Role of tri18 gene in Epiroridin E production and toxin resistance mechanisms in Paramyrothecium roridum.

Type D trichothecene toxins represent a class of macrocyclic trichothecene toxins with significant cytotoxicities towards human and crops. These toxins can also be used as anti-tumor compounds by the combination of antibody-drug conjugate. Therefore, it is urgent to investigate the biosynthetic routine of type D trichothecene toxins and explore type D trichothecene toxin-resistant genes, in order to ameliorate the hazard of trichothecene toxins and to facilitate the heterologous expression of toxin-biosynthetic cluster. In this study, tri18 gene was firstly knocked out in Paramyrothecium roridum, leading to the complete absence of type D trichothecene toxin epiroridin E, which can be restored by the complement of tri18 gene. Additionally, the knockout of tri18 gene led to a significant reduction in the pathogenicity of P. roridum towards pumpkin. Meanwhile, the enzymatic properties of Tri18 protein towards trichothecene deoxynivalenol (DON) toxin were also characterized. Moreover, tri3 and tri17KR with broad spectrum toxin-resistance function within the tri cluster were initially discovered through heterologous expression in toxin-sensitive Saccharomyces cerevisiae. And this study provides innovative type D trichothecene toxin resistant enzymes, which can provides green platform for the production of type D trichothecene toxins, thus promoting the application of these toxins in biomedical field.

LncRNA OIP5-AS1 regulates ferroptosis and mitochondrial dysfunction-mediated apoptosis in spinal cord injury by targeting the miR-128-3p/Nrf2 axis.

Background: Ferroptosis is an important way of neuronal cell death in acute phase and participates in the inflammatory cascade after spinal cord injury (SCI). It is reported that microRNA (miRNA) and long non-coding RNA (lncRNA) are key mediators in the regulation of ferroptosis. This study will explore the inhibitory effect of LncRNA OIP5-AS1 on ferroptosis and mitochondrial dysfunction-mediated apoptosis in SCI. Methods: The ferric ammonium citrate (FAC)-induced cell model and the SCI rat model were established. The expression of LncRNA OIP5-AS1, miR-128-3p and Nrf2 were transfected to evaluated the effect on the viability and apoptosis of FAC-induced cell. The interaction between LncRNA OIP5-AS1 and miR-128-3p or miR-128-3p and Nrf2 were analyzed. In addition, expressions of markers related to ferroptosis and mitochondrial dysfunction were analyzed in vitro and in vivo. Histopathologic slide staining was used to analyze spinal cord injury in vivo. Results: LncRNA OIP5-AS1 expression was abnormally down-regulated in FAC-induced SCI cell model and SCI rats. The LncRNA OIP5-AS1 deficiency induced decreased Nrf2 level by less sponging miR-128-3p, thus, aggravating spinal cord injury and inducing more apoptosis, ferroptosis and mitochondrial dysfunction in neural stem cells with SCI. However, overexpression of LncRNA OIP5-AS1 inhibited apoptosis, ferroptosis and mitochondrial dysfunction, thus effectively ameliorating spinal cord injury. Conclusion: This finding demonstrates that LncRNA OIP5-AS1 overexpression could enhance the recovery of spinal cord injury by regulating the miR-128-3p/Nrf2 axis.

Perpendicular crossing chains enable high mobility in a noncrystalline conjugated polymer.

The nature of interchain π-system contacts, and their relationship to hole transport, are elucidated for the high-mobility, noncrystalline conjugated polymer C16-IDTBT by the application of scanning tunneling microscopy, molecular dynamics, and quantum chemical calculations. The microstructure is shown to favor an unusual packing motif in which paired chains cross-over one another at near-perpendicular angles. By linking to mesoscale microstructural features, revealed by coarse-grained molecular dynamics and previous studies, and performing simulations of charge transport, it is demonstrated that the high mobility of C16-IDTBT can be explained by the promotion of a highly interconnected transport network, stemming from the adoption of perpendicular contacts at the nanoscale, in combination with fast intrachain transport.

