Accumulation of γδT cells in the decidua is promoted by RANKL which upregulates ICAM-1 via NF-κB.

In brief: The mechanism underlying the accumulation of γδT cells in the decidua, which helps maintain maternal-fetal immunotolerance in early pregnancy, is unknown. This study reveals that DSC-derived RANKL upregulates ICAM-1 expression via the NF-κB pathway to enable γδT cell accumulation in the early decidua. Abstract: Decidual γδT (dγδT) cells help maintain maternal-fetal immunotolerance in early pregnancy. However, the mechanism underlying the accumulation of γδT cells in the decidua is unknown. Previous work showed that RANKL upregulated intercellular adhesion molecule 1 (ICAM-1) in decidual stromal cells (DSCs), and Rankl knockout mice had limited dγδT cell populations. In this study, we measured the expression levels of RANKL/RANK and ICAM-1 in DSCs, in addition to the integrins of ICAM-1 on dγδT cells, and the number of dγδT cells from patients with recurrent spontaneous abortion (RSA) and normal pregnant women in the first trimester. RSA patients showed significantly decreased RANKL/RANK and ICAM-1/CD11a signaling in decidua, and a decreased percentage of dγδT cells, which was positively correlated with DSC-derived RANKL and ICAM-1. Next, an in vitro adhesion experiment showed that the enhanced attraction of human DSCs to dγδT cells after RANKL overexpression was almost completely aborted by anti-ICAM-1. Furthermore, Rankl knockout mice showed a significant reduction in NF-κB activity compared with wild-type controls. Finally, we applied a selective NF-κB inhibitor named PDTC to validate the role of NF-κB in RANKL-mediated ICAM-1 upregulation. Taken together, our data show that DSC-derived RANKL upregulates ICAM-1 expression via the NF-κB pathway to enable γδT cell accumulation in the early decidua. A reduction in RANKL/ICAM-1 signaling in DSCs may result in insufficient accumulation of γδT cells in decidua and, in turn, RSA.

ABA functions in low phosphate-induced anthocyanin accumulation through the transcription factor ABI5 in Arabidopsis.

KEY MESSAGE: ABI5 functions in ABA-mediated anthocyanin accumulation in plant response to low phosphate. Low phosphate (LP)-induced anthocyanin biosynthesis and accumulation play an important role in plant adaptive response to phosphate starvation conditions. However, whether and how the stress phytohormone abscisic acid (ABA) participates in LP-induced anthocyanin accumulation remain elusive. Here, we report that ABA is required for LP-induced anthocyanin accumulation in Arabidopsis thaliana. Disrupting ABA DEFICIENT2 (ABA2), a key ABA-biosynthetic gene, or BETA-GLUCOSIDASE1 (BG1), a major gene implicated in converting conjugated ABA to active ABA, significantly impairs LP-induced anthocyanin accumulation, as LP-induced expression of the anthocyanin-biosynthetic genes Chalcone Synthase (CHS) is dampened in the aba2 and bg1 mutant. In addition, LP-induced anthocyanin accumulation is defective in the mutants of ABA signaling pathway, including ABA receptors, ABA Insensitive2, and the transcription factors ABA Insensitive5 (ABI5), suggesting a role of ABI5 in ABA-mediated upregulation of anthocyanin-biosynthetic genes in plant response to LP. Indeed, LP-induced expression of CHS is repressed in the abi5-7 mutant but further promoted in the ABI5-overexpressing plants compared to the wild-type. Moreover, ABI5 can bind to and transcriptionally activate CHS, and the defectiveness of LP-induced anthocyanin accumulation in abi5-7 can be restored by overexpressing CHS. Collectively, our findings illustrates that ABI5 functions in ABA-mediated LP-induced anthocyanin accumulation in Arabidopsis.

Interferon therapy improves survival in patients with hepatitis B virus-related hepatocellular carcinoma after curative surgery: a meta-analysis.

