PC4 promotes bladder cancer progression and stemness by directly interacting with Sp1 to transcriptionally activate the Wnt5a/ß-catenin pathway.

Bladder cancer is a common malignancy with a poor prognosis worldwide. Positive cofactor 4 (PC4) is widely reported to promote malignant phenotypes in various tumors. Nonetheless, the biological function and mechanism of PC4 in bladder cancer remain unclear. Here, for the first time, we report that PC4 is elevated in bladder cancer and is associated with patient survival. Moreover, PC4 deficiency obviously inhibited bladder cancer cell proliferation and metastasis by reducing the expression of genes related to cancer stemness (CD44, CD47, KLF4 and c-Myc). Through RNA-seq and experimental verification, we found that activation of the Wnt5a/ß-catenin pathway is involved in the malignant function of PC4. Mechanistically, PC4 directly interacts with Sp1 to promote Wnt5a transcription. Thus, our study furthers our understanding of the role of PC4 in cancer stemness regulation and provides a promising strategy for bladder cancer therapy.

Outbreak of Septoria leaf spot caused by Sphaerulina musiva on Populus × euramericana in China.

In June 2023, severe leaf spots were noted in Populus × euramericana cv 'Nanlin95' plantations located in the Nanjing Baguazhou Wetland Park (32°09'16.97″N, 118°48'16.74″E) of Jiangsu Province and Populus × canadensis cv 'Sacrau 79' and Populus × canadensis cv 'Guariento' in the Liyuan Village in Nanyang City (32°53'43.70″N, 112°17'29.12″E) of Henan Province, respectively. The disease incidence in both locations could reach 97.9% (556 out of 568 trees) and 98.9% (2409 out of 2436 trees), respectively. The initial symptoms appear as numerous small and circular spots (1.59 to 3.18 mm in diameter) with gray or tan centers and dark-brown margins on the leaves. As the spots age, they sometimes enlarge, often coalesce, and may extend down the petioles. Diseased leaves and petioles were both surface sterilized with 75% ethanol for 30 seconds. With the aid of a hand lens, pycnidia (brown to black, spherical in profile, 90 to 250 µm diam) were easily picked out in the center of the spots and subsequently transferred into 1 mL sterilized water for preparing the spore suspension plated on KV8 medium amended with 100 mg/liter streptomycin sulfate and 50 mg/liter chloramphenicol. After 12 days of incubation, 86 single-spore isolates were obtained and identified as typical Septoria-like fungi according to morphological features, including slow-growing, gray or black colonies with pink mucilaginous matrix and hyaline, straight or curved conidia (size = 25 to 59 × 3.5 to 4 µm; septa = 1 to 6). Species identification was further validated by PCR amplification and sequencing of the internal transcribed spacer (ITS) region with ITS1/ITS4 primer pairs. Multiple sequence alignments with ClustalW revealed that the obtained ITS sequences of 86 isolates were 100% identical to each other. A BLAST search in GenBank indicated that the selfsame sequences of two representative isolates (isolate BGZ11 of Jiangsu Province, accession no. OR660379; isolate KZB22 of Henan Province, accession no. OR711499) shared 99.8% identity (494 of 495 bp) and 100% identity (504 of 504 bp) with related sequences of Sphaerulina musiva (Peck) Quaedvlieg, Verkley, and Crous (syn. = Septoria musiva Peck) in GenBank (MN275187; KF251619), respectively. Furthermore, we used a S. musiva-specific PCR assay (Abraham et al. 2018) on symptomatic leaf samples collected from the plantation. Each sample consisted of 20 cut-out leaf spots per leaf. Eight of the 10 samples were positive for S. musiva DNA. To confirm pathogenicity, six sterile tissue culture of poplar plants (Populus trichocarpa and Populus × euramericana cv 'Nanlin895') were respectively transplanted into pots and grown in a greenhouse for a week and for a month with an 18-h photoperiod augmented with sodium lamps and a 20°C (day)/16°C (night) temperature regime. Inoculations were conducted by spraying the plants with conidia suspension (106 conidia/mL) (LeBoldus et al. 2010). Control plants were sprayed with distilled water. Leaf spots were developed on the inoculated P. trichocarpa leaves at one week and P. × euramericana cv 'Nanlin895' leaves at 10 days after inoculation while no symptoms were observed on the control plants. The fungus S. musiva was successfully reisolated from all symptomatic leaves fulfilling Koch's postulates. Sphaerulina musiva only causes an endemic leaf spot disease on its natural North American host Populus. deltoides (Feau et al. 2010; Ostry 1987). However, on susceptible Populus species (e.g., P. balsamifera, P. trichocarpa, P. maximowiczii) and hybrids, S. musiva causes not only leaf spots but also severely damaging stem and branch cankers (Jeger et al. 2018; LeBoldus et al. 2009; Sondreli et al. 2020). To our knowledge, this is the first report of S. musiva causing leaf spots on poplar in China. Large-scale timber imports (e.g., cut branches, isolated bark, wood with and without bark) potentially lead to anthropogenic-facilitated transport of this pathogen. This outbreak of Septoria leaf spot underscores the potential threat of this pathogen to P. × euramericana in China, where it is widely planted as a keystone forestry species.

