Source-free collaborative domain adaptation via multi-perspective feature enrichment for functional MRI analysis.

Resting-state functional MRI (rs-fMRI) is increasingly employed in multi-site research to analyze neurological disorders, but there exists cross-site/domain data heterogeneity caused by site effects such as differences in scanners/protocols. Existing domain adaptation methods that reduce fMRI heterogeneity generally require accessing source domain data, which is challenging due to privacy concerns and/or data storage burdens. To this end, we propose a source-free collaborative domain adaptation (SCDA) framework using only a pretrained source model and unlabeled target data. Specifically, a multi-perspective feature enrichment method (MFE) is developed to dynamically exploit target fMRIs from multiple views. To facilitate efficient source-to-target knowledge transfer without accessing source data, we initialize MFE using parameters of a pretrained source model. We also introduce an unsupervised pretraining strategy using 3,806 unlabeled fMRIs from three large-scale auxiliary databases. Experimental results on three public and one private datasets show the efficacy of our method in cross-scanner and cross-study prediction.

Tensorized Soft Label Learning Based on Orthogonal NMF.

Recently, a strong interest has been in multiview high-dimensional data collected through cross-domain or various feature extraction mechanisms. Nonnegative matrix factorization (NMF) is an effective method for clustering these high-dimensional data with clear physical significance. However, existing multiview clustering based on NMF only measures the difference between the elements of the coefficient matrix without considering the spatial structure relationship between the elements. And they often require postprocessing to achieve clustering, making the algorithms unstable. To address this issue, we propose minimizing the Schatten p -norm of the tensor, which consists of a coefficient matrix of different views. This approach considers each element's spatial structure in the coefficient matrices, crucial for effectively capturing complementary information presented in different views. Furthermore, we apply orthogonal constraints to the cluster index matrix to make it sparse and provide a strong interpretation of the clustering. This allows us to obtain the cluster label directly without any postprocessing. To distinguish the importance of different views, we utilize adaptive weights to assign varying weights to each view. We introduce an unsupervised optimization scheme to solve and analyze the computational complexity of the model. Through comprehensive evaluations of six benchmark datasets and comparisons with several multiview clustering algorithms, we empirically demonstrate the superiority of our proposed method.

Proteomic characterization of murine hematopoietic stem progenitor cells reveals dynamic fetal-to-adult changes in metabolic-related pathways.

Hematopoietic stem progenitor cells (HSPCs) give rise to the hematopoietic system, maintain hematopoiesis throughout the lifespan, and undergo molecular and functional changes during their development and aging. The importance of hematopoietic stem cell (HSC) biology has led to their extensive characterization at genomic and transcriptomic levels. However, the proteomics of HSPCs throughout the murine lifetime still needs to be fully completed. Here, using mass spectrometry (MS)-based quantitative proteomics, we report on the dynamic changes in the proteome of HSPCs from four developmental stages in the fetal liver (FL) and the bone marrow (BM), including E14.5, young (2 months), middle-aged (8 months), and aging (18 months) stages. Proteomics unveils highly dynamic protein kinetics during the development and aging of HSPCs. Our data identify stage-specific developmental features of HSPCs, which can be linked to their functional maturation and senescence. Our proteomic data demonstrated that FL HSPCs depend on aerobic respiration to meet their proliferation and oxygen supply demand, while adult HSPCs prefer glycolysis to preserve the HSC pool. By functional assays, we validated the decreased mitochondrial metabolism, glucose uptake, reactive oxygen species (ROS) production, protein synthesis rate, and increased glutathione S-transferase (GST) activity during HSPC development from fetal to adult. Distinct metabolism pathways and immune-related pathways enriched in different HSPC developmental stages were revealed at the protein level. Our study will have broader implications for understanding the mechanism of stem cell maintenance and fate determination and reversing the HSC aging process.

Neurotransmitter metabolites in milk ferments of Leuconostoc mesenteroides regulate temperature-sensitive heartbeats in an ex ovo model.

