Effect of delayed diagnosis on neuroendocrine function in individuals with suprasellar germ cell tumors.

Purpose: The impact of delayed diagnosis on tumor-related prognosis appears to be minimal in individuals with intracranial germ cell tumors (iGCTs). However, its effect on neuroendocrine functions remains unclear. We aimed to assess the effects of delayed diagnosis on neuroendocrine function in individuals with suprasellar GCTs. Methods: We conducted a retrospective cohort study of 459 individuals with suprasellar GCTs and categorized them into two groups based on disease duration: delayed diagnosis (> 6 months) and non-delayed diagnosis (≤ 6 months). We compared endocrinological symptoms, neuroendocrine dysfunction and its grading (categorized into 0-3 grades based on severity), and recovery from neuroendocrine dysfunction in both groups. Results: Patients with delayed diagnosis exhibited higher incidences of amenorrhea, slow growth, fatigue, and polyuria/polydipsia. Neuroendocrine dysfunction, including central adrenal insufficiency (CAI), central hypothyroidism (CHT), arginine vasopressin deficiency (AVP-D), growth hormone deficiency, hypogonadism, and hyperprolactinemia, was more pronounced in the delayed diagnosis group at diagnosis, the end of treatment, and the last follow-up. Furthermore, individuals with delayed diagnosis showed higher grades of neuroendocrine dysfunction at diagnosis (OR=3.005, 95% CI 1.929-4.845, p<0.001), end of oncologic treatment (OR=4.802, 95% CI 2.878-8.004, p<0.001), and last follow-up(OR=2.335, 95% CI 1.307-4.170, p=0.005) after adjusting for confounders. Finally, less recovery, particularly in CAI, CHT, and AVP-D, was seen among the group with delayed diagnosis after treatment. Conclusion: Among individuals with suprasellar GCTs, delayed diagnosis is associated with increased, more severe, and less recovered neuroendocrine dysfunction, emphasizing the importance of early diagnosis and treatment to reduce neuroendocrine dysfunction.

Psychometric property and measurement invariance of perceived benefits and barriers of physical activity in Chinese adolescents.

Background: The perceived benefits and barriers to physical activity play crucial roles in determining daily physical activity levels. However, previous studies have employed tools lacking adequate validation, leading to inconsistent conclusions about the impact of these two factors. Therefore, this national, population-based study was conducted to assess the psychometric properties, measurement invariance, and predictive validity of the Chinese versions of the perceived benefits (C-PBEPA) and barriers to physical activity (C-PBAPA) scales. Methods: The final sample (N = 2942, 49.3 % for boys) was randomly split into two subsamples. The first subsample was used for exploratory factor analysis and the second subsample was used for confirmatory factor analysis. Measurement invariance across gender and age groups were examined. Structural equation models were developed to examine the predictive validity of the revised C-PBEPA and C-PBAPA on moderate to vigorous PA. Results: The results showed that both scales were unidimensional, had excellent model fit (e.g., X 2/df < 3, CFI >0.9, RMSEA <0.06) and demonstrated convergent validity. Findings also revealed lack of scalar invariance for C-PBAPA between preadolescents and adolescents' groups (ΔCFI >0.01) and supported the predictive validity of both scales (p < 0.001). Conclusion: The study demonstrated that the revised C-PBEPA and C-PBAPA are valid scales for measuring Chinese adolescents' perceived benefits and barriers to PA.

Dimethyl fumarate ameliorates oxidative stress-induced acute kidney injury after traumatic brain injury by activating Keap1-Nrf2/HO-1 signaling pathway.

