The hemostatic activity and Mechanistic roles of glucosyloxybenzyl 2-isobutylmalate extract (BSCE) from Bletilla striata (Thunb.) Rchb.f. in Inhibiting pulmonary hemorrhage.

Background: Hemorrhagic events cause numerous deaths annually worldwide, highlighting the urgent need for effective hemostatic drugs. The glucosyloxybenzyl 2-isobutylmalates Control Extract (BSCE) from the orchid plant Bletilla striata (Thunb.) Rchb.f. has demonstrated significant hemostatic activity in both in vitro and in vivo studies. However, the effect and mechanism of BSCE on non-traumatic bleeding remain unclear. Methods: Pulmonary hemorrhage was induced in 40 Sprague-Dawley rats by administering Zingiber officinale Roscoe. for 14 days. These rats were then randomly divided into five groups: model (Mod), positive control (YNBY), and BSCE low, medium, and high-dose groups. An additional 8 rats served as the control group (Con). The BSCE groups received different doses of BSCE for 10 days, while the YNBY group received Yunnan Baiyao suspension. The effects on body weight, food and water intake, red blood cell count (RBC), hemoglobin concentration (HGB), lung tissue pathology, platelet count, coagulation parameters, and fibrinolytic system markers were evaluated. Network pharmacology and molecular docking analyses were also conducted to identify potential targets and pathways involved in BSCE's effects. Results: BSCE treatment significantly improved body weight, food intake, and water consumption in rats with pulmonary hemorrhage. RBC and HGB levels increased significantly in the BSCE medium and high-dose groups compared to the Mod group (P < 0.05). Pathological examination revealed that BSCE reduced lung tissue hemorrhage and inflammation, with improvements in alveolar structure. BSCE also positively affected platelet count, thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (FIB) levels, and fibrinolytic markers (D-dimer, PAI-1, and t-PA). Network pharmacology and molecular docking identified key targets such as MMPs, CASPs, and pathways including IL-17 and TNF signaling, suggesting BSCE's involvement in hemostasis and anti-inflammatory processes. Conclusions: BSCE exhibits significant hemostatic and protective effects on Z.officinale-induced pulmonary hemorrhage in rats by improving hematological parameters, reducing lung tissue damage, and modulating the coagulation and fibrinolytic systems. The study provides evidence supporting the potential of BSCE as a therapeutic agent for hemorrhagic diseases, with its efficacy linked to multi-target and multi-pathway interactions.

Phloridzin prevents diabetic cardiomyopathy by reducing inflammation and oxidative stress.

Oxidative stress and inflammation significantly contribute to the pathogenesis of diabetic cardiomyopathy (DCM). Persistent inflammatory stimuli drive the progression of myocardial fibrosis and impaired cardiac function. Phloridzin (Phl), a natural compound, demonstrates both anti-inflammatory and antioxidant properties. Nevertheless, its therapeutic potential and underlying mechanisms in DCM remain unclear. This study aimed to elucidate the mechanisms through which Phl inhibited myocardial fibrosis and exerted its antioxidative effects. The impact of Phl on DCM was evaluated using a high-fat/high-sugar diet combined with streptozotocin to induce an animal model and an in vitro H9C2 cell model stimulated by high glucose (HG). Untargeted metabolomics identified potential mechanisms underlying myocardial fibrosis. Phl treatment significantly enhanced left ventricular ejection fraction (EF%) and shortening fraction (FS%), while reducing myocardial injury markers, such as lactate dehydrogenase and creatine phosphokinase-MB, and suppressing myocardial collagen fiber accumulation. Simultaneously, Phl attenuated myocardial inflammation via inhibition of MyD88/NF-κB signaling, modulated the Nrf2/GPX4 axis to counter oxidative stress, and mitigated ferroptosis. In vitro, Phl inhibited high glucose-induced myocardial hypertrophy and fibrosis in H9C2 cells, while also repressing NF-κB activation in cardiomyocytes. Metabolomic profiling revealed that Phl ameliorated DCM through modulation of glycerophospholipid metabolic pathways, linking these metabolic shifts to enhanced antioxidant capacity, thereby reflecting its ability to reduce oxidative stress in the myocardium. Collectively, Phl provides cardioprotective effects by alleviating inflammation and oxidative damage.