BACKGROUND AND AIM: A novel study found interferon enhanced antitumor activity of anti-PD-1-based immunotherapy and played a crucial role in improving efficacy on HCC, but the opposite results about the efficacy of interferon on HBV-related HCC were obtained from previous clinical studies and meta-analyses. Thus, this meta-analysis aimed to re-evaluate whether interferon could improve survival and reduce recurrence of patients with HBV-related HCC after curative surgery. METHODS: MEDLINE/PubMed, Cochrane Library, EMBASE, Web of Science and CNKI were searched for eligible studies from inception to November 2022 and a meta-analysis was done. RESULTS: 10 trials with a total of 2062 subjects were screened. Interferon significantly improved 1-, 2-, 3- and 5-year OS and 1-, 2- and 3-year DFS, and reduced 2-, 3- and 5-year recurrence rates of patients with HBV-related HCC after curative surgery. However, interferon did not improve 8-year OS and 5-year DFS, did not reduce 1-year recurrence rate. CONCLUSIONS: Interferon may significantly reduce recurrence and improve DFS of patients with HBV-related HCC after curative surgery, and finally improve the OS. However, the efficacy advantage may gradually weaken as time goes on. The clinical application of interferon combined with NAs recommended in this meta-analysis is needed to be further studied.

Chaperone Mimetic Strategy for Achieving Organic Room-Temperature Phosphorescence based on Confined Supramolecular Assembly.

The development of organic materials that deliver room-temperature phosphorescence (RTP) is highly interesting for potential applications such as anticounterfeiting, optoelectronic devices, and bioimaging. Herein, a molecular chaperone strategy for controlling isolated chromophores to achieve high-performance RTP is demonstrated. Systematic experiments coupled with theoretical evidence reveal that the host plays a similar role as a molecular chaperone that anchors the chromophores for limited nonradiative decay and directs the proper conformation of guests for enhanced intersystem crossing through noncovalent interactions. For deduction of structure-property relationships, various structure-related descriptors that correlate with the RTP performance are identified, thus offering the possibility to quantitatively design and predict the phosphorescent behaviors of these systems. Furthermore, application in thermal printing is well realized for these RTP materials. The present work discloses an effective strategy for efficient construction of organic RTP materials, delivering a modular model which is expected to help expand the diversity of desirable RTP systems.

A cavitand-based supramolecular artificial light-harvesting system with sequential energy transfer for photocatalysis.

A novel artificial light-harvesting system, featuring sequential energy transfer processes, has been successfully constructed, which demonstrated white light emission through a precise adjustment of the donor-acceptor ratio. To better mimic natural photosynthesis, the system is employed as a nanoreactor for the photocatalysis of a cross-dehydrogenative coupling (CDC) reaction in aqueous solution.

Gastro­oesophageal reflux disease in liver cirrhosis: Possible pathogenesis and clinical intervention (Review).

Oesophageal variceal bleeding is a common complication of decompensated liver cirrhosis (LC). Some studies have reported that reflux oesophagitis (RE) is a risk factor for upper gastrointestinal bleeding, and greatly impacts the quality of life. However, the frequency and mechanism of gastro-oesophageal reflux disease (GERD) in LC remain unclear. The present review explored the possible pathogenesis, and analysed the advantages and disadvantages of the interventional measures and the need for implementation of these measures. By combining the comprehensive terms associated with LC, GERD and RE, EMBASE, Medline/PubMed and the Cochrane Library were systematically searched. The underlying pathological mechanism of GERD in LC was summarized: Transient relaxation of the lower oesophageal sphincter, delayed gastric emptying, increased intra-abdominal pressure, increased intragastric pressure and excessive nitric oxide production destroyed the 'anti-reflux barrier', causing gastric content reflux. Proton pump inhibitors (PPIs) have been widely used empirically to lower the risk of oesophageal venous rupture and bleeding. However, long-term use of acid inhibitors in patients with LC may induce complications, such as spontaneous bacterial peritonitis. The metabolic half-life of PPIs is prolonged in patients with severe liver function impairment. Therefore, the indications for using acid inhibitors lack clarity. However, after endoscopic oesophageal variceal eradication, additional benefits may be gained from the long-term use of PPIs in small doses.

Identifying priority protection areas of key food resources of the giant panda.

