AC092100.1 promotes angiogenesis in pre-eclampsia through YTHDC2/VEGFA signaling.

Aberrant long non-coding RNA (lncRNA) expression has been shown to be involved in the pathological process of pre-eclampsia (PE), yet only a small portion of lncRNAs has been characterized concerning the function and molecular mechanisms involved in PE. This study aimed to investigate the regulatory mechanism of the lncRNA AC092100.1 (AC092100.1) in angiogenesis in PE. In our study, bioinformatics analysis was performed to screen for differentially expressed lncRNAs between normal subjects and PE patients. The levels of AC092100.1 in placental tissues of patients with or without PE were validated using qRT-PCR. The effect of AC092100.1 overexpression on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) was investigated. The binding of AC092100.1 and YT521-B homology domain-containing 2 (YTHDC2) was predicted and verified. The effect of AC092100.1/YTHDC2 on the expression of vascular endothelial growth factor-A (VEGFA) in HUVECs was determined. Finally, a PE mice model was conducted. Fetal mouse growth, the abundance of mesenchymal morphology markers, including hypoxia-inducible factor 1-alpha (HIF-1α), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), Slug, and Vimentin, and endothelial markers, including placental growth factor (PLGF), CD31, and vascular endothelial (VE)-cadherin, in placental tissues were assessed. Here, we found that AC092100.1 was abnormally downregulated in placental tissues from PE patients. We established that AC092100.1 overexpression promoted HUVEC proliferation, migration, and tube formation in vitro. Mechanistically, AC092100.1 induced the accumulation of YTHDC2 and VEGFA through binding to YTHDC2 in HUVECs. Inhibition of YTHDC2 or VEGFA reversed AC092100.1-promoted tube formation. AC092100.1 overexpression contributed to alleviating fetal growth disorder, decreased levels of sEng, HIF-1α, sFlt-1, Slug, and Vimentin, and increased levels of VEGFA, PLGF, CD31, and VE-cadherin in PE mice. Our findings provided evidence supporting the role of the AC092100.1/YTHDC2/VEGFA axis in regulating angiogenesis, which demonstrated a therapeutic pathway for PE targeting angiogenesis.

Bioinformatics and experimental validation were combined to explore lactylation-related biomarkers in HBV-associated acute liver failure.

BACKGROUND AND AIM: Currently, hepatitis B virus-related acute liver failure (HBV-ALF) has limited treatment options. Studies have shown that histone lactylation plays a role in the progression of liver-related diseases. Therefore, it is essential to explore lactylation-related gene (LRGs) biomarkers in HBV-ALF to provide new information for the treatment of HBV-ALF. METHODS: Two HBV-ALF-related datasets (GSE38941 and GSE14668) and 65 LRGs were used. First, the differentially expressed genes (DEGs) were derived from differential expression analysis, the key module genes from weighted gene co-expression network analysis; and LRGs were used to intersect to obtain the candidate genes. Subsequently, the feature genes obtained from least absolute shrinkage and selection operator regression analysis and support vector machine analysis were intersected to obtain the candidate key genes. Among them, genes with consistent and significant expression trends in both GSE38941 and GSE14668 were used as biomarkers. Subsequently, biomarkers were analyzed for functional enrichment, immune infiltration, and sensitive drug prediction. RESULTS: In this study, five candidate genes (PIGM, PIGA, EGR1, PIGK, and PIGL) were identified by intersecting 6461 DEGs and 2496 key module genes with 65 LRGs. We then screened four candidate key genes from the machine learning algorithm, among which PIGM and PIGA were considered biomarkers in HBV-ALF. Moreover, the results of enrichment analysis showed that the significant enrichment signaling pathways for biomarkers included allograft rejection and valine, leucine, and isoleucine degradation. Thereafter, 11 immune cells differed significantly between groups, with resting memory CD4+ T cells having the strongest positive correlation with biomarkers. Methylphenidate hydrochloride is a potential therapeutic drug for PIGM. CONCLUSION: Two genes, PIGM and PIGA, were identified as biomarkers related to LRGs in HBV-ALF, providing a basis for understanding HBV-ALF pathogenesis.

Evaluation of a new scoring system for assessing nerve invasion in resected pancreatic cancer: A single-center retrospective analysis.