Shuanghuanglian volatile oil exerts antipyretic, anti-inflammatory, and antibacterial synergistic effects through multiple pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) has a rich history spanning 2000 years. Shuanghuanglian, a traditional Chinese herbal formula composed of three botanicals, is primarily used to treat colds, respiratory infections (including bacterial pneumonia), and pharyngitis. Previous research has found that the volatile oil of Shuanghuanglian is crucial for its efficacy. However, there is a lack of studies investigating its mechanisms. AIM OF THE STUDY: This study aims to explore the antibacterial and anti-inflammatory mechanisms of Shuanghuanglian volatile oil and its potential to enhance the antibacterial effects when used in conjunction with antibiotics. METHODS: Determination of the GC-MS fingerprint of SVO using Gas Chromatography-Mass Spectrometry (GC-MS), The antibacterial effects of SVO on multidrug-resistant Klebsiella pneumoniae (MDR-KP) were assessed by detecting MIC, checkerboard method assay, time-kill curves, resistance growth curves, transcriptome sequencing analysis, scanning electron microscopy(SEM), purification, and quantitative analysis of extracellular polysaccharides(EPS). In vivo part, an MDR-KP induced mouse pneumonia model was established to evaluate the mitigating effects of SVO on mouse pneumonia, using comprehensive network pharmacology and bioinformatics to identify genes related to bacterial pneumonia and potential targets of SVO. Validation was performed through molecular docking, qPCR, and ELISA tests. RESULTS: SVO modulates the expression of MDR-KP mRNA for wecB, wecC, murA, murD, murE, murF, inhibiting the synthesis of O-antigen polysaccharides and peptidoglycans, thereby compromising bacterial cell wall integrity and affecting the synthesis of biofilms. These actions not only exhibit antibacterial effects but also enhance antibacterial activity, restoring the sensitivity of CEF to MDR-KP. SVO suppresses the biological activity of PTGS2, reducing the production of Prostaglandin E2 (PGE2), thereby exerting antipyretic and anti-inflammatory effects, providing new insights for the development of natural non-steroidal anti-inflammatory drugs (NSAIDs). CONCLUSIONS: Our research indicates that SVO exerts antipyretic, anti-inflammatory, and antibacterial synergistic effects through multiple pathways.

Double-chambered left ventricle misdiagnosed as ventricular septal defect.

A 35-year-old woman was initially misdiagnosed with a muscular ventricular septal defect but was later correctly diagnosed with a double-chambered left ventricle following evaluation by echocardiography and cardiac computed tomography.

Coconut milk allergenicity: Insight into reducing the affinity of coconut globulin to immunoglobulin E by atmospheric cold plasma.

Atmospheric cold plasma (ACP) presents a promising method for the sterilization of coconut milk and exhibits a modifying effect on coconut globulin (CG), the primary allergen in coconut milk. This study investigated the potential role of ACP treatment in mitigating the allergenic properties of coconut milk by examining changes in protein structure. ACP treatment induced structural alterations in CG, disrupting binding sites with immunoglobulin E (IgE). Consequently, this led to a reduction in the affinity between CG and IgE, evidenced by a decrease in Ka from 2.17 × 104/M to 0.64 × 104/M, thereby diminishing IgE-mediated allergic reactions. The findings from allergenic and cellular models further corroborated that ACP treatment decreased the allergenicity of CG by 55.18%, while inhibiting degranulation and the release of allergic mediators. This study presents an innovative methodology for producing hypoallergenic coconut milk, thereby expanding the applicability of ACP technology within the food industry.

[Design and simulation study of positive pressure ventilation system in a simulated human biological lung].

