Advances in the biosynthesis of tetraacetyl phytosphingosine, a key substrate of ceramides.

Ceramides, formed by the dehydration of long-chain fatty acids with phytosphingosine and its derivatives, are widely used in skincare, cosmetics, and pharmaceuticals. Due to the exceedingly low concentration of phytosphingosine in plant seeds, relying on the extraction method is highly challenging. Currently, the primary method for obtaining phytosphingosine is the deacetylation of tetraacetyl phytosphingosine (TAPS) derived from fermentation. Wickerhamomyces ciferrii, an unconventional yeast from the pods of Dipteryx odorata, is the only known microorganism capable of naturally secreting TAPS, which is of great industrial value. In recent years, research and applications focused on modifying W. ciferrii for TAPS overproduction have increased rapidly. This review first describes the discovery history, applications, microbial synthesis pathway of TAPS. Research progress in using haploid breeding, mutagenesis breeding, and metabolic engineering to improve TAPS production is then summarized. In addition, the future prospects of TAPS production using the W. ciferrii platform are discussed in light of the current progress, challenges, and trends in this field. Finally, guidelines for future researches are also emphasized.

The green footprint of anammox processes under simulated actual operating conditions: Focusing on the nitrous oxide and methane production.

The anammox process has attracted increasing attention due to its advantages of low-carbon and energy-saving, nevertheless, greenhouse gas was still generated during its engineering applications process. Hence, it is vital to comprehensively understand the production characteristics and mechanisms of N2O and CH4 in anammox processes by responding to practical conditions including dissolved oxygen, temperature, and salinity. Results showed that N2O production increased by 192 %-358 %, while nitrogen removal efficiency (NRE) increased by 64.2 %-86.8 % with increasing temperature. The increased salinity inhibits 40.60 %-65.33 % N2O production with a decrease NRE of 7.85 %-18.2 %. CH4 production was the highest at 18-27 °C, reaching 3.07 ±â€¯0.11-4.06 ±â€¯0.16 mg·L-1, which were 1.59-2 and 1.29-1.38 times higher than that at 8-17 °C and 28-37 °C, respectively. Denitratisoma, Thauera, and Nitrosomonas were the main functional microbes for greenhouse gas production in anammox consortia. Notably, H2O2-induced intracellular Fenton reaction may be critical for the CH4 production in anammox consortia. This work provides valuable insights into achieving efficient nitrogen removal and minimizing carbon footprint in anammox systems and provides a theoretical basis for implementing the net-zero emission idea in wastewater treatment plants.

Mass Spectrometry Probe Combined with Machine Learning to Capture the Relationship between Metabolites and Mitochondrial Complex Activity at the Whole-Cell Level.

Mitochondrial complex activity controls a multitude of physiological processes by regulating the cellular metabolism. Current methods for evaluating mitochondrial complex activity mainly focus on single metabolic reactions within mitochondria. These methods often require fresh samples in large quantities for mitochondria purification or intact mitochondrial membranes for real-time monitoring. Confronting these limitations, we shifted the analytical perspective toward interactive metabolic networks at the whole-cell level to reflect mitochondrial complex activity. To this end, we compiled a panel of mitochondrial respiratory chain-mapped metabolites (MRCMs), whose perturbations theoretically provide an overall reflection on mitochondrial complex activity. By introducing N-dimethyl-p-phenylenediamine and N-methyl-p-phenylenediamine as a pair of mass spectrometry probes, an ultraperformance liquid chromatography-tandem mass spectrometry method with high sensitivity (LLOQ as low as 0.2 fmol) was developed to obtain accurate quantitative data of MRCMs. Machine learning was then combined to capture the relationship between MRCMs and mitochondrial complex activity. Using Complex I as a proof-of-concept, we identified NADH, alanine, and phosphoenolpyruvate as metabolites associated with Complex I activity based on the whole-cell level. The effectiveness of using their concentrations to reflect Complex I activity was further validated in external data sets. Hence, by capturing the relationship between metabolites and mitochondrial complex activity at the whole-cell level, this study explores a novel analytical paradigm for the interrogation of mitochondrial complex activity, offering a favorable complement to existing methods particularly when sample quantities, type, and treatment timeliness pose challenges. More importantly, it shifts the focus from individual metabolic reactions within mitochondria to a more comprehensive view of an interactive metabolic network, which should serve as a promising direction for future research into the functional architecture between mitochondrial complexes and metabolites.

