Role of UFMylation in tumorigenesis and cancer immunotherapy.

Protein post-translational modifications (PTMs) represent a crucial aspect of cellular regulation, occurring after protein synthesis from mRNA. These modifications, which include phosphorylation, ubiquitination, acetylation, methylation, glycosylation, Sumoylation, and palmitoylation, play pivotal roles in modulating protein function. PTMs influence protein localization, stability, and interactions, thereby orchestrating a variety of cellular processes in response to internal and external stimuli. Dysregulation of PTMs is linked to a spectrum of diseases, such as cancer, inflammatory diseases, and neurodegenerative disorders. UFMylation, a type of PTMs, has recently gained prominence for its regulatory role in numerous cellular processes, including protein stability, response to cellular stress, and key signaling pathways influencing cellular functions. This review highlights the crucial function of UFMylation in the development and progression of tumors, underscoring its potential as a therapeutic target. Moreover, we discuss the pivotal role of UFMylation in tumorigenesis and malignant progression, and explore its impact on cancer immunotherapy. The article aims to provide a comprehensive overview of biological functions of UFMylation and propose how targeting UFMylation could enhance the effectiveness of cancer immunotherapy strategies.

High throughput mRNA sequencing reveals potential therapeutic targets of Si-Ni-San in the pons for a stress-induced depression model.

Background: An accumulating body of research indicates that the pons is related to the occurrence of depression. Si-Ni-San (SNS) is a well-known Chinese herbal formula that is used to treat depression. Chinese herbal formulae have multiple therapeutic characteristics. Although it has been proven that SNS can exert antidepressant effects by improving changes in the limbic system, it is currently unclear whether SNS has therapeutic targets in the pons. This study aimed to explore the therapeutic targets of SNS in the pons for depression treatment. Materials and methods: Two experiments were conducted. In Experiment 1, 32 rats were divided into four groups: (1) a Control (C) group that received distilled water as a vehicle; (2) a Model (M) group that received the chronic unpredictable mild stress (CUMS) procedure and was administered distilled water; (3) a Stress + SNS (MS) group that received the CUMS procedure and was administered SNS dissolved in distilled water; and (4) a Stress + Fluoxetine (MF) group that received the CUMS procedure and was administered fluoxetine dissolved in distilled water. The open field test (OFT), the sucrose preference test (SPT), and the novel object recognition test (NOR) were performed to test the antidepressant effects of SNS. High-throughput mRNA sequencing (RNA-seq) was used to explore possible gene targets of SNS in the pons, and quantitative real-time PCR was performed to verify the results. High-performance liquid chromatography was used to detect neurotransmitters. Finally, correlation analyses were conducted between behaviors, genes expression, and neurotransmitters. In Experiment 2, 18 rats were divided into the same three groups as in Experiment 1: (1) C, (2) M, and (3) MS. fMRI was used to confirm whether SNS altered the pons in a rat model of depression. Results: SNS significantly improved sucrose preference in the SPT and TN-TO in the NOR compared to the M group (P < 0.05). RNA-seq filtered 49 differentially expressed genes(DEGs) that SNS could reverse in the pons of the CUMS depression model. Real-time PCR detected six genes, including Complexin2 (Cplx2), Serpinf1, Neuregulin1 (Nrg1), Annexin A1 (Anxa1), ß-arrestin 1 (Arrb1) and presenilin 1 (Psen1). SNS significantly reversed changes in the expression of Anxa1, Nrg1, and Psen1 caused by CUMS (P < 0.05), which is consistent with the DEGs results. Additionally, SNS significantly reversed norepinephrine (NE) changes in the pons. There were 18 noteworthy correlations between behavior, genes, and neurotransmitters (P < 0.05). fMRI showed that SNS can decrease the amplitude of low-frequency fluctuations (ALFF) in the pons of living depressed rats. Conclusion: The pons is an important target brain region for SNS to exert its antidepressant effects. SNS may improve pontine NE levels by regulating the Anxa1, Nrg1, and Psen1 genes, thereby exerting antidepressant effects and improving cognitive function.

Improvement of early miscarriage rates in women with adenomyosis via oxytocin receptor antagonist during frozen embryo transfer-a propensity score-matched study.