Accumulated evidence has supported the probiotic activity of Leuconostoc mesenteroides (L. mesenteroides) which can yield beneficial metabolites via fermentation. Here, bovine milk rich in phenylalanine（PHE) was used as a source for fermentation of L. mesenteroides. The complexes of PHE with bacterial phenylalanine hydroxylase (PheH) at two temperatures were revealed via molecular dynamics simulation. Two carbon hydrogen bonds and a Pi-Alkyl T-shaped interaction were newly formed at an active site of the PheH-PHE complex. The PheH interacted with two different hydrogen atoms in an amine of PHE via conventional hydrogen bonds at 37 °C, a temperature that accelerated the milk fermentation of L. mesenteroides. Twenty-eight metabolites including various neurotransmitters in fermented milk were identified and quantified by liquid chromatography coupled to quadrupole ion trap (Q-Trap) tandem mass spectrometry. Ex ovo injection of milk ferments into the yolk sac of chicken embryos enhanced a rising temperature-induced increase in heartbeats towards the normal resting level. The neurotransmitter-rich milk ferments hold potential for using to adjust energy metabolism, referred from heart rates, during fluctuating temperature conditions.

Cyano-functionalized porous hyper-crosslinked cationic polymers for efficient preconcentration and detection of phenolic endocrine disruptors in fresh water and fish.

Sensitively analyzing phenolic endocrine-disrupting chemicals (EDCs) in environmental substrates and aquatic organisms provides a significant challenge. Here, we developed a novel porous hyper-crosslinked ionic polymer bearing cyano groups (CN-HIP) as adsorbent for the highly efficient solid phase extraction (SPE) of phenolic EDCs in water and fish. The CN-HIP gave an excellent adsorption capability for targeted EDCs over a wide pH range, and the adsorption capacity was superior to that of several common commercial SPE adsorbents. The coexistence of electrostatic forces, hydrogen bond, and π-π interactions was confirmed as the main adsorption mechanism. A sensitive quantitative method was established by coupling CN-HIP based SPE method with high-performance liquid chromatography for the simultaneously determining trace bisphenol A, bisphenol F, bisphenol B and 4-tert-butylphenol in fresh water and fish. The method afforded lower detection limits (S/N = 3) (at 0.03-0.10 ng mL-1 for water and 0.8-4.0 ng g-1 for fish), high accuracy (the recovery of spiked sample at 88.0%-112 %) and high precision (the relative standard deviation < 8.5 %). This work provides a feasible method for detecting phenolic EDCs, and also opens a new perspective in developing functionalized cationic adsorbent.

Single-cell RNA-seq in diabetic foot ulcer wound healing.

Diabetic foot ulcer (DFU) is a chronic and serious complication of diabetes mellitus. It is mainly caused by hyperglycaemia, diabetic peripheral vasculopathy and diabetic peripheral neuropathy. These conditions result in ulceration of foot tissues and chronic wounds. If left untreated, DFU can lead to amputation or even endanger the patient's life. Single-cell RNA sequencing (scRNA-seq) is a technique used to identify and characterise transcriptional subpopulations at the single-cell level. It provides insight into cellular function and the molecular drivers of disease. The objective of this paper is to examine the subpopulations, genes and molecules of cells associated with chronic wounds of diabetic foot by using scRNA-seq. The paper aims to explore the wound-healing mechanism of DFU from three aspects: inflammation, angiogenesis and extracellular matrix remodelling. The goal is to gain a better understanding of the mechanism of DFU wound healing and identify possible DFU therapeutic targets, providing new insights for the application of DFU personalised therapy.

ß-Cyclodextrin based magnetic hyper-crosslinked polymer: A recyclable adsorbent for effective preconcentration of triazine herbicides in complex sample matrices.

High efficiency enrichment and trace analysis of triazine herbicide residues are crucial for ensuring environmental and food safety. Herein, a series of magnetic hyper-crosslinked polymers (CD-gs-MHCPs) were synthesized with different crosslinkers, which might possess different pore structure and surface area, so they might dispay variable adsorption performance. CD-gs-MHCP2 with dichloroxylene as crosslinker delivered superior adsorption ability for triazine herbicides (THs). The synergistic effect of hydrogen bonds, hydrophobic interaction, π-π stacking interaction and pore adsorption were proved to be the main adsorption mechanism. Combined CD-gs-MHCP2 based magnetic solid-phase extraction (MSPE) with high-performance liquid chromatography, the quantitative analysis of THs in river water and vegetable samples (zucchini, pakchoi) was achieved. Under the optimal conditions, the enrichment factors for three different samples ranged from 94 to 244 and low detection limit (S/N = 3) of the four THs were obtained from 0.05 to 0.15 ng mL-1 for river water and 0.31-3.10 ng g-1 for vegetable samples. The method recoveries were in the range of 86.2 %-120 % with relative standard deviations lower than 7.4 %. This work not only offers a new strategy for fabrication ß-CD-based HCPs, but also provided a practical and effective method for efficient isolation and sensitive detection of trace THs residues in complex samples.