Dual-Anionic Coordination Manipulation Induces Phosphorus and Boron-Rich Gradient Interphase Towards Stable and Safe Sodium Metal Batteries.

High-voltage sodium metal batteries (SMBs) present a viable pathway towards high-energy-density sodium-based batteries due to the competitive cost advantage and abundant supply of sodium resources. However, they still suffer from severe capacity decay induced by the notorious decomposition of the electrolyte under high voltage and unstable cathode/electrolyte interphase (CEI). In addition, the high reactivity of Na metal and flammable electrolytes push SMBs to their safety limits. Herein, a special dual-anion aggregated Na+ solvation structure is designed in a nonflammable trimethyl phosphate-based localized high-concentration electrolyte, and a gradient CEI enriched with phosphorus and boron compounds is formed on the cathode. This thin and stable interphase effectively suppresses the parasitic reaction, improves the interfacial stability of the cathode, and facilitates Na+ transport through the interface by the synergistic effect of multi-components, thus optimizing the cycling stability and safety of SMBs. The Na0.95Ni0.4Fe0.15Mn0.3Ti0.15O2//Na batteries employing such electrolyte provide a discharge capacity of 167.5 mA h g-1 and high retention in the capacity of 85.2% after 800 cycles at 1 C. This approach offers a general strategy for the design of flame-retardant high-voltage electrolytes and the practical application of SMBs.

Helmet Ventilation in a Child with COVID-19 and Acute Respiratory Distress Syndrome.

Background: In pediatric patients with severe COVID-19, if the respiratory support provided using high-flow nasal cannula (HFNC) becomes insufficient, no definitive evidence exists to support the escalation to noninvasive ventilation (NIV) or mechanical ventilation (MV). Case Presentation. A 9-year-old boy being treated with face mask-delivered biphasic positive airway pressure ventilation developed fever, tachypnea, and frequent desaturation. The COVID-19 polymerase chain reaction test and urine antigen test for Streptococcus pneumoniae were both positive, and sputum culture yielded Pseudomonas aeruginosa. The do-not-resuscitate order precluded the use of endotracheal intubation. After 2 h of HFNC support, the respiratory rate oxygenation (ROX) index declined from 7.86 to 3.71, indicating impending HFNC failure. A helmet was used to deliver NIV, and SpO2 was maintained at >90%. Dyspnea and desaturation gradually improved, and the patient was switched to HFNC 6 days later and discharged 10 days later. Conclusion: In some cases, acute respiratory distress syndrome severity cannot be measured using the oxygenation index or oxygenation saturation index, and the SpO2/FiO2 ratio and ROX index may serve as useful alternatives. Although NIV delivered through a facemask or HFNC is more popular than helmet-delivered NIV, in certain circumstances, it can help escalate respiratory support while providing adequate protection to healthcare professionals.

Electrolyte Design Enables Stable and Energy-dense Potassium-ion Batteries.

Free from strategically important elements such as lithium, nickel, cobalt, and copper, potassium-ion batteries (PIBs) are heralded as promising low-cost and sustainable electrochemical energy storage systems that complement the existing lithium-ion batteries (LIBs). However, the reported electrochemical performance of PIBs is still suboptimal, especially under practically relevant battery manufacturing conditions. The primary challenge stems from the lack of electrolytes capable of concurrently supporting both the low-voltage anode and high-voltage cathode with satisfactory Coulombic efficiency (CE) and cycling stability. Herein, we report a promising electrolyte that facilitates the commercially mature graphite anode (> 3 mAh cm-2) to achieve an initial CE of 91.14% (with an average cycling CE around 99.94%), fast redox kinetics, and negligible capacity fading for hundreds of cycles. Meanwhile, the electrolyte also demonstrates good compatibility with the 4.4 V (vs. K+/K) high-voltage K2Mn[Fe(CN)6] (KMF) cathode. Consequently, the KMF||graphite full-cell without precycling treatment of both electrodes can provide an average discharge voltage of 3.61 V with a specific energy of 316.5 Wh kg-1-(KMF+graphite), comparable to the LiFePO4||graphite LIBs, and maintain 71.01% capacity retention after 2000 cycles.