Nonpathogenic Pseudomonas syringae derivatives and its metabolites trigger the plant "cry for help" response to assemble disease suppressing and growth promoting rhizomicrobiome.

Plants are capable of assembling beneficial rhizomicrobiomes through a "cry for help" mechanism upon pathogen infestation; however, it remains unknown whether we can use nonpathogenic strains to induce plants to assemble a rhizomicrobiome against pathogen invasion. Here, we used a series of derivatives of Pseudomonas syringae pv. tomato DC3000 to elicit different levels of the immune response to Arabidopsis and revealed that two nonpathogenic DC3000 derivatives induced the beneficial soil-borne legacy, demonstrating a similar "cry for help" triggering effect as the wild-type DC3000. In addition, an increase in the abundance of Devosia in the rhizosphere induced by the decreased root exudation of myristic acid was confirmed to be responsible for growth promotion and disease suppression of the soil-borne legacy. Furthermore, the "cry for help" response could be induced by heat-killed DC3000 and flg22 and blocked by an effector triggered immunity (ETI) -eliciting derivative of DC3000. In conclusion, we demonstrate the potential of nonpathogenic bacteria and bacterial elicitors to promote the generation of disease-suppressive soils.

Antibacterial Mechanism, Control Efficiency, and Nontarget Toxicity Evaluation of Actinomycin X2 against Xanthomonas citri Subsp. citri.

The present study investigated the antibacterial mechanism, control efficiency, and nontarget toxicity of actinomycin X2 (Act-X2) against Xanthomonas citri subsp. citri (Xcc) for the first time. Act-X2 almost completely inhibited the proliferation of Xcc in the growth curve assay at a concentration of 0.25 MIC (minimum inhibitory concentration, MIC = 31.25 µg/mL). This inhibitory effect was achieved by increasing the production of reactive oxygen species (ROS), blocking the formation of biofilms, obstructing the synthesis of intracellular proteins, and decreasing the enzymatic activities of malate dehydrogenase (MDH) and succinate dehydrogenase (SDH) of Xcc. Molecular docking and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis results indicated that Act-X2 steadily bonded to the RNA polymerase, ribosome, malate dehydrogenase, and succinate dehydrogenase to inhibit their activities, thus drastically reducing the expression levels of related genes. Act-X2 showed far more effectiveness than the commercially available pesticide Cu2(OH)3Cl in the prevention and therapy of citrus canker disease. Furthermore, the nontarget toxicity evaluation demonstrated that Act-X2 was not phytotoxic to citrus trees and exhibited minimal toxicity to earthworms in both contact and soil toxic assays. This study suggests that Act-X2 has the potential as an effective and environmentally friendly antibacterial agent.

Control of citrus blue and green molds by Actinomycin X2 and its possible antifungal mechanism.

Citrus blue and green molds caused by Penicillium digitatum, P. italicum, and P. polonicum, are the major postharvest diseases of citrus fruit. In the present study, Actinomycin X2 (Act-X2), a naturally occurring antibiotic produced by Streptomyces species, was found to show excellent antifungal effect against these three pathogens with a minimum inhibitory concentration (MIC) value of 62.5 µg/mL for them all, which was better than the positive control thiophanate-methyl. Act-X2 significantly reduced the percentage of spore germination, and highly inhibited the mycelial growth of P. italicum, P. digitatum, and P. polonicum with EC50 values being 34.34, 13.76, and 37.48 µg/mL, respectively. In addition, Act-X2 greatly decreased the intracellular protein content while increasing the reactive oxygen species (ROS) level and superoxide anion (O2-) content in the mycelia of pathogens. In vivo test indicated that Act-X2 strongly inhibited the infection of navel oranges by these three Penicillium species, with an inhibition percentage of >50% for them all at the concentration of 10 MIC. Transcriptome analysis suggested that Act-X2 might highly influence the ribosomal functions of P. polonicum, which was supported as well by the molecular docking analysis of Act-X2 with some key functional proteins and RNAs of the ribosome. Furthermore, Act-X2 significantly reduced the decay percentage and improved the firmness, color, and sugar-acid ratio of navel oranges spray-inoculated with P. polonicum during the postharvest storage at 4 °C for 60 d.

