Lipid droplets in the nervous system: involvement in cell metabolic homeostasis.

Lipid droplets serve as primary storage organelles for neutral lipids in neurons, glial cells, and other cells in the nervous system. Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum. Previously, lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis; however, recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system. In addition to their role in regulating cell metabolism, lipid droplets play a protective role in various cellular stress responses. Furthermore, lipid droplets exhibit specific functions in neurons and glial cells. Dysregulation of lipid droplet formation leads to cellular dysfunction, metabolic abnormalities, and nervous system diseases. This review aims to provide an overview of the role of lipid droplets in the nervous system, covering topics such as biogenesis, cellular specificity, and functions. Additionally, it will explore the association between lipid droplets and neurodegenerative disorders. Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

Integration of Epigenome and Lactylome Reveals the Regulation of Lipid Production in Nannochloropsis oceanica.

Lysine lactylation (Kla) is a kind of novel post-translational modification (PTM) that participates in gene expression and various metabolic processes. Nannochloropsis has a remarkable capacity for triacylglycerol (TAG) production under nitrogen stress. To elucidate the involvement of lactylation in lipid synthesis, we conducted chromatin immunoprecipitation sequencing (ChIP-seq) and mRNA-seq analyses to monitor lactylation modifications and transcriptome alterations in Nannochloropsis oceanica. In all, 2057 genes showed considerable variation between nitrogen deprivation (ND) and nitrogen repletion (NR) conditions. Moreover, a total of 5375 differential Kla peaks were identified, including 5331 gain peaks and 44 loss peaks under ND vs NR. The differential Kla peaks were primarily distributed in the promoter (≤1 kb) (71.07%), 5'UTR (22.64%), and exon (4.25%). Integrative analysis of ChIP-seq, transcriptome, and previous proteome and lactylome data elucidates the potential mechanism by which lactylation promotes lipid accumulation under ND. Lactylation facilitates autophagy and protein degradation, leading to the recycling of carbon into the tricarboxylic acid (TCA) cycle, thereby providing carbon precursors for lipid synthesis. Additionally, lactylation induces the redirection of carbon from membrane lipids to TAG by upregulating lipases and enhancing the TCA cycle and ß-oxidation pathways. This research offers a new perspective for the investigation of lipid biosynthesis in Nannochloropsis.

Effects of long-term intake of carotenoid-enriched eggs on healthy people: a randomized controlled study.

Red palm oil, a natural repository abundant in tocotrienols, tocopherols and carotenoids, is frequently employed as a pigment and nutritional enhancer in food products. The principal aim of this study is to explore the disparities in vitamin A levels, fatty acid profiles and gut microbiota among healthy adults who consume carotenoid-enriched eggs compared to those who consume normal eggs. A total of 200 hens were randomly assigned to either the red palm oil group or the soybean oil group, with the objective of producing carotenoid-enriched eggs and normal eggs. Throughout a six-month, double-blinded, randomized controlled trial, participants were instructed to consume one carotenoid-enriched or normal egg daily at a fixed time. Fecal and blood samples were collected from the participants at the start and conclusion of the six-month intervention period for further analysis. Our findings indicated that there was no significant change in the vitamin A level for daily supplementation with one carotenoid-enriched egg, but there were significant changes in some indicators of fatty acid profiles and gut microbiota compared to the control group of the population. Nonetheless, the consumption of eggs, regardless of carotenoid-enriched eggs or normal eggs, positively influenced dietary habits by reducing the intake of saturated fatty acids and enhancing the intake of monounsaturated and polyunsaturated fatty acids of the population.

Effects of Sweet and Forge Sorghum Silages Compared to Maize Silage without Additional Grain Supplement on Lactation Performance and Digestibility of Lactating Dairy Cows.