Nerve invasion (NI) is a characteristic feature of pancreatic cancer. Traditional dichotomous statements on the presence of NI are unreasonable because almost all cases exhibit NI when sufficient pathological sections are examined. The critical implications of NI in pancreatic cancer highlight the need for a more effective criterion. This study included 511 patients, who were categorized into a training group and a testing group at a ratio of 7:3. According to the traditional definition, NI was observed in 91.2 % of patients using five pathological slides in our study. The prevalence of NI increased as more pathological slides were used. The criterion of 'two points of intraneural (endoneural) invasion in the case of four pathological slides' has the highest receiver operating characteristic (ROC) score. Based on this new criterion, NI was proved to be an independent prognostic factor for overall survival (OS) and disease-free survival (DFS) and was also correlated with tumor recurrence (P = 0.004). Interestingly, gemcitabine-based chemotherapy regimen is an independent favorable factor for patients with high NI. In the high NI group, patients who received a gemcitabine-based regimen exhibited a better prognosis than those who did not receive the gemcitabine-based regimen for OS (P = 0.000) and DFS (P = 0.001). In conclusion, this study establishes assessment criteria to evaluate the severity of NI in order to predict patient outcomes.

Metabonomic analysis to identify exometabolome changes underlying antifungal and growth promotion mechanisms of endophytic Actinobacterium Streptomyces albidoflavus for sustainable agriculture practice.

In recent years, there has been an increasing focus on microbial ecology and its possible impact on agricultural production, owing to its eco-friendly nature and sustainable use. The current study employs metabolomics technologies and bioinformatics approaches to identify changes in the exometabolome of Streptomyces albidoflavus B24. This research aims to shed light on the mechanisms and metabolites responsible for the antifungal and growth promotion strategies, with potential applications in sustainable agriculture. Metabolomic analysis was conducted using Q Exactive UPLC-MS/MS. Our findings indicate that a total of 3,840 metabolites were identified, with 137 metabolites exhibiting significant differences divided into 61 up and 75 downregulated metabolites based on VIP >1, |FC| >1, and p < 0.01. The interaction of S. albidoflavus B24 monoculture with the co-culture demonstrated a stronger correlation coefficient. The Principal Component Analysis (PCA) demonstrates that PCA1 accounted for 23.36%, while PCA2 accounted for 20.28% distinction. OPLS-DA score plots indicate significant separation among different groups representing (t1) 24% as the predicted component (to1) depicts 14% as the orthogonal component. According to the findings of this comprehensive study, crude extracts from S. albidoflavus demonstrated varying abilities to impede phytopathogen growth and enhance root and shoot length in tested plants. Through untargeted metabolomics, we discovered numerous potential molecules with antagonistic activity against fungal phytopathogens among the top 10 significant metabolites with the highest absolute log2FC values. These include Tetrangulol, 4-Hydroxybenzaldehyde, and Cyclohexane. Additionally, we identified plant growth-regulating metabolites such as N-Succinyl-L-glutamate, Nicotinic acid, L-Aspartate, and Indole-3-acetamide. The KEGG pathway analysis has highlighted these compounds as potential sources of antimicrobial properties. The inhibitory effect of S. albidoflavus crude extracts on pathogen growth is primarily attributed to the presence of specific gene clusters responsible for producing cyclic peptides such as ansamycins, porphyrin, alkaloid derivatives, and neomycin. Overall, it is apparent that crude extracts from S. albidoflavus exhibited varying abilities to inhibit the growth of three phytopathogens and enhancement in both root and shoot length of tested plants. This research enhances our understanding of how secondary metabolites contribute to growth promotion and biocontrol, supporting ecosystem sustainability and resilience while boosting productivity in sustainable agriculture.

Discovery of a potential bladder cancer inhibitor CHNQD-01281 by regulating EGFR and promoting infiltration of cytotoxic T cells.

