Multivalent Polyanionic 2D Nanosheets Functionalized Nanofibrous Stem Cell-based Neural Scaffolds

Because developed neural cells are no longer regenerative and proliferative, achieving neural regenerations by using induced pluripotent stem cells (IPS cells) for nerve diseases have recently attracted much attention. Since the IPS cells' growth and differentiation can be manipulated by different physical and chemicals cues, scaffolds combining the beneficial nanostructures and extracellular matrix may become an ideal interface to promote IPS cells' neural differentiation. In this work, a biocompatible and multivalent polyanion, hyperbranched polyglycerol sulfate, is used to modify the graphene oxide to obtain bio-adhesive 2D nanosheets. After coating electrospinning nanofibers, the 2D nanosheets-functionalized nanofibrous scaffolds are applied to mediate the proliferation, lineage specification, and neural differentiation of IPS cells. The results suggest that the modified scaffolds can improve the adhesion and proliferation of IPS cells combined with high efficiency in maintaining their stemness. During the neural differentiation process, the scaffolds can promote neural differentiation and their maturity, meanwhile decreasing the lineage specification toward astrocyte. Overall, this study not only provides new multivalent/bio-adhesive nanofibrous scaffolds that integrate the chemical and physical cues to facilitate the targeted neural differentiation of IPS cells but also presents a novel pathway for the fabrication of carbon nanomaterials-based biocomposites in regenerative therapies

LTe2 induces cell apoptosis in multiple myeloma by suppressing AKT phosphorylation at Thr308 and Ser473

Multiple myeloma (MM) is a highly heterogeneous hematological malignancy originating from B lymphocytes, with a high recurrence rate primarily due to drug resistance. 2-((1H-indol-3-yl)methyl)-3-((3-((1H-indol-3-yl)methyl)-1H-indol-2-yl)methyl)-1H-indole (LTe2), a tetrameric indole oligomer, possesses a wide range of anticancer activities through various mechanisms. Here, we aim to explore the anti-tumor efficiency and potential downstream targets of LTe2 in MM. Its bioactivity was assessed by employing MTT assays, flow cytometry, and the 5TMM3VT mouse model. Additionally, transcriptomic RNA-seq analysis and molecular dynamics (MD) experiments were conducted to elucidate the mechanism underlying LTe2 induced MM cell apoptosis. The results demonstrated that LTe2 significantly inhibited MM cell proliferation both in vitro and in vivo, and revealed that LTe2 exerts its effect by inhibiting the phosphorylation of AKT at the Thr308 and Ser473 sites. In summary, our findings highlight the potential of LTe2 as a novel candidate drug for MM treatment and provided a solid foundation for future clinical trials involving LTe2

Gold Nanostar@Polyaniline Theranostic Agent with High Photothermal Conversion Efficiency for Photoacoustic Imaging-Guided Anticancer Phototherapy at a Low Dosage

10.1021/acsami.2c05679ACS Applied Materials & Interfaces142528570-2858

Interaction and Assembly of Bacterial Communities in High-Latitude Coral Habitat Associated Seawater

Threatened by climate change and ocean warming, coral reef ecosystems have been shifting in geographic ranges toward a higher latitude area. The water-associated microbial communities and their potential role in primary production contribution are well studied in tropical coral reefs, but poorly defined in high-latitude coral habitats to date. In this study, amplicon sequencing of 16S rRNA and cbbL gene, co-occurrence network, and βNTI were used. The community structure of bacterial and carbon-fixation bacterial communities showed a significant difference between the center of coral, transitional, and non-coral area. Nitrite, DOC, pH, and coral coverage ratio significantly impacted the β-diversity of bacterial and carbon-fixation communities. The interaction of heterotrophs and autotrophic carbon-fixers was more complex in the bottom than in surface water. Carbon-fixers correlated with diverse heterotrophs in surface water but fewer lineages of heterotrophic taxa in the bottom. Bacterial community assembly showed an increase by deterministic process with decrease of coral coverage in bottom water, which may correlate with the gradient of nitrite and pH in the habitat. A deterministic process dominated the assembly of carbon-fixation bacterial community in surface water, while stochastic process dominated t the bottom. In conclusion, the structure and assembly of bacterial and carbon-fixer community were affected by multi-environmental variables in high-latitude coral habitat-associated seawater

Assisted biomimetic electrostimulation therapy can improve the clinical pregnancy rate of patients with abnormal endometrial receptivity undergoing frozen-thawed embryo transfer cycles