Animals that live in seasonal environments adjust their reproduction cycle to optimize seasonal forage quality. Giant pandas ( Ailuropoda melanoleuca) are seasonal altitudinal migrants that feed on bamboo shoots and leaves with different nutritional quality. However, the importance of bamboo shoots to giant pandas, especially small and isolated populations, is not fully appreciated. Here, we explored whether mating time of giant pandas is shaped by bamboo shoot phenology. We also assessed the intensity of ongoing bamboo shoot harvesting by local communities in 42 giant panda reserves based on questionnaire surveys. Varying intensity and protection levels of bamboo shoot harvesting were found. From these data, we developed a priority ranking scheme of protection areas for this key food resource. Our study showed that pandas time their mating behavior to coincide with bamboo shoot phenology due to the high nutritional demands associated with mating and pregnancy. We also found that bamboo shoots were not well protected in many places. Liangshan, Daxiangling, and Xiaoxiangling, containing the most isolated panda populations, were identified as the areas with the most urgent need of protection. Furthermore, equal attention should be paid to the QiongL-B population, as this region holds considerable potential to serve as a corridor between the Minshan and Qionglai populations. To address the challenges posed by bamboo shoot harvesting, we recommend establishing more practical bamboo shoot management policies, increasing public awareness of bamboo shoot protection, and providing alternative sources of income for local communities.

CycC1;1-WRKY75 complex-mediated transcriptional regulation of SOS1 controls salt stress tolerance in Arabidopsis.

SALT OVERLY SENSITIVE1 (SOS1) is a key component of plant salt tolerance. However, how SOS1 transcription is dynamically regulated in plant response to different salinity conditions remains elusive. Here, we report that C-type Cyclin1;1 (CycC1;1) negatively regulates salt tolerance by interfering with WRKY75-mediated transcriptional activation of SOS1 in Arabidopsis (Arabidopsis thaliana). Disruption of CycC1;1 promotes SOS1 expression and salt tolerance in Arabidopsis because CycC1;1 interferes with RNA polymerase II recruitment by occupying the SOS1 promoter. Enhanced salt tolerance of the cycc1;1 mutant was completely compromised by an SOS1 mutation. Moreover, CycC1;1 physically interacts with the transcription factor WRKY75, which can bind to the SOS1 promoter and activate SOS1 expression. In contrast to the cycc1;1 mutant, the wrky75 mutant has attenuated SOS1 expression and salt tolerance, whereas overexpression of SOS1 rescues the salt sensitivity of wrky75. Intriguingly, CycC1;1 inhibits WRKY75-mediated transcriptional activation of SOS1 via their interaction. Thus, increased SOS1 expression and salt tolerance in cycc1;1 were abolished by WRKY75 mutation. Our findings demonstrate that CycC1;1 forms a complex with WRKY75 to inactivate SOS1 transcription under low salinity conditions. By contrast, under high salinity conditions, SOS1 transcription and plant salt tolerance are activated at least partially by increased WRKY75 expression but decreased CycC1;1 expression.

Immunization effect of recombinant Lactobacillus casei displaying Aeromonas veronii Aha1 with an LTB adjuvant in carp.

Aeromonas veronii is an important aquatic zoonotic, which elicits a range of diseases, such as haemorrhagic septicemia. To develop an effective oral vaccine against Aeromonas veronii infection in carp, the Aeromonas veronii adhesion (Aha1) gene was used as a target molecule to attach to intestinal epithelial cells. Two anchored recombinant. Lactic acid bacteria strains (LC-pPG-Aha1 1038 bp and LC-pPG-Aha1-LTB 1383 bp) were constructed by fusing them with the E. coli intolerant enterotoxin B subunit (LTB) gene and using Lactobacillus casei as antigen delivery vector to evaluate immune effects of these in carp. Western blotting and immunofluorescence were used to confirm that protein expression was successful. Additionally, levels of specific IgM in serum and the activities of ACP, AKP, SOD, LYS, C3, C4, and lectin enzymes-were assessed. Cytokines IL-10, IL-1ß, TNF-α, IgZ1, and IgZ2 were measured in the liver, spleen, kidney, intestines, and gills tissue by qRT-PCR, which showed an increasing trend compared with the control group (P < 0.05). A colonization assay showed that the two L. casei recombinants colonized the middle and hind intestines of immunized fish. When immunized carp were experimentally challenged with Aeromonas veronii the relative percentage protection of LC-pPG-Aha1 was 53.57%, and LC-pPG-Aha1-LTB was 60.71%. In conclusion, these results demonstrate that Aha1 is a promising candidate antigen when it is displayed on lactic acid bacteria (Lc-pPG-Aha1 and Lc-pPG-Aha1-LTB) seems promising for a mucosal therapeutic approach. We plan to investigate the molecular mechanism of the L. casei recombinant in regulating the intestinal tissue of carp in future studies.