As one of the common malignancies that threaten human life, bladder cancer occurs frequently with a high mortality rate in the world, due to its invasion, recurrence and drug resistance. Natural products from marine microorganisms are becoming the hotspots in discovery of new candidate drug entities, especially in the area of cancer. Brefeldin A (BFA) is a natural Arf-GEFs inhibitor, but due to the low aqueous solubility, strong toxicity, and poor bioavailability, it is urgent to conduct structural optimization research. Herein, a new BFA pyridine acrylate derivative CHNQD-01281 with improved solubility was prepared and found to exert moderate to strong antiproliferative activity on a variety of human cancer cell lines. It was noteworthy that CHNQD-01281 was most sensitive to two bladder cancer cell lines T24 and J82 (IC50 = 0.079 and 0.081 µmol/L) with high selectivity index (SI = 14.68 and 14.32), suggesting a superior safety to BFA. In vivo studies revealed that CHNQD-01281 remarkably suppressed tumor growth in a T24 nude mice xenograft model (TGI = 52.63%) and prolonged the survival time (ILS = 68.16%) in an MB49 allogeneic mouse model via inducing infiltration of cytotoxic T cells. Further mechanism exploration indicated that CHNQD-01281 regulated both EGFR/PI3K/AKT and EGFR/ERK pathways and mediated the chemotactic effect of chemokines on immune effector cells. Overall, CHNQD-01281 may serve as a potential therapeutic agent for bladder cancer through multiple mechanisms. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00246-w.

Myocardial ischemia-reperfusion injury: The balance mechanism between mitophagy and NLRP3 inflammasome.

Myocardial ischemia-reperfusion injury (MIRI) is an injury to cardiomyocytes due to restoration of blood flow after myocardial infarction (MI). It has recently gained much attention in clinical research with special emphasis on the roles of mitochondrial autophagy and inflammation. A mild inflammatory response promotes recovery of post-ischemic cardiomyocyte function and vascular regeneration, but a severe inflammatory response can cause irreversible and substantial cellular damage. Similarly, moderate mitochondrial autophagy can help inhibit excessive inflammation and protect cardiomyocytes. However, MIRI is aggravated when mitochondrial function is disrupted, such as inadequate clearance of damaged mitochondria or excessive activation of mitophagy. How to moderately control mitochondrial autophagy while promoting its balance with nucleotide-binding oligomerization structural domain receptor protein 3 (NLRP3) inflammasome activation is critical. In this paper, we reviewed the molecular mechanisms of mitochondrial autophagy and NLRP3 inflammasome, described the interaction between NLRP3 inflammasome and mitochondrial autophagy, and the effects of different signaling pathways and molecular proteins on MIRI, to provide a reference for future research.

Quantifying internal and external training loads in collegiate male volleyball players during a competitive season.

BACKGROUND: The long-term monitoring of internal and external training load is crucial for the training effectiveness of athletes. This study aims to quantify the internal and external training loads of collegiate male volleyball players during the competitive season. The internal and external training load variables were analyzed across mesocycles and playing positions. METHODS: Fourteen participants with age of 20.2 ± 1.3 years, height of 1.81 ± 0.05 m, and body weight of 70.8 ± 5.9 kg were recruited. The data were collected over a 29-week period that was divided into four mesocycles: preparation 1 (P1, weeks 1-7), competition 1 (C1, weeks 8-14, including a 5-day tournament in week 14), preparation 2 (P2, weeks 15-23), and competition 2 (C2, weeks 24-29, including a 6-day tournament in week 29). Each participant wore an inertial measurement unit and reported the rating of perceived exertion in each training session. The internal training load variables included weekly session rating of perceived exertion, acute: chronic workload ratio, and training monotony and strain. The external training load variables included jump count and height and the percentage of jumps exceeding 80% of maximal height. RESULTS: C2 had the highest average weekly internal training load (3022 ± 849 AU), whereas P2 had the highest average weekly acute: chronic workload ratio (1.46 ± 0.13 AU). The number of weekly jumps in C1 (466.0 ± 176.8) was significantly higher than in other mesocycles. Weekly jump height was significantly higher in C1, P2, and C2. Internal training load was positively correlated with jump count (ρ = 0.477, p < 0.001). Jump count was negatively correlated with jump height (ρ = -0.089, p = 0.006) and the percentage of jumps exceeding 80% of maximal height (ρ = -0.388, p < 0.001). The internal and external training load variables were similar among different playing positions. CONCLUSION: The participants exhibited significantly higher internal training load in C2 and higher jump height after P1. A high jump count was associated with higher internal training load and lower jump height. Excessive jumps may result in fatigue and reduce height.

Oncoprotein-induced transcript 3 protein-enriched extracellular vesicles promotes NLRP3 ubiquitination to alleviate acute lung injury after cardiac surgery.