This study aimed to explore whether assisted biomimetic electrostimulation (BES) therapy can improve clinical outcomes in patients with abnormal endometrial receptivity undergoing frozen-thawed embryo transfer (FET) cycles. We retrospectively collected data from 132 patients who underwent FET cycles and divided them into the BES (n = 86) and non-BES (NBES) groups (n = 46). The clinical pregnancy rate (55.8 vs. 37.0%), biochemical pregnancy rate (59.3 vs. 41.3%), and live birth rate (44.2 vs. 23.9%) of the BES group were significantly higher than those of the NBES group (p p > 0.05). The logistic regression analysis indicated that blastocyst transfer (adjusted OR = 3.617; 1.337–9.783; p = 0.011) and BES (adjusted OR = 2.398; 1.094–5.256; p = 0.029) were positively associated with the clinical pregnancy rate. These results suggested that assisted BES therapy can improve clinical outcomes in patients with diseases affecting endometrial receptivity.Impact statementWhat is already known on this subject? Biomimetic electrostimulation (BES) therapy can increase endometrial thickness in patients with thin endometria undergoing embryo transfers and to some extent improve their clinical outcomes.What do the results of this study add? Assisted BES therapy can improve clinical pregnancy rates in patients with abnormal endometrial receptivity undergoing FET cycles (55.8 vs. 37.0%, p = 0.039). After adjusting for covariates, BES was still positively associated with the clinical pregnancy rate (adjusted OR = 2.398; 1.094–5.256; p = 0.029).What are the implications of these findings for clinical practice and/or further research? BES therapy can improve endometrial receptivity. Further studies are needed to understand its specific mechanisms. What is already known on this subject? Biomimetic electrostimulation (BES) therapy can increase endometrial thickness in patients with thin endometria undergoing embryo transfers and to some extent improve their clinical outcomes. What do the results of this study add? Assisted BES therapy can improve clinical pregnancy rates in patients with abnormal endometrial receptivity undergoing FET cycles (55.8 vs. 37.0%, p = 0.039). After adjusting for covariates, BES was still positively associated with the clinical pregnancy rate (adjusted OR = 2.398; 1.094–5.256; p = 0.029). What are the implications of these findings for clinical practice and/or further research? BES therapy can improve endometrial receptivity. Further studies are needed to understand its specific mechanisms.</p

Nomogram for evaluating obvious liver inflammation in treatment-naïve HBeAg positive chronic hepatitis B virus infection patients with normal ALT

ABSTRACTThe purpose of this study was to develop an effective and non-invasive nomogram for evaluating liver obvious inflammation in untreated HBeAg positive patients with chronic hepatitis B virus (HBV) infection. A nomogram was established on a model cohort of 292 treatment-naïve HBeAg positive patients with normal alanine aminotransferase (ALT ≤40 U/L) at Beijing Ditan Hospital from January 2008 to March 2018. Then the nomogram was prospectively validated in a cohort of 88 patients from July 2019 to May 2021. Calibration curves and Concordance index were used to evaluate the accuracy of prediction and identification performance of the model. In untreated HBeAg positive chronic hepatitis B virus infection patients with normal ALT, the formula for predicting liver inflammation was Logit (P) =-0.91-0.41×log10 (qHBeAg)+0.11×AST-0.01×PLT. The nomogram had C-index of 0.751 (95% CI, 0.688–0.815), indicating a good consistency between prediction and real observation on the model cohort. The validation cohort confirmed its good performance. In this study, liver inflammation nomograms based on HBeAg, AST, and PLT were established and verified in treatment-naïve HBeAg positive chronic HBV patients with normal ALT

A Versatile G‐quadruplex (G4)‐coated Upconverted Metal‐Organic Framework for Hypoxic Tumor Therapy

International audienceGiven the complexity of the tumor microenvironment, multiple strategies are being explored to tackle hypoxic tumors. One of the most efficient strategies combines several therapeutic modalities and typically requires the development of multifunctional nanocomposites through sophisticated synthetic procedures. Here, the G-quadruplex (G4)-forming sequence AS1411-A (d-(G2T)4TG(TG2)4A) was designed and used for its anti-tumor and biocatalytic properties, such as increasing the production of O2 ca. 2fold as compared to the parent AS1411 sequence. Subsequently, the AS1411-A/hemin complex (GH) was grafted on the surface and pores of a core-shell upconverted metalorganic framework (UMOF) to generate a UMGH nanoplatform. Compared with UMOF, UMGH exhibited enhanced colloidal stability, increased targeting of tumor cells and improved O2 production (8.5-fold) in situ. When irradiated with near-infrared (NIR) light, the UMGH antitumor properties were bolstered by photodynamic therapy (PDT), thanks to its ability to convert O2 into singlet oxygen (1 O2). Combined with the antiproliferative activity of AS1411-A, this novel approach herein lays the foundation for a new type of G4-based nanomedicine