BACKGROUND: Dysfunctional uterine peristalsis seems to play a pivotal role in hindering embryo implantation among women diagnosed with adenomyosis. This research aims to investigate whether administering an oxytocin receptor antagonist during a frozen embryo transfer (FET) cycle using a hormone replacement therapy (HRT) protocol can enhance in vitro fertilization (IVF) outcomes for infertile women affected by adenomyosis. METHODS: Between January 2018 and June 2022, our reproductive center conducted IVF-FET HRT cycles for infertile women diagnosed with adenomyosis. Propensity score matching was employed to select matched subjects between the two groups in a 1:1 ratio. Following this, 168 women received an oxytocin receptor antagonist during FET, constituting the study group, while the matched 168 women underwent FET without this antagonist, forming the control group. We conducted comparative analyses of baseline and cycle characteristics between the two groups, along with additional subgroup analyses. RESULTS: The study group exhibited notably lower rates of early miscarriage compared to the control group, although there were no significant differences in clinical pregnancy rates, ongoing pregnancy rates, and live birth rates between the two groups. Multivariate analysis revealed a negative correlation between the use of oxytocin receptor antagonists and early miscarriage rates in women with adenomyosis. Subgroup analyses, categorized by age, infertility types, and embryo transfer day, showed a substantial decrease in early miscarriage rates within specific subgroups: women aged ≥ 37 years, those with secondary infertility, and individuals undergoing day 3 embryo transfers in the study group compared to the control group. Furthermore, subgroup analysis based on adenomyosis types indicated significantly higher clinical pregnancy rates, ongoing pregnancy rates and live birth rates in the study group compared to the control group among women with diffuse adenomyosis. CONCLUSIONS: Administering an oxytocin receptor antagonist during FET may reduce the early miscarriage rates in women with adenomyosis.

TGF-ß1 mediates hypoxia-preconditioned olfactory mucosa mesenchymal stem cells improved neural functional recovery in Parkinson's disease models and patients.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN). Activation of the neuroinflammatory response has a pivotal role in PD. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for various nerve injuries, but there are limited reports on their use in PD and the underlying mechanisms remain unclear. METHODS: We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa (hOM)-MSCs on neural functional recovery in both PD models and patients, as well as the preventive effects on mouse models of PD. To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure, we employed single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) combined with full-length transcriptome isoform-sequencing (ISO-seq), and functional assay. Furthermore, we present the findings from an initial cohort of patients enrolled in a phase I first-in-human clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients. RESULTS: A functional assay identified that transforming growth factor-ß1 (TGF-ß1), secreted from hOM-MSCs, played a critical role in modulating mitochondrial function recovery in dopaminergic neurons. This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN, which are closely associated with neuroinflammatory responses. Mechanistically, exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-ß1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B (ALK/PI3K/Akt) signaling pathway in microglia located in the SN of PD patients. Furthermore, intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD. CONCLUSIONS: These findings provide compelling evidence for the involvement of TGF-ß1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD. Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD. Additionally, TGF-ß1 may be used alone or combined with hOM-MSCs therapy for treating PD.

Intravascular Laser Blood Irradiation (ILIB) Enhances Antioxidant Activity and Energy Metabolism in Aging Ovaries.

BACKGROUND: Ovarian aging is characterized by the accumulation of free radicals, leading to tissue damage and affecting reproductive health. Intravascular laser irradiation of blood (ILIB, using a low-energy He-Ne laser) is known for its efficacy in treating vascular-related diseases by reducing free radicals and inflammation. However, its impact on ovarian aging remains unexplored. This study aimed to investigate the effects of ILIB on oxidative stress and energy metabolism in aging ovaries. METHODS: Genetic analysis was conducted on 75 infertile patients with aging ovaries, divided into ILIB-treated and control (CTRL) groups. Patients underwent two courses of laser treatment, and clinical parameters were evaluated. Cumulus cells were collected for the genetic analysis of oxeiptosis, glycolysis, and the tricarboxylic acid (TCA) cycle. RESULTS: The analysis of gene expression patterns revealed intriguing findings in ILIB-treated patients compared to the untreated group. Notably, ILIB treatment resulted in significant upregulation of oxeiptosis-related genes AIFM1 and NRF2, suggesting a potential protective effect against oxidative stress-induced cell death. Furthermore, ILIB treatment led to a downregulation of glycolysis-associated gene hexokinase 2 (HK2), indicating a shift away from anaerobic metabolism, along with an increase in PDHA levels, indicative of enhanced mitochondrial function. Consistent with these changes, ILIB-treated patients exhibited elevated expression of the key TCA cycle genes citrate synthase (CS), succinate dehydrogenase complex subunit A (SDHA), and fumarate hydratase (FH), signifying improved energy metabolism. CONCLUSION: The findings from this study underscore the potential of ILIB as a therapeutic strategy for mitigating ovarian aging. By targeting oxidative stress and enhancing energy metabolism, ILIB holds promise for preserving ovarian function and reproductive health in aging individuals. Further research is warranted to elucidate the underlying mechanisms and optimize the application of ILIB in clinical settings, with the ultimate goal of improving fertility outcomes in women experiencing age-related ovarian decline.