Analysis of risk factors for pneumonia in patients with catatonia: a cross-sectional analysis.

Objective: The clinical management of catatonia has always been a focus of psychiatric nursing. Unfortunately, there is still limited research on the risk factors and nursing methods for patients with catatonia and bacterial pneumonia. Few studies have identified and analyzed the clinical risk factors for catatonia patients with bacterial pneumonia. This study aims to explore the risk factors and preventive nursing measures for pneumonia in patients with catatonia. Methods: A total of 88 patients with catatonia treated in the emergency department of a psychiatric hospital from January 2019 to October 2021 were selected. They were divided into bacterial pneumonia group (n=17) and non-pneumonia group (n=71) based on whether they had pneumonia. The demographic data and clinical characteristics of the two groups were compared. Logistic regression analysis and point-biserial correlation were used to analyze the risk factors for developing pneumonia in patients with catatonia. Results: The incidence of pneumonia in patients with catatonia was 19.32%. Correlation analysis showed that age (r=0.216, p=0.043), The Activities of Daily Living Scale (ADL) score (r=0.265, p=0.013), cell count of white blood (r=0.591, p<0.001), neutrophil count (r=0.599, p<0.001), percentage of neutrophils (r=0.311, p=0.003), C-reactive protein (r=0.558, p<0.001), bedridden days (r=0.470, p<0.001), and albumin level (r=-0.288, p=0.007) were significantly associated with pneumonia. Multivariate logistic regression analysis showed that smoking, bedridden days, family support, and nutritional status were risk factors for pneumonia in patients with catatonia. Conclusion: Reducing smoking and bedridden days, improving nutrition, and providing timely preventive nursing care by family members can reduce the occurrence of pneumonia in patients with catatonia.

Sensory impairments associated with cognitive impairment among older adults in China: A community-based, 10-year prospective cohort study.

Background: To address an existing gap in knowledge due to limited and inconclusive evidence, we aimed to investigate the association between sensory impairments and cognitive decline among older Chinese individuals. Methods: We retrieved data on 6862 adults aged ≥65 years that were collected through the Chinese Longitudinal Healthy Longevity Study (CLHLS), a nationwide, prospective, community-based elderly cohort study. Visual or hearing impairment in the CLHLS were identified through self-reported questionnaire. Sensory impairments were categorised as no sensory impairment, hearing impairment only, visual impairment only, and dual sensory impairment according to hearing and vision function. Cognitive impairment was defined as having a score <18 on the Chinese version of the Mini Mental State Examination. We used a Cox proportional hazard model to evaluate the relationship between sensory and cognitive impairments. Results: Among 6862 participants, 5.7% had dual sensory impairment, 7.4% had hearing impairment only, and had 17.2% visual impairment only. Compared with participants with no sensory impairment, those with hearing impairment only (adjusted hazard ratio (aHR) = 1.65; 95% confidence interval (CI) = 1.41, 1.92), visual impairment only (aHR = 1.25; 95% CI = 1.11, 1.41), and dual sensory impairment (aHR = 1.47; 95% CI = 1.25, 1.74) were significantly associated with higher risk of cognitive impairment in the fully adjusted model. Conclusions: Our results show that having hearing impairment only, visual impairment only, and dual sensory impairment was significantly associated with a higher risk of cognitive impairment among Chinese older adults aged ≥65 years. This suggest a need for the timely identification and management of sensory impairments for the elderly to reduce dementia risk.

Differentiation of the Anammox core microbiome: Unraveling the evolutionary impetus of scalable gene flow.

Anaerobic ammonium oxidation bacteria (AAOB), distinguished by their unique autotrophic nitrogen metabolism, hold pivotal positions in the global nitrogen cycle and environmental biotechnologies. However, the ecophysiology and evolution of AAOB remain poorly understood, attributed to the absence of monocultures. Hence, a comprehensive elucidation of the AAOB-dominated core microbiome, anammox core, is imperative to further completing the theory of engineered nitrogen removal and ecological roles of anammox. Performing taxonomic and phylogenetic analyses on collected genome repertoires, we show here that Candidatus Brocadia and Candidatus Kuenenia possesses a more compact core than Candidatus Jettenia, which partly explains why the latter has a less common ecological presence. Evidence of gene flow is particularly striking in functions related to biosynthesis and oxygen detoxification, underscoring the evolutionary forces driving lineage and core differentiation. Furthermore, CRISPR spacer traceback of the AAOB metagenome-assembled genomes (MAGs) reveals a series of genetic traces for the concealed phages. By reconceptualizing the functional divergence of AAOB with the historical role of phages, we ultimately propose a coevolutionary framework to understand the evolutionary trajectory of anammox microecology. The discoveries provided in this study offer new insights into understanding the evolution of AAOB and the ecology of anammox.