Crop sensitivity to waterlogging mediated by soil temperature and growth stage.

Waterlogging constrains crop yields in many regions around the world. Despite this, key drivers of crop sensitivity to waterlogging have received little attention. Here, we compare the ability of the SWAGMAN Destiny and CERES models in simulating soil aeration index, a variable contemporaneously used to compute three distinct waterlogging indices, denoted hereafter as WI Destiny, WIASD1, and WIASD2. We then account for effects of crop growth stage and soil temperature on waterlogging impact by introducing waterlogging severity indices, WI Growth, which accommodates growth stage tolerance, and WI Plus, which accounts for both soil temperature and growth stage. We evaluate these indices using data collected in pot experiments with genotypes "Yang mai 11" and "Zheng mai 7698" that were exposed to both single and double waterlogging events. We found that WI Plus exhibited the highest correlation with yield (-0.82 to -0.86) suggesting that waterlogging indices which integrate effects of temperature and growth stage may improve projections of yield penalty elicited by waterlogging. Importantly, WI Plus not only allows insight into physiological determinants, but also lends itself to remote computation through satellite imagery. As such, this index holds promise in scalable monitoring and forecasting of crop waterlogging.

Development and validation of a predictive model for febrile seizures.

Febrile seizures (FS) are the most prevalent type of seizures in children. Existing predictive models for FS exhibit limited predictive ability. To build a better-performing predictive model, a retrospective analysis study was conducted on febrile children who visited the Children's Hospital of Shanghai from July 2020 to March 2021. These children were divided into training set (n = 1453), internal validation set (n = 623) and external validation set (n = 778). The variables included demographic data and complete blood counts (CBCs). The least absolute shrinkage and selection operator (LASSO) method was used to select the predictors of FS. Multivariate logistic regression analysis was used to develop a predictive model. The coefficients derived from the multivariate logistic regression were used to construct a nomogram that predicts the probability of FS. The calibration plot, area under the receiver operating characteristic curve (AUC), and decision curve analysis (DCA) were used to evaluate model performance. Results showed that the AUC of the predictive model in the training set was 0.884 (95% CI 0.861 to 0.908, p < 0.001) and C-statistic of the nomogram was 0.884. The AUC of internal validation set was 0.883 (95% CI 0.844 to 0.922, p < 0.001), and the AUC of external validation set was 0.858 (95% CI 0.820 to 0.896, p < 0.001). In conclusion, the FS predictive model constructed based on CBCs in this study exhibits good predictive ability and has clinical application value.

Insight into the Inhibitory Mechanisms of Hesperidin on α-Glucosidase through Kinetics, Fluorescence Quenching, and Molecular Docking Studies.

The α-glucosidase inhibitor is of interest to researchers due to its association with type-II diabetes treatment by suppressing postprandial hyperglycemia. Hesperidin is a major flavonoid in orange fruit with diverse biological properties. This paper evaluates the effects of hesperidin on α-glucosidase through inhibitory kinetics, fluorescence quenching, and molecular docking methods for the first time. The inhibition kinetic analysis shows that hesperidin reversibly inhibited the α-glucosidase activity with an IC50 value of 18.52 µM and the inhibition was performed in an uncompetitive type. The fluorescence quenching studies indicate that the intrinsic fluorescence of α-glucosidase was quenched via a static quenching process and only one binding site was present between the hesperidin and α-glucosidase. The interaction between them was spontaneous and mainly driven by hydrogen bonds, as well as hydrophobic forces. Furthermore, the molecular docking results suggest that hesperidin might bond to the entrance or outlet part of the active site of α-glucosidase through a network of five hydrogen bonds formed between hesperidin and the four amino acid residues (Trp709, Arg422, Asn424, and Arg467) of α-glucosidase and the hydrophobic effects. These results provide new insight into the inhibitory mechanisms of hesperidin on α-glucosidase, supporting the potential application of a hesperidin-rich orange product as a hypoglycemic functional food.

