Rapid detection of ingested acetaminophen on face mask by ambient ionization tandem mass spectrometry.

BACKGROUND: A regular face mask is comprised of three layers for resisting moisture, filtration, and absorbing oral fluid, respectively. Since the polymers with different polarities are used to make the layers, a face mask can be used as a sampling tool to retain polar or non-polar chemical and biochemical substances in the exhaled breath. In this study, thermal desorption-electrospray ionization tandem mass spectrometry (TD-ESI/MS/MS), an ambient ionization mass spectrometric technique, was used to detect trace acetaminophen that were exhaled and retained on the surface of different layers in a face mask. RESULTS: With probe sampling combined with TD-ESI/MS/MS, the acetaminophen ion signal can be detected at the mouth/nostril region of the face mask after taking the acetaminophen tablet. The experimental results were similar to previous studies for the detection of acetaminophen in blood over time using LC/MS/MS. In addition, the intensities of acetaminophen on different layers of the face mask could reveal the differing distributions of exhaled acetaminophen on each layer. To explore the distribution of acetaminophen on the face mask surface, multiple probes were used to collect samples from different locations of the face mask for analysis. The molecular mapping of acetaminophen on the face mask was rendered by scaling the analyte ion signal intensity based on a temperature color gradient. The cartography showed a higher acetaminophen ion signal distribution on the mouth and nostril regions than in other areas of the face mask. SIGNIFICANCE: Owing to the advantages of a simple, sensitive, and non-invasive sampling approach, drug monitoring could be potentially performed to provide useful information for anti-drug of precision medicine in the future.

Luteolin Mitigates Dopaminergic Neuron Degeneration and Restrains Microglial M1 Polarization by Inhibiting Toll Like Receptor 4.

BACKGROUND: Luteolin is a natural flavonoid and its neuroprotective and anti-inflammatory effects have been confirmed to mitigate neurodegeneration. Despite these findings, the underlying mechanisms responsible for these effects remain unclear. Toll-like receptor 4 (TLR4) is widely distributed in microglia and plays a pivotal role in neuroinflammation and neurodegeneration. Here studies are outlined that aimed at determining the mechanisms responsible for the anti-inflammatory and neuroprotective actions of luteolin using a rodent model of Parkinson's disease (PD) and specifically focusing on the role of TLR4 in this process. METHODS: The mouse model of PD used in this experiment was established through a single injection of lipopolysaccharide (LPS). Mice were then subsequently randomly allocated to either the luteolin or vehicle-treated group, then motor performance and dopaminergic neuronal injury were evaluated. BV2 microglial cells were treated with luteolin or vehicle saline prior to LPS challenge. MRNA expression of microglial specific marker ionized calcium-binding adapter molecule 1 (IBA-1) and M1/M2 polarization markers, as well as the abundance of indicated pro-inflammatory cytokines in the mesencephalic tissue and BV2 were quantified by real time-polymerase chain reaction (RT-PCR) and Enzyme-linked Immunosorbent Assay (ELISA), respectively. Cell viability and apoptosis of neuron-like PC12 cell line co-cultured with BV2 were detected. TLR4 RNA transcript and protein abundance in mesencephalic tissue and BV2 cells were detected. Nuclear factor kappa-gene binding (NF-κB) p65 subunit phosphorylation both in vitro and in vivo was evaluated by immunoblotting. RESULTS: Luteolin treatment induced functional improvements and alleviated dopaminergic neuronal loss in the PD model. Luteolin inhibited apoptosis and promoted cell survival in PC12 cells. Luteolin treatment shifted microglial M1/M2 polarization towards an anti-inflammatory M2 phenotype both in vitro and in vivo. Finally, it was found that luteolin treatment significantly downregulated both TLR4 mRNA and protein expression as well as restraining NF-κB p65 subunit phosphorylation. CONCLUSIONS: Luteolin restrained dopaminergic degeneration in vitro and in vivo by blocking TLR4-mediated neuroinflammation.

Ghrelin may protect against vascular endothelial injury in Acute traumatic coagulopathy by mediating the RhoA/ROCK/MLC2 pathway.