Dimeric Pillar[5]arene as a Novel Fluorescent Host for Controllable Fabrication of Supramolecular Assemblies and Their Photocatalytic Applications.

A dimeric fluorescent macrocycle m-TPE Di-EtP5 (meso-tetraphenylethylene dimeric ethoxypillar[5]arene) is synthesized based on the meso-functionalized ethoxy pillar[5]arene. Through the connectivity of two pillar[5]arenes by CC double bond, the central tetraphenylethylene (TPE) moiety is simultaneously formed. The resultant bicyclic molecule not only retains the host-guest properties of pillararenes but also introduces the interesting aggregation-induced emission properties inherent in the embedded TPE structure. Three dinitrile derivatives with various linkers are designed as guests (G1, G2, and G3) to form host-guest assemblies with m-TPE Di-EtP5. The morphological control and fluorescence properties of the assemblies are successfully realized. G1 with a shorter alkyl chain as the linker completely threads into the cavities of the host. G2, due to its longer chain length, forms a linear supramolecular polymer upon binding to m-TPE Di-EtP5. G3 differs from G2 by possessing a bulky phenyl group in the middle of the chain, which can be further assembled with m-TPE Di-EtP5 to form supramolecular layered polymer and precipitated out in solution, and can be efficiently applied to photocatalytic reactions.

Pillar[5]arene Derivatives Embedded with Aggregation-Induced Emission Luminogens and Their Fluorescence Regulation.

Through McMurry coupling reaction, three meso-position functionalized pillar[5]arene derivatives (H-1, H-2, and H-3) have been successfully prepared by embedding aggregation-induced emission luminogens (AIEgens, diphenyldibenzofulvene (DPDBF) and tetraphenylethylene (TPE)) into the skeleton of supramolecular macrocycles. H-1, bearing [15 ]paracyclophane ([15 ]PCP) and DPDBF moiety, exhibits yellow emission and demonstrates obvious AIE effect. In order to further improve the host-guest properties of this type of structure, H-2 and H-3 are prepared by replacing the [15 ]PCP moiety with pillar[5]arene backbone, both of which show significant AIE effect and excellent host-guest complexation properties with pyrazine salt guest G-1 and 1,4-dicyanobutane G-2. Our findings indicate that G-1 can decrease the fluorescence intensity of the AIE macrocycles, while G-2 can increase their fluorescence intensity in solution.

p85S6K sustains synaptic GluA1 to ameliorate cognitive deficits in Alzheimer's disease.

BACKGROUND: Ribosomal protein S6 kinase 1 (S6K1) is a serine-threonine kinase that has two main isoforms: p70S6K (70-kDa isoform) and p85S6K (85-kDa isoform). p70S6K, with its upstream mammalian target of rapamycin (mTOR), has been shown to be involved in learning and memory and participate in the pathophysiology of Alzheimer's disease (AD). However, the function of p85S6K has long been neglected due to its high similarity to p70S6k. The role of p85S6K in learning and memory is still largely unknown. METHODS: We fractionated the postsynaptic densities to illustrate the differential distribution of p85S6K and p70S6K. Coimmunoprecipitation was performed to unveil interactions between p85S6K and the GluA1 subunit of AMPA receptor. The roles of p85S6K in synaptic targeting of GluA1 and learning and memory were evaluated by specific knockdown or overexpression of p85S6K followed by a broad range of methodologies including immunofluorescence, Western blot, in situ proximity ligation assay, morphological staining and behavioral examination. Further, the expression level of p85S6K was measured in brains from AD patients and AD model mice. RESULTS: p85S6K, but not p70S6K, was enriched in the postsynaptic densities. Moreover, knockdown of p85S6K resulted in defective spatial and recognition memory. In addition, p85S6K could interact with the GluA1 subunit of AMPA receptor through synapse-associated protein 97 and A-kinase anchoring protein 79/150. Mechanistic studies demonstrated that p85S6K could directly phosphorylate GluA1 at Ser845 and increase the amount of GluA1 in synapses, thus sustaining synaptic function and spine densities. Moreover, p85S6K was found to be specifically decreased in the synaptosomal compartment in the brains of AD patients and AD mice. Overexpression of p85S6K ameliorated the synaptic deficits and cognitive impairment in transgenic AD model mice. CONCLUSIONS: These results strongly imply a significant role for p85S6K in maintaining synaptic and cognitive function by interacting with GluA1. The findings provide an insight into the rational targeting of p85S6K as a therapeutic potential for AD.