Acute lung injury (ALI) including acute respiratory distress syndrome (ARDS) is a major complication and increase the mortality of patients with cardiac surgery. We previously found that the protein cargoes enriched in circulating extracellular vesicles (EVs) are closely associated with cardiopulmonary disease. We aimed to evaluate the implication of EVs on cardiac surgery-associated ALI/ARDS. The correlations between "oncoprotein-induced transcript 3 protein (OIT3) positive" circulating EVs and postoperative ARDS were assessed. The effects of OIT3-overexpressed EVs on the cardiopulmonary bypass (CPB) -induced ALI in vivo and inflammation of human bronchial epithelial cells (BEAS-2B) were detected. OIT3 enriched in circulating EVs is reduced after cardiac surgery with CPB, especially with postoperative ARDS. The "OIT3 positive" EVs negatively correlate with lung edema, hypoxemia and CPB time. The OIT3-overexpressed EVs can be absorbed by pulmonary epithelial cells and OIT3 transferred by EVs triggered K48- and K63-linked polyubiquitination to inactivate NOD-like receptor protein 3 (NLRP3) inflammasome, and restrains pro-inflammatory cytokines releasing and immune cells infiltration in lung tissues, contributing to the alleviation of CPB-induced ALI. Overexpression of OIT3 in human bronchial epithelial cells have similar results. OIT3 promotes the E3 ligase Cbl proto-oncogene B associated with NLRP3 to induce the ubiquitination of NLRP3. Immunofluorescence tests reveal that OIT3 is reduced in the generation from the liver sinusoids endothelial cells (LSECs) and secretion in liver-derived EVs after CPB. In conclusion, OIT3 enriched in EVs is a promising biomarker of postoperative ARDS and a therapeutic target for ALI after cardiac surgery.

Oxysophoridine inhibits oxidative stress and inflammation in hepatic fibrosis via regulating Nrf2 and NF-κB pathways.

BACKGROUND: Hepatic fibrosis (HF) runs through multiple stages of liver diseases and promotes these diseases progression. Oxysophoridine (OSR), derived from Sophora alopecuroides l., is a bioactive alkaloid that has been reported to antagonize alcoholic hepatic injury. However, whether OSR suppresses HF and the mechanisms involved in Nrf2 remain unknown. PURPOSE: Since the dysregulation of inflammation and oxidative stress is responsible for the excessive accumulation of extracellular matrix (ECM) and fibrosis in the liver. We hypothesized that OSR may attenuate HF by inhibiting inflammation and oxidative stress through activating Nrf2 signaling. METHODS: In this study, we employed LPS-stimulated HSC-T6 cells, RAW264.7 cells, and a CCl4-induced C57BL/6 mouse fibrotic model to evaluate its suppressing inflammation and oxidative stress, as well as fibrosis. RESULTS: The result showed that OSR significantly reduced α-SMA and TGF-ß1 at a low dose of 10 µM in vitro and at a dose of 50 mg/kg in vivo, which is comparable to Silymarin, the only Chinese herbal active ingredient that has been marketed for anti-liver fibrosis. Moreover, OSR effectively suppressed the expression of iNOS at a dose of 10 µM and COX-2 at a dose of 40 µM, respectively. Furthermore, OSR demonstrated inhibitory effects on the IL-1ß, IL-6, and TNF-α in vitro and almost extinguished cytokine storm in vivo. OSR exhibited antioxidative effects by reducing MDA and increasing GSH, thereby protecting the cell membrane against oxidative damage and reducing LDH release. Moreover, OSR effectively upregulated the protein levels of Nrf2, HO-1, and p62, but decreased p-NF-κB p65, p-IκBα, and Keap1. Alternatively, mechanisms involved in Nrf2 were verified by siNrf2 interference, siNrf2 interference revealed that the anti-fibrotic effect of OSR was attributed to its activation of Nrf2. CONCLUSION: The present study provided an effective candidate for HF involved in both activation of Nrf2 and blockage of NF-κB, which has not been reported in the published work. The present study provides new insights for the identification of novel drug development for HF.

Nomogram for Predicting Emergent Conversion to General Anaesthesia in Stroke Patients During Thrombectomy.

