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For birds, the uterus is an important part for eggshell mineralization, and the establishment of the endometrial epithelial cell (EEC) model was beneficial to the study of uterine function. This study was conducted to establish a culture model of primary EECs of laying hens and explore the effects of zinc on primary EEC proliferation, zinc transport, and calcium deposition in vitro. The EECs were isolated and cultured via type I collagenase digestion, and in the logarithmic phase during 2–5 days, and then reached the plateau phase on the 7th day of inoculation. Results showed that the proliferation of EECs treated by 50 μM ZnSO4 or zinc-methionine (Zn-Met) were markedly promoted at 24-h or 48-h treating time (P

Electrocatalytic water splitting is a promising technology for large-scale hydrogen production. However, it requires efficient catalysts to overcome the large overpotentials in the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). Herein, we report a novel heterostructure catalyst Co9S8/Cu2S on copper foam (Co9S8/Cu2S/CF) with multistep impregnation and electrodeposition. Due to the strong interfacial interaction, the interfacial electrons transfer from Co sites to S sites, which promote the adsorption of oxygen-containing intermediates, water molecules, as well as the dissociation of water molecules. Therefore, the heterostructure catalyst exhibits low overpotentials of 195 mV for OER and 165 mV for HER at 10 mA cm-2, respectively. Moreover, it only needs 1.6 V to realize water splitting at 10 mA cm-2 in a two-electrode cell. This work provides an efficient method to tailor the surface electronic structure through specific morphological design and construct a heterostructure interface to achieve alkaline water splitting.

The crosstalk between intestinal bacteria and the central nervous system, so called "the gut-brain axis", is critically important for maintaining brain homeostasis and function. This study aimed to investigate the integrity of the blood-brain barrier (BBB) and migration of bone marrow (BM)-derived cells to the brain parenchyma after intestinal microbiota depletion in adult mice. Gut microbiota dysbiosis was induced with 5 non-absorbable antibiotics in drinking water in mice that had received bone marrow transplantation (BMT) from green fluorescent protein (GFP) transgenic mice. Antibiotic-induced microbiome depletion reduced expression of tight-junction proteins of the brain blood vessels and increased BBB permeability. Fecal microbiota transplantation of antibiotics treated mice with pathogen-free gut microbiota decreased BBB permeability and up-regulated the expression of tight junction proteins. The BM-derived GFP+ cells were observed to infiltrate specific brain regions, including the nucleus accumbens (NAc), the septal nucleus (SPT) and the hippocampus (CA3). The infiltrated cells acquired a ramified microglia-like morphology and Iba1, a microglia marker, was expressed in all GFP+ cells, whereas they were negative for the astrocyte marker GFAP. Furthermore, treatment with CCR2 antagonist (RS102895) suppressed the recruitment of BM-derived monocytes to the brain. We report for the first time the migration of BM-derived monocytes to the brain regions involved in regulating emotional behaviors after depletion of intestinal microbiota in BMT background mice. However, mechanisms responsible for the migration and functions of the microglia-like infiltrated cells in the brain need further investigation. These findings indicate that monocyte recruitment to the brain in response to gut microbiota dysbiosis may represent a novel cellular mechanism that contributes to the development of brain disorders.

Accurate, in situ and long-term electrically monitoring of cell development plays an important role in cell study, which brings in challenges in terms of biocompatibility, processability, and sensing capability of electrochemical sensors. Based on biocompatible conductive polyaniline (PAni) hydrogels, we constructed a flexible sensor with flexible carbon cloth for electrical analysis of living cells. The carbon fiber substrate modified with conductive PAni hydrogels was selected as the electrode to promote the current collection of the sensor. The three dimensional nanostructured mesoporous matrix of PAni hydrogels is favorable for in situ generation of catalytic Pt nanoparticles and cell growth. With these hierarchically nanostructured features, the hydrogel electrochemical sensor was endowed with high sensitivity and selectivity in the detection of H2O2 (with a low detection limit of 1.6 μM in 0.01 M PBS and a wide linear range from 10 μM to 10 mM), and good biocompatibility for cell growth as long as 5 days. The accurate detection of H2O2 released from cells enabled us to differentiate the physiological states of cells and imitate the different stimuli-responsive behavior, which can provide real-time information on cell biological events. With outstanding biocompatibility, operability and repeatability, this strategy can be expanded to the fields of other biosensor fabrication and cell-related biomarker monitoring, which exhibits a broad application potential in bioanalysis catering to new generation sensors.