This study investigated the effects of replacing maize silage (MZS) with high-sugar sorghum silage (HSS) or forage sorghum silage (FSS) without additional grain supplement in the diets of dairy cows on nutrient digestibility, milk composition, nitrogen (N) use, and rumen fermentation. Twenty-four Chinese Holstein cows (545 ± 42.8 kg; 21.41 ± 0.62 kg milk yield; 150 ± 5.6 days in milk) were randomly assigned to three dietary treatments (n = 8 cows/treatment). The cows were fed ad libitum total mixed rations containing (dry matter basis) either 40% MZS (MZS-based diet), 40% HSS (HSS-based diet), or 40% FSS (FSS-based diet). The study lasted for 42 days, with 14 days devoted to adaptation, 21 days to daily feed intake and milk production, and 7 days to the sampling of feed, refusals, feces, urine, and rumen fluid. Milk production was measured twice daily, and digestibility was estimated using the method of acid-insoluble ash. The data were analyzed using a one-way ANOVA in SPSS 22.0 according to a completely randomized design. Dietary treatments were used as fixed effects and cows as random effects. The results indicate that MZS and HSS had greater crude protein but less neutral detergent fiber (NDF), acid detergent fiber (ADF), acid detergent lignin (ADL), and a lower pH than FSS (p ≤ 0.04). High starch contents in MZS and water-soluble carbohydrate (WSC) contents in HSS were observed (p < 0.01). While the highest starch intake was observed for the MZS-based diet, the highest WSC intake was noted for the HSS-based diet, and the highest NDF, ADF, ADL intake was observed for the FSS-based diet (p ≤ 0.05). The diets, including MZS and HSS, had greater digestibility than that of FSS (p ≤ 0.03). Feeding MZS- and HSS-based diets increased the yield, fat, and protein content of the milk, as well as feed conversion efficiency (p ≤ 0.03). However, feeding the MZS- and HSS-based diets decreased the contents of milk urea N, urinary urea N, and urinary N excretion more than the FSS-based diet (p ≤ 0.05). The N use efficiency tended to increase relative to diets containing MZS and HSS compared with FSS (p = 0.06 and p = 0.09). Ruminal ammonia-N and pH were lower, but total volatile fatty acids, acetate, and propionate were higher in cows fed the HSS- and MZS-based diets compared to those fed the FSS-based diet (p ≤ 0.03). It appears as though replacing MZS with HSS in the diet of cows without additional grain supplements has no negative influence on feed intake, milk yield, N utilization, or ruminal fermentation.

Factors affecting meibomian gland area loss in symptomatic adults.

AIM: To characterize the distribution of meibomian gland (MG) area loss (MGL) and its relationship with demographic characteristics, mites, and symptoms. METHODS: This retrospective observational study included patients who visited the Dry Eye Clinic of Shenzhen Eye Hospital between June 2020 and August 2021. General patient characteristics, ocular symptoms, Demodex test results of the eyelid edges, and the results of a comprehensive ocular surface analysis were collected. MGL was analyzed using Image J software. RESULTS: This study enrolled 1204 outpatients aged 20-80 (40.70±13.44)y, including 357 males (29.65%) and 847 females (70.35%). The patients were classified into mild (n=155; 12.87%), moderate (n=795; 66.03%), severe (n=206; 17.11%), and extremely severe (n=48; 3.99%) MGL groups. MGL was significantly larger in female than in male (P=0.006). The degree of MGL also significantly differed in age (P<0.001) and the more numbers of mites with severity (P<0.001). Multivariate disordered multinomial logistic regression analysis identified that female sex, older age, secretory symptoms, and a large number of mites were risk factors for MGL (P<0.05). CONCLUSION: Patients with MGL are more likely to be older, female, more numbers of mites, and increased secretion.

Nicotinamide metabolism face-off between macrophages and fibroblasts manipulates the microenvironment in gastric cancer.