Microbiome-Mediated Protection against Pathogens in Woody Plants.

Pathogens, especially invasive species, have caused significant global ecological, economic, and social losses in forests. Plant disease research has traditionally focused on direct interactions between plants and pathogens in an appropriate environment. However, recent research indicates that the microbiome can interact with the plant host and pathogens to modulate plant resistance or pathogen pathogenicity, thereby altering the outcome of plant-pathogen interactions. Thus, this presents new opportunities for studying the microbial management of forest diseases. Compared to parallel studies on human and crop microbiomes, research into the forest tree microbiome and its critical role in forest disease progression has lagged. The rapid development of microbiome sequencing and analysis technologies has resulted in the rapid accumulation of a large body of evidence regarding the association between forest microbiomes and diseases. These data will aid the development of innovative, effective, and environmentally sustainable methods for the microbial management of forest diseases. Herein, we summarize the most recent findings on the dynamic structure and composition of forest tree microbiomes in belowground and aboveground plant tissues (i.e., rhizosphere, endosphere, and phyllosphere), as well as their pleiotropic impact on plant immunity and pathogen pathogenicity, highlighting representative examples of biological control agents used to modulate relevant tree microbiomes. Lastly, we discuss the potential application of forest tree microbiomes in disease control as well as their future prospects and challenges.

Long-term exposures to ambient particulate matter and ozone pollution with lower extremity deep vein thrombosis after surgical operations: a retrospective case-control study in Beijing, China.

BACKGROUND: Lower extremity deep vein thrombosis (LEDVT) after surgical operations is a common and fatal disease leading to unfavorable outcomes including death. Nevertheless, there has been insufficient evidence on the associations between ambient air pollution and LEDVT, particularly studies from developing regions. METHODS: Based on 302 LEDVT cases and 302 controls in a general hospital in Beijing, China, this unmatched retrospective case-control study investigated the associations of fine particulate matter (PM2.5), inhalable particulate matter (PM10), and ozone (O3) with odds of LEDVT. RESULTS: Per 10 µg/m3 increase in PM2.5, PM10, and O3 at 3-month, 6-month, and 2-year average was associated with increased LEDVT odds [odds ratios (ORs) for PM2.5: 1.10 (95%CI: 1.05, 1.14), 1.14 (95%CI: 1.09, 1.18), and 1.30 (95%CI: 1.06, 1.61); ORs for PM10: 1.06 (95%CI: 1.02, 1.10), 1.12 (95%CI: 1.08, 1.16), and 1.29 (95%CI: 1.03, 1.61); ORs for O3: 1.00 (95%CI: 0.96, 1.04), 1.16 (95%CI: 1.02, 1.31), and 2.08 (95%CI: 1.03, 4.18), respectively]. The stratified analyses, exposure-responses curves, and sensitivity analyses further highlighted the robustness of our findings. CONCLUSIONS: Long-term exposures to ambient PM2.5, PM10, and O3 may increase the risk of LEDVT in patients after surgical operations. The results may be implicated in the prevention and control of adverse clinical outcomes of surgical patients associated with ambient air pollution.

Elevated serum uric acid is associated with cognitive impairment in acute minor ischemic stroke patients.

Background: Acute minor ischemic stroke (AMIS) has been proven to be strongly associated with post-stroke cognitive impairment (PSCI). Few studies have reported that uric acid (UA) levels are linked to PSCI in patients with AMIS, and those results are debatable. We investigated the relationship between serum UA levels and cognitive impairment in patients with AMIS. Methods: A total of 318 patients who were diagnosed with AMIS were recruited from Suining Central Hospital. Fasting serum samples were collected the day after admission for UA measurement. Cognitive function was evaluated at admission and 3 months after stroke using the Montreal Cognitive Assessment (MoCA). The relationship between UA and PSCI was examined using a multivariate binary logistic regression model. The optimal cut-off point for UA levels to predict PSCI was determined using the receiver operating characteristic (ROC) curve. Results: A total of 197 (61.9 %) of the 318 participants in this study exhibited cognitive impairment at 3 months. Serum UA was strongly linked with PSCI after adjusting for confounding factors (OR = 1.82, 95 % CI: 1.56 to 2.11, P < 0.0001). The ROC curve revealed a cut-off of 363.58 µmol/L serum UA, and the predicted sensitivity and specificity for PSCI were 67.5 % and 83.5 %, respectively. Subgroup analysis showed that confounding factors had no impact on the association between serum UA and PSCI risk. Conclusions: Higher baseline serum UA levels might be an independent risk factor for cognitive impairment in AMIS patients. Serum UA levels above 363.58 µmol/L may have clinical implications in predicting PSCI.