Simulation of the human biological lung is a crucial method for medical professionals to learn and practice the use of new pulmonary interventional diagnostic and therapeutic devices. The study on ventilation effects of the simulation under positive pressure ventilation mode provide valuable guidance for clinical ventilation treatment. This study focused on establishing an electrical simulation ventilation model, which aims to address the complexities in parameter configuration and slow display of air pressure and airflow waveforms in simulating the human biological lung under positive pressure ventilation mode. A simulated ventilation experiment was conducted under pressure-regulated volume control (PRVC) positive pressure ventilation mode, and the resulting ventilation waveform was compared with that of normal adults. The experimental findings indicated that the average error of the main reference index moisture value was 9.8% under PRVC positive pressure ventilation mode, effectively simulating the ventilatory effect observed in normal adults. So the established electrical simulation ventilation model is feasible, and provides a foundation for further research on the simulation of human biological lung positive pressure ventilation experimental platform.

A comprehensive foodomics analysis of rambutan seed oils: Focusing on the physicochemical parameters, lipid concomitants and lipid profiles.

A foodomics approach was employed to systematically characterize and compare the quality parameters, antioxidant activity, minor-components, fatty acid composition, and lipid profiles of the seed oils from the three most popular rambutan varieties in China. The total lipid content ranged from 23.40 to 25.77 g/100 g. The fatty acids 9cC18:1 (39.84%-40.92%) and C20:0 (28.45%-30.23%) were identified as the dominant ones, which are uncommon among higher plants. All oil samples exhibited low AI and TI values. BR-7 exhibited the highest levels of squalene (21.48 mg/kg), cholesterol (144.43 mg/kg), and tocopherol (17.42 mg/kg), and the lowest levels of polyphenols (24.21 mg GAE/kg). Additionally, a total of 807 lipid species were identified, with TAG, DGTS, and PE being the predominant ones. Multivariate statistical analyses revealed significant variations in lipid profiles among the varieties, particularly in glycerophospholipids and sphingolipids. Fifty-seven distinct lipids were identified as potential markers for distinguishing between rambutan varieties. Furthermore, a hypothetical scenario was developed by linking relevant lipid metabolism pathways. These findings establish a theoretical framework for comprehending rambutan seed oil in depth and unlocking its high-value potential.

Enhancement of hydrogen bonds between proteins and polyphenols through magnetic field treatment: Structure, interfacial properties, and emulsifying properties.

In food systems, proteins and polyphenols typically coexist in a non-covalent manner. However, the inherent rigid structure of proteins may hinder the binding sites of polyphenols, thereby limiting the strength of their interaction. In the study, magnetic field (MF) treatment was used to enhance non-covalent interactions between coconut globulin (CG) and tannic acid (TA) to improve protein flexibility, enhancing their functional properties without causing oxidation of polyphenols. Based on protein structure results, the interaction between CG and TA caused protein structure to unfold, exposing hydrophobic groups. Treatment with a MF, particularly at 3 mT, further promoted protein unfolding, as evidenced by a decrease in α-helix structure and an increase in coil random. These structural transformations led to the exposure of the internal binding site bound to TA and strengthening the CG-TA interaction (polyphenol binding degree increased from 62.3 to 68.2%). The characterization of molecular forces indicated that MF treatment strengthened hydrogen bonding-dominated non-covalent interactions between CG and TA, leading to improved molecular flexibility of the protein. Specifically, at a MF treatment at 3 mT, CG-TA colloidal particles with small size and high surface hydrophobicity exhibited optimal interfacial activity and wettability (as evidenced by a three-phase contact angle of 89.0°). Consequently, CG-TA-stabilized high internal phase Pickering emulsions (HIPPEs) with uniform droplets and dense gel networks at 3 mT. Furthermore, the utilization of HIPPEs in 3D printing resulted in consistent geometric shapes, uniform surface textures, and distinct printed layers, demonstrating superior printing stability. As a result, MF treatment at 3 mT was identified as the most favorable. This research provides novel insights into how proteins and polyphenols interact, thereby enabling natural proteins to be utilized in a variety of food applications.

A rare case of giant left sinus of Valsalva aneurysm complicated by thrombus formation.

A rare transthoracic echocardiographic image of left sinus of Valsalva aneurysm complicated by thrombus formation.