The electrochemical stability and catalytic activity of palladium catalysts are key issues in polymer electrolyte membrane fuel cells (PEMFCs). Here, to take full advantage of the strong metal–support interaction (SMSI), Pd nanoparticles (NPs, ∼4.1 nm) were in situ reduced onto the TiO2 surface of a TiO2–C heterostructure by photo-generated electrons under light irradiation. By means of experimental characterization studies, electron transfer from the support (TiO2–C heterostructure) to Pd NPs results in an electron-rich Pd surface and a downshift in the d-band structure. A photochemical strategy strengthens the SMSI effect and hence improves the catalytic activity and durability of the Pd catalyst. Compared with commercial Pd/C (Com. Pd/C, 10.0 wt%) and Pd/TiO2 (22.0 wt%) catalysts, as-prepared Pd/TiO2–C (7.2 wt%) shows excellent ORR activity with MA up to 0.16 A mg−1Pd at 0.9 V. The results demonstrate that for metal oxide supports with photocatalytic activity, the photochemical route is conducive to the formation of the SMSI effect between the metal and support, thus improving the activity and durability of the metal catalyst.

Here, PtPd nanoframes were prepared by etching Pd@PdPt core–shell rhombic dodecahedrals (RDs) with Fe3+ provided by iron chloride hexahydrate (FeCl3·6H2O). Based on the experimental results, PtPd nanoframes were formed due to the etching of Pd cores. In terms of catalytic performance, the measured specific activity and mass activity of PtPd nanoframes were 1.11 mA cm−2 and 840.38 mA mg−1, respectively, which were much higher than those of Pd@PdPt core–shell RDs, Pt black and Pt/C, suggesting the preeminent activity of PtPd nanoframes. Meanwhile, PtPd nanoframes showed better stability compared with Pd@PdPt core–shell RDs, Pt black and Pt/C. The strengthened catalytic properties may be caused by the larger surface area owing to the novel structure and the strong electronic interaction between Pt and Pd.

It is still a big challenge to design Gd3+ based nanoparticles (NPs) for T1 MRI (Magnetic Resonance Imaging) with high performance and clarify the effects of relative time parameters on longitudinal relaxivity r1. In this paper, we simulated the influences of different time parameters on the longitudinal relaxivity of Gd3+ based NPs with inner-sphere and outer-sphere theories, respectively. In particular, we investigated the effects of τR (the rotational time), τM (the residence time), Tie (the electronic relation time) and τd (the diffusion time) on longitudinal relaxivity. In the relaxation process of Gd3+ based NPs, the inner-sphere plays a dominant role, in which τR and τM have a greater impact on r1. Based on the simulation results, we proposed a design strategy of Gd3+ based NPs for T1 MRI, which focuses on the rational decrease of hydrated radius, and the optimal range of the hydrated radius is about 0.8–2.5 nm. In addition, we synthesized ultrasmall Gd2O3 NPs with a hydrated radius of about 2.5 nm, which have a high longitudinal relaxivity r1 of 10.8 mM−1 s−1 at 3.0 T. Moreover, the in vivo imaging results confirm that the ultrasmall Gd2O3 NPs have a good imaging effect on the tumor, and it can be a good candidate as a T1 MRI contrast agent with high performance.

To reduce the over-dependence on Pt, Pd-based catalysts have become one of the most effective candidates for oxygen reduction reaction (ORR). In order to further accelerate the ORR kinetics and strengthen the catalytic performance of Pd catalysts, component optimization and morphology design have been adopted. Although great progress has been made, it is still difficult to obtain porous ultrathin nanosheets with excellent performance by a simple method. Here, ultrathin PdCuMo porous nanosheets (PdCuMo NSs) were successfully prepared. This structure possessed a large specific surface area with rich cavities and structural defects, significantly enhancing its ORR performance. In special, the mass activity of PdCuMo NSs was 1.46 A mg

