenesis in vivo, accompanied with down-regulated miR-433 and up-regulated FXYD3-PI3K-AKT axis in tumour tissues. Lastly, KDM5A activates the FXYD3-PI3K-AKT axis to enhance angiogenesis in HCC by suppressing miR-433.

Phosphatase-associated protein MoTip41 interacts with the phosphatase MoPpe1 to mediate crosstalk between TOR and cell wall integrity signalling during infection by the rice blast fungus Magnaporthe oryzae.

The type 2A (PP2A) and type 2A-like (PP4 and PP6) serine/threonine phosphatases participate in a variety of cellular processes, such as cell cycle progression, signal transduction and apoptosis. Previously, we reported that the PP6 catalytic subunit MoPpe1, which interacts with and is suppressed by type 2A associated protein of 42 kDa (MoTap42), an essential protein involved in the target of rapamycin (TOR) signalling pathway, has important roles in development, virulence and activation of the cell wall integrity (CWI) pathway in the rice blast fungus Magnaporthe oryzae. Here, we show that Tap42-interacting protein 41 (MoTip41) mediates crosstalk between the TOR and CWI signalling pathways; and participates in the TOR pathway via interaction with MoPpe1, but not MoTap42. The deletion of MoTIP41 resulted in disruption of CWI signalling, autophagy, vegetative growth, appressorium function and plant infection, as well as increased sensitivity to rapamycin. Further investigation revealed that MoTip41 modulates activation of the CWI pathway in response to infection by interfering with the interaction between MoTap42 and MoPpe1. These findings enhance our understanding of how crosstalk between TOR and CWI signalling modulates the development and pathogenicity of M. oryzae.

Intravenously injected lidocaine or magnesium improves the quality of early recovery after laparoscopic cholecystectomy: A randomised controlled trial.

BACKGROUND: Previous data show that lidocaine or magnesium has unique characteristics of stress inhibition and antiinflammation. OBJECTIVE: We aimed to observe the effects of lidocaine or magnesium on the quality of recovery (QoR) after laparoscopic cholecystectomy. DESIGN: Single-centre, prospective, randomised, double-blind study. SETTING: The Affiliated Hospital of Xuzhou Medical University from March 2019 to October 2019. PATIENTS: One hundred and fourteen patients scheduled for laparoscopic cholecystectomy. INTERVENTION: The enrolled patients were randomly divided into three groups. Lidocaine (group L), magnesium sulphate (group M) or 0.9% saline (group C) was administered intravenously 10 min before induction. MAIN OUTCOME MEASURES: The quality of recovery 15 (QoR-15) score, the Hospital Anxiety and Depression Scale (HADS), and the Numerical Rating Scale (NRS) score were selected. The usage of propofol and remifentanil, haemodynamic parameters, anaesthesia recovery parameters and adverse events were also evaluated. RESULTS: The QoR-15 scores for group L (132.0) and group M (134.0) were 6 and 8 points higher than that of group C (126.0) on POD1 (postoperative day 1) (adjP < 0.05). However, the decrease of QoR-15 in Group L is less than the minimal clinically important difference (8).The NRS scores on POD1 in group C 3, were higher than other two groups (adjP < 0.05). The dosage of remifentanil in group L was lower than other two groups (adjP < 0.05).The physical independence of group L and group M and physical comfort of group M were improved compared with group C. CONCLUSION: The results show that magnesium sulphate improved the QoR through improving physical comfort and physical independence in patients after laparoscopic cholecystectomy. However, lidocaine had limited effects on QoR under current conditions. TRIAL REGISTRATION: ChiCTR1800019092 (www.chictr.org.cn). CLINICAL TRIAL NUMBER AND REGISTRY URL: The study was registered in the Chinese Clinical Trials Register (ChiCTR1800019092) https://www.chictr.org.cn.

MoYvh1 subverts rice defense through functions of ribosomal protein MoMrt4 in Magnaporthe oryzae.

The accumulation of the reactive oxygen species (ROS) in rice is important in its interaction with the rice blast fungus Magnaporthe oryzae during which the pathogen scavenges ROS through the production of extracellular enzymes that promote blast. We previously characterized the MoYvh1 protein phosphatase from M. oryzae that plays a role in scavenging of ROS. To understand the underlying mechanism, we found that MoYvh1 is translocated into the nucleus following oxidative stress and that this translocation is dependent on MoSsb1 and MoSsz1 that are homologous to heat-shock protein 70 (Hsp70) proteins. In addition, we established a link between MoYvh1 and MoMrt4, a ribosome maturation factor homolog whose function also involves shuttling between the cytoplasm and the nucleus. Moreover, we found that MoYvh1 regulates the production of extracellular proteins that modulate rice-immunity. Taking together, our evidence suggests that functions of MoYvh1 in regulating ROS scavenging require its nucleocytoplasmic shuttling and the partner proteins MoSsb1 and MoSsz1, as well as MoMrt4. Our findings provide novel insights into the mechanism by which M. oryzae responds to and subverts host immunity through the regulation of ribosome biogenesis and protein biosynthesis.