Immune checkpoint blockade has led to breakthroughs in the treatment of advanced gastric cancer. However, the prominent heterogeneity in gastric cancer, notably the heterogeneity of the tumor microenvironment, highlights the idea that the antitumor response is a reflection of multifactorial interactions. Through transcriptomic analysis and dynamic plasma sample analysis, we identified a metabolic "face-off" mechanism within the tumor microenvironment, as shown by the dual prognostic significance of nicotinamide metabolism. Specifically, macrophages and fibroblasts expressing the rate-limiting enzymes nicotinamide phosphoribosyltransferase and nicotinamide N-methyltransferase, respectively, regulate the nicotinamide/1-methylnicotinamide ratio and CD8+ T cell function. Mechanistically, nicotinamide N-methyltransferase is transcriptionally activated by the NOTCH pathway transcription factor RBP-J and is further inhibited by macrophage-derived extracellular vesicles containing nicotinamide phosphoribosyltransferase via the SIRT1/NICD axis. Manipulating nicotinamide metabolism through autologous injection of extracellular vesicles restored CD8+ T cell cytotoxicity and the anti-PD-1 response in gastric cancer.

Exploitation of Multiple Host-Derived Nutrients by the Yellow Catfish Epidermal Environment Facilitates Vibrio mimicus to Sustain Infection Potency and Susceptibility.

Infection with Vibrio mimicus in the Siluriformes has demonstrated a rapid and high infectivity and mortality rate, distinct from other hosts. Our earlier investigations identified necrosis, an inflammatory storm, and tissue remodeling as crucial pathological responses in yellow catfish (Pelteobagrus fulvidraco) infected with V. mimicus. The objective of this study was to further elucidate the impact linking these pathological responses within the host during V. mimicus infection. Employing metabolomics and transcriptomics, we uncovered infection-induced dense vacuolization of perimysium; Several genes related to nucleosidase and peptidase activities were significantly upregulated in the skin and muscles of infected fish. Concurrently, the translation processes of host cells were impaired. Further investigation revealed that V. mimicus completes its infection process by enhancing its metabolism, including the utilization of oligopeptides and nucleotides. The high susceptibility of yellow catfish to V. mimicus infection was associated with the composition of its body surface, which provided a microenvironment rich in various nucleotides such as dIMP, dAMP, deoxyguanosine, and ADP, in addition to several amino acids and peptides. Some of these metabolites significantly boost V. mimicus growth and motility, thus influencing its biological functions. Furthermore, we uncovered an elevated expression of gangliosides on the surface of yellow catfish, aiding V. mimicus adhesion and increasing its infection risk. Notably, we observed that the skin and muscles of yellow catfish were deficient in over 25 polyunsaturated fatty acids, such as Eicosapentaenoic acid, 12-oxo-ETE, and 13-Oxo-ODE. These substances play a role in anti-inflammatory mechanisms, possibly contributing to the immune dysregulation observed in yellow catfish. In summary, our study reveals a host immune deviation phenomenon that promotes bacterial colonization by increasing nutrient supply. It underscores the crucial factors rendering yellow catfish highly susceptible to V. mimicus, indicating that host nutritional sources not only enable the establishment and maintenance of infection within the host but also aid bacterial survival under immune pressure, ultimately completing its lifecycle.

[Assessment of carbon reduction and sink enhancement potential of photovoltaic+mining ecological restoration model]. / å ‰ä¼+矿山生态修复模式的减碳增汇潜力评估.