RATIONALE AND OBJECTIVES: The aim of this study was to develop and validate a nomogram for predicting emergent conversion to general anaesthesia (GA) in stroke patients during thrombectomy. METHODS: In this retrospective study, 458 patients (320 and 138 were randomised into the training and validation cohorts) were enroled. Univariable and multivariable logistic regression analyses were employed to identify risk factors for emergent conversion to GA. Subsequently, a nomogram was constructed based on the identified risk factors. The discriminative ability, calibration, and clinical utility of the nomogram were assessed in both the training and validation cohorts using receiver operating characteristic (ROC) curve analysis, Hosmer-Lemeshow test, and decision curve analysis (DCA). RESULTS: The emergent conversion to GA occurred in 56 cases (12.2%). In the training cohort, four independent predictors of emergent conversion to GA were identified and incorporated into the nomogram: core infarct volume > 70 mL, severe aphasia, severe cerebral vessel tortuosity, and vertebrobasilar occlusion. The ROC curves illustrated area under curve values of 0.931 (95% CI: 0.863-0.998) and 0.893 (95% CI: 0.852-0.935) for the training and validation cohorts, respectively. Hosmer-Lemeshow testing resulted in average absolute errors of 0.028 and 0.031 for the two cohorts. DCA demonstrated the nomogram's exceptional utility and accuracy across a majority of threshold probabilities. CONCLUSION: The constructed nomogram displayed promising predictive accuracy for emergent conversion to GA in stroke patients during thrombectomy, thereby providing potential assistance for clinical decision-making.

Prognostic role of the stromal cell derived factor-1 in patients with hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND: Stromal cell derived factor-1 (SDF-1) plays a pivotal role in the recruitment of stem cells to injured livers. However, the changes of SDF-l in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) have yet to be elucidated. AIM: To study the SDF-1 changes in patients with HBV-related ACLF. METHODS: 30 patients with HBV-related ACLF, 27 patients with chronic hepatitis B and 20 healthy individuals are involved in our study. The SDF-l mRNA expression in liver tissue was detected by quantitative real-time polymerase chain reaction. Immunohistochemical staining was performed to illustrate the expression of SDF-l, CXC receptor 4 (CXCR4) and Ki67. The serum SDF-l concentrations were also detected by enzyme-linked immunosorbent assays. RESULTS: The expression of SDF-1 mRNA from ACLF patients was remarkably higher than that from other patients (both P < 0.05). The expression of SDF-l, CXCR4 and Ki67 from ACLF were the highest among the three groups (all P < 0.01). The serum SDF-l levels in ACLF patients were significantly lower than that in other patients (both P < 0.01). Moreover, in ACLF patients, the serum SDF-1 Levels were positively correlated with serum total bilirubin and international normalized ratio. In addition, the serum SDF-l levels in survival were significantly lower compared with the non-survivals (P < 0.05). The area under the curve for the serum SDF-1 level in predicting 28-d mortality was 0.722 (P < 0.05). CONCLUSION: This study provides the SDF-1 changes in patients with HBV-related ACLF. The SDF-1 Level at admission may serve as a promising prognostic marker for predicting short-term prognosis.

Cultivation of novel Atribacterota from oil well provides new insight into their diversity, ecology, and evolution in anoxic, carbon-rich environments.

BACKGROUND: The Atribacterota are widely distributed in the subsurface biosphere. Recently, the first Atribacterota isolate was described and the number of Atribacterota genome sequences retrieved from environmental samples has increased significantly; however, their diversity, physiology, ecology, and evolution remain poorly understood. RESULTS: We report the isolation of the second member of Atribacterota, Thermatribacter velox gen. nov., sp. nov., within a new family Thermatribacteraceae fam. nov., and the short-term laboratory cultivation of a member of the JS1 lineage, Phoenicimicrobium oleiphilum HX-OS.bin.34TS, both from a terrestrial oil reservoir. Physiological and metatranscriptomics analyses showed that Thermatribacter velox B11T and Phoenicimicrobium oleiphilum HX-OS.bin.34TS ferment sugars and n-alkanes, respectively, producing H2, CO2, and acetate as common products. Comparative genomics showed that all members of the Atribacterota lack a complete Wood-Ljungdahl Pathway (WLP), but that the Reductive Glycine Pathway (RGP) is widespread, indicating that the RGP, rather than WLP, is a central hub in Atribacterota metabolism. Ancestral character state reconstructions and phylogenetic analyses showed that key genes encoding the RGP (fdhA, fhs, folD, glyA, gcvT, gcvPAB, pdhD) and other central functions were gained independently in the two classes, Atribacteria (OP9) and Phoenicimicrobiia (JS1), after which they were inherited vertically; these genes included fumarate-adding enzymes (faeA; Phoenicimicrobiia only), the CODH/ACS complex (acsABCDE), and diverse hydrogenases (NiFe group 3b, 4b and FeFe group A3, C). Finally, we present genome-resolved community metabolic models showing the central roles of Atribacteria (OP9) and Phoenicimicrobiia (JS1) in acetate- and hydrocarbon-rich environments. CONCLUSION: Our findings expand the knowledge of the diversity, physiology, ecology, and evolution of the phylum Atribacterota. This study is a starting point for promoting more incisive studies of their syntrophic biology and may guide the rational design of strategies to cultivate them in the laboratory. Video Abstract.