Clinical application of magnetic resonance lymphangiography in the vascularized omental lymph nodes transfer with or without lymphaticovenous anastomosis for cancer-related lower extremity lymphedema.

Background: The recent increase in the number of patients with lower extremities lymphedema and the development of microsurgery techniques have led to a rise in lymphedema treatment. Vascularized omental lymph node transfer (VOLT), an emerging treatment modality for extremity lymphedema, has shown its unique advantages in reconstructing lymphatic circulation and absorbing exudated lymphatic fluid. Patients who underwent radical tumor resection with/without radiation therapy treatment often present with impairment or degeneration of the inguinal lymph nodes. For such cases, VOLT could provide adequate lymph nodes and tissue to absorb edema fluid in these areas. Therefore, we analyzed the operative outcomes of VOLT under the guidance of magnetic resonance lymphangiography (MRL) in this study, as this individualized and precise surgical procedure could benefit patients and improve their quality of life. Methods: From November 2021 to September 2022, a total of 14 patients' 19 legs with extremity lymphedema underwent a VOLT with or without lymphaticovenous anastomosis (LVA). Outcomes, including circumference reduction rates, preoperative and postoperative MRL results, and other complications, were analyzed. Results: The mean follow-up period was 8.86±1.41 months (range, 7-11 months). The mean circumference reduction rates {circumference reduction rate (%) = [1 - (postoperative affected limb - healthy limb)/(preoperative affected limb - healthy limb)] × 100%} of different planes (i.e., ankle, 10 cm above the knee, 10 cm below the knee, 10 cm above the ankle, and 20 cm above the knee) were 15.64%±40.08%, 11.79%±30.69%, 20.25%±24.94%, 7.73%±30.05%, -1.517%±16.75%. Notably, one patient had multi-drug-resistant gram-negative infections, which resulted in the loss of three flaps. The postoperative MRL showed improved lymphatic drainage and lower extremity volume in the remaining 13 cases. Conclusions: The precision evaluation of inguinal lymph nodes and lower extremities lymphatic system through MRL using VOLT can provide surgeons with a comprehensive understanding and reliable evidence for the treatment of cancer-related lower extremity lymphedema.

The safety of colorectal cancer surgery during the COVID-19: a systematic review and meta-analysis.

Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic has placed unprecedented pressure on the healthcare systems. This study evaluated the safety of colorectal cancer (CRC) surgery during the COVID-19 pandemic. Methods: A systematic review and meta-analysis were performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO ID: CRD 42022327968). Relevant articles were systematically searched in the PubMed, Embase, Web of Science, and Cochrane databases. The postoperative complications, anastomotic leakage, postoperative mortality, 30-day readmission, tumor stage, total hospitalization, postoperative hospitalization, preoperative waiting, operation time, and hospitalization in the intensive care unit (ICU) were compared between the pre-pandemic and during the COVID-19 pandemic periods. Results: Among the identified 561 articles, 12 met the inclusion criteria. The data indicated that preoperative waiting time related to CRC surgery was higher during the COVID-19 pandemic (MD, 0.99; 95%CI, 0.71-1.28; p < 0.00001). A similar trend was observed for the total operative time (MD, 25.07; 95%CI, 11.14-39.00; p =0.0004), and on T4 tumor stage during the pandemic (OR, 1.77; 95%CI, 1.22-2.59; p=0.003). However, there was no difference in the postoperative complications, postoperative 90-day mortality, anastomotic leakage, and 30-day readmission times between pre-COVID-19 pandemic and during the COVID-19 pandemic periods. Furthermore, there was no difference in the total hospitalization time, postoperative hospitalization time, and hospitalization time in ICU related to CRC surgery before and during the COVID-19 pandemic. Conclusion: The COVID-19 pandemic did not affect the safety of CRC surgery. The operation of CRC during the COVID-19 pandemic did not increase postoperative complications, postoperative 90-day mortality, anastomotic leakage, 30-day readmission, the total hospitalization time, postoperative hospitalization time, and postoperative ICU hospitalization time. However, the operation of CRC during COVID-19 pandemic increased T4 of tumor stage during the COVID-19 pandemic. Additionally, the preoperative waiting and operation times were longer during the COVID-19 pandemic. This provides a reference for making CRC surgical strategy in the future. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022327968.