Pilot Study on Next-Generation Sequencing Analysis of Vaginal Microbiota in Clinically Infertile Patients Treated with Probiotics.

Background: In this investigation, we aimed to understand the influence of oral probiotic supplementation on the vaginal microbiota of women preparing for assisted reproductive technology (ART) procedures. Given the importance of a healthy microbiome for reproductive success, this study sought to explore how probiotics might alter the bacterial composition in the vaginal environment. Methods: We recruited a cohort of 30 women, averaging 37 years of age (ranging from 31 to 43 years), who were scheduled to undergo ART. Using 16S ribosomal RNA (rRNA) sequencing, we meticulously analyzed the vaginal microbiota composition before and after the administration of oral probiotic supplements. Results: Our analysis identified 17 distinct microorganisms, including 8 species of Lactobacillus. Following probiotic supplementation, we observed subtle yet notable changes in the vaginal microbiota of some participants. Specifically, there was a decrease in Gardnerella abundance by approximately 20%, and increases in Lactobacillus and Bifidobacterium by 10% and 15%, respectively. Additionally, we noted a significant reduction in the Firmicutes/Bacteroidetes (F/B) ratio in the probiotic group, indicating potential shifts in the overall bacterial composition. Conclusions: These preliminary findings suggest that oral probiotic supplementation can induce significant changes in the vaginal microbiota of middle-aged women undergoing ART, potentially improving their overall bacterial profile. Future studies should consider a larger sample size and a narrower age range to validate these results. Investigating factors related to female hormone production could also provide deeper insights. Understanding the effects of probiotics on the vaginal microbiota in patients with ovarian aging may lead to personalized interventions and better reproductive outcomes.

Discovery of Novel Spike Inhibitors against SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current coronavirus disease pandemic. With the rapid evolution of variant strains, finding effective spike protein inhibitors is a logical and critical priority. Angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor for SARS-CoV-2 viral entry, and thus related therapeutic approaches associated with the spike protein-ACE2 interaction show a high degree of feasibility for inhibiting viral infection. Our computer-aided drug design (CADD) method meticulously analyzed more than 260,000 compound records from the United States National Cancer Institute (NCI) database, to identify potential spike inhibitors. The spike protein receptor-binding domain (RBD) was chosen as the target protein for our virtual screening process. In cell-based validation, SARS-CoV-2 pseudovirus carrying a reporter gene was utilized to screen for effective compounds. Ultimately, compounds C2, C8, and C10 demonstrated significant antiviral activity against SARS-CoV-2, with estimated EC50 values of 8.8 µM, 6.7 µM, and 7.6 µM, respectively. Using the above compounds as templates, ten derivatives were generated and robust bioassay results revealed that C8.2 (EC50 = 5.9 µM) exhibited the strongest antiviral efficacy. Compounds C8.2 also displayed inhibitory activity against the Omicron variant, with an EC50 of 9.3 µM. Thus, the CADD method successfully discovered lead compounds binding to the spike protein RBD that are capable of inhibiting viral infection.

Establishment of a Dual-Signal Enhanced Fluorescent Aptasensor for Highly Sensitive Detection of Ochratoxin A.