Proteomics reveals dynamic metabolic changes in human hematopoietic stem progenitor cells from fetal to adulthood.

BACKGROUND: Hematopoietic stem progenitor cells (HSPCs) undergo phenotypical and functional changes during their emergence and development. Although the molecular programs governing the development of human hematopoietic stem cells (HSCs) have been investigated broadly, the relationships between dynamic metabolic alterations and their functions remain poorly characterized. METHODS: In this study, we comprehensively described the proteomics of HSPCs in the human fetal liver (FL), umbilical cord blood (UCB), and adult bone marrow (aBM). The metabolic state of human HSPCs was assessed via a Seahorse assay, RT‒PCR, and flow cytometry-based metabolic-related analysis. To investigate whether perturbing glutathione metabolism affects reactive oxygen species (ROS) production, the metabolic state, and the expansion of human HSPCs, HSPCs were treated with buthionine sulfoximine (BSO), an inhibitor of glutathione synthetase, and N-acetyl-L-cysteine (NAC). RESULTS: We investigated the metabolomic landscape of human HSPCs from the fetal, perinatal, and adult developmental stages by in-depth quantitative proteomics and predicted a metabolic switch from the oxidative state to the glycolytic state during human HSPC development. Seahorse assays, mitochondrial activity, ROS level, glucose uptake, and protein synthesis rate analysis supported our findings. In addition, immune-related pathways and antigen presentation were upregulated in UCB or aBM HSPCs, indicating their functional maturation upon development. Glutathione-related metabolic perturbations resulted in distinct responses in human HSPCs and progenitors. Furthermore, the molecular and immunophenotypic differences between human HSPCs at different developmental stages were revealed at the protein level for the first time. CONCLUSION: The metabolic landscape of human HSPCs at three developmental stages (FL, UCB, and aBM), combined with proteomics and functional validations, substantially extends our understanding of HSC metabolic regulation. These findings provide valuable resources for understanding human HSC function and development during fetal and adult life.

Using Doppler ultrasound to assess fetal cardiac function and pregnancy outcomes in obstetric antiphospholipid syndrome pregnancies: a case-control study.

PURPOSE: This study aimed to evaluate fetal left ventricular function (LVF) in pregnant women with obstetric antiphospholipid syndrome (OAPS) by Doppler ultrasound and developed a clinical nomogram to predict adverse perinatal outcomes. METHODS: In this prospective observational study, 105 pregnant women were enrolled and divided into the OAPS cohort (n = 60) and the control cohort (n = 45). Fetal cardiac function parameters were collected and compared between two cohorts. Univariate and multivariate analysis was conducted to select the risk factors associated with adverse perinatal outcomes, and a clinical nomogram was developed based on these selected risk factors. The predictive performance of corresponding indicators for adverse perinatal outcomes was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: The OAPS cohort revealed an increase in the isovolumic relaxation time (IVRT) and myocardial performance index (MPI), a decrease in the ejection time (ET), middle cerebral artery pulsatility index (MCA-PI) and cerebroplacental ratio (CPR) compared to the control cohort. Through univariate and multivariate analysis, gravidity, CPR, and MPI were the risk factors associated with adverse perinatal outcomes. A model predicting adverse perinatal outcomes in OAPS pregnant women was constructed based on these three factors and visualized as a nomogram. The nomogram could accurately predict adverse perinatal outcomes with an area under the curve of 0.923 (95% CI: 0.858-0.982). This performance was better than evaluating individual factors such as MPI (0.825, 95% CI: 0.739-0.911) and CPR (0.816, 95% CI: 0.705-0.927) for efficacy. CONCLUSION: MPI can be used to assess fetal LVF and predict adverse perinatal outcomes. We developed a nomogram to predict adverse perinatal outcomes in OAPS women. This imaging-based evidence can provide timely clinical intervention, enabling personalized clinical decision-making.