Secreted Effector Proteins of Poplar Leaf Spot and Stem Canker Pathogen Sphaerulina musiva Manipulate Plant Immunity and Contribute to Virulence in Diverse Ways.

Fungal effectors play critical roles in manipulating plant immune responses and promoting colonization. Sphaerulina musiva is a heterothallic ascomycete fungus that causes Septoria leaf spot and stem canker disease in poplar (Populus spp.) plantations. This disease can result in premature defoliation, branch and stem breakage, increased mortality, and plantation failure. However, little is known about the interaction between S. musiva and poplar. Previous work predicted 142 candidate secreted effector proteins in S. musiva (SmCSEPs), 19 of which were selected for further functional characterization in this study. SmCSEP3 induced plant cell death in Nicotiana benthamiana, while 8 out of 19 tested SmCSEPs suppressed cell death. The signal peptides of these eight SmCSEPs exhibited secretory activity in a yeast signal sequence trap assay. Confocal microscopy revealed that four of these eight SmCSEPs target both the cytoplasm and the nucleus, whereas four predominantly localize to discrete punctate structures. Pathogen challenge assays in N. benthamiana demonstrated that the transient expression of six SmCSEPs promoted Fusarium proliferatum infection. The expression of these six SmCSEP genes were induced during infection. SmCSEP2, SmCSEP13, and SmCSEP25 suppressed chitin-triggered reactive oxygen species burst and callose deposition in N. benthamiana. The candidate secreted effector proteins of S. musiva target multiple compartments in the plant cell and modulate different pattern-triggered immunity pathways. [Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 "No Rights Reserved" license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2023.

Isolation, identification, and antibacterial evaluation of endophytic fungi from Gannan navel orange.

Gannan navel orange is a famous brand in China but the isolation of its endophytic fungi was rarely reported. In this study, a total of 54 strains of endophytic fungi were successfully isolated from the pulp, peel, twig, and leaf of Gannan navel orange; they were successfully identified to belong to 17 species of 12 genera. All these strains were fermented using potato-dextrose agar (PDA) medium, and their secondary metabolites were then extracted with ethyl acetate (EtOAc). The antibacterial assays of Escherichia coli (E. coli), methicillin-resistant Staphylococcus aureus (MRSA), and Xanthomonas citri subsp. citri (Xcc) were also performed for the EtOAc extracts of these strains. As a result, the extracts of both Geotrichum sp. (gc-1-127-30) and Diaporthe biconispora (gc-1-128-79) demonstrated significant antibacterial activities against Xcc, and the MIC value for the extract of Colletotrichum gloeosporioides against MRSA was low to 62.5 µg/mL. Moreover, the chemical components of the extracts of Colletotrichum sp., Diaporthe biconispora, and Annulohypoxylon atroroseum were primarily investigated, and they successfully led to the isolation of 24 compounds involving a new botryane sesquiterpene. Among the isolated products, compound 2 showed significant inhibitory activities toward SA, MRSA, E. coli, and Xcc with MIC values of 12.5, 3.1, 125, and 12.5 µg/mL, respectively. This study revealed that the endophytic fungi of Gannan navel orange showed high potency to produce secondary metabolites with significant antibacterial effects.

Identification of N7-methylguanosine-related lncRNAs for the risk stratification of hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. The N7-methylguanosine (m7G) modification is related to the biological processes and regulation of various diseases. This study investigated the role and predictive value of m7G-related long non-coding RNAs (lncRNAs) in HCC. Methods: HCC patients were clustered by consensus clustering, and a prognostic signature was developed using Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression analysis. The immune landscape and clinicopathological features of the distinct clusters and subgroups were investigated. Results: A total of 32 m7G-related lncRNAs were confirmed to be prognostic lncRNAs. Two molecular clusters showed significant differences in terms of their clinicopathological features, prognoses, and immune checkpoint gene (ICG) expression levels. Cluster II was associated with upregulated ICG expression and poor overall survival (OS). The Cancer Genome Atlas training cohort was then used to create an m7G-related lncRNA signature for predicting OS. The signature exhibited excellent predictive performance in the training, test, and all cohorts. The high-risk patients had worse clinical outcomes than the low-risk patients. Further study revealed that this signature was an independent prognostic indicator, and a predictive nomogram was developed based on the clinicopathological features and risk score. In addition, we discovered that this model was correlated with ICG expression and tumor immune cell infiltration. Conclusions: Our findings demonstrated that m7G-related lncRNAs are associated with the tumor immune landscape and prognosis and can serve as independent prognostic markers for HCC. These findings provide new insights into the functions of m7G-related lncRNAs in HCC.