Acute kidney injury (AKI) frequently emerges as a consequential non-neurological sequel to traumatic brain injury (TBI), significantly contributing to heightened mortality risks. The intricate interplay of oxidative stress in the pathophysiology of TBI underscores the centrality of the Keap1-Nrf2/HO-1 signaling pathway as a pivotal regulator in this context. This study endeavors to elucidate the involvement of the Keap1-Nrf2/HO-1 pathway in modulating oxidative stress in AKI subsequent to TBI and concurrently explore the therapeutic efficacy of dimethyl fumarate (DMF). A rat model of TBI was established via the Feeney free-fall method, incorporating interventions with varying concentrations of DMF. Assessment of renal function ensued through measurements of serum creatinine and neutrophil gelatinase-associated lipocalin. Morphological evaluation of renal pathology was conducted employing quantitative hematoxylin and eosin staining. The inflammatory response was scrutinized by quantifying interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α levels. Oxidative stress levels were discerned through quantification of malondialdehyde and superoxide dismutase. The apoptotic cascade was examined via the terminal deoxynucleotidyl transferase dUTP deletion labeling assay. Western blotting provided insights into the expression dynamics of proteins affiliated with the Keap1-Nrf2/HO-1 pathway and apoptosis. The findings revealed severe kidney injury, heightened oxidative stress, inflammation, and apoptosis in the traumatic brain injury model. Treatment with DMF effectively reversed these changes, alleviating oxidative stress by activating the Keap1-Nrf2/HO-1 signaling pathway, ultimately conferring protection against AKI. Activating Keap1-Nrf2/HO-1 signaling pathway may be a potential therapeutic strategy for attenuating oxidative stress-induced AKI after TBI.

Lymphovenous Anastomosis for the External and Internal Types of Head and Neck Lymphedema: A Case Series and Preliminary Clinical Results.

Background: Head and neck lymphedema (HNL), including external and internal types, could be a possible consequence for patients who have received neck dissection and radiotherapy for head and neck cancer. Initially, the common presentations are heaviness or tightness, followed by swelling in appearance, or difficulty speaking and swallowing in internal edema cases. Lymphovenous anastomosis (LVA) is an established approach to treat extremity lymphedema. We hereby present our preliminary experience in using LVA to treat HNL. Methods: Between March 2021 and January 2024, six patients with HNL were treated with LVA via a preauricular or submandibular incision of the obstructed side. Lymphedema Symptom Intensity and Distress Surveys-Head and Neck (LSIDS-H&N) were used for evaluation. In addition, for the external type, MD Anderson Cancer Center Head and Neck Lymphedema (MDACC HNL) rating scale was used for evaluation. For the internal type, Swallowing Quality of Life was used for evaluation. Results: With an average follow-up period of 15.4 ±â€…15.9 months, LSIDS-H&N improved from 1.11 ±â€…0.54 to 0.44 ±â€…0.66 (P = 0.02). For patients with the external type, within an average follow-up period of 15 ±â€…16.1 months, the MDACC HNL rating scale improved from level 2 to 0 or 1a (P = 0.008). For patients with the internal type, within an average follow-up period of 21 ±â€…17.3 months, Swallowing Quality of Life improved from 130.5 ±â€…9.2 to 151 ±â€…19.8 (P = 0.5). Conclusions: Based on our preliminary results, LVA could be a potential solution to both external and internal HNL.

Dynamic Phase Transformations of Prussian Blue Analogue Crystals in Hydrotherms.

Prussian blue analogue (PBA)/metal-organic frameworks (MOFs) are multifunctional precursors for the synthesis of metal/metal compounds, carbon, and their derived composites (P/MDCs) in chemical, medical, energy, and other applications. P/MDCs combine the advantages of both the high specific surface area of PBA/MOF and the electronic conductivity of metal compound/carbon. Although the calcination under different atmospheres has been extensively studied, the transformation mechanism of PBA/MOF under hydrothermal conditions remains unclear. The qualitative preparation of P/MDCs in hydrothermal conditions remains a challenge. Here, we select PBA to construct a machine-learning model and measure its hydrothermal phase diagram. The architecture-activity relationship of substances among nine parameters was analyzed for the hydrothermal phase transformation of PBA. Excitingly, we established a universal qualitative model to accurately fabricate 31 PBA derivates. Additionally, we performed three-dimensional reconstructed transmission electron microscopy, X-ray absorption fine structure spectroscopy, ultraviolet photoelectron spectroscopy, in situ X-ray powder diffraction, and theoretical calculation to analyze the advantages of hydrothermal derivatives in the oxygen evolution reaction and clarify their reaction mechanisms. We uncover the unified principles of the hydrothermal phase transformation of PBA, and we expect to guide the design for a wide range of composites.