Ghrelin exerts widespread effects in several diseases, but its role and mechanism in Acute Traumatic Coagulopathy (ATC) are largely unknown. The effect of ghrelin on cell proliferation was examined using three assays: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), Lactate Dehydrogenase (LDH), and flow cytometry. The barrier function of the endothelial cells was evaluated using the Trans-Endothelial Electrical Resistance (TEER) and the endothelial permeability assay. An ATC mouse model was established to evaluate the in vivo effects of ghrelin. The Ras homolog family member A (RhoA) overexpression plasmid or adenovirus was used to examine the molecular mechanism of ghrelin. Ghrelin enhanced Human Umbilical Vein Endothelial Cells (HUVEC) proliferation and endothelial cell barrier function and inhibited HUVEC permeability damage in vitro. Additionally, ghrelin decreased the activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT) in mice blood samples in the ATC mouse model. Ghrelin also improved the pathological alterations in postcava. Mechanistically, ghrelin acts through the RhoA/ Rho-associated Coiled-coil Containing Kinases (ROCK)/ Myosin Light Chain 2 (MLC2) pathway. Furthermore, the protective effects of ghrelin, both in vitro and in vivo, were reversed by RhoA overexpression. Our findings demonstrate that ghrelin may reduce vascular endothelial cell damage and endothelial barrier dysfunction by blocking the RhoA pathway, suggesting that ghrelin may serve as a potential therapeutic target for ATC treatment.

A Novel RNA Methylation-Related Prognostic Signature and its Tumor Microenvironment Characterization in Hepatocellular Carcinoma.

INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system. RNA methylation plays an important role in tumorigenesis and metastasis, which could alter gene expression and even function at multiple levels, such as RNA splicing, stability, translocation, and translation. In this study, we aimed to conduct a comprehensive analysis of RNA methylation-related genes (RMGs) in HCC and their relationship with survival and clinical features. METHODS: A retrospective analysis was performed using publicly available HCC-related datasets. The differentially expressed genes (DEGs) between HCC and controls were identified from TCGA-LlHC and intersected with RMGs to obtain differentially expressed RNA methylation-related genes (DERMGs). Regression analysis was used to screen for prognostic genes and construct risk models. Simultaneously, clinical, immune infiltration and therapeutic efficacy analyses were performed. Finally, multivariate cox regression was used to identify independent risk factors, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the expression levels of the core genes of the model. RESULTS: A 21-gene risk model for HCC was established with excellent performance based on ROC curves and survival analysis. Risk scores correlated with tumor grade, pathologic T, and TNM stage. Immune infiltration analysis showed correlations with immune scores, 11 immune cells, and 30 immune checkpoints. Low-risk patients showed a higher susceptibility to immunotherapy. The risk score and TNM stage were independent prognostic factors. qRT-PCR confirmed higher expression of PRDM9, ALPP, and GAD1 in HCC. CONCLUSIONS: This study identified RNA methylation-related signature genes in HCC and constructed a risk model that predicts patient outcomes and reflects the immune microenvironment. Prognostic genes are involved in complex regulatory mechanisms, which may be useful for cancer diagnosis, prognosis, and therapy.

Paxlovid reduces the 28-day mortality of patients with COVID-19: a retrospective cohort study.

PURPOSE: In this study, we aim to explore the efficacy of paxlovid on reducing mortality of COVID-19 patients in clinical setting, especially whether paxlovid modifies the risk of death in these severe and critical patients. METHODS: Our retrospective cohort study was conducted on the medical records of patients, consecutively admitted for COVID-19 to five hospitals in Chongqing, China from Dec 8, 2022 to Jan 20, 2023. Based on whether patients received paxlovid during their hospitalization, patients were grouped as paxlovid group and non-paxlovid group. We used 1:1 ratio propensity score matching (PSM) in our study to adjust for confounding factors and differences between groups. Statistical analysis were performed by SPSS 23.0. The differences in 28-day mortality between these two groups and its influencing factors were the main results we focused on. RESULTS: There were 1018 patients included in our study cohort. With 1:1 ratio PSM, each of the paxlovid group and non-paxlovid group included 237 patients. The results showed that patients using paxlovid have a lower 28-day mortality in overall population either before PSM (OR 0.594, 95% CI 0.385-0.917, p = 0.019) or after PSM (OR 0.458, 95% CI 0.272-0.774, p = 0.003) with multivariable adjusted logistic regression models. Meanwhile, in severe subgroup, it showed similar findings.With paxlovid treatment, it showed a significantly lower 28-day mortality in severe subgroup both before PSM (28% vs.41%, p = 0.008) and after PSM (19% vs.32%, p = 0.007). CONCLUSION: Paxlovid can significantly reduce the risk of 28-day mortality in overall population and severe subgroup patients.This study distinguished the severe subgroup patients with COVID-19 who benefit more from paxlovid treatment.