A robust and versatile dual-signal enhanced fluorescent aptasensor was developed for ochratoxin A (OTA) detection based on fluorescence resonance energy transfer between 5-carboxyfluorescein (FAM) and Super Green I (SG) fluorophores as the donor and graphene oxide (GO) nanosheet as the acceptor. Abundant SG probes were adsorbed into the FAM-complementary DNA (cDNA)-aptamer double-stranded structure to achieve remarkably enhanced fluorescence responses. Without OTA, the FAM-cDNA-SG conjugates coexisted with GO nanosheets, exhibiting strong fluorescence signals. In the presence of OTA, it was captured by the aptamers to release cDNA-FAM and SG probes, which were adsorbed by GO, leading to OTA-dependent fluorescence quenching. The changed fluorescence intensity was measured for accurate quantitation of OTA. Under optimum conditions, the dual-signal enhanced fluorescent aptasensor realized fascinating sensitivity with a limit of detection of 0.005 ng/mL and a wide concentration range of 0.02-20 ng/mL, as well as high selectivity for OTA over other interfering substances, excellent accuracy with average recoveries of 91.37-116.83% in the fortified malt matrices, and superior reliability and practicability in actual samples. This FAM-cDNA-aptamer-SG/GO nanosheet-based aptasensing platform could be extended to monitor other contaminants or trace molecules in food, environmental, and diagnostic fields by altering the corresponding aptamers.

Examining the Effects of Nutrient Supplementation on Metabolic Pathways via Mitochondrial Ferredoxin in Aging Ovaries.

As women age, oocytes are susceptible to a myriad of dysfunctions, including mitochondrial dysfunction, impaired DNA repair mechanisms, epigenetic alterations, and metabolic disturbances, culminating in reduced fertility rates among older individuals. Ferredoxin (FDX) represents a highly conserved iron-sulfur (Fe-S) protein essential for electron transport across multiple metabolic pathways. Mammalian mitochondria house two distinct ferredoxins, FDX1 and FDX2, which share structural similarities and yet perform unique functions. In our investigation into the regulatory mechanisms governing ovarian aging, we employed a comprehensive multi-omics analysis approach, integrating spatial transcriptomics, single-cell RNA sequencing, human ovarian pathology, and clinical biopsy data. Previous studies have highlighted intricate interactions involving excessive lipid peroxide accumulation, redox-induced metal ion buildup, and alterations in cellular energy metabolism observed in aging cells. Through a multi-omics analysis, we observed a notable decline in the expression of the critical gene FDX1 as ovarian age progressed. This observation prompted speculation regarding FDX1's potential as a promising biomarker for ovarian aging. Following this, we initiated a clinical trial involving 70 patients with aging ovaries. These patients were administered oral nutritional supplements consisting of DHEA, ubiquinol CoQ10, and Cleo-20 T3 for a period of two months to evaluate alterations in energy metabolism regulated by FDX1. Our results demonstrated a significant elevation in FDX1 levels among participants receiving nutritional supplementation. We hypothesize that these nutrients potentiate mitochondrial tricarboxylic acid cycle (TCA) activity or electron transport chain (ETC) efficiency, thereby augmenting FDX1 expression, an essential electron carrier in metabolic pathways, while concurrently mitigating lipid peroxide accumulation and cellular apoptosis. In summary, our findings underscore the potential of nutritional intervention to enhance in vitro fertilization outcomes in senescent cells by bolstering electron transport proteins, thus optimizing energy metabolism and improving oocyte quality in aging women.

Genetic predisposition to bone mineral density and their health conditions in East Asians.

Osteoporosis, a condition defined by low BMD (typically < -2.5 SD), causes a higher fracture risk and leads to significant economic, social, and clinical impacts. Genome-wide studies mainly in Caucasians have found many genetic links to osteoporosis, fractures, and BMD, with limited research in East Asians (EAS). We investigated the genetic aspects of BMD in 86 716 individuals from the Taiwan Biobank and their causal links to health conditions within EAS. A genome-wide association study (GWAS) was conducted, followed by observational studies, polygenic risk score assessments, and genetic correlation analyses to identify associated health conditions linked to BMD. GWAS and gene-based GWAS studies identified 78 significant SNPs and 75 genes related to BMD, highlighting pathways like Hedgehog, WNT-mediated, and TGF-ß. Our cross-trait linkage disequilibrium score regression analyses for BMD and osteoporosis consistently validated their genetic correlations with BMI and type 2 diabetes (T2D) in EAS. Higher BMD was linked to lower osteoporosis risk but increased BMI and T2D, whereas osteoporosis linked to lower BMI, waist circumference, hemoglobinA1c, and reduced T2D risk. Bidirectional Mendelian randomization analyses revealed that a higher BMI causally increases BMD in EAS. However, no direct causal relationships were found between BMD and T2D, or between osteoporosis and either BMI or T2D. This study identified key genetic factors for bone health in Taiwan, and revealed significant health conditions in EAS, particularly highlighting the genetic interplay between bone health and metabolic traits like T2D and BMI.