The 2017 Women's Health Initiative study and use of hormone therapy: an emulated repeated cross-sectional study.

BACKGROUND: Hormone therapy (HT) use among menopausal women declined after negative information from the 2002 Women's Health Initiative (WHI) HT study. The 2017 post-intervention follow-up WHI study revealed that HT did not increase long-term mortality. However, studies on the effects of the updated WHI findings are lacking. Thus, we assessed the impact of the 2017 WHI findings on HT use in Taiwan. METHODS: We identified 1,869,050 women aged 50-60 years, between June and December 2017, from health insurance claims data to compare HT use in the 3 months preceding and following September 2017. To address the limitations associated with interval-censored data, we employed an emulated repeated cross-sectional design. Using logistic regression analysis, we evaluated the impact of the 2017 WHI study on menopausal symptom-related outpatient visits and HT use. In a scenario analysis, we examined the impact of the 2002 trial on HT use to validate our study design. RESULTS: Study participants' baseline characteristics before and after the 2017 WHI study were not significantly different. Logistic regressions demonstrated that the 2017 study had no significant effect on outpatient visits for menopause-related symptoms or HT use among women with outpatient visits. The scenario analysis confirmed the negative impact of the 2002 WHI trial on HT use. CONCLUSIONS: The 2017 WHI study did not demonstrate any impact on either menopause-related outpatient visits or HT use among middle-aged women in Taiwan. Our emulated cross-sectional study design may be employed in similar population-based policy intervention studies using interval-censored data.

Accelerometer-derived physical activity and mortality in individuals with type 2 diabetes.

Physical activity (PA) has been shown to reduce diabetes mortality, but largely based on imprecise self-reported data, which may hinder the development of related recommendations. Here, we perform a prospective cohort study of 19,624 individuals with type 2 diabetes (T2D) from the UK Biobank with a median follow-up of 6.9 years. Duration and intensity of PA are measured by wrist-worn accelerometers over a 7-day period. We observe L-shaped associations of longer duration of PA, regardless of PA intensity, with risks of all-cause and cancer mortality, as well as a negatively linear association with cardiovascular disease mortality. 12.7%, 15.8%, and 22.3% of deaths are attributable to the lowest level of light-intensity, moderate-intensity PA, and vigorous-intensity PA, respectively. Collectively, our findings provide insights for clinical guidelines that should highlight the potential value of adherence to greater intensity and duration of PA for patients with T2D.

Recent advances in rational design for high-performance potassium-ion batteries.

The growing global energy demand necessitates the development of renewable energy solutions to mitigate greenhouse gas emissions and air pollution. To efficiently utilize renewable yet intermittent energy sources such as solar and wind power, there is a critical need for large-scale energy storage systems (EES) with high electrochemical performance. While lithium-ion batteries (LIBs) have been successfully used for EES, the surging demand and price, coupled with limited supply of crucial metals like lithium and cobalt, raised concerns about future sustainability. In this context, potassium-ion batteries (PIBs) have emerged as promising alternatives to commercial LIBs. Leveraging the low cost of potassium resources, abundant natural reserves, and the similar chemical properties of lithium and potassium, PIBs exhibit excellent potassium ion transport kinetics in electrolytes. This review starts from the fundamental principles and structural regulation of PIBs, offering a comprehensive overview of their current research status. It covers cathode materials, anode materials, electrolytes, binders, and separators, combining insights from full battery performance, degradation mechanisms, in situ/ex situ characterization, and theoretical calculations. We anticipate that this review will inspire greater interest in the development of high-efficiency PIBs and pave the way for their future commercial applications.

SARS-CoV-2 inflammation durably imprints memory CD4 T cells.