Background Although FOXO3a can inhibit the cell proliferation of prostate cancer, its relationship with reactive oxygen species (ROS) in prostate cancer (PCa) has not been reported. Methods We analyzed the correlation between the expression of FOXO3a and the antioxidant enzyme catalase in prostate cancer with the TCGA and GEPIA databases. We also constructed a PPI network of FOXO3a via the STRING database. The mRNA and protein expression of FOXO3a and catalase were detected by qRT-PCR or western blotting in LNCaP and 22RV1 cells treated with DHT, R1881, or Enzalutamide. The effects of FOXO3a on catalase expression were tested by over-expressing or knocking down FOXO3a in LNCaP cells. Furthermore, the catalase activity and ROS level were detected in LNCaP cells treated with DHT. Cell proliferation and ROS were also analyzed in LNCaP which was treated with antioxidant. Results Results showed that the catalase expression was down-regulated in prostate cancer. A positive correlation between FOXO3a and catalase existed. DHT treatment could significantly reduce FOXO3a and catalase expression at mRNA and protein level in LNCaP cells. Catalase expression partly depended on FOXO3a as over-expression and knockdown of FOXO3a could result in the expresssion change of catalase. DHT treatment was found to inhibit catalase activity and increase ROS level in prostate cancer cell. Our study also demonstrated that antioxidant treatment reduced DHT-induced proliferation and ROS production in prostate cancer cell. Conclusions We discovered a novel mechanism by which DHT promotes prostate cancer cell proliferation via suppressing catalase activity and activating ROS signaling via a FOXO3a dependent manner.

Objective:To evaluate the effects of dietary Ca intake and Ca supplementation during pregnancy on low birth weight (LBW) and small for gestational age (SGA) infants.Design:A birth cohort study was conducted in 2010–2012 at the Gansu Provincial Maternity and Child Care Hospital in Lanzhou, China.Setting:A birth cohort study.Participants:Totally, 9595 pregnant women who came to the hospital for delivery at 20 weeks of gestation or more, and who were 18 years of age or older.Results:Compared with non-users, Ca supplement users had a reduced risk of LBW infants (OR = 0·77, 95 % CI: 0·63, 0·95) and a reduced risk of nulliparous women giving birth to LBW infants (OR = 0·75, 95 % CI: 0·58, 0·98) (P < 0·05). More specifically, both the use of Ca supplement before conception and during pregnancy (OR = 0·44, 95 % CI: 0·19, 0·99) and during pregnancy only (OR = 0·80, 95 % CI: 0·65, 0·99) had the main effect of reducing risk of nulliparous women giving birth to LBW infants (P < 0·05). There was no association between Ca supplementation and SGA (OR = 0·87, 95 % CI: 0·75, 1·01) (P > 0·05). However, higher dietary Ca intake during pregnancy decreases the risk of both LBW (quartile 2: OR = 0·72, 95 % CI: 0·55, 0·94; quartile 3: OR = 0·68, 95 % CI: 0·50, 0·62) and SGA infants (quartile 2: OR = 0·77, 95 % CI: 0·63, 0·95; quartile 3: OR = 0·71, 95 % CI: 0·57, 0·88, quartile 4: OR = 0·71, 95 % CI: 0·57, 0·88) (P < 0·05).Conclusions:Ca supplementation and adequate dietary intake of Ca during pregnancy are associated with a decreased risk of LBW infants born to nulliparous women.

As a promising chemical hydrogen storage material, ammonia borane (AB, NH3BH3) has been receiving significant attention for its hydrogen release property. Researches on the development of effective catalysts for AB hydrolysis under mild conditions have been of potential application interest. In the last few years, some non-noble metal-based materials have been developed for dehydrogenation of AB via hydrolysis, due to their low cost, high activity, and high durability. Therefore, the summary and analysis of the rapidly developing non-noble metal catalyst systems without noble metals can better grasp the current development status to guide subsequent design and research. In this review, the latest advances in non-noble metal-based catalysts are summarized, which can be divided into the following categories: pure metal-based materials, metal-based compounds (borides, phosphides, and oxides), and metal/metal compound heterogeneous structures. Investigations into the composition, structure, and activity enhancement of the catalyst are further highlighted. Besides, hydrolysis mechanisms, catalyst persistence, and AB regeneration are also discussed.