Advancements in prokaryotic systematics and the role of Bergey's International Society for Microbial Systematicsin addressing challenges in the meta-data era.

Prokaryotes are ubiquitous in the biosphere, important for human health and drive diverse biological and environmental processes. Systematics of prokaryotes, whose origins can be traced to the discovery of microorganisms in the 17th century, has transitioned from a phenotype-based classification to a more comprehensive polyphasic taxonomy and eventually to the current genome-based taxonomic approach. This transition aligns with a foundational shift from studies focused on phenotypic traits that have limited comparative value to those using genome sequences. In this context, Bergey's Manual of Systematics of Archaea and Bacteria (BMSAB) and Bergey's International Society for Microbial Systematics (BISMiS) play a pivotal role in guiding prokaryotic systematics. This review focuses on the historical development of prokaryotic systematics with a focus on the roles of BMSAB and BISMiS. We also explore significant contributions and achievements by microbiologists, highlight the latest progress in the field and anticipate challenges and opportunities within prokaryotic systematics. Additionally, we outline five focal points of BISMiS that are aimed at addressing these challenges. In conclusion, our collaborative effort seeks to enhance ongoing advancements in prokaryotic systematics, ensuring its continued relevance and innovative characters in the contemporary landscape of genomics and bioinformatics.

Reversed oxidative TCA (roTCA) for carbon fixation by an Acidimicrobiia strain from a saline lake.

Acidimicrobiia are widely distributed in nature and suggested to be autotrophic via the Calvin-Benson-Bassham (CBB) cycle. However, direct evidence of chemolithoautotrophy in Acidimicrobiia is lacking. Here, we report a chemolithoautotrophic enrichment from a saline lake, and the subsequent isolation and characterization of a chemolithoautotroph, Salinilacustristhrix flava EGI L10123T, which belongs to a new Acidimicrobiia family. Although strain EGI L10123T is autotrophic, neither its genome nor Acidimicrobiia metagenome-assembled genomes (MAGs) from the enrichment culture encode genes necessary for the CBB cycle. Instead, genomic, transcriptomic, enzymatic, and stable-isotope probing data hinted at the activity of the reversed oxidative TCA (roTCA) coupled with the oxidation of sulfide as the electron donor. Phylogenetic analysis and ancestral character reconstructions of Acidimicrobiia suggested that the essential CBB gene rbcL was acquired through multiple horizontal gene transfer events from diverse microbial taxa. In contrast, genes responsible for sulfide- or hydrogen-dependent roTCA carbon fixation were already present in the last common ancestor of extant Acidimicrobiia. These findings imply the possibility of roTCA carbon fixation in Acidimicrobiia and the ecological importance of Acidimicrobiia. Further research in the future is necessary to confirm whether these characteristics are truly widespread across the clade.

Intraguild species presence alters Aphidoletes aphidimyza (Diptera: Cecidomyiidae) and Aphidius gifuensis (Hymenoptera: Braconidae) foraging responses.

The predatory gall midge, Aphidoletes aphidimyza (Rondani), and tobacco aphid cocoon wasp, Aphidius gifuensis Ashmead, are important natural enemies of Myzus persicae (Sulzer) (Hemiptera: Aphididae). Predation by A. aphidimyza and A. gifuensis can regulate M. persicae; however, how interspecific interference competition affects their foraging efficiency is unknown. Here, we investigated the consumption and parasitization abilities of A. aphidimyza 3rd instar larva and A. gifuensis adults under various conditions. Consumption of parasitized aphids by A. aphidimyza 3rd instar larvae was significantly lower than that of nonparasitized controls, with a substantial increase in handling time. The presence of A. gifuensis adults did not significantly affect the predation capacity of A. aphidimyza larvae. Relative to controls, A. aphidimyza larvae predation trace (PT) and imago activity significantly decreased A. gifuensis parasitism rates at different aphid densities. Further, A. aphidimyza larvae PT increased the A. gifuensis handling time of M. persicae, whereas the presence of A. aphidimyza adults had the opposite effect. Coexistence with heterospecific natural enemies reduced the parasitic capacity of A. gifuensis, whereas A. aphidimyza larvae predation capability was influenced to a lesser extent. Our results demonstrate that intraguild interactions strongly influence the predatory and parasitic efficacy of A. aphidimyza and A. gifuensis, although the effect on A. gifuensis was more pronounced. For effective biological control of M. persicae using A. aphidimyza and A. gifuensis, we recommend releasing A. aphidimyza first to mitigate intraguild predation and enhance the overall success of the pest control program.