Memory CD4 T cells are critical to human immunity, yet it is unclear whether viral inflammation during memory formation has long-term consequences. Here, we compared transcriptional and epigenetic landscapes of Spike (S)-specific memory CD4 T cells in 24 individuals whose first exposure to S was via SARS-CoV-2 infection or mRNA vaccination. Nearly 2 years after memory formation, S-specific CD4 T cells established by infection remained enriched for transcripts related to cytotoxicity and for interferon-stimulated genes, likely because of a chromatin accessibility landscape altered by inflammation. Moreover, S-specific CD4 T cells primed by infection had reduced proliferative capacity in vitro relative to vaccine-primed cells. Furthermore, the transcriptional state of S-specific memory CD4 T cells was minimally altered by booster immunization and/or breakthrough infection. Thus, infection-associated inflammation durably imprints CD4 T cell memory, which affects the function of these cells and may have consequences for long-term immunity.

The microbiome compositional and functional differences between rectal mucosa and feces.

In recent years, most studies on the gut microbiome have primarily focused on feces samples, leaving the microbial communities in the intestinal mucosa relatively unexplored. To address this gap, our study employed shotgun metagenomics to analyze the microbial compositions in normal rectal mucosa and matched feces from 20 patients with colonic polyps. Our findings revealed a pronounced distinction of the microbial communities between these two sample sets. Compared with feces, the mucosal microbiome contains fewer genera, with Burkholderia being the most discriminating genus between feces and mucosa, highlighting its significant influence on the mucosa. Furthermore, based on the microbial classification and KEGG Orthology (KO) annotation results, we explored the association between rectal mucosal microbiota and factors such as age, gender, BMI, and polyp risk level. Notably, we identified novel biomarkers for these phenotypes, such as Clostridium ramosum and Enterobacter cloacae in age. The mucosal microbiota showed an enrichment of KO pathways related to sugar transport and short chain fatty acid metabolism. Our comprehensive approach not only bridges the knowledge gap regarding the microbial community in the rectal mucosa but also underscores the complexity and specificity of microbial interactions within the human gut, particularly in the Chinese population. IMPORTANCE: This study presents a system-level map of the differences between feces and rectal mucosal microbial communities in samples with colorectal cancer risk. It reveals the unique microecological characteristics of rectal mucosa and its potential influence on health. Additionally, it provides novel insights into the role of the gut microbiome in the pathogenesis of colorectal cancer and paves the way for the development of new prevention and treatment strategies.

Congenital Syphilis in Live Births: Adverse Outcomes, Hospital Length of Stay, and Costs.

OBJECTIVE: To examine temporal trends and risk factors for congenital syphilis in newborn hospitalizations and to evaluate the association between adverse outcomes and congenital syphilis and health care utilization for newborn hospitalizations complicated by congenital syphilis. METHODS: We conducted a retrospective, cross-sectional study using data from the National Inpatient Sample to identify newborn hospitalizations in the United States between 2016 and 2020. Newborns with congenital syphilis were identified with International Classification of Diseases, Tenth Revision, Clinical Modification codes. Adverse outcomes, hospital length of stay, and hospital costs were examined. The annual percent change was calculated to assess congenital syphilis trend. A multivariable Poisson regression model with robust error variance was used to examine the association between congenital syphilis and adverse outcomes. Adjusted relative risks (RRs) with 95% CIs were calculated. A multivariable generalized linear regression model was used to examine the association between congenital syphilis and hospital length of stay and hospital costs. Adjusted mean ratios with 95% CIs were calculated. RESULTS: Of 18,119,871 newborn hospitalizations in the United States between 2016 and 2020, the rate of congenital syphilis increased over time (annual percent change 24.6%, 95% CI, 13.0-37.3). Newborn race and ethnicity, insurance, household income, year of admission, and hospital characteristics were associated with congenital syphilis. In multivariable models, congenital syphilis was associated with preterm birth before 37 weeks of gestation (adjusted RR 2.22, 95% CI, 2.02-2.44) and preterm birth before 34 weeks of gestation (adjusted RR 2.39, 95% CI, 2.01-2.84); however, there was no association with low birth weight or neonatal in-hospital death. Compared with newborns without congenital syphilis, hospital length of stay (adjusted mean ratio 3.53, 95% CI, 3.38-3.68) and hospital costs (adjusted mean ratio 4.93, 95% CI, 4.57-5.32) were higher among those with congenital syphilis. CONCLUSION: Among newborn hospitalizations in the United States, the rate of congenital syphilis increased from 2016 to 2020. Congenital syphilis was associated with preterm birth, longer hospital length of stay, and higher hospital costs.