Liver autotransplantation and atrial reconstruction on a patient with multiorgan alveolar echinococcosis: a case report.

BACKGROUND: Alveolar echinococcosis (AE) primarily affects the liver and potentially spreads to other organs. Managing recurrent AE poses significant challenges, especially when it involves critical structures and multiple major organs. CASE PRESENTATION: We present a case of a 59-year-old female with recurrent AE affecting the liver, heart, and lungs following two previous hepatectomies, the hepatic lesions persisted, adhering to major veins, and imaging revealed additional diaphragmatic, cardiac, and pulmonary involvement. The ex vivo liver resection and autotransplantation (ELRA), first in human combined with right atrium (RA) reconstruction were performed utilizing cardiopulmonary bypass, and repairs of the pericardium and diaphragm. This approach aimed to offer a potentially curative solution for lesions previously considered inoperable without requiring a donor organ or immunosuppressants. The patient encountered multiple serious complications, including atrial fibrillation, deteriorated liver function, severe pulmonary infection, respiratory failure, and acute kidney injury (AKI). These complications necessitated intensive intraoperative and postoperative care, emphasizing the need for a comprehensive management strategy in such complicated high-risk surgeries. CONCLUSIONS: The multidisciplinary collaboration in this case proved effective and yielded significant therapeutic outcomes for a rare case of advanced hepatic, cardiac, and pulmonary AE. The combined approach of ELRA and RA reconstruction under extracorporeal circulation demonstrated distinct advantages of ELRA in treating complex HAE. Meanwhile, assessing diaphragm function during the perioperative period, especially in patients at high risk of developing pulmonary complications and undergoing diaphragmectomy is vital to promote optimal postoperative recovery. For multi-resistant infection, it is imperative to take all possible measures to mitigate the risk of AKI if vancomycin administration is deemed necessary.

Impact of refining on phytochemicals and anti-inflammatory activity of papaya (Carica papaya L.) seed oil in LPS-stimulated THP-1 cells.

This study investigated the changes in phytochemical composition and inflammatory response of crude papaya (Carica papaya L.) seed oil (CPO) and its refined forms (degummed, PDG; deacidified, PDA; decolorized, PDC; deodorized, PDO). Oils were analyzed for their phytochemical composition, oil quality parameters, antioxidant activity, and their inflammatory response in LPS-stimulated THP-1 macrophages. At higher refining degrees, particularly after deacidification, the contents of phytochemicals (sterols, tocopherols, and polyphenols) decreased while oxidation products increased. Both CPO (0.1-1.0 mg/mL) and PDG reduced the secretion and mRNA expression of LPS-stimulated inflammatory cytokines and mediators and also blocked the activation of the NF-κB pathway. PDA, PDC, and PDO showed low anti-inflammatory or even pro-inflammatory activity. Correlation analysis showed that 4 polyphenols and 2 phytosterols were responsible for the oil's anti-inflammatory effects. These findings indicated that moderate refining is suggested for papaya seed oil processing for retaining bioactive ingredients and anti-inflammatory ability.

Expression of Tshb and Tshr in the ricefield eel Monopterus albus: Potential paracrine/autocrine roles in gonads.