The energy oriented mine ecological restoration mode of photovoltaic+ecological restoration provides a breakthrough for alleviating the dilemma of photovoltaic land development and solving the urgent need for restoration of abandoned mining land. Taking a mining area in central Liaoning Province as an example, we established three photovoltaic+mining ecological restoration modes, including forest-photovoltaic complementary, agriculture-photovoltaic, and grass photovoltaic complementation. Combined with the life cycle assessment method, we calculated and assessed the potential of photovoltaic+mining ecological restoration in carbon reduction and sink enhancement. The average annual carbon reduction and sink increase was 514.93 t CO2·hm-2 under the photovoltaic+mining ecological restoration mode, while the average annual carbon reduction per megawatt photovoltaic power station was 1242.94 t CO2. The adoption of photovoltaic+ecological restoration mode in this mining area could make carbon reduction and sink enhancement 6.30-7.79 Mt CO2 during 25 years. The carbon reduction and sink increment mainly stemmed from the photovoltaic clean power generation induced carbon reduction, accounting for 96.4%-99.4%, while the contribution of ecosystem carbon sink increment was small, accounting for only 0.6%-3.7% of the total. Among different photovoltaic+ecological restoration modes, the carbon reduction and sink increment was the largest in forest-photovoltaic complementary (7.11 Mt CO2), followed by agriculture-photovoltaic (7.04 Mt CO2), and the least in grass photovoltaic complementation (6.98 Mt CO2). Constructing the development mode of "photovoltaic+mining ecological restoration" could effectively leverage the dual benefits of reducing emissions from photovoltaic power generation and increase sinks from mining ecological restoration, which would be helpful for achieving the goal of carbon neutrality in China.

Hypoxia inducible factor 2α promotes tolerogenic macrophage development during cardiac transplantation through transcriptional regulation of colony stimulating factor 1 receptor.

Solid organ transplantation mobilizes myeloid cells, including monocytes and macrophages, which are central protagonists of allograft rejection. However, myeloid cells can also be functionally reprogrammed by perioperative costimulatory blockade to promote a state of transplantation tolerance. Transplantation tolerance holds promise to reduce complications from chronic immunosuppression and promote long-term survival in transplant recipients. We sought to identify different mediators of transplantation tolerance by performing single-cell RNA sequencing of acute rejecting or tolerized cardiac allografts. This led to the unbiased identification of the transcription factor, hypoxia inducible factor (HIF)-2α, in a subset of tolerogenic monocytes. Using flow cytometric analyses and mice with conditional loss or gain of function, we uncovered that myeloid cell expression of HIF-2α was required for costimulatory blockade-induced transplantation tolerance. While HIF-2α was dispensable for mobilization of tolerogenic monocytes, which were sourced in part from the spleen, it promoted the expression of colony stimulating factor 1 receptor (CSF1R). CSF1R mediates monocyte differentiation into tolerogenic macrophages and was found to be a direct transcriptional target of HIF-2α in splenic monocytes. Administration of the HIF stabilizer, roxadustat, within micelles to target myeloid cells, increased HIF-2α in splenic monocytes, which was associated with increased CSF1R expression and enhanced cardiac allograft survival. These data support further exploration of HIF-2α activation in myeloid cells as a therapeutic strategy for transplantation tolerance.

Association of Cardiovascular Health With Brain Age Estimated Using Machine Learning Methods in Middle-Aged and Older Adults.

BACKGROUND AND OBJECTIVES: Cardiovascular health (CVH) has been associated with cognitive decline and dementia, but the extent to which CVH affects brain health remains unclear. We investigated the association of CVH, assessed using Life's Essential 8 (LE8), with neuroimaging-based brain age and brain-predicted age difference (brain-PAD). METHODS: This longitudinal community-based study was based on UK Biobank participants aged 40-69 years who were free from dementia and other neurologic diseases at baseline. LE8 score at baseline was assessed with 8 measures and tertiled as low, moderate, and high CVH. Structural and functional brain MRI scans were performed approximately 9 years after baseline, and 1,079 measures from 6 neuroimaging modalities were used to model brain age. A Least Absolute Shrinkage and Selection Operator regression model was trained in 4,355 healthy participants and then used to calculate brain age and brain-PAD in the whole population. Data were analyzed using linear regression models. RESULTS: The study included 32,646 participants (mean age at baseline 54.74 years; 53.44% female; mean LE8 score: 71.90). In multivariable-adjusted linear regression, higher LE8 score was associated with younger brain age (ß [95% CI] -0.037 [-0.043 to -0.031]) and more negative brain-PAD (ß [95% CI] -0.043 [-0.048 to -0.038]) (brain looks younger for chronological age). Compared with high CVH, low/moderate CVH was associated with older brain age (ß [95% CI] 1.030 [0.852-1.208]/0.475 [0.303-0.647]) and increased brain-PAD (ß [95% CI] 1.193 [1.029-1.357]/0.528 [0.370-0.686]). The associations between low CVH and older brain age/brain-PAD remained similar and significant in both middle-aged (ß [95% CI] 1.199 [0.992-1.405]/1.351 [1.159-1.542]) and older adults (ß [95% CI] 0.764 [0.417-1.110]/0.948 [0.632-1.263]). DISCUSSION: Low CVH is associated with older brain age and greater brain-PAD, even among middle-aged adults. Our findings suggest that optimizing CVH could support brain health. The main limitation of our study is that the study sample was healthier than the general population, thus caution is required when generalizing our findings to other populations.