Identification and characterization of Lacticaseibacillus rhamnosus HP-B1083-derived ß-glucuronidase and its application for baicalin biotransformation.

Baicalein, showing higher bioavailability and stronger pharmacological activity, can be obtained via a ß-glucuronidase (GUS)-catalyzed transformation of baicalein 7-O-ß-D-glucuronide (baicalin). Recently, we have found that the fermentation broth of Lacticaseibacillus rhamnosus HP-B1083 can efficiently convert baicalin to baicalein. In this study, the L. rhamnosus HP-B1083-derived enzyme involved in baicalin biotransformation was identified and characterized. First, the LruidA gene, encoding the responsible enzyme, was cloned and sequenced. Sequence analysis revealed that the deduced enzyme (designated as LrUidA) belonged to the glycosyl hydrolase family 2. The recombinant LrUidA was expressed and purified for characterization. LrUidA had a molecular weight of 70 kDa, with an optimal temperature of 50 °C and pH 4.5. Although LrUidA was susceptible to temperature, it possessed a relative pH stability. Its Michaelis-Menten constant, maximum reaction velocity and catalytic constant values were 9.710 mM, 13.08 mM/min/mg, and 14.95 s-1, respectively. Site-directed mutagenesis experiment results demonstrated that the enzyme reaction uses side chains of E509 and E415 to hydrolyze the glycosidic bond of baicalin and involves three negatively charged residues, E450, D451, and D452, respectively. Surprisingly, biotransformation was performed under optimized reaction conditions by incubating the purified enzyme with 0.1 % baicalin for 4 h, resulting in a considerable conversion ratio of 99 %. Altogether, our findings provide insights into the properties of L. rhamnosus HP-B1083-derived enzyme and expand our understanding regarding using GUS for the industrial production of baicalein.

Engineering Yarrowia lipolytica for Efficient Synthesis of Geranylgeraniol.

Geranylgeraniol (GGOH) is a crucial component in fragrances and essential oils, and a valuable precursor of vitamin E. It is primarily extracted from the oleoresin of Bixa orellana, but is challenged by long plant growth cycles, severe environmental pollution, and low extraction efficiency. Chemically synthesized GGOH typically comprises a mix of isomers, making the separation process both challenging and costly. Advancements in synthetic biology have enabled the construction of microbial cell factories for GGOH production. In this study, Yarrowia lipolytica was engineered to efficiently synthesize GGOH by expressing heterologous phosphatase genes, enhancing precursor supplies of farnesyl diphosphate, geranylgeranyl pyrophosphate, and acetyl-CoA, and downregulating the squalene synthesis pathway by promoter engineering. Additionally, optimizing fermentation conditions and reducing reactive oxygen species significantly increased the GGOH titer to 3346.47 mg/L in a shake flask. To the best of our knowledge, this is the highest reported GGOH titer in shaking flasks to date, setting a new benchmark for terpenoid production.

Advances in multi-enzyme co-localization strategies for the construction of microbial cell factory.

Biomanufacturing, driven by technologies such as synthetic biology, offers significant potential to advance the bioeconomy and promote sustainable development. It is anticipated to transform traditional manufacturing and become a key industry in future strategies. Cell factories are the core of biomanufacturing. The advancement of synthetic biology and growing market demand have led to the production of a greater variety of natural products and increasingly complex metabolic pathways. However, this progress also presents challenges, notably the conflict between natural product production and chassis cell growth. This conflict results in low productivity and yield, adverse side effects, metabolic imbalances, and growth retardation. Enzyme co-localization strategies have emerged as a promising solution. This article reviews recent progress and applications of these strategies in constructing cell factories for efficient natural product production. It comprehensively describes the applications of enzyme-based compartmentalization, metabolic pathway-based compartmentalization, and synthetic organelle-based compartmentalization in improving product titers. The article also explores future research directions and the prospects of combining multiple strategies with advanced technologies.