Rumen metagenome reveals the mechanism of mitigation methane emissions by unsaturated fatty acid while maintaining the performance of dairy cows.

Dietary fat content can reduce the methane production of dairy cows; however, the relevance fatty acid (FA) composition has towards this inhibitory effect is debatable. Furthermore, in-depth studies elucidating the effects of unsaturated fatty acids (UFA) on rumen function and the mechanism of reducing methane (CH4) production are lacking. This study exposed 10 Holstein cows with the same parity, similar milk yield to two total mixed rations: low unsaturated FA (LUFA) and high unsaturated FA (HUFA) with similar fat content. The LUFA group mainly added fat powder (C16:0 > 90%), and the HUFA group mainly replaced fat powder with extruded flaxseed. The experiment lasted 26 d, the last 5 d of which, gas exchange in respiratory chambers was conducted to measure gas emissions. We found that an increase in the UFA in diet did not affect milk production (P > 0.05) and could align the profile of milk FAs more closely with modern human nutritional requirements. Furthermore, we found that increasing the UFA content in the diet lead to a decrease in the abundance of Methanobrevibacter in the rumen (|linear discriminant analysis [LDA] score| > 2 and P < 0.05), which resulted in a decrease in the relative abundance of multiple enzymes (EC:1.2.7.12, EC:2.3.1.101, EC:3.5.4.27, EC:1.5.98.1, EC:1.5.98.2, EC:6.2.1.1, EC:2.1.1.86 and EC:2.8.4.1) during methanogenesis (P < 0.05). Compared with the LUFA group, the pathway of CH4 metabolism was inhibited in the HUFA group (|LDA| > 2 and P < 0.05), which ultimately decreased CH4 production (P < 0.05). Our results illustrated the mechanism involving decreased CH4 production when fed a UFA diet in dairy cows. We believe that our study provides new evidence to explore CH4 emission reduction measures for dairy cows.

Active dual quasi-BICs in a dielectric metasurface with VO2 for slow light and optical modulation.

We investigate the temperature tunable dual quasi-bound states in the continuum (qBICs) in a silicon/vanadium dioxide (Si/VO2) hybrid metasurface with Q-factor being as large as 9.3 × 106 and 2.8 × 107 by breaking the in-plane C2 symmetry. The far-field scattering of multipoles and near-field distributions confirm that the toroidal dipole and magnetic quadrupole dominate the dual qBICs resonance. The high performance of slow light with ultralarge group index exceeding 5.6 × 105 and the inverse quadratic law between the group index and asymmetric parameter are achieved. By temperature tuning of the VO2 thin film at the sub-10 K scale, a modulation depth of 90% and the ON/OFF ratio exceeding 12.8 dB are obtained. The proposed temperature tunable dual qBICs have potential applications in the fields of tunable slow light, temperature switches, and sensors.

Mesenchymal stem cells improve depressive disorder via inhibiting the inflammatory polarization of microglia.

Depressive disorder (DD) ranks among the most prevalent, burdensome, and costly psychiatric conditions globally. It manifests through a range of emotional, cognitive, somatic, and behavioral symptoms. Mesenchymal Stem Cells (MSCs) have garnered significant attention due to their therapeutic potential via immunomodulation in neurological disorders. Our research indicates that MSCs treatment demonstrates a notable effect on a Chronic Unpredictable Mild Stress (CUMS)-induced DD model in mice, surpassing even Fluoxetine in its antidepressant efficacy. MSCs mitigate DD by inhibiting central nervous system inflammation and facilitating the conversion of microglial cells into an Arg1high anti-inflammatory state. The MSCs-derived TGF-ß1 is crucial for this Arg1high microglial cell transformation in DD treatment.

Association of oxidative balance score, cardiovascular, and all-cause mortality among patients with type 2 diabetes mellitus.