Riboflavin-induced photo-ATRP electrochemical strategy for detection of biomarker trypsin.

The detection of trypsin and its inhibitors is important for both clinical diagnosis and disease treatment. Abnormal trypsin activity affects pancreatic function and leads to corresponding pathological changes in the body. Therefore, the study presented a riboflavin-induced photo-ATRP electrochemical assay of trypsin activity and its inhibitor, including detection of trypsin activity in real urine samples. Experiments were performed on indium tin oxide (ITO) electrodes modified with sulfhydryl groups of 3-mercaptopropionic acid, and target trypsin-specific cleavage of BSA-Au nanocluster (BSA-Au NCs) was followed by the modification of Au NCs to the electrodes using Au-S. The Au NCs immobilized monodeoxy-monomercapto-ß-cyclodextrin@adamantan-2-amine (SH-ß-CD@2-NH2-Ada) host-guest inclusion complexes to the electrode surfaces via Au-S. In a two-component photo-initiator system consisting of riboflavin as an initiator and ascorbic acid (AA) as a mild reducing agent under mild blue light radiation, a large number of electroactive substances were grafted onto the electrode surface to generate electrochemical signals. In addition, we have successfully realized the detection of clinical drug inhibitors of trypsin. The detection limit of the system is as low as 0.0024 ng/mL, which much littler than the average standard of trypsin in the patient's urine or serum. It's worth noting that this work will provide researchers with a different route to design electrochemical sensors based on non-covalent recognition strategies.

In vivo reactive astrocyte imaging using [18F]SMBT-1 in tauopathy and familial Alzheimer's disease mouse models: A multi-tracer study.

BACKGROUND: Reactive astrocytes play an important role in the development of Alzheimer's disease and primary tauopathies. Here, we aimed to investigate the relationships between reactive astrocytes. Microgliosis and glucose metabolism with Tau and amyloid beta pathology by using multi-tracer imaging in widely used tauopathy and familial Alzheimer's disease mouse models. RESULTS: Positron emission tomography imaging using [18F]PM-PBB3 (tau), [18F]florbetapir (amyloid-beta), [18F]SMBT-1 (monoamine oxidase-B), [18F]DPA-714 (translocator protein) and [18F]fluorodeoxyglucose was carried out in 3- and 7-month-old rTg4510 tau mice, 5 × FAD familial Alzheimer's disease mice and wild-type mice. Immunofluorescence staining was performed to validate the pathological distribution in the mouse brain after in vivo imaging. We found increased regional levels of [18F]PM-PBB3, [18F]SMBT-1, and [18F]DPA-714 and hypoglucose metabolism in the brains of 7-month-old rTg4510 mice compared to age-matched wild-type mice. Increased [18F]SMBT-1 uptake was observed in the brains of 3, 7-month-old 5 × FAD mice, with elevated regional [18F]florbetapir and [18F]DPA-714 uptakes in the brains of 7-month-old 5 × FAD mice, compared to age-matched wild-type mice. Positive correlations were shown between [18F]SMBT-1 and [18F]PM-PBB3, [18F]DPA-714 and [18F]PM-PBB3 in rTg4510 mice, and between [18F]florbetapir and [18F]DPA-714 SUVRs in 5 × FAD mice. CONCLUSION: In summary, these findings provide in vivo evidence that reactive astrocytes, microglial activation, and cerebral hypoglucose metabolism are associated with tau and amyloid pathology development in animal models of tauopathy and familial Alzheimer's disease.