The lncRNA LINC01605 promotes the progression of pancreatic ductal adenocarcinoma by activating the mTOR signaling pathway.

BACKGROUND: This study investigated the molecular mechanism of long intergenic non-protein coding RNA 1605 (LINC01605) in the process of tumor growth and liver metastasis of pancreatic ductal adenocarcinoma (PDAC). METHODS: LINC01605 was filtered out with specificity through TCGA datasets (related to DFS) and our RNA-sequencing data of PDAC tissue samples from Renji Hospital. The expression level and clinical relevance of LINC01605 were then verified in clinical cohorts and samples by immunohistochemical staining assay and survival analysis. Loss- and gain-of-function experiments were performed to estimate the regulatory effects of LINC01605 in vitro. RNA-seq of LINC01605-knockdown PDAC cells and subsequent inhibitor-based cellular function, western blotting, immunofluorescence and rescue experiments were conducted to explore the mechanisms by which LINC01605 regulates the behaviors of PDAC tumor cells. Subcutaneous xenograft models and intrasplenic liver metastasis models were employed to study its role in PDAC tumor growth and liver metastasis in vivo. RESULTS: LINC01605 expression is upregulated in both PDAC primary tumor and liver metastasis tissues and correlates with poor clinical prognosis. Loss and gain of function experiments in cells demonstrated that LINC01605 promotes the proliferation and migration of PDAC cells in vitro. In subsequent verification experiments, we found that LINC01605 contributes to PDAC progression through cholesterol metabolism regulation in a LIN28B-interacting manner by activating the mTOR signaling pathway. Furthermore, the animal models showed that LINC01605 facilitates the proliferation and metastatic invasion of PDAC cells in vivo. CONCLUSIONS: Our results indicate that the upregulated lncRNA LINC01605 promotes PDAC tumor cell proliferation and migration by regulating cholesterol metabolism via activation of the mTOR signaling pathway in a LIN28B-interacting manner. These findings provide new insight into the role of LINC01605 in PDAC tumor growth and liver metastasis as well as its value for clinical approaches as a metabolic therapeutic target in PDAC.

Exploring the Origins and Evolution of Oxygenic and Anoxygenic Photosynthesis in Deeply Branched Cyanobacteriota.

Cyanobacteriota, the sole prokaryotes capable of oxygenic photosynthesis (OxyP), occupy a unique and pivotal role in Earth's history. While the notion that OxyP may have originated from Cyanobacteriota is widely accepted, its early evolution remains elusive. Here, by using both metagenomics and metatranscriptomics, we explore 36 metagenome-assembled genomes from hot spring ecosystems, belonging to two deep-branching cyanobacterial orders: Thermostichales and Gloeomargaritales. Functional investigation reveals that Thermostichales encode the crucial thylakoid membrane biogenesis protein, vesicle-inducing protein in plastids 1 (Vipp1). Based on the phylogenetic results, we infer that the evolution of the thylakoid membrane predates the divergence of Thermostichales from other cyanobacterial groups and that Thermostichales may be the most ancient lineage known to date to have inherited this feature from their common ancestor. Apart from OxyP, both lineages are potentially capable of sulfide-driven AnoxyP by linking sulfide oxidation to the photosynthetic electron transport chain. Unexpectedly, this AnoxyP capacity appears to be an acquired feature, as the key gene sqr was horizontally transferred from later-evolved cyanobacterial lineages. The presence of two D1 protein variants in Thermostichales suggests the functional flexibility of photosystems, ensuring their survival in fluctuating redox environments. Furthermore, all MAGs feature streamlined phycobilisomes with a preference for capturing longer-wavelength light, implying a unique evolutionary trajectory. Collectively, these results reveal the photosynthetic flexibility in these early-diverging cyanobacterial lineages, shedding new light on the early evolution of Cyanobacteriota and their photosynthetic processes.

Phylogenomic analyses and comparative genomic studies of Thermus strains isolated from Tengchong and Tibet Hot Springs, China.