Background: To investigate the association between oxidative balance score (OBS), cardiovascular mortality (CVM), and all-cause mortality (ACM) in type 2 diabetes mellitus (T2DM) patients. Methods: We included 6,119 participants with T2DM from the 2005-2020 National Health and Nutrition Examination Surveys (NHANES). The status of CVM and ACM of participants was followed through December 31, 2019. Multivariable Cox regression models, Kaplan-Meier curves, log-rank test, restricted cubic spline regression, and subgroup analysis, were used to evaluate the relationship between OBS, CVM, and ACM. Results: During a median of 100.9 months follow-up, 1,790 ACM cases had occurred, 508 of which were due to cardiovascular disease. The T2DM participants were divided into four groups based on the quartiles of OBS. Participants with Q4 tended to be younger, financially better-off, married, highly educated, had lower alcohol consumption rates, were non-smokers, and exhibited a lower likelihood of ACM and CVM. In multivariate Cox regression models, compared with the patients with Q4, those with Q1 had a 30% increased risk for ACM (Q1, reference; Q4, HR: 0.70, 95%CI: 0.58-0.86) and a 43% increased risk for CVM (Q1, reference; Q4, HR: 0.57, 95%CI: 0.36-0.88). The restricted cubic spline regression models have no nonlinear relationship between OBS, CVM, and ACM. Kaplan-Meier survival curves showed that patients with Q4 had a lower risk of ACM and CVM (log-rank P < 0.05). Conclusions: We find that ACM and CVM increase with higher OBS in T2DM patients. Moreover, there are linear relationships between OBS, ACM, and CVM.

EFFECT OF ARTESUNATE TREATMENT ON INTESTINAL INJURY AFTER CARDIOPULMONARY RESUSCITATION IN SWINE.

INTRODUCTION: Intestinal injury is often caused by systemic ischemia-reperfusion injury early after cardiac arrest (CA) and resuscitation. Artesunate (Art) has been confirmed to protect vital organs against diverse of regional I/R injury. This study aimed to investigate the effect of Art on intestinal injury after CA and cardiopulmonary resuscitation (CPR) in swine. METHODS: Twenty-two swine were randomly divided into three groups: sham (n = 6), CA/CPR (n = 8), and CA/CPR + Art (n = 8). The CA/CPR swine model was established by inducing 9 minutes of untreated ventricular fibrillation (VF) followed by 6 minutes of CPR. Five minutes after resuscitation, 4.8 mg/kg of Art was intravenously administered for 2 hours in the CA/CPR + Art group. Intestinal fatty acid-binding protein (iFABP) and diamine oxidase (DAO) concentrations were compared among the three groups before CA and at 1, 2, 4, and 24 hours after resuscitation. At 24 hours post-resuscitation, intestinal zonula occluden-1(ZO-1), occludin, apoptosis, caspase-3/gasdermin E (GSDME)-mediated pyroptosis proteins concentrations, and proinflammatory cytokine concentrations were examined to evaluate intestinal injury. RESULTS: During CPR, spontaneous circulation was achieved in 7 and 6 swine in the CA/CPR and CA/CPR + Art groups, respectively. Serum iFABP and DAO concentrations were significantly higher and intestinal tissue ZO-1 and occludin concentrations were significantly lower in the CA/CPR and CA/CPR + Art groups than in the sham group. However, Art treatment resulted in markedly improved levels of intestinal injury biomarkers compared with those in the CA/CPR group. Additionally, intestinal apoptosis and concentrations of caspase-3/GSDME-mediated pyroptosis proteins and proinflammatory cytokines were significantly higher in the CA/CPR and CA/CPR + Art groups than in the sham group. However, these variables were significantly lower in the CA/CPR + Art group than in the CA/CPR group. CONCLUSIONS: Art treatment effectively alleviates post-resuscitation intestinal injury, possibly by inhibiting the caspase-3/GSDME-mediated pyroptosis pathway in a swine CA and CPR model.

Robot-assisted transosseous repair of triangular fibrocartilage complex: a cadaver study.

The feasibility and accuracy of robot-assisted bone tunnel construction in the transosseous repair of the triangular fibrocartilaginous complex (TFCC) were compared with those of freehand arthroscopic repair. A total of 20 cadaveric specimens were randomized into robotic-assisted and arthroscopy-guided groups. Three bone tunnels were constructed in the ulnar foveal region in each specimen. The discrepancy between the planned and actual tunnel exits was determined in the robot-assisted group by merging images. The success rate of tunnel construction, time consumption and number of drilling attempts were compared between groups. The median planned/actual exit discrepancy was 0.8 mm in the robot-assisted group, with 90% of tunnel exits successfully placed in the footprint region, compared to 63.3% in the arthroscopy-guided group. The robot-assisted group spent less time and required fewer drilling attempts to construct bone tunnels. These results indicated that the robot-assisted technique can accurately construct multiple bone tunnels in the foveal region and reduce the difficulty of TFCC transosseous repair.Level of evidence: III.