Purpose Glioblastoma (GBM) is the most commonly diagnosed primary brain tumor in adults. Despite a variety of advances in the understanding of GBM cancer biology during recent decades, very few of them were applied into treatment, and the survival rate of GBM patients has not been improved majorly due to the low chemosensitivity to temozolomide (TMZ) or low radiosensitivity. Therefore, it is urgent to elucidate mechanisms of TMZ- and IR-resistance and develop novel therapeutic strategies to improve GBM treatment. Methods TMZ- and IR-resistant cell lines were acquired by continuous exposing parental GBM cells to TMZ or IR for 3 months. Cell viability was determined by using Sulforhodamine B (SRB) assay. Protein and mRNA expression were examined by Western blotting assay and quantitative polymerase chain reaction (qPCR) assay, respectively. Homologous recombination (HR) and nonhomologous end joining (NHEJ) efficiency were measured by HR and NHEJ reporter assay. Cell apoptosis was determined by Caspase3/7 activity. Autophagy was analyzed using CYTO-ID® Autophagy detection kit. Tumor growth was examined by U87 xenograft mice model. Results DNA repair efficiency of non-homologous end joining (NHEJ) pathway is significantly increased in TMZ- and IR-resistant GBM cells. Importantly, APLF, which is one of the DNA end processing factors in NHEJ, is upregulated in TMZ- and IR-resistant GBM cells and patients. APLF deficiency significantly decreases NHEJ efficiency and improves cell sensitivity to TMZ and IR both in vitro and in vivo. Conclusion Our study provides evidence for APLF serving as a promising, novel target in GBM chemo- and radio-therapy.

Objective Mesenchymal stem cells (MSCs) show unique advantages in cardiomyocyte repairment. Exosomes derived from MSCs can enhance the viability of myocardial cells after ischemia/reperfusion (I/R) injury and regulate inflammation response. The study was designed to ascertain whether MSCs-exo protect the myocardium against I/R injury through inhibiting pyroptosis, and the underlying mechanisms. Methods and results Experiments were carried out in H/R and I/R model. Cell viability was inhibited and NLRP3 and caspase1 protein levels were upregulated in H/R model. However, MSCs could inhibit cell apoptosis and pyroptosis in H/R model. Moreover, we used MSCs-exo to treated H/R model, and flow cytometric analysis results showed the inhibition function of MSCs-exo on cell apoptosis, and Western blot data suggested that NLRP3 and Caspase-1 expressions were downregulated in H/R model. Furthermore, exosomal miR-320b targeted NLRP3 protein, and MSCs-exo OE could inhibit NLRP3 expression and pyroptosis in H/R. In addition, the inhibition function of MSCs-exo on pyroptosis also was found in I/R model, and HE and Tunel staining also got similar results. Conclusion Exosomes derived from mesenchymal stem cells could protect the myocardium against ischemia/reperfusion injury through inhibiting pyroptosis.

Inflammation is intimately related to the pathogenesis of numerous acute and chronic diseases like cardiovascular disease, inflammatory bowel disease, rheumatoid arthritis, and neurodegenerative diseases. Therefore anti-inflammatory therapy is a very promising strategy for the prevention and treatment of these inflammatory diseases. To overcome the shortcomings of existing anti-inflammatory agents and their traditional formulations, such as nonspecific tissue distribution and uncontrolled drug release, bioresponsive drug delivery systems have received much attention in recent years. In this review, we first provide a brief introduction of the pathogenesis of inflammation, with an emphasis on representative inflammatory cells and mediators in inflammatory microenvironments that serve as pathological fundamentals for rational design of bioresponsive carriers. Then we discuss different materials and delivery systems responsive to inflammation-associated biochemical signals, such as pH, reactive oxygen species, and specific enzymes. Also, applications of various bioresponsive drug delivery systems in the treatment of typical acute and chronic inflammatory diseases are described. Finally, crucial challenges in the future development and clinical translation of bioresponsive anti-inflammatory drug delivery systems are highlighted., Graphical abstract Unlabelled Image, Highlights • Inflammation is closely related to the pathogenesis of many acute/chronic diseases. • Low pH and high reactive oxygen species or enzymes are typical inflammatory cues. • Inflammatory cues are useful triggers for rational design of drug delivery systems. • Bioresponsive drug delivery systems are beneficial for treating inflammation. • Translation studies are necessary for anti-inflammatory bioresponsive therapies.