Establishment of qRT-PCR for absolute quantitative detection of Chikungunya virus / 中国热带医学

@#Abstract: Objective　To develop a real-time fluorescent quantitative RT-PCR (qRT-PCR) method for qualitative and quantitative Chikungunya virus (CHIKV) analysis. Methods Based on the systematic analysis of the genomic sequences of Chikungunya and its related arboviruses, the specific nucleic acid sequences for Chikungunya virus were screened and identified, and then the primers and TaqMan probe were designed. Meanwhile, the human GAPDH gene was used as an internal reference. The reaction system for qRT-PCR was systematically optimized by L9(34) orthogonal design, and a rapid detection method for Chikungunya by qRT-PCR based on TaqMan probe methods was established. The sensitivity, specificity, reproducibility, and coverage of the established method were analyzed in detail. The standard curve was made, and the absolute quantitative method was established using the cloned nucleic acid fragments as positive samples. Results　A real-time fluorescent quantitative RT-PCR assay was developed for the qualitative and quantitative analysis of Chikungunya virus. The reaction system included Chikungunya virus and reference internal gene specific primers and probe, RT/Taq enzyme mixture, reaction buffer, and negative and positive reference. The established method obtained positive results with the ROSS strain of ECSA subtype, LR2006 strain of IOL branch, 181/25 strain of Asian type and Dongguan 2010 epidemic strains of Chikungunya virus, but there was no cross-reaction with other 18 arboviruses belonging to Flaviviruses, Alphaviruses and Bunyavirus. The minimum detection limit of the established method was 5.80 copies/mL, and a linear relationship was observed between the amount of input plasmid DNA and fluorescence signal value over a range of 5.80×102 copies/mL to 5.80×1010 copies/mL, and the correlation coefficient was 0.999 5. The qRT-PCR amplification efficiency was 91%, and the intra-assay variations and inter-assay variations were 0.01-0.07 and 0.03-0.11, respectively. Conclusions　The TaqMan qRT-PCR method developed in this study can qualitatively and quantitatively detect Chikungunya virus rapidly with specificity and sensitivity, providing a technical method for the prevention and control of this viral disease.

Fecal HBD-2 and Claudin-3 may be potential biomarkers to predict the deterioration of necrotizing enterocolitis: A prospective study.

Background and purpose: Necrotizing enterocolitis (NEC) is a critical gastrointestinal disease. We aim to explore the value of fecal human ß-defensin 2 (HBD-2), Claudin-3, high-mobility group box-1 protein (HMGB-1), and resistin-like molecule ß (Relmß) as well as some laboratory metrics to predict the deterioration of NEC. Methods: Infants diagnosed with NEC at Stage II were enrolled in our study. Those who progressed to Stage III were included in the Stage III group and the rest were included in the Stage II group. Clinical data and laboratory metrics of the infants were collected. Fecal samples of HBD2, HMGB-1, Claudin-3, and Relmß collected during their enrollment were determined by using enzyme-linked immunosorbent assay (ELISA) kits. Student's t-test, the Mann-Whitney U test, the chi-square test, receiver operating characteristic (ROC), and logistic regression analysis were performed. Results: Sixty infants diagnosed with NEC at Stage II were enrolled in our study, with 27 in the Stage III group (n = 27) and 33 in the Stage II group (n = 33). Although many of these NEC cases were late preterm and term infants, the infants in the Stage III group had a lower gestational age (P < 0.05). The incidence of gestational diabetes mellitus, peritonitis, intestinal adhesion, and sepsis was higher and more infants in the Stage III group underwent surgeries (P < 0.05). The levels of HBD-2 and Claudin-3 were higher and neutrophil count was lower in the Stage III group than in the Stage II Group, and the area under the curve (AUC) was 0.754, 0,755, and 0.666, respectively (P < 0.05). HBD-2 ≥ 1649.02 ng/g and Claudin-3 ≥ 2488.71 pg/g were included in the multivariate stepwise logistic regression analysis (P < 0.05), and the AUC of the model was 0.805 (95% CI: 0.688-0.922). Conclusion: Fecal HBD-2 and Claudin-3 may be potential biomarkers to predict the deterioration of NEC from Stage II to Stage III.