Blueberry extract attenuates DSS-induced inflammatory bowel disease in mice through inhibiting ER stress-mediated colonic apoptosis in mice.

Inflammatory bowel disease (IBD) is a chronic, debilitating condition with limited therapeutic options. Dietary components like blueberries have emerged as potential modulators of inflammation and tissue repair in gastrointestinal diseases. This study investigated endoplasmic reticulum (ER) stress-mediated apoptosis mediated protective effects of blueberries in ameliorating dextran sulfate sodium (DSS)-induced IBD. Firstly, a total of 86 anthocyanin compounds were identified in blueberry extract by LC-MS spectroscopy, including 35 cyanidin, 9 delphinidin, 14 malvidin, 10 peonidin, and 9 petunidin. Then, the animal study showed that blueberry supplementation notably ameliorated DSS-induced IBD symptoms, as evidenced by improved histopathological scores and a reduced disease activity index (DAI) score. Additionally, blueberries attenuated ER stress by inhibiting the colonic PERK/eIF2α/ATF4/CHOP signaling pathway. Furthermore, blueberries inhibited the expression of the pro-apoptotic protein, caspase-3, and decreased colonic apoptosis, as evidenced by TUNEL assay results. However, it did not affect the expression of anti-apoptotic proteins, bcl-2 and bcl-xl. Finally, blueberries enhanced the intestinal barrier by upregulating ZO-1, claudin-1, occludin, and E-cadherin. In conclusion, blueberries demonstrate therapeutic potential against DSS-induced IBD-like symptoms in mice, possibly by regulating ER stress-mediated apoptosis pathways. These findings suggest that blueberries might be an effective dietary intervention for IBD management.

Combining Clinical-Radiomics Features With Machine Learning Methods for Building Models to Predict Postoperative Recurrence in Patients With Chronic Subdural Hematoma: Retrospective Cohort Study.

BACKGROUND: Chronic subdural hematoma (CSDH) represents a prevalent medical condition, posing substantial challenges in postoperative management due to risks of recurrence. Such recurrences not only cause physical suffering to the patient but also add to the financial burden on the family and the health care system. Currently, prognosis determination largely depends on clinician expertise, revealing a dearth of precise prediction models in clinical settings. OBJECTIVE: This study aims to use machine learning (ML) techniques for the construction of predictive models to assess the likelihood of CSDH recurrence after surgery, which leads to greater benefits for patients and the health care system. METHODS: Data from 133 patients were amassed and partitioned into a training set (n=93) and a test set (n=40). Radiomics features were extracted from preoperative cranial computed tomography scans using 3D Slicer software. These features, in conjunction with clinical data and composite clinical-radiomics features, served as input variables for model development. Four distinct ML algorithms were used to build predictive models, and their performance was rigorously evaluated via accuracy, area under the curve (AUC), and recall metrics. The optimal model was identified, followed by recursive feature elimination for feature selection, leading to enhanced predictive efficacy. External validation was conducted using data sets from additional health care facilities. RESULTS: Following rigorous experimental analysis, the support vector machine model, predicated on clinical-radiomics features, emerged as the most efficacious for predicting postoperative recurrence in patients with CSDH. Subsequent to feature selection, key variables exerting significant impact on the model were incorporated as the input set, thereby augmenting its predictive accuracy. The model demonstrated robust performance, with metrics including accuracy of 92.72%, AUC of 91.34%, and recall of 93.16%. External validation further substantiated its effectiveness, yielding an accuracy of 90.32%, AUC of 91.32%, and recall of 88.37%, affirming its clinical applicability. CONCLUSIONS: This study substantiates the feasibility and clinical relevance of an ML-based predictive model, using clinical-radiomics features, for relatively accurate prognostication of postoperative recurrence in patients with CSDH. If the model is integrated into clinical practice, it will be of great significance in enhancing the quality and efficiency of clinical decision-making processes, which can improve the accuracy of diagnosis and treatment, reduce unnecessary tests and surgeries, and reduce the waste of medical resources.