We investigated how genetics affect bone health and related conditions like diabetes and obesity in 86 716 EAS. Previously, most studies focused on Caucasian populations, but our work helps to understand these issues in EAS. Our findings show that stronger bones are linked to a lower chance of osteoporosis but a higher risk of obesity and T2D. On the other hand, those with osteoporosis tend to have lower body weight and a decreased risk of diabetes, illustrating a complex relationship between bone health and body metabolism. Future research will focus on deeper genetic interactions and developing targeted interventions for bone health and related metabolic disorders in EAS.

A comparative analysis reveals the genomic diversity among 8 Muscovy duck populations.

The Muscovy duck (Cairina moschata) is a waterfowl indigenous to the neotropical regions of Central and South America. It has low demand for concentrated feed and strong adaptability to different rearing conditions. After introduced to China through Eurasian commercial trade, Muscovy ducks have a domestication history of around 300 years in the Fujian Province of China. In the 1990s, the commodity Muscovy duck breed "Crimo," cultivated in Europe, entered the Chinese market for consumption and breeding purposes. Due to the different selective breeding processes, Muscovy ducks have various populational traits and lack transparency of their genetic background. To remove this burden in the Muscovy duck breeding process, we analyzed genomic data from 8 populations totaling 83 individuals. We identify 11.24 million single nucleotide polymorphisms (SNPs) and categorized these individuals into the Fujian-bred and the Crimo populations according to phylogenetic analyses. We then delved deeper into their evolutionary relationships through assessing population structure, calculating fixation index (FST) values, and measuring genetic distances. Our exploration of runs of homozygosity (ROHs) and homozygous-by-descent (HBD) uncovered genomic regions enriched for genes implicated in fatty acid metabolism, development, and immunity pathways. Selective sweep analyses further indicated strong selective pressures exerted on genes including TECR, STAT2, and TRAF5. These findings provide insights into genetic variations of Muscovy ducks, thus offering valuable information regarding genetic diversity, population conservation, and genome associated with the breeding of Muscovy ducks.

Two swords combination: Smartphone-assisted ratiometric fluorescent and paper sensors for dual-mode detection of glyphosate in edible malt.

The long-term and excessive use of glyphosate (GLY) in diverse matrices has caused serious hazard to the human and environment. However, the ultrasensitive detection of GLY still remains challenging. In this study, the smartphone-assisted dual-signal mode ratiometric fluorescent and paper sensors based on the red-emissive gold nanoclusters (R-AuNCs) and blue-emissive carbon dots (B-CDs) were ingeniously designed accurate and sensitive detection of GLY. Upon the presence of GLY, it would quench the fluorescence of B-CDs through dynamic quenching effect, and strengthen the fluorescence response of R-AuNCs due to aggregation-induced enhancement effect. Through calculating the GLY-induced fluorescence intensity ratio of B-CDs to R-AuNCs by using a fluorescence spectrophotometer, low to 0.218 µg/mL of GLY could be detected in lab in a wide concentration range of 0.3-12 µg/mL with high recovery of 94.7-103.1% in the spiked malt samples. The smartphone-assisted ratiometric fluorescent sensor achieved in the 96-well plate could monitor 0-11 µg/mL of GLY with satisfactory recovery of 94.1-107.0% in real edible malt matrices for high-throughput analysis. In addition, a portable smartphone-assisted ratiometric paper sensor established through directly depositing the combined B-CDs/R-AuNCs probes on the test strip could realize on-site measurement of 2-8 µg/mL of GLY with good linear relationship. This study provides new insights into developing the dual-signal ratiometric sensing platforms for the in-lab sensitive detection, high-throughput analysis, and on-site portable measurement of more trace contaminants in foods, clinical and environmental samples.

Cyclic peroxides and analogs: Antibacterial, antimalarial, and cytotoxic marine products from Xisha sponge Diacarnus sp.