Efficient removal of methyl orange and ciprofloxacin by reusable Eu-TiO2/PVDF membranes with adsorption and photocatalysis methods.

The presence of methyl orange (MO) and ciprofloxacin (CIP) in wastewater poses a serious threat to the environment and human health. Titanium dioxide nanoparticles (TiO2 NPs) are widely studied as photocatalysts for wastewater treatment. However, TiO2 NPs have the drawbacks of high energy required for activation, fast electron-hole pair recombination and difficulty in recovering from water. To overcome these problems, europium decorated titanium dioxide/poly(vinylidene fluoride) (Eu-TiO2/PVDF) membranes were successful prepared in this work by combining the modified sol-gel method and the immersion phase inversion method. The Eu-TiO2/PVDF membranes obtained with the increase of Eu-TiO2 NPs content during the preparation process were named M1, M2 and M3, respectively. The pure PVDF membrane without the addition of Eu-TiO2 NPs was named M0, which was prepared by the immersion phase inversion method and served as a reference. The prepared Eu-TiO2/PVDF membranes could not only adsorb MO, but also degrade CIP under visible-light irradiation. Moreover, the Eu-TiO2/PVDF membranes exhibited adsorption-photocatalytic activity towards a mixture of MO and CIP under visible-light irradiation. Last but not the least, the Eu-TiO2/PVDF membranes exhibited excellent recyclability and reusability, opening the avenue for a possible use of these membranes in sewage-treatment plants.

Coronary microvascular dysfunction and myocardial area at risk assessed by cadmium zinc telluride single photon emission computed tomography after primary percutaneous coronary intervention in acute myocardial infarction patients.

Background: A high proportion of coronary microvascular dysfunction (CMD) has been observed in patients with acute myocardial infarction (AMI) who have received primary percutaneous coronary intervention (PCI), which may affect their prognosis. This study used cadmium zinc telluride (CZT) single photon emission computed tomography (SPECT) to evaluate the prevalence and characteristics of CMD and myocardial area at risk (AAR) in AMI patients who had undergone primary PCI. Methods: We conducted a single-center cross-sectional retrospective study at TEDA International Cardiovascular Hospital from September 2021 to June 2022. A total of 83 patients received primary PCI for AMI. Subsequently, a rest/stress dynamic and routine gated myocardial perfusion imaging (MPI) were performed 1 week after PCI. The CMD group was defined as having a residual stenosis of infarct-related artery (IRA) <50% and myocardial flow reserve (MFR) <2.0 in this corresponding territory, whereas MFR ≥2.0 of IRA pertained to the normal control group. Rest-AAR of infarction (%) and stress-AAR (%) were expressed by the percentage of measured rest-defect-size and stress-defect-size in the left ventricular area, respectively. Logistic regression analyses were performed to identify significant predictors of CMD. Results: A total of 53 patients with a mean age of 57.06±11.99 years were recruited, of whom 81.1% were ST-segment elevation myocardial infarction (STEMI). The proportion of patients with CMD was 79.2% (42/53). The time of pain to SPECT imaging was 7.50±1.27 days in the CMD group and 7.45±1.86 days among controls. CMD patients had a higher body mass index (BMI) than controls (26.48±3.26 vs. 24.36±2.73 kg/m2, P=0.053), and a higher proportion of STEMI, thrombolysis in myocardial infarction (TIMI) 0 grade of IRA prior PCI than controls (88.1% vs. 54.5%, P=0.011; 61.9% vs. 18.2%, P=0.004, respectively). No significant difference was identified in the rest-myocardial blood flow (MBF) of IRA between the 2 groups, whereas the stress-MBF and MFR of IRA, rest-AAR, and stress-AAR in the CMD group were remarkably lowered. Higher BMI [odds ratio (OR): 1.332, 95% confidence interval (CI): 1.008-1.760, P=0.044] and stress-AAR (OR: 1.994, 95% CI: 1.122-3.543, P=0.019) were used as independent predictors of CMD occurrence. Conclusions: The prevalence of CMD is high in AMI patients who received primary PCI. Each 1 kg/m2 increase in BMI was associated with a 1.3-fold increase in CMD risk. A 5% increase in stress-AAR was associated with a nearly 2-fold increase in CMD risk. Increased BMI and stress-AAR predicts decreased coronary reserve function.