The Asymmetric Total Synthesis of the Female-Produced Sex Pheromone of the Tea Tussock Moth.

The tea tussock moth is a pest that damages tea leaves, affecting the quality and yield of tea and causing huge economic losses. The efficient asymmetric total synthesis of the sex pheromone of the tea tussock moth was achieved using commercially available starting materials with a 25% overall yield in 11 steps. Moreover, the chiral moiety was introduced by Evans' template and the key C-C bond construction was accomplished through Julia-Kocienski olefination coupling. The synthetic sex pheromone of the tea tussock moth will facilitate the subsequent assessment and implementation of pheromones as environmentally friendly tools for pest management.

APOE ε4-associated downregulation of the IL-7/IL-7R pathway in effector memory T cells: Implications for Alzheimer's disease.

INTRODUCTION: The apolipoprotein E (APOE) ε4 allele exerts a significant influence on peripheral inflammation and neuroinflammation, yet the underlying mechanisms remain elusive. METHODS: The present study enrolled 54 patients diagnosed with late-onset Alzheimer's disease (AD; including 28 APOE ε4 carriers and 26 non-carriers). Plasma inflammatory cytokine concentration was assessed, alongside bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs). RESULTS: Plasma tumor necrosis factor α, interferon γ, and interleukin (IL)-33 levels increased in the APOE ε4 carriers but IL-7 expression notably decreased. A negative correlation was observed between plasma IL-7 level and the hippocampal atrophy degree. Additionally, the expression of IL-7R and CD28 also decreased in PBMCs of APOE ε4 carriers. ScRNA-seq data results indicated that the changes were mainly related to the CD4+ Tem (effector memory) and CD8+ Tem T cells. DISCUSSION: These findings shed light on the role of the downregulated IL-7/IL-7R pathway associated with the APOE ε4 allele in modulating neuroinflammation and hippocampal atrophy. HIGHLIGHTS: The apolipoprotein E (APOE) ε4 allele decreases plasma interleukin (IL)-7 and aggravates hippocampal atrophy in Alzheimer's disease. Plasma IL-7 level is negatively associated with the degree of hippocampal atrophy. The expression of IL-7R signaling decreased in peripheral blood mononuclear cells of APOE ε4 carriers Dysregulation of the IL-7/IL-7R signal pathways enriches T cells.

A review of tanshinone compounds in prostate cancer treatment.

Prostate cancer (PCa) is one of the most common malignant epithelial tumors in men worldwide. PCa patients are initially sensitive to chemotherapy, but patients in the advanced stages of PCa eventually develop resistance, leaving them with limited therapeutic options. Therefore, it is very important to screen new drugs for treating PCa. Salvia miltiorrhiza is a common Chinese herbal medicine used in some Asian countries. It has many functions and is widely used to treat a variety of diseases, including heart diseases and cancers. For the past few years, research has shown that liposoluble constituents of tanshinones (TANs), including cryptotanshinone, TAN IIA, dihydrotanshinone I, and TAN I, exhibit good anticancer activity in PCa. In this study, we review the progress of TAN compounds (cryptotanshinone, TAN IIA, dihydrotanshinone I, and TAN I) in treating PCa over the past decade. These compounds can act on the same molecular mechanisms, as they have a very similar structure; they are also found to work slightly differently in PCa. According to current studies, compared with other TAN compounds, TAN IIA appears to hold more potential for treating PCa. The toxicity, side effects or biodistribution of Salvia miltiorrhiza and these four TANs need to be confirmed with further research. Findings obtained in this study may provide important information for the potential clinical application of cryptotanshinone, TAN IIA, dihydrotanshinone I, and TAN I in the treatment of PCa.

Endoscopic detection and diagnostic strategies for minute gastric cancer: A real-world observational study.