The value of tissue quantitative diffusion analysis of ultrasound elastography in the diagnosis of early-stage chronic kidney disease.

PURPOSE: To explore the value of tissue quantitative diffusion analysis of ultrasound elastography in the diagnosis of early-stage chronic kidney disease (CKD). METHODS: The observation group comprised 54 patients with early-stage CKD treated at Fuzhou No 7 Hospital, and the control group consisted of 40 healthy individuals who underwent physical examinations at the same hospital. The renal parenchyma of the participants were examined using ultrasonography, color Doppler ultrasonography, and tissue quantitative diffusion analysis of ultrasound elastography. Renal dimensions (diameter, thickness, and renal parenchyma thickness), interlobar artery blood flow parameters, and 11 elastic characteristic values were analyzed and compared between the two groups. The area under the receiver-operating characteristic (ROC) curve, cut-off values, sensitivity, and specificity were calculated using the ROC curve analysis. RESULTS: There were no significant differences in the blood flow parameters of the interlobar artery and the dimensions of renal meridians between the two groups. In the observation group, the mean (MEAN) decreased, while the blue area ratio and skewness, increased, compared to the control group (p < 0.05). In addition, the ROC curve revealed that the blue area ratio, MEAN, and skewness had significant diagnostic value (the area under the curve > 0.7). Notably, the best cut-off value of the MEAN was found to be 106, indicating that a MEAN value less than 106 represented early-stage CKD. Also, this cutoff value had a sensitivity of 80% and a specificity of 81%. CONCLUSION: Tissue quantitative diffusion analysis of ultrasound elastography can quantitatively evaluate renal parenchymal damage in early-stage CKD using quantitative diffusion parameters, with the MEAN parameter, having a cutoff of 106, being particularly effective. This parameter and cutoff value offer a valuable tool for the early detection and diagnosis of CKD, potentially improving patient outcomes through earlier intervention. CLINICAL TRIAL NUMBER: Not applicable.

Metarhiziumpuerense (Hypocreales, Clavicipitaceae): a new species from Yunnan, south-western China.

Background: As a genus within the Clavicipitaceae, Metarhizium exhibits rich morphological and ecological diversity, with a wide distribution and a variety of hosts. Currently, sixty-eight species of Metarhizium have been described. New information: A new species of Metarhizium, M.puerense (Hong Yu bis), was described in Pu'er City, Yunnan Province, south-western China. Based on morphological characteristics and multilocus phylogenetic analyses, Metarhiziumpuerense was confirmed to be phylogenetically related to M.album, but was clearly separated and formed a distinct branch. In contrast, the host of Metarhiziumalbum was plants and leafhoppers and that lepidopteran larvae were the host of M.puerense. The diagnostic features of M.puerense were solitary to multiple stromata and smooth-walled, cylindrical with rounded apices conidia.

Crosstalk among plant hormone regulates the root development.

The plant root absorbs water and nutrients, anchors the plant in the soil, and promotes plant development. Root is developed from root apical meristem (RAM), which is formed during embryo stage and is maintained by dividing stem cells. Plant hormones have a predominant role in RAM maintenance. This review evaluates the functional crosstalk among three major hormones (auxin, cytokinin, and brassinolide) in RAM development in Arabidopsis, integrating a variety of experimental data into a regulatory network and revealing multiple layers of complexity in the crosstalk among these three hormones. We also discuss possible directions for future research on the roles of hormones in regulating RAM development and maintenance.

Two new phenolic glycosides from the roots of Iris domestica (L.) Goldblatt & Mabb and their cytotoxic activity.

Two new phenolic glycosides, Diplostephioside D (1) and Diplostephioside E (2) together with ten known phenols (3-12) were isolated from the dried roots of Iris domestica (L.) Goldblatt & Mabb. Among them, compounds 4-9 have not been reported previously from the family Iridaceae. The chemical structures were elucidated based on extensive spectroscopic experiments, including 1D and 2D NMR as well as HR-ESI-MS, and comparison with those reported in the literature. All of the isolated compounds were evaluated for their cytotoxic activity against HeLa cells. Compounds 1, 2, 4, 8 and 12 showed cytotoxic activities with IC50 values ranging from 13.52 ± 1.52 to 53.33 ± 1.40 µM.