A chemical investigation of the dichloromethane extract from the Xisha sponge Diacarnus sp. revealed seven undescribed norterpene cyclic peroxides, named diacarperoxides T-Z, and five unreported related norterpenes, named diacarnoids E-I, and eleven previously reported compounds. The structures of these isolated compounds, including their absolute configurations, were elucidated based on extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, Snatzke's method, [Rh2(OCOCF3)4]-induced ECD spectra, and modified Mosher's method. Bioassays were performed to assess the antibacterial activity against six pathogenic bacteria, cytotoxicities toward three cancer cell lines, and antimalarial activity against Plasmodium parasites. Most of the cyclic peroxides exhibited substantial antibacterial activity (MIC 1-8 µg/mL). Diacarperoxide W and nuapapuin A showed substantial antimalarial activity with IC50 values of 0.98 and 2.83 µM. Moreover, many compounds exhibited <50% cell survival rates, and IC50 values of 0.22-6.33 µM. The apoptosis assay showed that nuapapuin A induced cancer cell apoptosis in a dose-dependent manner.

Cuproptosis-Related Gene FDX1 Identified as a Potential Target for Human Ovarian Aging.

Cuproptosis is a recently discovered mode of cell death that has garnered attention due to its association with various diseases. However, the intricate genetic relationship between cuproptosis and ovarian aging has remained largely unexplored. This study aimed to bridge this knowledge gap by leveraging data sets related to ovarian aging and cuproptosis. Through comprehensive bioinformatics analyses, facilitated by R software, we uncovered FDX1 as a potential cuproptosis-related gene with relevance to ovarian aging. To gain insights into FDX1's role, we conducted spatial transcriptome analyses in the ovaries of both young and aged female mice. These experiments revealed a significant reduction in FDX1 expression in the aging group compared to the young group. To substantiate these findings at the genetic level, we turned to clinical infertility biopsies. Impressively, we observed consistent results in biopsies from elderly infertile patients, reinforcing the link between FDX1 and ovarian aging. Moreover, we delved into the pharmacogenomics of ovarian cell lines and discovered that FDX1 expression levels were intricately associated with heightened sensitivity to specific small molecule drugs. This observation suggests that modulating FDX1 could potentially be a strategy to influence drug responses in ovarian-related therapies. In sum, this study marks a pioneering effort in identifying FDX1 as a cuproptosis-related gene implicated in ovarian aging. These findings hold substantial promise, not only in shedding light on the underlying mechanisms of ovarian aging but also in positioning FDX1 as a potential diagnostic biomarker and therapeutic target. With further research, FDX1 could play a pivotal role in advancing precision medicine and therapies for ovarian-related conditions.

New Diterpenes and Diterpene Glycosides with Antibacterial Activity from Soft Coral Lemnalia bournei.

Five new biflorane-type diterpenoids, biofloranates E-I (1-5), and two new bicyclic diterpene glycosides, lemnaboursides H-I (6-7), along with the known lemnabourside, were isolated from the South China Sea soft coral Lemnalia bournei. Their chemical structures and stereochemistry were determined based on extensive spectroscopic methods, including time-dependent density functional theory (TDDFT) ECD calculations, as well as a comparison of them with the reported values. The antibacterial activities of the isolated compounds were evaluated against five pathogenic bacteria, and all of these diterpenes and diterpene glycosides showed antibacterial activities against Staphylococcus aureus and Bacillus subtilis, with MICs ranging from 4 to 64 µg/mL. In addition, these compounds did not exhibit noticeable cytotoxicities on A549, Hela, and HepG2 cancer cell lines, at 20 µM.

Exposure and health risk assessment of volatile organic compounds among drivers and passengers in long-distance buses.