Prognostic value of oxidative phosphorylation-related genes in hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is the most prevalent malignancies worldwide. Recently, oxidative phosphorylation (OXPHOS) has received extensive concern as an emerging target in antitumor therapy. However, the OXPHOS-involved underlying genes and clinical utilization in HCC remain worth exploring. The present research aimed to create an OXPHOS-relevant signature in HCC. PATIENTS AND METHODS: In this study, the prognostic signature genes linked with OXPHOS were identified, and prognostic models were built using least absolute shrinkage and selection operator (LASSO) cox regression analysis. Furthermore, the combination study of immune microenvironment and signature genes looked into the involvement of immune cells in signature-based genes in HCC. Following that, chemotherapeutic drug sensitivity and immunotherapy analysis was implemented to predict clinical efficacy in HCC patients. Finally, clinical samples were collected to measure the expression of OXPHOS-related signature genes. RESULTS: Following a series of screens, six prognostic signature genes related with OXPHOS were identified: MRPS23, MPV17, MAPK3, IGF2BP2, CDK5, and IDH2, on which a risk model was built. The findings revealed a significant drop in the survival rate of HCC patients as their risk score increased. Meanwhile, independent prognostic study demonstrated that the risk score could accurately identify HCC patients. Immuno-microenvironmental correlation research suggested that the prognostic characteristics could serve as a reference index for both immunotherapy and chemotherapy. Finally, RT-qPCR exhibited a trend in signature gene expression that was consistent with the results. CONCLUSION: In this study, a total of six prognostic genes associated with OXPHOS were selected and a prognostic model was constructed, providing an essential reference for the study of OXPHOS in HCC.

Comparing life cycle environmental impacts of food access and consumption pre- and during COVID 19 in New York State's Capital Region.

The COVID-19 pandemic has significantly influenced household food shopping, food consumption, and food waste generation. However, the dietary environmental impacts for different income groups during COVID-19 remain unknown. To analyze dietary environmental impacts for various income groups, a process-based life cycle assessment (LCA) was conducted based on two electronic food access surveys implemented in the New York State's Capital Region during the COVID-19 pandemic and public and proprietary databases. We found that life cycle global warming potential, cumulative energy demand, acidification potential, and water resource depletion of per capital food consumption in the studied area tended to be lower during COVID-19 than pre-COVID-19. In contrast, life cycle eutrophication during COVID-19 was slightly higher than pre-COVID-19. The environmental impacts occurring at the food production stage were higher than those at the local transportation and waste disposal stages. The lowest income group had the lowest dietary environmental impacts due to their lowest food consumption of all the food categories. The second-highest income group had the highest dietary environmental impacts, since they consumed the most red meat which has a high impact intensity. This is the first study to our knowledge to investigate the differences in dietary environmental impacts among income groups during COVID-19.

Fruit and Vegetable Consumption, Food Acquisition Behavior, and Food Insecurity Before and After the COVID-19 Vaccine Rollout.