Actinomycins produced by endophyte Streptomyces sp. GLL-9 from navel orange plant exhibit high antimicrobial effect against Xanthomonas citri susp. citri and Penicillium italicum.

BACKGROUND: Citrus canker and citrus blue mold are two severe diseases in citrus plants, which are mainly caused by Xanthomonas citri susp. citri (Xcc) and Penicillium italicum, respectively. The currently widely used pesticides for these two diseases are harmful to human health and the environment. Therefore, searching for novel antimicrobial agents, especially from natural resources, is getting increasing interest. RESULTS: In this study, the crude extract of Streptomyces sp. GLL-9, an endophyte from a navel orange tree, was found to exhibit excellent antimicrobial effects against Xcc and P. italicum. Bioassay-guided isolation led to the discovery of three actinomycins (Acts), actinomycin X2 (Act-X2 ), actinomycin D (ActD), and actinomycin XOß (Act-XOß ). The MIC (minimum inhibitory concentration) values of Act-X2 , ActD, and Act-XOß were 31.25, 62.50, and 62.50 µg mL-1 against Xcc, respectively, while 62.50 (Act-X2 ) and 125.00 µg mL-1 (ActD) against P. italicum, being better or comparable to the positive controls. The highest yield of Acts was obtained by solid-state fermentation with rice containing 1% L-tryptophan as a culture medium, being 6.03, 3.07, and 1.02 mg g-1 , for Act-X2 , ActD, and Act-XOß , respectively. The ethyl acetate extract of Streptomyces sp. GLL-9 cultivated under the optimal fermentation conditions (EAE-1) can efficiently control these two citrus diseases by excessively producing reactive oxygen species (ROS) in both pathogens, damaging the cell membranes of P. italicum, and inhibiting the growth of Xcc. In addition, Act-X2 , ActD, and EAE-1 displayed broad-spectrum antifungal activity. CONCLUSION: EAE-1 and Acts produced by Streptomyces sp. GLL-9 have high potential as novel antimicrobial agents against plant pathogens. © 2023 Society of Chemical Industry.

Targeting the gut microbiota and its metabolites for type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia and insulin resistance. The incidence of T2DM is increasing globally, and a growing body of evidence suggests that gut microbiota dysbiosis may contribute to the development of this disease. Gut microbiota-derived metabolites, including bile acids, lipopolysaccharide, trimethylamine-N-oxide, tryptophan and indole derivatives, and short-chain fatty acids, have been shown to be involved in the pathogenesis of T2DM, playing a key role in the host-microbe crosstalk. This review aims to summarize the molecular links between gut microbiota-derived metabolites and the pathogenesis of T2DM. Additionally, we review the potential therapy and treatments for T2DM using probiotics, prebiotics, fecal microbiota transplantation and other methods to modulate gut microbiota and its metabolites. Clinical trials investigating the role of gut microbiota and its metabolites have been critically discussed. This review highlights that targeting the gut microbiota and its metabolites could be a potential therapeutic strategy for the prevention and treatment of T2DM.

Plant commensal type VII secretion system causes iron leakage from roots to promote colonization.

Competition for iron is an important factor for microbial niche establishment in the rhizosphere. Pathogenic and beneficial symbiotic bacteria use various secretion systems to interact with their hosts and acquire limited resources from the environment. Bacillus spp. are important plant commensals that encode a type VII secretion system (T7SS). However, the function of this secretion system in rhizobacteria-plant interactions is unclear. Here we use the beneficial rhizobacterium Bacillus velezensis SQR9 to show that the T7SS and the major secreted protein YukE are critical for root colonization. In planta experiments and liposome-based experiments demonstrate that secreted YukE inserts into the plant plasma membrane and causes root iron leakage in the early stage of inoculation. The increased availability of iron promotes root colonization by SQR9. Overall, our work reveals a previously undescribed role of the T7SS in a beneficial rhizobacterium to promote colonization and thus plant-microbe interactions.