Primary and Secondary Succession Mediate the Accumulation of Biogenic Amines during Industrial Semidry Chinese Rice Wine Fermentation.

The use of exogenous functional microorganisms to regulate biogenic amine (BA) content is a common approach in fermentation systems. Here, to better understand the microbial traits of succession trajectories in resource-based and biotic interference systems, the BA-related primary and secondary succession were tracked during industrial semidry Chinese rice wine (CRW) fermentation. Dominant abundance and BA-associated microbial functionality based on phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) indicated that Citrobacter, Acinetobacter, Lactobacillus, Exiguobacterium, Bacillus, Pseudomonas, and Enterobacter spp. prominently contributed to the decarboxylase gene family in CRW. The expression levels of tyrosine decarboxylase (tyrDC), ornithine decarboxylase (odc), and agmatine deiminase (aguA) genes were assessed by quantitative PCR (qPCR). The transcription levels of these genes did not correlate with the BA formation rate during postfermentation, indicating that acidification and carbon source depletion upregulated the expression and microbes launch the dormancy strategy to respond to unfavorable conditions. Furthermore, microbial interference with CRW fermentation by Lactobacillus plantarum (ACBC271) and Staphylococcus xylosus (CGMCC1.8382) coinoculated at a ratio of 1:2 exhibited the best synergetic control of BA content. Spearman correlations revealed that Lactobacillus and Staphylococcus exhibited influence on BA-associated microbiota (|ρ| > 0), Exiguobacterium and Pseudomonas were strongly suppressed by Lactobacillus (ρ = -0.867 and ρ = -0.782, respectively; P < 0.05), and Staphylococcus showed the strongest inhibitory effect toward Lactobacillus (ρ = -0.115) and Citrobacter (ρ = -0.188) in the coinoculated 1:2 group. The high inhibitory effect of exogenous added strains on specific bacteria presented evidence for the obtained BA-associated contributors. Overall, this work provides important insight into the microbial traits that rely on resource usage and functional microbiota within food microbial ecology.IMPORTANCE Understanding the shifting patterns of substance usage and microbial interactions is a fundamental objective within microbiology and ecology. Analyses of primary and secondary microbial succession allow for determinations of taxonomic diversity, community traits, and functional transformations over time or after a disturbance. The kinetics of BA generation and the patterns of resource consumption, functional metagenome prediction, and microbial interactions were profiled to elucidate the equilibrium mechanism of microbial systems. Secondary succession after a disturbance triggers a change in resource usage, which in turn affects primary succession and metabolism. In this study, the functional potential of exogenous microorganisms under disturbance synergized with secondary succession strategies, including rebalancing and dormancy, which ultimately reduced BA accumulation. Thus, this succession system could facilitate the settling of essential issues with respect to microbial traits that rely on resource usage and microbial interactions that occur in natural ecosystems.

Effect of Monoamine oxidase A (MAOA) inhibitors on androgen-sensitive and castration-resistant prostate cancer cells.

BACKGROUND: Monoamine oxidase A (MAOA) is best known for its role in neuro-transmitter regulation. Monoamine oxidase inhibitors are used to treat atypical depression. MAOA is highly expressed in high grade prostate cancer and modulates tumorigenesis and progression in prostate cancer. Here, we investigated the potential role of MAOA inhibitors (MAOAIs) in relation to the androgen receptor (AR) pathway and resistance to antiandrogen treatment in prostate cancer. METHODS: We examined MAOA expression and the effect of MAOI treatment in relation to AR-targeted treatments using the LNCaP, C4-2B, and 22Rv1 human prostate cancer cell lines. MAOA, AR-full length (AR-FL), AR splice variant 7 (AR-V7), and PSA expression was evaluated in the presence of MAOAIs (clorgyline, phenelzine), androgenic ligand (R1881), and antiandrogen (enzalutamide) treatments. An enzalutamide resistance cell line was generated to test the effect of MAOAI treatment in this model. RESULTS: We observed that MAOAIs, particularly clorgyline and phenelzine, were effective at decreasing MAOA activity in human prostate cancer cells. MAOAIs significantly decreased growth of LNCaP, C4-2B, and 22Rv1 cells and produced additive growth inhibitory effects when combined with enzalutamide. Clorgyline decreased expression of AR-FL and AR-V7 in 22Rv1 cells and was effective at decreasing growth of an enzalutamide-resistant C4-2B cell line with increased AR-V7 expression. CONCLUSIONS: MAOAIs decrease growth and proliferation of androgen-sensitive and castration-resistant prostate cancer cells. Clorgyline, in particular, decreases expression of AR-FL and AR-V7 expression and decreases growth of an enzalutamide-resistant cell line. These findings provide preclinical validation of MAOA inhibitors either alone or in combination with antiandrogens for therapeutic intent in patients with advanced forms of prostate cancer.