Thyroid stimulating hormone (TSH), a glycoprotein synthesized and secreted from thyrotrophs of the pituitary gland, is composed of a glycoprotein hormone common alpha subunit (CGA) and a specific beta subunit (TSHB). The major biological function of TSH is to stimulate thyroidal follicles to synthesize and secrete thyroid hormones through activating its cognate receptor, the thyroid stimulating hormone receptor (TSHR). In the present study, polyclonal antisera against ricefield eel Tshb and Tshr were generated respectively, and the expression of Tshb and Tshr was examined at mRNA and protein levels. RT-PCR analysis showed that tshb mRNA was expressed mainly in the pituitary as well as in some extrapituitary tissues including the ovary and testis. Tshr mRNA was also expressed in a tissue-specific manner, with transcripts detected in tissues including the kidney, ovary, and testis. The immunoreactive Tshb signals in the pituitary were shown to be localized to the inner areas of adenohypophysis which are close to the neurohypophysis of adult ricefield eels. Tshb-immunoreatvie cells in the pituitary of ricefield eel larvae were firstly observed at hatching. The expression of immunoreactive Tshb and Cga was also detected in ricefield eel ovary and testis together with Tshr. In the ovary, immunoreactive Tshb, Cga, and Tshr were observed in oocytes and granulosa cells. In the testis, immunoreactive Tshb was mainly observed in Sertoli cells while immunoreactive Cga and Tshr were detected in germ cells as well as somatic cells. Results of the present study suggest that Tsh may be synthesized both in the ovary and testis locally, which may play paracrine and/or autocrine roles in gonadal development in ricefield eels.

Retrospective analysis of interpretable machine learning in predicting ICU thrombocytopenia in geriatric ICU patients.

We developed an interpretable machine learning algorithm that prospectively predicts the risk of thrombocytopenia in older critically ill patients during their stay in the intensive care unit (ICU), ultimately aiding clinical decision-making and improving patient care. Data from 2286 geriatric patients who underwent surgery and were admitted to the ICU of Dongyang People's Hospital between 2012 and 2021 were retrospectively analyzed. Integrated algorithms were developed, and four machine-learning algorithms were used. Selected characteristics included common demographic data, biochemical indicators, and vital signs. Eight key variables were selected using the Least Absolute Shrinkage and Selection Operator and Random Forest Algorithm. Thrombocytopenia occurred in 18.2% of postoperative geriatric patients, with a higher mortality rate. The C5.0 model showed the best performance, with an area under the receiver operating characteristic curve close to 0.85, along with unparalleled accuracy, precision, specificity, recall, and balanced accuracy scores of 0.88, 0.98, 0.89, 0.98, and 0.85, respectively. The support vector machine model excelled at predictively assessing thrombocytopenia severity, demonstrating an accuracy rate of 0.80 in the MIMIC database. Thus, our machine learning-based models have considerable potential in effectively predicting the risk and severity of postoperative thrombocytopenia in geriatric ICU patients for better clinical decision-making and patient care.

Nlp-dependent ER-to-Golgi transport.

The mechanism that maintains ER-to-Golgi vesicles formation and transport is complicated. As one of the adapters, Ninein-like protein (Nlp) participated in assembly and transporting of partial ER-to-Golgi vesicles that contained specific proteins, such as ß-Catenin and STING. Nlp acted as a platform to sustain the specificity and continuity of cargoes during COPII and COPI-coated vesicle transition and transportation through binding directly with SEC31A as well as Rab1B. Thus, we proposed an integrated transport model that particular adapter participated in specific cargo selection or transportation through cooperating with different membrane associated proteins to ensure the continuity of cargo trafficking. Deficiency of Nlp led to vesicle budding failure and accumulation of unprocessed proteins in ER, which further caused ER stress as well as Golgi fragmentation, and PERK-eIF2α pathway of UPR was activated to reduce the synthesis of universal proteins. In contrast, upregulation of Nlp resulted in Golgi fragmentation, which enhanced the cargo transport efficiency between ER and Golgi. Moreover, Nlp deficient mice were prone to spontaneous B cell lymphoma, since the developments and functions of lymphocytes significantly depended on secretory proteins through ER-to-Golgi vesicle trafficking, including IL-13, IL-17 and IL-21. Thus, perturbations of Nlp altered ER-to-Golgi communication and cellular homeostasis, and might contribute to the pathogenesis of B cell lymphoma.

Genomic characterization and risk stratification of esophageal squamous dysplasia.