VMP1: a multifaceted regulator of cellular homeostasis with implications in disease pathology.

Vacuole membrane protein 1 (VMP1) is an integral membrane protein that plays a pivotal role in cellular processes, particularly in the regulation of autophagy. Autophagy, a self-degradative mechanism, is essential for maintaining cellular homeostasis by degradation and recycling damaged organelles and proteins. VMP1 involved in the autophagic processes include the formation of autophagosomes and the subsequent fusion with lysosomes. Moreover, VMP1 modulates endoplasmic reticulum (ER) calcium levels, which is significant for various cellular functions, including protein folding and cellular signaling. Recent studies have also linked VMP1 to the cellular response against viral infections and lipid droplet (LD). Dysregulation of VMP1 has been observed in several pathological conditions, including neurodegenerative diseases such as Parkinson's disease (PD), pancreatitis, hepatitis, and tumorogenesis, underscoring its potential as a therapeutic target. This review aims to provide an overview of VMP1's multifaceted roles and its implications in disease pathology.

The ROS Mediates MCUb in Mitochondria-Regulated Apoptosis of TM4 Cells Induced by Titanium Dioxide Nanoparticles.

Titanium dioxide nanoparticles (TiO2 NPs) can cause mitochondrial apoptosis of TM4 cells associated with reactive oxygen species (ROS) accumulation and Ca2+ overload, but the relations among these processes remain unclear. This study aimed to evaluate whether the accumulation of ROS caused by TiO2 NPs inhibits MCUb expression, leading to mitochondrial calcium overload and subsequent cell apoptosis through the mitochondrial pathway. TM4 cells were exposed to different concentrations of TiO2 NPs (0, 25, 50, 75, 100 µg/mL) for 24 h. We assessed cell viability, ROS level, MCUb and VDAC1 expression, mitochondrial and cytoplasmic Ca2+ levels, mitochondrial membrane potential (MMP), apoptosis rate, and key proteins related to mitochondrial apoptosis (Bcl-2, Bax, Caspase 3, Caspase 9, p53 and Cyt c). Additionally, the effect of N-acetylcysteine (NAC) on MCUb expression, calcium homeostasis, and cell apoptosis was evaluated. Compared to control group, TiO2 NPs significantly increased ROS level, downregulated MCUb expression, elevated Ca2+ levels in mitochondria and cytoplasm, and enhanced mitochondria-regulated apoptosis, starting from the 50 µg/mL TiO2 NPs group. However, NAC significantly increased MCUb expression, attenuated Ca2+ levels in mitochondria and cytoplasm, and reduced mitochondria-related apoptosis. In conclusion, TiO2 NPs induced ROS accumulation, which inhibited the expression of MCUb. The decreased MCUb level led to Ca2+ overload in mitochondria, causing TM4 cell apoptosis via the mitochondrial pathway. This research elucidates, for the first time, the role of MCUb and its relation with ROS in apoptosis of TM4 cells induced by TiO2 NPs, which supplementing the molecular mechanism of cell apoptosis caused by TiO2 NPs.

Screening of anti-inflammatory activities components of Angelica dahurica root based on spectrum-effect relationship analysis and NF-κB pathway.