Ultrasonographic assessment of the risk of free-floating thrombus detachment in the lower extremity deep veins in patients with fracture.

OBJECTIVE: To explore the ultrasonographic features and influencing factors of free-floating thrombus (FFT) detachment in the lower extremity deep veins (LEDVs) of patients with fractures. METHODS: Clinical data of patients diagnosed with FFT in the LEDVs and implanted with an inferior vena cava filter (IVCF) in our hospital between July 2021 and August 2023 were retrospectively analysed. The patients were divided into the thrombus detachment group (the experimental group, n = 92) and the non-thrombus detachment group (the control group, n = 103) based on the presence of detached thrombus in the IVCF. The effects of thrombus echogenicity, floating degree, thrombus location, thrombin time, D-dimer and fibrinogen on thrombus shedding were analysed. The nomogram method was used to establish the model and predict the probability of delayed postoperative recovery. RESULTS: The proportions of patients with extremely hypoechoic thrombus and medium and high floating degrees increased in the experimental group compared with those in the control group, and the differences between the two groups were statistically significant (P < 0.05). Extremely hypoechoic thrombus (P = 0.021, 95 % CI: 1.109-13.748) and high (P = 0.001, 95 % CI: 3.854-28.573) and medium floating degrees (P = 0.004, 95 % CI: 1.792-13.453) were risk factors for deep veins FFT (DV FFT) detachment. The results of receiver operating characteristic curve analysis showed that the area under the curve of the model was 0.893, with a 95 % CI of 0.856-0.937, indicating a high prediction accuracy. CONCLUSION: Ultrasonographic parameters, including thrombus echogenicity and floating degree, are valuable in predicting DV FFT detachment in patients with traumatic fractures, providing references for IVCF implantation.

Synthesis, characterization and anticancer, antibacterial activities of pentacyclic triterpenoid glycoside derivatives.

As a kind of glycoside, pentacyclic triterpenoid saponins have good biological activities, such as anticancer, antibacterial, antiviral and hypoglycemic effects [1]. In this paper, twenty-four pentacyclic triterpenoid derivatives, including twelve monosaccharide derivatives, were designed and synthesized. The anticancer effect and antibacterial activities of all compounds were evaluated. It is noteworthy that compound UA-2b has the strongest inhibitory effect on the growth of A549, Hela and HepG2 cancer cells (IC50 = 5.37 ± 0.22 µM, 5.82 ± 0.25 µM and 5.47 ± 0.06 µM, respectively). Compounds OA-2b, OA-6a, OA-6b, UA-2b and UA-6a have the best activity against Escherichia coli 1924 (MIC = 16 µg/ml).

Systemic contact dermatitis in a family: Case report.

BACKGROUND: Systemic contact dermatitis (SCD) is an allergic inflammatory skin disease. We report that 3 family members developed SCD after exposing to laundry detergent containing benzalkonium chloride, which is rare. SCD caused by benzalkonium chloride has been reported. However, Similar symptoms in the whole family caused by it have not been reported yet. In our case, a 36-year-old man was diagnosed as SCD, and his symptoms had not controlled after 7 days treatment, until he stopped dressing the clothes washed by the laundry detergent containing benzalkonium chloride. It was interesting that both his wife and the daughter developed SCD successively, and they have not exposed to any haptens besides the benzalkonium chloride in the laundry detergent. METHODS: Dermoscopic examination showed bright-red background, focal branching vessels and white scales. HE staining from the lesion revealed hyperkeratosis and parakeratosis, focal subcorneal microabscess, ocal hyperkeratosis, koilocyte in the epidermis, and erythrocyte extravasation, fibroplasia, hyaline degeneration and scattered aggregates of lymphocytes in the dermis. Then path test was performed 1 month after recovery with benzalkonium chloride 0.05% and 0.1% in petrolatum. RESULTS: Stop the laundry detergent containing benzalkonium chloride. The symptoms had controlled after they stopped the laundry detergent containing benzalkonium chloride. CONCLUSION: The case highlights that benzalkonium chloride with very low concentration and repeated exposure may be an active agent of SCD. It is of the utmost importance to pay close attention to patients presenting with similar symptoms within the family. A thorough examination of the medical history is essential to determine the underlying cause.