Increased FGF2 expression promotes immune cell infiltration and correlates with an unfavorable prognosis in thyroid cancer.

To delve into the expression and functions of FGF2 in patient with thyroid cancer (THCA), we conducted a systematic analysis of the association of FGF2 with immune cell infiltration, and prognosis in THCA patients. The transcription and protein levels, methylation, and biological properties of FGF2 were examined, along with its correlation with prognosis and immune cell infiltration in THCA patients using online databases UALCAN, Human Protein Atlas, Kaplan-Meier Plotter, DNMIVD, cBioPortal, GEPIA, Metascape, Linkedomics and TIMER. Clinical samples were collected for Western blot analyses. FGF2 was substantially overexpressed in the tumor group and shown correlations with age, tumor histology, nodal metastasis, and cancer stages. Moreover, higher expression of FGF2 (HR = 3.42, 95 % CI:1.57-7.44, p = 0.00099) was greatly correlated with poorer relapse-free survival in THCA patients, particularly in female patients. FGF2 methylation level was increased in the tumor group (p = 1.29E-6), and higher methylation levels of FGF2 were positively correlated with the poorer progression-free interval in THCA patients (p = 0.015). FGF2 mutations were markedly associated with shorter disease-free survival, with a mutation rate of 6 % among the total 498 THCA patients. FGF2 functions were potentially related to cell adhesion, cytokine-cytokine receptor interaction and angiogenesis. FGF2 expression showed positive correlations with the infiltration of B cells (Cor = 0.569, p = 1.04e-42), CD4+ T cells (Cor = 0.555, p = 9.43e-41), macrophages (Cor = 0.438, p = 2.94e-42), neutrophils (Cor = 0.578, p = 9.354e-45), and dendritic cells (Cor = 0.591, p = 5.00e-47). FGF2 is a potential prognostic marker in THCA patients, with its functions possibly related to cell adhesion, interaction of the cytokine-cytokine receptor, angiogenesis, and the promotion of multiple immune cell infiltration.

Protective effect of unsaturated fatty acids on cognitive impairment in CKD patients: Results from the National Health and Nutrition Examination Survey (2011-2014).

BACKGROUND: It is still unknown whether unsaturated fatty acids (UFA) have the same effect on preventing cognitive impairment in chronic kidney disease (CKD) patients as in healthy people. OBJECTIVE: To investigate the protective effect of dietary UFA intake and proportion on cognitive impairment in patients with CKD. METHODS: We extracted data from the National Health and Nutrition Examination Survey (NHANES, 2011-2014) on participants with a previous diagnosis of CKD and at least one complete cognitive assessment (Consortium to Establish a Registry for Alzheimer's Disease test, Animal Fluency Test and Digit Symbol Substitution Test). We used the lower quartile of the total scores of these three tests as the cut-off point, and divided the participants into two groups of normal cognitive performance and low cognitive performance to extract participants' intake of various UFA from the NHANES dietary module.

Denitrificimonas halotolerans sp. nov., a novel species isolated from UASB sludge treating landfill leachate.