Angelica dahurica root (ADR), a commonly utilized herbal medicine in China and other Asian nations, which has anti-inflammatory effects on diverse inflammatory ailments. However, the bioactive components and underlying mechanism responsible for the anti-inflammatory effect of ADR are still unclear. This work attempted to discover the anti-inflammatory bioactive compounds and explore their underlying mechanism in ADR based on spectrum-effect relationship analysis and NF-κB signaling pathway. Chromatographic fingerprints of ADR samples were established by high performance liquid chromatography with diode array detection (HPLC-DAD), and a total of eleven common peaks were selected. Then, high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-Q/TOF-MS) was employed for identification of eleven common peaks in ADR Meanwhile, the anti-inflammatory activities of ADR samples were assessed by inhibition of NO, interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production in LPS-induced RAW264.7 cells. The spectrum-effect relationships between the eleven common peaks in HPLC fingerprints and anti-inflammatory effects of ADR samples were investigated to identify the potential anti-inflammatory bioactive compounds by grey relational analysis (GRA) and partial least squares regression (PLSR). The spectrum-effect relationship analysis results indicated that six coumarin compounds, including bergapten, xanthotoxin, phellopterin, isoimperatorin, xanthotoxol and imperatorin could be potential anti-inflammatory bioactive compounds in ADR. The further validation experiments also showed that these six coumarins demonstrated significant inhibition of NO, IL-1ß, IL-6, and TNF-α production in LPS-induced RAW264.7 cells. In addition, western blot analysis was conducted to explore the mechanisms of two potential anti-inflammatory bioactive compounds (phellopterin and isoimperatorin) by assessing the protein levels in the NF-κB signaling pathway. The western blot results illustrated that phellopterin and isoimperatorin could significantly down-regulate the phosphorylated NF-κB p65 (p-p65), phosphorylated IκBα (p-IκBα) and iNOS, and depress the pro-portion of p-p65/p65 and p-IκBα/IκBα, which indicated that these two coumarins in ADR could potentially exert anti-inflammatory effects by suppressing of NF-κB pathway.

Polysaccharide Nanocrystals-Based Chiral Nematic Structures: From Self-Assembly Mechanisms, Regulation, to Applications.

Chiral architectures, one of the key structural features of natural systems ranging from the nanoscale to macroscale, are an infinite source of inspiration for functional materials. Researchers have been, and still are, strongly pursuing the goal of constructing such structures with renewable and sustainable building blocks via simple and efficient strategies. With the merits of high sustainability, renewability, and the ability to self-assemble into chiral nematic structures in aqueous suspensions that can be preserved in the solid state, polysaccharide nanocrystals (PNs) including cellulose nanocrystals (CNCs) and chitin nanocrystals (ChNCs) offer opportunities to reach the target. We herein provide a comprehensive review that focuses on the development of CNCs and ChNCs for the use in advanced functional materials. First, the introduction of CNCs and ChNCs, and cellulose- and chitin-formed chiral nematic organizations in the natural world, are given. Then, the self-assembly process of such PNs and the factors influencing this process are comprehensively discussed. After that, we showcased the emerging applications of the self-assembled chiral nematic structures of CNCs and ChNCs. Finally, this review concludes with perspectives on the challenges and opportunities in this field.

Discovery of an 8-oxoguanine regulator PCBP1 inhibitor by virtual screening and its synergistic effects with ROS-modulating agents in pancreatic cancer.

Introduction: Drugs that target reactive oxygen species (ROS) metabolism have progressed the treatment of pancreatic cancer treatment, yet their efficacy remains poor because of the adaptation of cancer cells to high concentration of ROS. Cells cope with ROS by recognizing 8-oxoguanine residues and processing severely oxidized RNA, which make it feasible to improve the efficacy of ROS-modulating drugs in pancreatic cancer by targeting 8-oxoguanine regulators. Methods: Poly(rC)-binding protein 1 (PCBP1) was identified as a potential oncogene in pancreatic cancer through datasets of The Cancer Genome Atlas (TCGA) project and Gene Expression Omnibus (GEO). High-throughput virtual screening was used to screen out potential inhibitors for PCBP1. Computational molecular dynamics simulations was used to verify the stable interaction between the two compounds and PCBP1 and their structure-activity relationships. In vitro experiments were performed for functional validation of silychristin. Results: In this study, we identified PCBP1 as a potential oncogene in pancreatic cancer. By applying high-throughput virtual screening, we identified Compound 102 and Compound 934 (silychristin) as potential PCBP1 inhibitors. Computational molecular dynamics simulations and virtual alanine mutagenesis verified the structure-activity correlation between PCBP1 and the two identified compounds. These two compounds interfere with the PCBP1-RNA interaction and impair the ability of PCBP1 to process RNA, leading to intracellular R loop accumulation. Compound 934 synergized with ROS agent hydrogen peroxide to strongly improve induced cell death in pancreatic cancer cells. Discussion: Our results provide valuable insights into the development of drugs that target PCBP1 and identified promising synergistic agents for ROS-modulating drugs in pancreatic cancer.