OBJECTIVES: To assess changes in food acquisition behavior, food insecurity, and dietary behavior and identify factors associated with fruit and vegetable (FV) consumption during the transitional period (before and after the initial vaccine rollout for all adults) of the COVID-19 pandemic. DESIGN: Successive independent samples design. Online surveys were conducted from October 2020 to February 2021 (time 1, before the vaccine rollout) and from October 2021 to December 2021 (time 2, after the vaccine rollout). Descriptive analysis examined changes in food sources, food security, and daily FV consumption in cup equivalents (CEs) from time 1 to time 2. A multivariable logistic regression analysis examined factors associated with FV consumption. SETTING: The Capital Region of New York State. PARTICIPANTS: 1553 adults 18 years of age and older. MAIN OUTCOME MEASURE: Meeting the 2020-2025 MyPlate daily FV consumption recommendations. RESULTS: There were statistically significant (P < .05) increases in the use of supermarkets, eat-in restaurants, farmers' markets, and convenience stores from time 1 to time 2. Food insecurity (40.1% vs 39.4%) and FV consumption (2.6 CE vs 2.4 CE) slightly declined but not significantly. Home food procurement such as gardening and foraging (OR, 1.61; 95% CI, 1.08-2.37) and shopping at food co-op/health food stores (OR, 1.64; 95% CI, 1.07-2.49) were significantly associated with the FV outcome, and these relationships were not modified by food security status. CONCLUSIONS: The present study highlights the importance of food sources in understanding adult dietary behavior during the transitional period of the pandemic. Continuing efforts to monitor access to food sources, food insecurity, and dietary behavior are warranted as various COVID-related emergency food assistance measures have expired.

Postural control and cognitive flexibility in skilled athletes: Insights from dual-task performance and event-related potentials.

Athletes of skill-oriented sports (hereinafter referred to as "skilled athletes"), such as gymnasts and rhythmic gymnasts, have demonstrated better postural control than nonathletes. However, previous studies have mainly focused on single postural tasks and have not considered how skilled athletes use and allocate attentional resources during postural control. This research used the event-related potential (ERP) to explore the postural control performance of skilled athletes under cognitive processes and their utilization and allocation of attentional resources. A dual-task paradigm was used to simulate the actual situation in sports. 26 skilled athletes and 26 nonathletes were required to perform postural control and task-switching simultaneously. The results showed that skilled athletes demonstrated more postural control stability and a higher accuracy of task-switching than nonathletes in all dual tasks. Compared with nonathletes, they showed a stable enhanced N1 (electrodes: Oz, O1, and O2) amplitude during three postures. Moreover, larger N2 component on Fz, FCz, and Cz and theta band power was found in the frontal cortex (on Fz, FCz) of skilled athletes under feet together and single leg standing posture. The study illustrated that skilled athletes show greater frontal activation during dual tasks, which allows for more rational and flexible brain attentional resource input and allocation in cognitive processes, this may be due to long-term professional training, which enables them to have a higher level of automation of postural control and cognitive flexibility. This study's results offer valuable insights into the interplay between postural control and multitasking in skilled athletes, and its outcomes carry significant implications for the training and assessment of athletes across various sports.

Interface-Compatible Gel-Polymer Electrolyte Enabled by NaF-Solubility-Regulation toward All-Climate Solid-State Sodium Batteries.

Gel-polymer electrolyte (GPE) is a pragmatic choice for high-safety sodium batteries but still plagued by interfacial compatibility with both cathode and anode simultaneously. Here, salt-in-polymer fibers with NaF salt inlaid in polylactide (PLA) fiber network was fabricated via electrospinning and subsequent in situ forming gel-polymer electrolyte in liquid electrolytes. The obtained PLA-NaF GPE achieves a high ion conductivity (2.50×10-3 S cm-1) and large Na+ transference number (0.75) at ambient temperature. Notably, the dissolution of NaF salt occupies solvents leading to concentrated-electrolyte environment, which facilitates aggregates with increased anionic coordination (anion/Na+ >1). Aggregates with higher HOMO realize the preferential oxidation on the cathode so that inorganic-rich and stable CEI covers cathode' surface, preventing particles' breakage and showing good compatibility with different cathodes (Na3V2(PO4)3, Na2+2xFe2-x(SO4)3, Na0.72Ni0.32Mn0.68O2, NaTi2(PO4)3). While, passivated Na anode induced by the lower LUMO of aggregates, and the lower surface tension between Na anode and PLA-NaF GPE interface, leading to the dendrites-free Na anode. As a result, the assembled Na || Na3V2(PO4)3 cells display excellent electrochemical performance at all-climate conditions.

Ni and Co Active Site Transition and Competition in Fluorine-Doped NiCo(OH)2 LDH Electrocatalysts for Oxygen Evolution Reaction.