LncRNA018392 promotes the proliferation of Liaoning cashmere goat skin fibroblasts by upregulating CSF1R through binding to SPI1.

BACKGROUND: Liaoning cashmere goat is recognized as a valuable genetic resource breed, with restrictions on genetic outflow in China. Hair follicle development in the cashmere goat is influenced by melatonin and long non-coding RNAs (lncRNAs). However, the role of lncRNAs in facilitating melatonin-promoted cashmere growth remains poorly understood. Previous studies have identified a new lncRNA, lncRNA018392, which is involved in the melatonin-promoted proliferation of cashmere skin fibroblasts. METHOD: Flow cytometry and CCK-8 assays confirmed that silencing lncRNA018392 negates the effects of melatonin on cell proliferation, and that proliferation was reduced when the gene CSF1R, located near lncRNA018392, was inhibited. Further investigation using a dual-luciferase reporter assay showed that lncRNA018392 could positively regulate the promoter of CSF1R. RESULTS: Results from RNA-binding protein immunoprecipitation (RIP) and chromatin immunoprecipitation sequencing (ChIP-Seq) revealed that lncRNA018392 interacts with the transcription factor SPI1, with CSF1R being a downstream target gene regulated by SPI1. This interaction was confirmed by ChIP-PCR, which demonstrated SPI1's binding to CSF1R. CONCLUSIONS: This study found that the melatonin-responsive lncRNA018392 accelerates the cell cycle and promotes cell proliferation by recruiting SPI1 to upregulate the expression of the neighboring gene CSF1R. These findings provide a theoretical foundation for elucidating the molecular mechanisms of cashmere growth and for the molecular breeding of cashmere goats.

Cycloaddition and Skeleton Rearrangement of Heterocyclic Ketene Aminals (HKAs) with 1-Diazonaphthalen-2(1H)-ones for the Synthesis of Functionalized 1,2,3-Triazoles.

We developed a protocol for the synthesis of highly functionalized 5,6-dihydro-imidazo[1,2-c][1,2,3]triazole derivatives 4-5 (DHITs) from 1-diazonaphthalen-2(1H)-one derivatives with heterocyclic ketene aminals (HKAs). This strategy involved cycloaddition and skeletal rearrangement entailing the heating of a mixture of substrates 1 with HKAs 2-3 and THF without any catalyst. As a result, a series of DHITs 4-5 were produced by cleaving one bond (1 C═N bond) and forming three bonds (1 N-N and 2 C-N bonds) in a single step. This protocol achieved the dual functionalization of diazo building blocks involving both the aromatic nitrogen alkylation reaction to form an ArC-N bond without any metal catalyst and the intermolecular cycloaddition of the N═N bond. These strategies can be used to synthesize functionalized DHITs for combinatorial and parallel syntheses via one-pot reactions without any catalyst.

Clinical outcomes and prognostic factors of parameningeal rhabdomyosarcoma in children and adolescents: results of two consecutive protocols.