Exposure to volatile organic compounds (VOCs) such as benzene, toluene, ethylbenzene, xylene, and formaldehyde from long-distance buses has been reported to adversely affect human health. This study investigates the concentrations of these five VOCs and evaluates their health risks to drivers and passengers on board. Ten trips from Taipei to Taichung were performed during the warm and cold seasons of 2021-2022. Two locations inside the bus were established to collect air samples by a 6-liter canister for drivers and passengers. Exposure concentrations of benzene, toluene, ethylbenzene, and xylene were analyzed via gas chromatography with a flame ionization detector and the formaldehyde concentration was monitored using a formaldehyde meter. Subsequently, a Monte Carlo simulation was conducted to evaluate the carcinogenic and non-carcinogenic risks of the five VOCs. Formaldehyde emerged as the highest detected compound (9.06 ± 3.77 µg/m3), followed by toluene (median: 6.11 µg/m3; range: 3.86-14.69 µg/m3). In particular, formaldehyde was identified to have the significantly higher concentration during non-rush hours (10.67 ± 3.21 µg/m3) than that during rush hours (7.45 ± 3.41 µg/m3) and during the warm season (10.71 ± 2.97 µg/m3) compared with that during the cold season (7.41 ± 4.26 µg/m3). Regarding non-carcinogenic risks to drivers and passengers, the chronic hazard indices for these five VOCs were under 1 to indicate an acceptable risk. In terms of carcinogenic risk, the median risks of benzene and formaldehyde for drivers were 2.88 × 10-6 (95% confidence interval [CI]: 2.11 × 10-6 - 5.13 × 10-6) and 1.91 × 10-6 (95% CI: 4.54 × 10-7 - 3.44 × 10-6), respectively. In contrast, the median carcinogenic risks of benzene and formaldehyde for passengers were less than 1 × 10-6 to present an acceptable risk. This study suggests that benzene and formaldehyde may present carcinogenic risks for drivers. Moreover, the non-carcinogenic risk for drivers and passengers is deemed acceptable. We recommended that the ventilation frequency be increased to mitigate exposure to VOCs in long-distance buses.

Chronic kidney disease and cognitive performance: NHANES 2011-2014.

PURPOSE: Previous studies suggest an association between chronic kidney disease (CKD) and cognitive impairment. The purpose of this study was to explore the association between the diverse stages of CKD and the cognitive performance of elderly American adults. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were used. Multivariate adjusted logistic regression, subgroup analysis, and the restricted cubic spline model were used to assess the associations of CKD stage and estimated glomerular filtration rate (eGFR) with cognitive performance. The measures used to evaluate cognitive function included the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test, the Animal Fluency test, and the Digit Symbol Substitution test (DSST). RESULTS: This study included 2234 participants aged ≥ 60 years. According to the fully adjusted model, stages 3-5 CKD were significantly associated with the CERAD test score (OR = 0.70, 95% CI [0.51, 0.97], p = 0.033), the Animal Fluency test score (OR = 0.64, 95% CI [0.48, 0.85], p = 0.005), and the DSST score (OR = 0.60, 95% CI [0.41, 0.88], p = 0.013). In addition, the incidence of poor cognitive function increased with decreasing eGFR, especially for individuals with low and moderate eGFRs. Both the DSST score (p nonlinearity < 0.0001) and the Animal Fluency test score (p nonlinearity = 0.0001) had nonlinear dose-response relationships with the eGFR. However, a linear relationship was shown between the eGFR and CERAD test score (p nonlinearity = 0.073). CONCLUSIONS: CKD, especially stages3-5 CKD, was significantly associated with poor cognitive performance in terms of executive function, learning, processing speed, concentration, and working memory ability. All adults with CKD should be screened for cognitive impairment.

Wallace melon juice fermented with Lactobacillus alleviates dextran sulfate sodium-induced ulcerative colitis in mice through modulating gut microbiota and the metabolism.

Fermented foods have shown promise in preventing or treating ulcerative colitis (UC) via regulating intestinal flora and correcting metabolic disorders. However, the prevention effect of fermented Wallace melon juice (FMJ) on UC is unclear. In this study, the effects of FMJ on dextran sodium sulfate (DSS)-induced UC were investigated via 16S rRNA sequencing and non-targeted metabolomics. The results showed that FMJ was effective in alleviating the symptoms of UC, reducing histological damage and oxidative stress, decreasing the levels of pro-inflammatory cytokines. After FMJ treatment, the level of propionic acid, butyric acid, and valeric acid increased by 14.1%, 44.4%, and 52.4% compared to DSS-induced UC mice. Meanwhile, the levels of harmful bacteria such as Oscillospira, Bacteroidetes, and Erysipelotrichaceae and Clostridium decreased, while the levels of beneficial bacteria such as Akkermansia, Lactobacillus, and Bifidobacterium increased. Fecal metabolomics analysis identified 31 differential metabolites, which could regulate metabolic disorders in UC mice by controlling the primary bile acid biosynthesis, purine metabolism, and pantothenate and CoA biosynthesis pathway. Additionally, the abundances of butyric acid, bile acids, and pantothenic acid were positively correlated with Allobaculum, Bifidobacterium, and other beneficial bacteria (R2 > 0.80, p < 0.01). The results indicated that FMJ played a role in regulating the structure of intestinal flora, which in turn helped in repairing metabolic disorders and alleviated colitis inflammation.