The oxygen evolution reaction (OER) performance of NiCo LDH electrocatalysts can be improved through fluorine doping. The roles of Ni and Co active sites in such catalysts remain ambiguous and controversial. In addressing the issue, this study draws upon the molecular orbital theory and proposes the active center competitive mechanism between Ni and Co. The doped F-atoms can directly impact the valence state of metal atoms or exert an indirect influence through the dehydrogenation, thereby modulating the active center. As the F-atoms are progressively aggregate, the eg orbitals of Ni and Co transition from e2 g to e1 g, and subsequently to e0 g. The corresponding valence state elevates from +2 to +3, and then to +4, signifying an initial increase followed by a subsequent decrease in the electrocatalytic performance. Furthermore, a series of F-NiCo LDH catalysts are synthesized to verify the eg orbital occupancy analysis, and the catalytic OER overpotentials are 303, 243, 240, and 246 mV at the current density of 10 mA cm-2, respectively, which coincides well with the theoretical prediction. This investigation not only provides novel mechanistic insights into the transition and competition of Ni and Co in F-NiCo LDH catalysts but also establishes a foundation for the design of high-performance catalysts.

Occurrence and fate of pharmaceuticals and personal care products in a wastewater treatment plant with Bacillus bio-reactor treatment.

Pharmaceuticals and personal care products (PPCPs) have attracted wide attention due to their environmental impacts and health risks. PPCPs released through wastewater treatment plants (WWTPs) are estimated to be 80 %. Nevertheless, the occurrence of PPCPs in the WWTPs equipped with Bacillus spec.-based bioreactors (BBR) treatment system remains unclear. In this study, sludge and waste water samples were collected during separate winter and summer sampling campaigns from a typical BBR treatment system. The results indicate that out of 58 target PPCPs, 27 compounds were detected in the waste water (0.06-1900 ng/L), and 23 were found in the sludge (0.6-7755 ng/g dw). Paraxanthine was the chemical of the highest abundance in the influent due to the high consumption of the parent compounds caffeine and theobromine. The profile for PPCPs in the wastewater and sludge exhibited no seasonal variation. Overall, the removal of target PPCPs in summer is more effective than the winter. In the BBR bio-reactor, it was found that selected PPCPs (at ng/L level) can be completely removed. The efficiency for individual PPCP removal was increased from 1.0 % to 50 % in this unit, after target specific adjustments of the process. The effective removal of selected PPCPs by the BBR treatment system is explained by combined sorption and biodegradation processing. The re-occurrence of PPCPs in the wastewater was monitored. Negative removal efficiency was explained by the cleavage of Phase II metabolites after the biotransformation process, and the lack of equilibrium for PPCPs in the sludge of the second clarifier. A compound specific risk quotient (RQ) was calculated and applied for studying the potential environmental risks. Diphenhydramine is found with the highest environmental risk in wastewater, and 15 other PPCPs show negligible risks in sewage sludge.

Glial fibrillary acidic protein astrocytopathy presented as meningitis: A case report.

Introduction: Glial fibrillary acidic protein (GFAP) astrocytopathy is a novel autoimmune neurological disorder and is diagnosed by GFAP-IgG in cerebrospinal fluid (CSF) measurement. Case report: Herein, we described a 10-year-old boy with abnormal neurological symptoms and signs. GFAP-IgG was detected in CSF using cell-based assay (CBA), and his CSF showed an increase in lymphocytes, a slight decrease in glucose and an increase in protein level in the early stage. The cranial MRI showed multiple strips of T2-FLAIR hyperintense signal changes on the surface of medulla oblongata, pons, and gyrus in bilateral cerebral hemispheres. He was treated with immunoglobulin (IVIG) and high-dose methylprednisolone pulse treatment, and his clinical presentations gradually improved. Conclusion: We highlight that patients with normal inflammatory markers in peripheral blood have obvious meningitis-like symptoms, and clinicians need to consider GFAP astrocytopathy. The early diagnosis and treatment of GFAP astrocytopathy are important for improving the prognosis.

Evaluation of the Expansion and Neuronal Differentiation Potency of Cultured Olfactory Epithelium Progenitor Cells from a Rat Model of Depression.