Background: Parameningeal rhabdomyosarcoma (PM-RMS) accounts for about 20% of all rhabdomyosarcoma (RMS) cases. At present, most research on PM-RMS has been conducted in Europe and the United States of America, and research in China has been very limited. This study sought to analyze the clinical outcomes and prognostic factors of PM-RMS in children and adolescents from two consecutive protocols at Beijing Children's Hospital (BCH). Methods: A total of 80 patients aged up to 18 years with previously untreated PM-RMS who had received treatment under two consecutive protocols [i.e., either the BCH-RMS-2006 protocol or the Chinese Children Cancer Group (CCCG)-RMS-2016 protocol] were included in the statistical analysis. The Kaplan-Meier method was used for the survival analysis, and Cox regression was used for the univariate and multivariate analyses. Results: Of the 80 patients enrolled in the study, 69 (86.2%) had meningeal invasion (MI). Of these 69 MI patients, 18 (22.5%) had cranial nerve palsy (CNP), 64 (80.0%) had cranial base bone erosion (CBBE), 25 (31.3%) had intracranial extension (ICE), and 2 (2.5%) had positive cerebrospinal fluid (CSF) tumor cells. The median follow-up time was 20.5 months (range, 5-100 months). The 5-year overall survival (OS) and progression-free survival (PFS) rates for the entire cohort were 51.7% and 45.6%, respectively. The 5-year OS rates of the patients who received the BCH-RMS-2006 protocol (18/80, 22.5%) and the CCCG-RMS-2016 protocol (62/80, 77.5%) were 33.3% and 57.0%, respectively (P<0.05), while the PFS rates of these patients were 22.2% and 53.6%, respectively (P<0.05). In relation to the PM-RMS patients with MI, the 5-year OS rates were 21.4% and 52.7%, and the 5-year PFS rates were 14.3% and 51.1% for the patients who received the old and new regimens, respectively (P<0.05). The extent of surgical resection had no significant effect on survival. The multivariate analysis showed that the coexistence of CBBE and ICE, no radiotherapy, a poor response to induction chemotherapy, and the BCH-RMS-2006 protocol were risk factors affecting PFS and OS. Conclusions: Of the patients examined in this study, those with PM-RMS with CBBE accompanied by ICE had the worst prognosis. The patients with MI benefited from intensive chemotherapy combined with radiation therapy, but the effect of surgery was very limited.

Construction of artificial microbial consortia for efficient degradation of chicken feathers and optimization of degradation conditions.

Microbes within a consortium exhibit a synergistic interaction, enhancing their collective capacity to perform functions more effectively than a single species, especially in the degradation of keratin-rich substrates. To achieve a more stable and efficient breakdown of chicken feathers, a comprehensive screening of over 9,000 microbial strains was undertaken. This meticulous selection process identified strains with the capability to degrade keratin effectively. Subsequently, antagonistic tests were conducted to isolate strains of fungi and bacteria that were non-antagonistic, which were then used to form the artificial microbial consortia. The optimal fermentation conditions for the keratinophilic microbial consortia were determined through the optimization of response surface methodology. The results revealed that 11 microbial strains-comprising of 4 fungi and 7 bacteria-were particularly proficient in degrading chicken feathers. The artificially constructed microbial consortia (AMC) comprised two bacterial strains and one fungal strain. The optimal conditions for feathers degradation were identified as a 10 g/L concentration of chicken feathers, a 2.6% microbial inoculation volume and a fermentation fluid pH of 9. Under these conditions, the degradation rate for chicken feathers reached a significant 74.02%, representing an 11.45% increase over the pre-optimization rate. The AMC developed in this study demonstrates the potential for efficient and economical process of livestock and poultry feathers. It provides innovative insights and a theoretical foundation for tackling the challenging degradation of keratin-rich materials. Furthermore, this research lays the groundwork for the separation and purification of keratins, as well as the development of novel proteases, which could have profound implications for a range of applications.

Radiogenomic analysis for predicting lymph node metastasis and molecular annotation of radiomic features in pancreatic cancer.

BACKGROUND: To provide a preoperative prediction model for lymph node metastasis in pancreatic cancer patients and provide molecular information of key radiomic features. METHODS: Two cohorts comprising 151 and 54 pancreatic cancer patients were included in the analysis. Radiomic features from the tumor region of interests were extracted by using PyRadiomics software. We used a framework that incorporated 10 machine learning algorithms and generated 77 combinations to construct radiomics-based models for lymph node metastasis prediction. Weighted gene coexpression network analysis (WGCNA) was subsequently performed to determine the relationships between gene expression levels and radiomic features. Molecular pathways enrichment analysis was performed to uncover the underlying molecular features. RESULTS: Patients in the in-house cohort (mean age, 61.3 years ± 9.6 [SD]; 91 men [60%]) were separated into training (n = 105, 70%) and validation (n = 46, 30%) cohorts. A total of 1,239 features were extracted and subjected to machine learning algorithms. The 77 radiomic models showed moderate performance for predicting lymph node metastasis, and the combination of the StepGBM and Enet algorithms had the best performance in the training (AUC = 0.84, 95% CI = 0.77-0.91) and validation (AUC = 0.85, 95% CI = 0.73-0.98) cohorts. We determined that 15 features were core variables for lymph node metastasis. Proliferation-related processes may respond to the main molecular alterations underlying these features. CONCLUSIONS: Machine learning-based radiomics could predict the status of lymph node metastasis in pancreatic cancer, which is associated with proliferation-related alterations.