Genus Thermus is the main focus of researcher among the thermophiles. Members of this genus are the inhabitants of both natural and artificial thermal environments. We performed phylogenomic analyses and comparative genomic studies to unravel the genomic diversity among the strains belonging to the genus Thermus in geographically different thermal springs. Sixteen Thermus strains were isolated and sequenced from hot springs, Qucai hot springs in Tibet and Tengchong hot springs in Yunnan, China. 16S rRNA gene based phylogeny and phylogenomic analyses based on concatenated set of 971 Orthologous Protein Families (supermatrix and gene content methods) revealed a mixed distribution of the Thermus strains. Whole genome based phylogenetic analysis showed, all 16 Thermus strains belong to five species; Thermus oshimai (YIM QC-2-109, YIM 1640, YIM 1627, 77359, 77923, 77838), Thermus antranikianii (YIM 73052, 77412, 77311, 71206), Thermus brokianus (YIM 73518, 71318, 72351), Thermus hydrothermalis (YIM 730264 and 77927) and one potential novel species 77420 forming clade with Thermus thalpophilus SYSU G00506T. Although the genomes of different strains of Thermus of same species were highly similar in their metabolic pathways, but subtle differences were found. CRISPR loci were detected through genome-wide screening, which showed that Thermus isolates from two different thermal locations had well developed defense system against viruses and adopt similar strategy for survival. Additionally, comparative genome analysis screened competence loci across all the Thermus genomes which could be helpful to acquire DNA from environment. In the present study it was found that Thermus isolates use two mechanism of incomplete denitrification pathway, some Thermus strains produces nitric oxide while others nitrious oxide (dinitrogen oxide), which show the heterotrophic lifestyle of Thermus genus. All isolated organisms encoded complete pathways for glycolysis, tricarboxylic acid and pentose phosphate. Calvin Benson Bassham cycle genes were identified in genomes of T. oshimai and T. antranikianii strains, while genomes of all T. brokianus strains and organism 77420 were lacking. Arsenic, cadmium and cobalt-zinc-cadmium resistant genes were detected in genomes of all sequenced Thermus strains. Strains 77,420, 77,311, 73,518, 77,412 and 72,351 genomes were found harboring genes for siderophores production. Sox gene clusters were identified in all sequenced genomes, except strain YIM 730264, suggesting a mode of chemolithotrophy. Through the comparative genomic analysis, we also identified 77420 as the genome type species and its validity as novel organism was confirmed by whole genome sequences comparison. Although isolate 77420 had 99.0% 16S rRNA gene sequence similarity with T. thalpophilus SYSU G00506T but based on ANI 95.86% (Jspecies) and digital DDH 68.80% (GGDC) values differentiate it as a potential novel species. Similarly, in the phylogenomic tree, the novel isolate 77,420 forming a separate branch with their closest reference type strain T. thalpophilus SYSU G00506T.

Multi-omics insights into the function and evolution of sodium benzoate biodegradation pathway in Benzoatithermus flavus gen. nov., sp. nov. from hot spring.

Biodegradation stands as an eco-friendly and effective approach for organic contaminant remediation. However, research on microorganisms degrading sodium benzoate contaminants in extreme environments remains limited. In this study, we report to display the isolation of a novel hot spring enriched cultures with sodium benzoate (400 mg/L) as the sole carbon source. The results revealed that the phylum Pseudomonadota was the potential sodium benzoate degrader and a novel genus within the family Geminicoccaceae of this phylum. The isolated strain was named Benzoatithermus flavus SYSU G07066T and was isolated from HNT-2 hot spring samples. Genomic analysis revealed that SYSU G07066T carried benABC genes and physiological experiments indicated the ability to utilize sodium benzoate as a sole carbon source for growth, which was further confirmed by transcriptomic data with expression of benABC. Phylogenetic analysis suggested that Horizontal Gene Transfer (HGT) plays a significant role in acquiring sodium benzoate degradation capability among prokaryotes, and SYSU G07066T might have acquired benABC genes through HGT from the family Acetobacteraceae. The discovery of the first microorganism with sodium benzoate degradation function from a hot spring enhances our understanding of the diverse functions within the family Geminicoccaceae. This study unearths the first novel genus capable of efficiently degrading sodium benzoate and its evolution history at high temperatures, holding promising industrial applications, and provides a new perspective for further exploring the application potential of hot spring "microbial dark matter".