BACKGROUND: Olfactory impairment has been reported in patients with depression and in rodent models of depression. Olfactory epithelium (OE) is the only peripheral neural tissue connected to the brain that has the potential for self-renewal. We hypothesized the olfactory deficit during depression may be related to the dysfunction of OE progenitor cells. The aim of the present study was therefore to evaluate the expansion and neuronal differentiation potency of cultured OE progenitor cells obtained from a rat model of depression. METHODS: Rats were exposed to chronic unpredictable mild stress procedures to establish a depressive-like state. Depressive-like behavior and olfactory sensing function were then evaluated and compared with control rats. Primary OE progenitor cells were cultured in vitro. The proliferation potency and survival of OE progenitor cells were assessed by 5-Ethynyl-2'-deoxyuridine staining and Cell Counting Kit-8 (CCK8), respectively, while cellular apoptosis was measured by flow cytometry. The neuronal differentiation potency of OE progenitor cells was evaluated by measurement of the protein and mRNA level of ß-3 tubulin, a marker of neural cells. mRNA expression associated with neural stemness was examined by quantitative reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Depressive-like rats showed decreased olfactory function. OE progenitor cells from depressive-like rats showed reduced cell proliferation/survival and neuronal differentiation potency. Moreover, OE progenitor cells from depressive-like rats showed decreased expression of mRNA related to neural stemness. CONCLUSIONS: These results indicate the impaired function of OE progenitor cells may contribute to the olfactory deficit observed during depression. The OE may therefore provide a window for the study of depression.

Metabotropic Glutamate Receptor 8 Suppresses M1 Polarization in Microglia by Alleviating Endoplasmic Reticulum Stress and Mitochondrial Dysfunction.

BACKGROUND: Microglia-mediated neuroinflammation is a hallmark of neurodegeneration. Metabotropic glutamate receptor 8 (GRM8) has been reported to promote neuronal survival in neurodegenerative diseases, yet the effect of GRM8 on neuroinflammation is still unclear. Calcium overload-induced endoplasmic reticulum (ER)-mitochondrial miscommunication has been reported to trigger neuroinflammation in the brain. The aim of this study was to investigate putative anti-inflammatory effects of GRM8 in microglia, specifically focusing on its role in calcium overload-induced ER stress and mitochondrial dysfunction. METHODS: BV2 microglial cells were pretreated with GRM8 agonist prior to lipopolysaccharide administration. Pro-inflammatory cytokine levels and the microglial polarization state in BV2 cells were then quantified. Cellular apoptosis and the viability of neuron-like PC12 cells co-cultured with BV2 cells were examined using flow cytometry and a Cell Counting Kit-8, respectively. The concentration of cAMP, inositol-1,4,5-triphosphate receptor (IP3R)-dependent calcium release, ER Ca2+ concentration, mitochondrial function as reflected by reactive oxygen species levels, ATP production, mitochondrial membrane potential, expression of ER stress-sensing protein, and phosphorylation of the nuclear factor kappa B (NF-κB) p65 subunit were also quantified in BV2 cells. RESULTS: GRM8 activation inhibited pro-inflammatory cytokine release and shifted microglia polarization towards an anti-inflammatory-like phenotype in BV2 cells, as well as promoting neuron-like PC12 cell survival when co-cultured with BV2 cells. Mechanistically, microglial GRM8 activation significantly inhibited cAMP production, thereby desensitizing the IP3R located within the ER. This process markedly limited IP3R-dependent calcium release, thus restoring mitochondrial function while inhibiting ER stress and subsequently deactivating NF-κB signaling. CONCLUSIONS: Our results indicate that GRM8 activation can protect against microglia-mediated neuroinflammation by attenuating ER stress and mitochondrial dysfunction, and that IP3R-mediated calcium signaling may play a vital role in this process. GRM8 may thus be a potential target for limiting neuroinflammation.

Calcitriol restrains microglial M1 polarization and alleviates dopaminergic degeneration in hemiparkinsonian mice by boosting regulatory T-cell expansion.