Objectives: The majority of esophageal squamous dysplasia (ESD) patients progress slowly, while a subset of patients can undergo recurrence rapidly or progress to invasive cancer even after proper treatment. However, the molecular mechanisms underlying these clinical observations are still largely unknown. Methods: By sequencing the genomic data of 160 clinical samples from 49 tumor-free ESD patients and 88 esophageal squamous cell carcinoma (ESCC) patients, we demonstrated lower somatic mutation and copy number alteration (CNA) burden in ESD compared with ESCC. Results: Cross-species screening and functional assays identified ACSM5 as a novel driver gene for ESD progression. Furthermore, we revealed that miR-4292 promoted ESD progression and could serve as a non-invasive diagnostic marker for ESD. Conclusions: These findings largely expanded our understanding of ESD genetics and tumorigenesis, which possessed promising significance for improving early diagnosis, reducing overtreatment, and identifying high-risk ESD patients.

Arginine Vasotocin Directly Regulates Spermatogenesis in Adult Zebrafish (Danio rerio) Testes.

The neuropeptide vasopressin is known for its regulation of osmotic balance in mammals. Arginine vasotocin (AVT) is a non-mammalian homolog of this neuropeptide that is present in fish. Limited information suggested that vasopressin and its homologs may also influence reproductive function. In the present study, we investigated the direct effect of AVT on spermatogenesis, using zebrafish as a model organism. Results demonstrate that AVT and its receptors (avpr1aa, avpr2aa, avpr1ab, avpr2ab, and avpr2l) are expressed in the zebrafish brain and testes. The direct action of AVT on spermatogenesis was investigated using an ex vivo culture of mature zebrafish testes for 7 days. Using histological, morphometric, and biochemical approaches, we observed direct actions of AVT on zebrafish testicular function. AVT treatment directly increased the number of spermatozoa in an androgen-dependent manner, while reducing mitotic cells and the proliferation activity of type B spermatogonia. The observed stimulatory action of AVT on spermiogenesis was blocked by flutamide, an androgen receptor antagonist. The present results support the novel hypothesis that AVT stimulates short-term androgen-dependent spermiogenesis. However, its prolonged presence may lead to diminished spermatogenesis by reducing the proliferation of spermatogonia B, resulting in a diminished turnover of spermatogonia, spermatids, and spermatozoa. The overall findings offer an insight into the physiological significance of vasopressin and its homologs in vertebrates as a contributing factor in the multifactorial regulation of male reproduction.

Electroacupuncture improves the learning and memory abilities of rats with PSCI by attenuating the TLR4/NF-κB/NLRP3 signaling pathway on the hippocampal microglia.

This study aims to investigate how electroacupuncture regulates the learning and memory abilities of poststroke cognitive impairment (PSCI) rats through the TLR4/NF-κB/NLRP3 signaling pathway on the hippocampal microglia. Thirty male rats were randomly divided into three groups: sham surgery group, PSCI model group, and electroacupuncture group, with 10 rats in each group. Middle cerebral artery occlusion was used to establish the PSCI model. The Zea Longa method was used to score the rats' neurological function. Electroacupuncture was utilized for 21 days to improve PSCI. The learning and memory abilities of rats were tested using the Morris water maze. Hematoxylin-eosin staining and immunofluorescence were used to find the hippocampus' pathological changes. The concentration of interleukin-1ß, interleukin-6, tumor necrosis factor-α, and interleukin-18 were detected by ELISA. The mRNA expression levels of associated inflammatory corpuscles were measured by quantitative real-time PCR. The protein expression levels of TLR4, MyD88, NF-κB, and NLRP3 were measured using western blotting. Electroacupuncture improved not only the learning and memory abilities of PSCI rats but also hippocampal morphology. Electroacupuncture inhibited the activation of microglia and the TLR4/NF-κB/NLRP3 signaling pathway. Electroacupuncture also reduced proinflammatory factors and restrained the mRNA levels of NLRP3-associated inflammatory cytokines. Its mechanism was related to inhibiting the expression of the TLR4/NF-κB/NLRP3 signaling pathway, attenuating the release of inflammatory factors, and regulating the activation of hippocampal microglia in the brain.