A Gram-stain-negative, facultative anaerobe, rod-shaped strain JX-1T was isolated from UASB sludge treating landfill leachate in Wuhan, China. The isolate is capable of growing under conditions of pH 6.0-11.0 (optimum, pH 7.0-8.0), temperature 4-42 â„ƒ (optimum, 20-30 â„ƒ), 0-8.0% (w/v) NaCl (optimum, 5.0%), and ammonia nitrogen concentration of 200-5000 mg/L (optimum, 500 mg/L) on LB plates. The microorganism can utilize malic acid, D-galactose, L-rhamnose, inosine, and L-glutamic acid as carbon sources, but does not reduce nitrates and nitrites. The major fatty acids are C18:1ω7c/C18:1ω6c, iso-C15:0, and anteiso-C15:0. The respiratory quinones are Q9 (91.92%) and Q8 (8.08%). Polar lipids include aminolipid, aminophospholipid, diphosphatidylglycerol, glycolipid, phosphatidylethanolamine, phosphatidylglycerol, and phospholipid. Compared with other strains, strain JX-1T and Denitrificimonas caeni HY-14T have the highest values in terms of 16S rRNA gene sequence similarity (96.79%), average nucleotide identity (ANI; 76.06%), and average amino acid identity (AAI; 78.89%). Its digital DNA-DNA hybridization (dDDH) result is 20.3%. The genome of strain JX-1T, with a size of 2.78 Mb and 46.12 mol% G + C content, lacks genes for denitrification and dissimilatory nitrate reduction to ammonium (DNRA), but contains genes for ectoine synthesis as a secondary metabolite. The results of this polyphasic study allow genotypic and phenotypic differentiation of the analysed strain from the closest related species and confirm that the strain represents a novel species within the genus Denitrificimonas, for which the name Denitrificimonas halotolerans sp. nov. is proposed with JX-1T (= MCCC 1K08958T = KCTC 8395T) as the type strain.

Enhancing Zinc Electrode Stability Through Pre-Desolvation and Accelerated Charge Transfer via a Polyimide Interface for Zinc-Ion Batteries.

Aqueous zinc-based energy storage devices possess superior safety, cost-effectiveness, and high energy density; however, dendritic growth and side reactions on the zinc electrode curtail their widespread applications. In this study, these issues are mitigated by introducing a polyimide (PI) nanofabric interfacial layer onto the zinc substrate. Simulations reveal that the PI nanofabric promotes a pre-desolvation process, effectively desolvating hydrated zinc ions from Zn(H2O)6 2+ to Zn(H2O)4 2+ before approaching the zinc surface. The exposed zinc ion in Zn(H2O)4 2+ provides an accelerated charge transfer process and reduces the activation energy for zinc deposition from 40 to 21 kJ mol-1. The PI nanofabric also acts as a protective barrier, reducing side reactions at the electrode. As a result, the PI-Zn symmetric cell exhibits remarkable cycling stability over 1200 h, maintaining a dendrite-free morphology and minimal byproduct formation. Moreover, the cell exhibits high stability and low voltage hysteresis even under high current densities (20 mA cm-2, 10 mAh cm-2) thanks to the 3D porous structure of PI nanofabric. When integrated into full cells, the PI-Zn||AC hybrid zinc-ion capacitor and PI-Zn||MnVOH@SWCNT zinc-ion battery achieve impressive lifespans of 15000 and 600 cycles with outstanding capacitance retention. This approach paves a novel avenue for high-performance zinc metal electrodes.

Study of the Correlation between Streaming Video Platform Content on Food Production Processes and the Behavioral Intentions of Generation Z.

With an estimated 2.4 million cases of foodborne illnesses recorded annually in the UK alone, food safety has become a paramount concern among stakeholders. Modern technology has positioned streaming platforms as pivotal conduits for disseminating information. Channels such as YouTube offer detailed recordings of the food production process, granting consumers extensive visibility of the food journey from farm to table. This increased transparency not only promotes vigilant monitoring of food safety practices but also solicits consumer feedback regarding the public exposure to food processing videos. Based on the Theory of Planned Behavior (TPB), this study augments its framework with constructs, such as perceived trust, perceived risk, community experience, and brand identity, to evaluate Taiwan's Generation Z consumer behavioral intentions. With 226 valid responses amassed, structural equation modeling facilitated elucidation of the relationships among the constructs. This analysis yielded three salient insights. First, Generation Z's engagement with food processing videos on streaming platforms is positively correlated with their subsequent purchasing behavior. Second, enriched community experience was correlated with strengthened brand identification. Third, both perceived trust and perceived risk had a constructive impact on behavioral intentions within Gen Z's demographic data. Based on these outcomes, food industry enterprises should proactively develop and bolster community experiential value, thereby encouraging streaming platform users to transform into brand consumers and advocates.

Research on a Corrosion Detection Method for Oil Tank Bottoms Based on Acoustic Emission Technology.