Hepatitis B core-related antigen serum levels may be a predictor of acute flare of chronic hepatitis B among pregnant women in the immune-tolerant phase of chronic HBV infection after short-course antiviral therapy

ABSTRACTBackground Studies have shown acute flares of chronic hepatitis B (CHB) might be related to immunologic changes that occur during pregnancy. However, the indicators for predicting acute flares of CHB among pregnant women still need further study. We aimed to distinguish the relevance between serum levels of HBcrAg and acute flares of CHB in pregnant women in the immune-tolerant phase of chronic HBV infection after short-course antiviral therapy.Methods A total of 172 chronic HBV-infected pregnant women who were judged to be in the immune-tolerant phase were recruited in our research. All patients received short-course antiviral therapy with TDF. The biochemical, serological, and virological parameters were measured using standard laboratory procedures. The serum levels of HBcrAg were tested by ELISA.Results Fifty-two (30.2%) out of 172 patients had acute flares of CHB. At postpartum week 12 (TDF cessation), serum HBcrAg (OR, 4.52; 95% CI, 2.58–7.92) and HBsAg (OR, 2.52; 95% CI, 1.13–5.65) were associated with acute flares of CHB. The serum HBcrAg levels were beneficial for confirmation of patients with acute flares of CHB, with an area under the ROC curve of 0.84 (95% CI, 0.78–0.91).Conclusions For pregnant women with chronic HBV infection in the immune-tolerant phase, serum HBcrAg and HBsAg levels at postpartum week 12 were associated with acute flares of CHB after short-course antiviral therapy with TDF. The serum HBcrAg level can correctly identify acute flares of CHB and may be a predictor of the need for continuing antiviral therapy after 12 weeks postpartum

Image_1_Functional molecular expression of nature killer cells correlated to HBsAg clearance in HBeAg-positive chronic hepatitis B patients during PEG-IFN α-2a therapy.tif

ObjectiveTo explore whether the frequencies and functional molecules expression of Natural Killer cells (NK cells) are related to hepatitis B surface antigen (HBsAg) disappearance in hepatitis B e envelope antigen (HBeAg)-positive patients with chronic hepatitis B (CHB) throughout peginterferon alpha-2a (PEG-IFN α-2a) treatment.MethodsIn this prospective research, HBeAg-positive patients with CHB received PEG-IFN α-2a treatment, completing 4-year follow-up. After PEG-IFN α-2a treatment, undetectable HBV DNA, HBsAg loss, and HBeAg disappearance were defined as functional cure. Proportions of NK, CD56dim, CD56bright, NKp46+, NKp46dim, NKp46high, and interferon alpha receptor 2 (IFNAR2)+ NK cells, and the mean fluorescence intensity (MFI) of NK cell surface receptors IFNAR2 and NKp46 were detected.Results66 patients were enrolled into the study in which 17 patients obtained functional cure. At baseline, hepatitis B virus desoxyribose nucleic acid (HBV DNA) titer in patients with functional cure was remarkably lower than that in Non-functional cure group. Compared with baseline, HBV DNA levels, HBsAg levels, and HBeAg levels significantly declined at week 12 and 24 of therapy in patients with functional cure. At baseline, the negative correlation between CD56bright NK% and HBV DNA and the negative correlation between CD56dim NK% and HBV DNA was showed; CD56bright NK% and IFNAR2 MFI in patients with functional cure were remarkably higher than those in patients without functional cure. After therapy, CD56bright NK% and NKp46high NK% in patients with functional cure were higher than those in patients without functional cure. In Functional cure group, after 24 weeks of treatment NK%, CD56bright NK%, IFNAR2 MFI weakly increased, and NKp46high NK% and NKp46 MFI significantly increased, meanwhile, CD56dim NK% and NKp46dim NK% decreased. Only NKp46 MFI increased after therapy in patients without functional cure.ConclusionThe lower HBV DNA load and the higher CD56bright NK% before therapy, and the higher the post-treatment CD56bright NK%, IFNAR2 MFI, NKp46high NK%, the easier to achieve functional cure.</p