Targeting STING in dendritic cells alleviates psoriatic inflammation by suppressing IL-17A production.

Psoriasis is a common chronic inflammatory skin disease driven by the aberrant activation of dendritic cells (DCs) and T cells, ultimately leading to increased production of cytokines such as interleukin (IL)-23 and IL-17A. It is established that the cGAS-STING pathway is essential for psoriatic inflammation, however, the specific role of cGAS-STING signaling in DCs within this context remains unclear. In this study, we demonstrated the upregulation of cGAS-STING signaling in psoriatic lesions by analyzing samples from both clinical patients and imiquimod (IMQ)-treated mice. Using a conditional Sting-knockout transgenic mouse model, we elucidated the impact of cGAS-STING signaling in DCs on the activation of IL-17- and IFN-γ-producing T cells in psoriatic inflammation. Ablation of the Sting hampers DC activation leads to decreased numbers of IL-17-producing T cells and Th1 cells, and thus subsequently attenuates psoriatic inflammation in the IMQ-induced mouse model. Furthermore, we explored the therapeutic potential of the STING inhibitor C-176, which reduces psoriatic inflammation and enhances the anti-IL-17A therapeutic response. Our results underscore the critical role of cGAS-STING signaling in DCs in driving psoriatic inflammation and highlight a promising psoriasis treatment.

Influenza A virus infection disrupts the function of syncytiotrophoblast cells and contributes to adverse pregnancy outcomes.

Pregnancy heightens susceptibility to influenza A virus (IAV) infection, thereby increasing the risk of severe pneumonia and maternal mortality. It also raises the chances of adverse outcomes in offspring, such as fetal growth restriction, preterm birth, miscarriage, and stillbirth in offsprings. However, the underlying mechanisms behind these effects remain largely unknown. Syncytiotrophoblast cells, crucial in forming the placental barrier, nutrient exchange and hormone secretion, have not been extensively studied for their responses to IAV. In our experiment, we used Forskolin-treated BeWo cells to mimic syncytiotrophoblast cells in vitro, and infected them with H1N1, H5N1 and H7N9 virus stains. Our results showed that syncytiotrophoblast cells, with their higher intensity of sialic acid receptors, strongly support IAV infection and replication. Notably, high-dose viral infection and prolonged exposure resulted in a significant decrease in fusion index, as well as gene and protein expression levels associated with trophoblast differentiation, ß-human chorionic gonadotropin secretion, estrogen and progesterone biosynthesis, and nutrient transport. In pregnant BALB/c mice infected with the H1N1 virus, we observed significant decreases in trophoblast differentiation and hormone secretion gene expression levels. IAV infection also resulted in preterm labor, fetal growth restriction, and increased maternal and fetal morbidity and mortality. Our findings indicate that IAV infection in syncytiotrophoblastic cells can result in adverse pregnancy outcomes by altering trophoblast differentiation, suppressing of ß-hCG secretion, and disrupting placental barrier function.