This paper presents an acoustic emission (AE) detection method for refined oil storage tanks which is aimed towards specialized places such as oil storage tanks with high explosion-proof requirements, such as cave oil tanks and buried oil tanks. The method utilizes an explosion-proof acoustic emission instrument to detect the floor of a refined oil storage tank. By calculating the time difference between the defective acoustic signal and the speed of acoustic wave transmission, a mathematical model is constructed to analyze the detected signals. An independent channel AE detection system is designed, which can store the collected data in a piece of independent explosion-proof equipment, and can analyze and process the data in a safe area after the detection, solving the problems of a short signal acquisition distance and the weak safety protection applied to traditional AE instruments. A location analysis of the AE sources is conducted on the bottom plate of the tank, evaluating its corrosion condition accurately. The consistency between the evaluation and subsequent open-tank tests confirms that using AE technology effectively captures corrosion signals from oil storage tanks' bottoms. The feasibility of carrying out online inspection under the condition of oil storage in vertical steel oil tanks was verified through a comparison with open inspections, which provided a guide for determining the inspection target and opening order of large-scale oil tanks.

Ent-eudesmane sesquiterpenoids with anti-neuroinflammatory activity from the marine-derived fungus Eutypella sp. F0219.

In this study, twenty-three ent-eudesmane sesquiterpenoids (1-23) including fifteen previously undescribed ones, named eutypelides A-O (1-15) were isolated from the marine-derived fungus Eutypella sp. F0219. Their planar structures and relative configurations were established by HR-ESIMS and extensive 1D and 2D NMR investigations. The absolute configurations of the previously undescribed compounds were determined by single-crystal X-ray diffraction analyses, modified Mosher's method, and ECD calculations. Structurally, eutypelide A (1) is a rare 1,10-seco-ent-eudesmane, whereas 2-15 are typically ent-eudesmanes with 6/6/-fused bicyclic carbon nucleus. The anti-neuroinflammatory activity of all isolated compounds (1-23) was accessed based on their ability to NO production in LPS-stimulated BV2 microglia cells. Compound 16 emerged as the most potent inhibitor. Further mechanistic investigation revealed that compound 16 modulated the inflammatory response by decreasing the protein levels of iNOS and increasing ARG 1 levels, thereby altering the iNOS/ARG 1 ratio and inhibiting macrophage polarization. qRT-PCR analysis showed that compound 16 reversed the LPS-induced upregulation of pro-inflammatory cytokines, including iNOS, TNF-α, IL-6, and IL-1ß, at both the transcriptional and translational levels. These effects were linked to the inhibition of the NF-κB pathway, a key regulator of inflammation. Our findings suggest that compound 16 may be a potential structure basis for developing neuroinflammation-related disease therapeutic agents.

Integrative multi-omics profiling in human decedents receiving pig heart xenografts.

In a previous study, heart xenografts from 10-gene-edited pigs transplanted into two human decedents did not show evidence of acute-onset cellular- or antibody-mediated rejection. Here, to better understand the detailed molecular landscape following xenotransplantation, we carried out bulk and single-cell transcriptomics, lipidomics, proteomics and metabolomics on blood samples obtained from the transplanted decedents every 6 h, as well as histological and transcriptomic tissue profiling. We observed substantial early immune responses in peripheral blood mononuclear cells and xenograft tissue obtained from decedent 1 (male), associated with downstream T cell and natural killer cell activity. Longitudinal analyses indicated the presence of ischemia reperfusion injury, exacerbated by inadequate immunosuppression of T cells, consistent with previous findings of perioperative cardiac xenograft dysfunction in pig-to-nonhuman primate studies. Moreover, at 42 h after transplantation, substantial alterations in cellular metabolism and liver-damage pathways occurred, correlating with profound organ-wide physiological dysfunction. By contrast, relatively minor changes in RNA, protein, lipid and metabolism profiles were observed in decedent 2 (female) as compared to decedent 1. Overall, these multi-omics analyses delineate distinct responses to cardiac xenotransplantation in the two human decedents and reveal new insights into early molecular and immune responses after xenotransplantation. These findings may aid in the development of targeted therapeutic approaches to limit ischemia reperfusion injury-related phenotypes and improve outcomes.