Serum Relmß combined with abdominal signs may predict surgical timing in neonates with NEC: A cohort study.

Aims: To examine the predictive value of serum biomarkers combined with other indicators for necrotizing enterocolitis (NEC) surgery decision-making. Methods: Clinical data, including baseline information, clinical features, imaging presentation and serum assessment, of the infants enrolled were collected, and the serum concentrations of HBD2, HMGB-1, Claudin-3 and Relmß were determined. Student's t test, the Mann-Whitney U test, the chi-square test and logistic regression analysis were used. Receiver operating characteristic (ROC) curves were also generated. Results: Forty-nine infants were enrolled, with 23 in the surgical NEC group and 26 in the medical NEC group. There were no differences in the baseline clinical information, including birth weight, gestational age, admission age and risk factors, during pregnancy and before enrollment (P > 0.05). Peritonitis, intestinal adhesion and sepsis were more common in the surgical group (P < 0.05). The incidences of abdominal distention, abdominal wall tenseness, abdominal tenderness and absent bowel sounds in the surgical group were significantly higher when NEC occurred (P < 0.05). There were no differences between the two groups in the imaging presentation (P > 0.05). The concentration of Relmß {[8.66 (4.29, 19.28) vs. 20.65 (9.51, 44.65)]} in the surgical group was significantly higher (P < 0.05). Abdominal wall tenseness, abdominal tenderness and a Relmß concentration > 19.7 µmol/L were included in the predictive model, and the AUC of the predictive score was 0.943 (95% CI: 0.891-1.000) (P < 0.05). Conclusion: Serum Relmß concentration combined with abdominal wall tenseness and abdominal tenderness may be useful in determining surgical timing in neonates with NEC.

Tetraphenylethylene-embedded pillar[5]arene-based orthogonal self-assembly for efficient photocatalysis in water.

Herein, we have designed and fabricated a simple and efficient supramolecular self-assembled nanosystem based on host-guest interactions between water-soluble tetraphenylethylene-embedded pillar[5]arene ( m -TPEWP5) and ammonium benzoyl-ʟ-alaninate (G) in an aqueous medium. The obtained assembly of m -TPEWP5 and G showed aggregation-induced emission (AIE) via the blocking of intramolecular phenyl-ring rotations and functioned as an ideal donor. After the loading of eosin Y (EsY) as acceptor on the surface of the assembly of m -TPEWP5 and G, the worm-like nanostructures changed into nanorods, which facilitates a Förster resonance energy transfer (FRET) from the m -TPEWP5 and G assembled donor to the EsY acceptor present in the nanorod assembly. The system comprising m -TPEWP5, G and EsY displayed moderate FRET efficiency (31%) at a 2:1 molar ratio of donor-to-acceptor. Moreover, the obtained supramolecular nanorod assembly could act as a nanoreactor mimicking natural photosynthesis and exhibited a high catalytic efficiency for the photocatalytic dehalogenation reaction of various bromoketone derivatives with good yields in short reaction time in water.

Tetraphenylethylene-embedded [15]paracyclophanes: AIEgen and macrocycle merged novel supramolecular hosts used for sensing Ni2+ ions.

Transformation of [15]paracyclophanes ([15]PCP) into fluorophores has been achieved by embedding tetraphenylethene (TPE) units into their skeletons at the meso-positions. The obtained two hosts demonstrated distinct aggregation-induced emission (AIE) properties and their fluorescence could be selectively quenched by Ni2+ ions.

An Open-Label Exploratory Clinical Trial Evaluating the Effects of GLS (Coptidis Rhizoma-Evodiae Fructus 2 : 1) on Fibroblast Growth Factor 21 in Patients with Nonalcoholic Fatty Liver Disease.