Value of catecholamine levels in the differential diagnosis of vasovagal syncope and psychogenic pseudosyncope in children.

Background and purpose: Vasovagal syncope (VVS) and psychogenic pseudosyncope (PPS) can be difficult to distinguish, given their similar clinical presentations. This study was conducted to explore the clinical value of catecholamine levels in the differential diagnosis of VVS and PPS in children. Methods: This retrospective case-control study was conducted with data from children with VVS and PPS who underwent head-up tilt tests (HUTTs) at the Children's Hospital of Hebei Province between March 2021 and March 2023. The data collected were baseline clinical characteristics, HUTT results, serum catecholamine levels in the supine and upright positions, and 24 h urinary catecholamine concentrations. These variables were compared between the VVS and PPS groups. Results: From 328 potentially eligible cases, 54 (16.46%) cases of VVS and 24 (7.32%) cases of PPS were included in the analysis. No significant difference in age, sex, body mass index, or syncope frequency was observed between the VVS and PPS groups. The main predisposing factors for syncope were body position changes in the VSS group (83.33%) and emotional changes in the PPS group (41.67%). The episode duration was significantly shorter in the VSS group than in the PPS group (4.01 ± 1.20 vs. 24.06 ± 5.56 min, p < 0.05). The recovery time was also shorter in the VVS group than in the PPS group (1.91 ± 0.85 vs. 8.62 ± 2.55 min, p < 0.05). Relative to patients with PPS, those with VVS had significantly higher serum epinephrine (EP) levels in the upright position [199.35 (102.88, 575.00) vs. 147.40 (103.55, 227.25), p < 0.05] and lower serum epinephrine levels in the supine position [72.70 (42.92, 122.85) vs. 114.50 (66.57, 227.50), p < 0.05]. Conclusions: Serum EP levels have potential value in the differential diagnosis of VVS and PPS.

Morphological and Phylogenetic Analyses Reveal Three New Species of Entomopathogenic Fungi Belonging to Clavicipitaceae (Hypocreales, Ascomycota).

This study aims to report three new species of Conoideocrella and Moelleriella from Yunnan Province, Southwestern China. Species of Conoideocrella and Moelleriella parasitize scale insects (Coccidae and Lecaniidae, Hemiptera) and whiteflies (Aleyrodidae, Hemiptera). Based on the phylogenetic analyses of the three-gene nrLSU, tef-1α, and rpb1, it showed one new record species (Conoideocrella tenuis) and one new species (Conoideocrella fenshuilingensis sp. nov.) in the genus Conoideocrella, and two new species, i.e., Moelleriella longzhuensis sp. nov. and Moelleriella jinuoana sp. nov. in the genus Moelleriella. The three new species were each clustered into separate clades that distinguished themselves from one another. All of them were distinguishable from their allied species based on their morphology. Morphological descriptions, illustrations, and comparisons of the allied taxa of the four species are provided in the present paper. In addition, calculations of intraspecific and interspecific genetic distances were performed for Moelleriella and Conoideocrella.

MARCH1 and MARCH2 inhibit pseudorabies virus replication by trapping the viral cell-to-cell fusion complex in trans-Golgi network.

The membrane-associated RING-CH (MARCH) family of proteins are members of the E3 ubiquitin ligase family and are essential for a variety of biological functions. Currently, MARCH proteins are discovered to execute antiviral functions by directly triggering viral protein degradation or blocking the furin cleavage of viral class I fusion proteins. Here, we report a novel antiviral mechanism of MARCH1 and MARCH2 (MARCH1/2) in the replication of Pseudorabies virus (PRV), a member of the Herpesviridae family. We discovered MARCH1/2 restrict PRV replication at the cell-to-cell fusion step. Furthermore, MARCH1/2 block gB cleavage, and this is dependent on their E3 ligase activity. Interestingly, the blocking of gB cleavage by MARCH1/2 does not contribute to their antiviral activity in vitro. We discovered that MARCH1/2 are associated with the cell-to-cell fusion complex of gB, gD, gH, and gL and trap these viral proteins in the trans-Golgi network (TGN) rather than degrading them. Overall, we conclude that MARCH1/2 inhibit PRV by trapping the viral cell-to-cell fusion complex in TGN.