Synchronously Sensitive Immunoassay and Efficient Inactivation of Living Zika Virus via DNAzyme Catalytic Amplification and In Situ Aggregation-Induced Emission Photosensitizer Generation.

Sensitive identification and effective inactivation of the virus are paramount for the early diagnosis and treatment of viral infections to prevent the risk of secondary transmission of viruses in the environment. Herein, we developed a novel two-step fluorescence immunoassay using antibody/streptavidin dual-labeled polystyrene nanobeads and biotin-labeled G-quadruplex/hemin DNAzymes with peroxidase-mimicking activity for sensitive quantitation and efficient inactivation of living Zika virus (ZIKV). The dual-labeled nanobeads can specifically bind ZIKV through E protein targeting and simultaneously accumulate DNAzymes, leading to the catalytic oxidation of Amplex Red indicators and generation of intensified aggregation-induced emission fluorescence signals, with a detection limit down to 66.3 PFU/mL and 100% accuracy. Furthermore, robust reactive oxygen species generated in situ by oxidized Amplex Red upon irradiation can completely kill the virus. This sensitive and efficient detection-inactivation integrated system will expand the viral diagnostic tools and reduce the risk of virus transmission in the environment.

Persimmon leaf polyphenols as potential ingredients for modulating starch digestibility: Effect of starch-polyphenol interaction.

The interaction mode between persimmon leaf polyphenols (PLP) and corn starch with different amylose content and its effect on starch digestibility was studied. Results of iodine binding test, TGA, and DSC revealed that PLP interacted with starch and reduced the iodine binding capacity and thermal stability of starch. High amylopectin corn starch (HAPS) interacted with PLP mainly via hydrogen bonds, since the FT-IR of HAPS-PLP complex showed higher intensity at 3400 cm-1 and an obvious shift of 21 cm-1 to shorter wavelength, and the chemical shifts of protons in 1H NMR and the shift of C-6 peak in 13C NMR of HAPS moved to low field with the addition of PLP. Results of 1H NMR also showed the preferential formation of hydrogen bonds between PLP and OH-3 of HAPS. Different from HAPS, PLP formed V-type inclusion complex with high amylose corn starch (HAS) because XRD of HAS-PLP complex showed characteristic feature peaks of V-type inclusion complex and C-1 signal in 13C NMR of PLP-complexed HAS shifted to low field. Interaction with PLP reduced starch digestibility and HAS-PLP complex resulted in more resistant starch production than HAPS-PLP complex. To complex PLP with starch might be a potential way to prepare functional starch with slower digestion.

Supramolecular interaction between berberine hydrochloride and baicalin in aqueous solution: Reaction kinetics, spectral analysis and dynamic simulation.

The current study presents a comprehensive investigation on the precipitation reaction and supramolecular interactions between berberine hydrochloride (BBR) and baicalin (BA) in an aqueous system. Utilizing a combination of multi-spectral analytical techniques and molecular dynamic simulations, we elucidated the mechanism of the complexion process. The precipitate formation was observed within a drug concentration range of 0.1-1.0 mM, and a 1:1 stoichiometry ratio of BBR to BA was established by the Job's plot method. Morphological and structural characterizations of the precipitates were conducted using DSC, FTIR and PXRD. Additionally, UV-Vis absorption and 1H NMR spectroscopy were employed to compare the spectral characteristics of the precipitates with those of individual drug solution. Molecular dynamic simulations further dissected the intermolecular interactions and self-assembly mechanisms. The precipitates formed were amorphous microparticles with an average diameter of approximately 20 µm, primarily stabilized by hydrogen bonding and π-π stacking. This study contributes foundational insights into the supramolecular interactions between BBR and BA, therefore facilitated a better understanding of the precipitation process involving flavonoid-alkaloid pairs in mixed aqueous solutions.