BACKGROUND: Minute gastric cancers (MGCs) have a favorable prognosis, but they are too small to be detected by endoscopy, with a maximum diameter ≤ 5 mm. AIM: To explore endoscopic detection and diagnostic strategies for MGCs. METHODS: This was a real-world observational study. The endoscopic and clinicopathological parameters of 191 MGCs between January 2015 and December 2022 were retrospectively analyzed. Endoscopic discoverable opportunity and typical neoplastic features were emphatically reviewed. RESULTS: All MGCs in our study were of a single pathological type, 97.38% (186/191) of which were differentiated-type tumors. White light endoscopy (WLE) detected 84.29% (161/191) of MGCs, and the most common morphology of MGCs found by WLE was protruding. Narrow-band imaging (NBI) secondary observation detected 14.14% (27/191) of MGCs, and the most common morphology of MGCs found by NBI was flat. Another three MGCs were detected by indigo carmine third observation. If a well-demarcated border lesion exhibited a typical neoplastic color, such as yellowish-red or whitish under WLE and brownish under NBI, MGCs should be diagnosed. The proportion with high diagnostic confidence by magnifying endoscopy with NBI (ME-NBI) was significantly higher than the proportion with low diagnostic confidence and the only visible groups (94.19% > 56.92% > 32.50%, P < 0.001). CONCLUSION: WLE combined with NBI and indigo carmine are helpful for detection of MGCs. A clear demarcation line combined with a typical neoplastic color using nonmagnifying observation is sufficient for diagnosis of MGCs. ME-NBI improves the endoscopic diagnostic confidence of MGCs.

Anthocyanins-rich cranberry extract attenuates DSS-induced IBD in an intestinal flora independent manner.

Cranberry is abundantly rich in anthocyanins, a type of flavonoid with potent antioxidant properties and the resistance against certain diseases. In this study, anthocyanin-rich cranberry extract was extracted, purified, and its components were analyzed. 92.18 % of anthocyanins was obtained and the total content of anthocyanins was 302.62 mg/g after AB-8 resin purification. Quantification analysis showed that the extract mainly contained cyanidin-3-galactoside, procyanidin B2 and procyanidin B4. Then we explored its effects on dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD) in mice. The supplementation of cranberry extract resulted in an alleviation of IBD symptoms, evidenced by improvements in the disease activity index (DAI), restoration of colon length and colonic morphology. Cranberry extract reversed the elevated iron and malondialdehyde (MDA) levels and restored glutathione (GSH) levels in IBD mice. Further analysis revealed that cranberry modulated ferroptosis-associated genes and reduced expression of pro-inflammatory cytokines. Although cranberry influenced the intestinal flora balance by reducing Proteobacteria and Escherichia-Shigella, and increasing Lactobacillus, as well as enhancing SCFAs content, these effects were not entirely dependent on intestinal flora modulation, as indicated by antibiotic intervention and fecal microbiota transplantation (FMT) experiments. In conclusion, our findings suggest that the beneficial impact of cranberry extract on IBD may primarily involve the regulation of colonic ferroptosis, independent of significant alterations in intestinal flora.

Artemisitene shows superiority over artemisinin in preventing Schistosoma japonica-induced liver disease.

BACKGROUND: Artemisinin (ART) analogs, such as dihydroartemisinin, arteether, artemether, and artesunate, all featuring an endoperoxide bridge, have demonstrated efficacy against schistosomiasis. Artemisitene (ATT), which contains an additional α, ß-unsaturated carbonyl structure, has shown enhanced biological activities. This study aims to evaluate the anti-schistosomaiasis japonica activity of ATT and compare it with ART. METHODS: We assessed liver inflammation and fibrosis in mice using hematoxylin and eosin staining and Sirius red staining, respectively. RNA sequencing analyzed transcriptomics in female and male Schistosoma japonicum (S. japonicum) adult worms and mice livers, with cytokine profiling and flow cytometry to study immune responses under ART or ATT treatment. RESULTS: ATT exhibits a marked reduction in female S. japonicum adult worms and egg numbers, damaging the adult worms' surface. It also influences the transcription of genes related to cellular anatomical structures. Notably, ATT treatment resulted in significant reductions in liver granuloma size and collagen area, alongside lowering serum levels of glutamic pyruvic and glutamic oxaloacetic transaminase more effectively than ART. Both ART and ATT markedly decreased neutrophil frequency in the liver and elevated eosinophil counts. However, only ATT treatment significantly reduced the M1/M2 and Th1/Th2 indices, indicating a pronounced shift in immune response profiles. ATT-affected host immunity correlated with the extent of liver fibrosis and the count of single males more strongly than ART. CONCLUSION: ATT, as a novel preventive strategy for schistosomiasis japonica in mice, significantly outperforms ART.