Biosynthesis and Assembly Logic of Fungal Hybrid Terpenoid Natural Products.

In recent decades, fungi have emerged as significant sources of diverse hybrid terpenoid natural products, and their biosynthetic pathways are increasingly unveiled. This review mainly focuses on elucidating the various strategies underlying the biosynthesis and assembly logic of these compounds. These pathways combine terpenoid moieties with diverse building blocks including polyketides, nonribosomal peptides, amino acids, p-hydroxybenzoic acid, saccharides, and adenine, resulting in the formation of plenty of hybrid terpenoid natural products via C-O, C-C, or C-N bond linkages. Subsequent tailoring steps, such as oxidation, cyclization, and rearrangement, further enhance the biological diversity and structural complexity of these hybrid terpenoid natural products. Understanding these biosynthetic mechanisms holds promise for the discovery of novel hybrid terpenoid natural products from fungi, which will promote the development of potential drug candidates in the future.

MARCH8 inhibits pseudorabies virus replication by trapping the viral cell-to-cell fusion complex in the trans-Golgi network.

The membrane-associated RING-CH 8 protein (MARCH8), a member of the E3 ubiquitin ligase family, has broad-spectrum antiviral activity. However, some viruses hijack MARCH8 to promote virus replication, highlighting its dual role in the viral lifecycle. Most studies on MARCH8 have focused on RNA viruses, leaving its role in DNA viruses largely unexplored. Pseudorabies virus (PRV) is a large DNA virus that poses a potential threat to humans. In this study, we found that MARCH8 inhibited PRV replication at the cell-to-cell fusion stage. Interestingly, our findings proved that MARCH8 blocks gB cleavage by recruiting furin but this activity does not inhibit viral infection in vitro. Furthermore, we confirmed that MARCH8 inhibits cell-to-cell fusion independent of its E3 ubiquitin ligase activity but dependent on the interaction with the cell-to-cell fusion complex (gB, gD, gH, and gL). Finally, we discovered that the distribution of the cell-to-cell fusion complex is significantly altered and trapped within the trans-Golgi network. Overall, our results indicate that human MARCH8 acts as a potent antiviral host factor against PRV via trapping the cell-to-cell fusion complex in the trans-Golgi network.

Exploring the oncogenic potential of circSOD2 in clear cell renal cell carcinoma: a novel positive feedback loop.

BACKGROUND: Existing studies have found that circular RNAs (circRNAs) act as sponges for micro RNAs (miRNAs) to control downstream genes. However, the specific functionalities and mechanisms of circRNAs in human clear cell renal cell carcinoma (ccRCC) have yet to be thoroughly investigated. METHODS: Patient cohorts from online databases were used to screen candidate circRNAs, while another cohort from our hospital was obtained for validation. CircSOD2 was identified as a potential oncogenic target, and its relevant characteristics were investigated during ccRCC progression through various assays. A positive feedback loop containing downstream miRNA and its target gene were identified using bioinformatics and validated by luciferase reporter assays, RNA pull-down, and high-throughput sequencing. RESULTS: CircSOD2 expression was elevated in tumor samples and significantly correlated with overall survival (OS) and the tumor stage of ccRCC patients, which appeared in the enhanced proliferation, invasion, and migration of tumor cells. Through competitive binding to circSOD2, miR-532-3p can promote the expression of PAX5 and the progression of ccRCC, and such regulation can be salvaged by miR-532-3p inhibitor. CONCLUSION: A novel positive feedback loop, PAX5/circSOD2/miR-532-3p/PAX5 was identified in the study, indicating that the loop may play an important role in the diagnosis and prognostic prediction in ccRCC patients.