OBJECTIVE: Vitamin D deficiency is a risk factor for Parkinson's disease (PD) and vitamin D supplementation robustly alleviates neurodegeneration in PD models. However, the mechanisms underlying this effect require further clarification. Current evidence suggests that harnessing regulatory T cells (Treg) may mitigate neuronal degeneration. In this study, we investigated the therapeutic effects of vitamin D receptor activation by calcitriol on PD, specifically focusing on its role in Treg. METHODS: Hemiparkinsonian mice model was established through the injection of 6-OHDA into the striatum. Mice were pretreated with calcitriol before 6-OHDA injection. The motor performance, dopaminergic neuronal survival, contents of dopamine, and dopamine metabolites were evaluated. The pro-inflammatory cytokines levels, T-cell infiltration, mRNA expression of indicated microglial M1/M2 phenotypic markers, and microglial marker in the midbrain were detected. Populations of Treg in the splenic tissues were assessed using a flow cytometry assay. PC61 monoclonal antibody was applied to deplete Treg in vivo. RESULTS: We show that calcitriol supplementation notably improved motor performance and reduced dopaminergic degeneration in the 6-OHDA-induced PD model. Mechanistically, calcitriol promoted anti-inflammatory/neuroprotective Treg and inhibited pro-inflammatory/neurodestructive effector T-cell generation in this model. This process significantly inhibited T-cell infiltration in the midbrain, restrained microglial activation, microglial M1 polarization, and decreased pro-inflammatory cytokines release. This more favorable inflammatory microenvironment rescued dopaminergic degeneration. To further verify that the anti-inflammatory effects of calcitriol are associated with Treg expansion, we applied an antibody-mediated Treg depletion assay. As predicted, the anti-inflammatory effects of calcitriol in the PD model were diminished following Treg depletion. CONCLUSION: These findings suggest that calcitriol's anti-inflammatory and neuroprotective effects in PD are associated with its potential to boost Treg expansion.

Prognostic value and gene regulatory network of CMSS1 in hepatocellular carcinoma.

BACKGROUND: Cms1 ribosomal small subunit homolog (CMSS1) is an RNA-binding protein that may play an important role in tumorigenesis and development. OBJECTIVE: RNA-seq data from the GEPIA database and the UALCAN database were used to analyze the expression of CMSS1 in liver hepatocellular carcinoma (LIHC) and its relationship with the clinicopathological features of the patients. METHODS: LinkedOmics was used to identify genes associated with CMSS1 expression and to identify miRNAs and transcription factors significantly associated with CMSS1 by GSEA. RESULTS: The expression level of CMSS1 in hepatocellular carcinoma tissues was significantly higher than that in normal tissues. In addition, the expression level of CMSS1 in advanced tumors was significantly higher than that in early tumors. The expression level of CMSS1 was higher in TP53-mutated tumors than in non-TP53-mutated tumors. CMSS1 expression levels were strongly correlated with disease-free survival (DFS) and overall survival (OS) in patients with LIHC, and high CMSS1 expression predicted poorer OS (P< 0.01) and DFS (P< 0.01). Meanwhile, our results suggested that CMSS1 is associated with the composition of the immune microenvironment of LIHC. CONCLUSIONS: The present study suggests that CMSS1 is a potential molecular marker for the diagnosis and prognostic of LIHC.

Exploring the Depth-Dependent Microviscosity inside a Micelle Using Butterfly-Motion-Based Fluorescent Probes.

The viscosity distribution of micellar interiors from the very center to the outer surface is dramatically varied, which has been distinguished in theoretical models, yet it remains highly challenging to quantify this issue experimentally. Herein, a series of fluorophore-substituted surfactants DPAC-Fn (n = 3, 5, 7, 9, 11, 13, and 15) are developed by functionalizing the different alkyl-trimethylammonium bromides with the butterfly motion-based viscosity sensor, N,N'-diphenyl-dihydrodibenzo[a,c]phenazine (DPAC). The immersion depth of DPAC units of DPAC-Fn in cetrimonium bromide (C16TAB) micelles depends on the alkyl chain lengths n. From deep (n = 15) to shallow (n = 3), DPAC-Fn in C16TAB micelles exhibits efficient viscosity-sensitive dynamic multicolor emissions. With external standards for quantification, the viscosity distribution inside a C16TAB micelle with the size of ∼4 nm is changed seriously from high viscosity (∼190 Pa s) in the core center to low viscosity (∼1 Pa s) near the outer surface. This work provides a tailored approach for powerful micelle tools to explore the depth-dependent microviscosity of micellar interiors.