Methods: In a 12-week, open-label, exploratory clinical trial, 126 NAFLD patients were randomly divided into the GLS group (lifestyle intervention plus GLS) or the polyene phosphatidylcholine (PPC) group (lifestyle intervention plus PPC). Random numbers generated by DPS software were used in combination with opaque, sealed envelopes for allocation concealment. At baseline as well as at the end of the study, anthropometric parameters, glucose, lipids, hepatic enzymes, and FGF 21 were measured, with hepatic fat accumulation assessed by ultrasound (US) and US-based controlled attenuation parameter (CAP). Results: 119 patients completed the study. Baseline parameters did not significantly differ between the two groups (P > 0.05). Compared with PPC, GLS decreased more significantly in hepatic fat accumulation, body weight index, waist circumference, waist-to-hip ratio, serum glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, alanine transaminase, aspartate transaminase, gamma-glutamyl transferase, and FGF 21 (P < 0.05). The effects of GLS on waist circumference, waist-to-hip ratio, CAP, and gamma-glutamyl transferase (GGT) were positively correlated with serum FGF 21 (r = 0.343, 0.342, 0.315, and 0.374, respectively, P < 0.05). The GGT and FGF-21 changes were also confirmed by multiple linear regression analysis (B, 0.777; 95% CI: 0.307-1.247, P < 0.05). Conclusion: GLS has a significant hepatoprotective effect on NAFLD patients, causing a decrease in FGF-21 secretion in response to the damage itself.

Orthogonal Design of Supramolecular Prodrug Vesicles via Water-Soluble Pillar[5]arene and Betulinic Acid Derivative for Dual Chemotherapy.

Supramolecular prodrug vesicles with efficient property for dual chemotherapy have been successfully constructed based on the orthogonal self-assembly between a water-soluble pillar[5]arene host (WP5) and a betulinic acid guest (BA-D) as well as doxorubicin (DOX). Under the acidic microenvironment of cancer cells, both the encapsulated anticancer drug DOX and prodrug BA-D can be effectively released from DOX-loaded WP5⊃BA-D prodrug vesicles for combinational chemotherapy. Furthermore, bioexperiments indicate that DOX-loaded prodrug vesicles can obviously enhance the anticancer efficiency based on the cooperative effect of DOX and BA-D, while remarkably reducing the systematic toxicity in tumor-mice, displaying great potential applications in combinational chemotherapy for cancer treatments.

GAS6-mediated dialogue between decidual stromal cells and macrophages is essential for early pregnancy maintenance by inducing M2-like polarization and cell proliferation of decidual macrophages.

Maternal immunotolerance towards the semi-allogeneic foetus is critical for normal pregnancy (NP). As a secretory protein, growth arrest-specific factor 6 (GAS6) promotes cancer progression by inducing the conversion of tumour-associated macrophages to an immunosuppressive M2-like phenotype. However, little is known about whether GAS6 regulates decidual macrophages (dMφs) in the early maternal-foetal interface. In this study, first-trimester decidual tissues were obtained from normal pregnant women undergoing elective terminations and patients with miscarriages. The expression of GAS6 and its receptors (AXL, TYRO3 and MERTK) in decidua and GAS6 secretion by decidual stromal cells (DSCs) was measured. Then, we investigated the effect of recombinant human GAS6 (rhGAS6) on dMφs isolated from NP and THP-1 cells, and revealed the underlying mechanism. Both the expression of GAS6 in DSCs and MERTK in dMφs, in addition to GAS6 secretion by DSCs, was found to be significantly decreased in miscarriage patients compared to that in NPs. Additionally, we observed that rhGAS6 polarized dMφs and THP-1 cells towards an M2-like phenotype, as evidenced by the up-regulated CD163 expression. Moreover, rhGAS6 enhanced the clearance of toxic cell-free haemoglobin by dMφs by up-regulating CD163 expression, and rhGAS6 also boosted cell proliferation of dMφs and THP-1 cells. Finally, we demonstrated that rhGAS6 stimulated CD163 expression and cell proliferation by activating the PI3K/Akt signalling pathway. Collectively, these findings suggest that GAS6-mediated dialogue between DSCs and dMφs is crucial for the establishment and maintenance of maternal-foetal immunotolerance, and decreased GAS6 secretion by DSCs may lead to the occurrence of miscarriage in the first trimester.