Postoperative epidural adhesion remains a clinically challenging problem in spine surgery. Currently there are no effective and safe antifibrotic and antiadhesion biomaterials that have been specifically developed for this complication in clinical practice. Herein we designed and engineered an advanced antiadhesion hydrogel with multiple functionalities, including temperature-responsive gelation, self-healing, tissue adhesiveness, antioxidation, anti-inflammation, and antifibrosis. This multifunctional supramolecular hydrogel can be facilely constructed by integrating three functional modules, i.e., a thermosensitive triblock copolymer, poloxamer 407 (PX); a reactive oxygen species-eliminating and anti-inflammatory nanoparticle (TPCD NP); and an adhesion-enhancing compound, tannic acid (TA). The optimal formulation (PXNT) was hierarchically screened based on in vitro properties and in vivo activities. Therapeutically, local treatment with PXNT hydrogel effectively prevented epidural fibrosis and adhesion after laminectomy in both rats and rabbits. Of note, PXNT hydrogel showed more beneficial efficacy than different control thermosensitive hydrogels and a commercially available barrier product, Interceed. Mechanistically, PXNT hydrogel significantly attenuated local oxidative stress, inhibited inflammatory responses, and reduced fibrotic tissue formation. Moreover, treatment with PXNT hydrogel did not cause systemic adverse effects and neurological symptoms. Consequently, PXNT hydrogel is a highly promising biomaterial for preventing postlaminectomy epidural adhesion and adhesions after other surgeries.

Because of the wide applications for photocatalysis, electronics and optoelectronics, two-dimensional (2D) van der Waals (vdW) heterojunctions have attracted substantial attentions. In this work, we carried out a systematic investigation on the geometry structures, electronic properties, optical properties and carrier mobilities of the M2CO2-II (M = Ti, Zr and Hf) and MoS2 heterostructures with a hybridized density functional theory (DFT). The BʹCʹ stacked M2CO2-II/MoS2 heterostructure with a short interlayer distance is energetically favorable. All M2CO2-II/MoS2 bilayer and sandwich-like structures are indirect semiconductors. The maximum of valence band (VBM) and conduction band minimum (CBM) of M2CO2-II/MoS2 heterostructures are dominated by different layers, implying the spatial separation of photogenerated electron-hole pairs. Three M2CO2-II/MoS2 heterostructures, including Zr2CO2-II/MoS2 –S-BʹCʹ, Hf2CO2-II/MoS2–B-BʹCʹ, and Hf2CO2-II/MoS2–S-BʹCʹ, are considered as the promising candidates for overall water splitting due to their appropriate band structures, suppressed recombination of photogenerated electron-hole pairs, enhanced optical absorption and carrier mobilities. In addition, the gaint hole mobility makes Ti2CO2-II/MoS2 heterostructure a potential candidate for the application for 2D electronic devices.

Among the various morphologies, the nanoflowers have attracted considerable attention because the nanoflowers own higher surface area and lower density, providing more reaction sites for the adsorbates involved in a close range. In this study, Pd@Pt core–shell nanoflowers were obtained by a simple method. From the experiment results, it would be concluded that the core–shell structure was generated owing to the separate reactions of Pt and Pd processors and the flower-like morphologies were generated because of the effect of CTAC. This special structure enabled excellent performance for the oxidation of methanol due to the synergistic effect between Pd and Pt elements and the resulted larger surface area. Specifically, the specific activity of Pd@Pt core–shell nanoflowers was 0.70 mA cm−2, which was more outstanding than that of Pt black according to the electrochemical tests. Moreover, the Pd@Pt core–shell nanoflowers exhibited better durability than Pt black.

The catalytic activity of the catalyst closely depends on its electronic structure, but the relationship between electronic structure and the catalytic activity in the ammonia borane (NH3BH3, AB) c...

Endohedral clusterfullerenes (ECFs) are fullerene cages with various metallic clusters trapped inside. So far, the actinide-based ECFs are rather scarce with their possible structures and chemistry...

The stability of endohedral clusterfullerenes is generally understood in terms of the metal cluster shape, cage structure, and metal-cage interactions, with the electronic state of the internal cluster mostly neglected. Herein, theoretical calculations reveal that the (Ti

TiO2–CdS nanotubes (NTs) were used for the first time as a support to load metal nanoparticles (NPs) for the hydrolysis of ammonia borane (AB) which is a new strategy. The TiO2–CdS NTs support was first synthesized using a hydrothermal method, and then the CuNi NPs were loaded using a liquid-phase reduction method. The synthesized samples were characterized by XRD, SEM-EDS, TEM, XPS, ICP, UV–Vis, and PL analyses. The characterization results show that the CuNi NPs existed in the form of an alloy with a size of ~1.2 nm and uniformly dispersed on the support. Compared with their single metal counterparts, the bimetallic CuNi-supported catalysts showed a higher catalytic activity in the hydrolysis of AB under visible-light irradiation: Cu0·45Ni0·55/TiO2–CdS catalyst had the fastest hydrogen evolution rate with a high conversion frequency (TOF) of 25.9 molH2·molcat−1 min−1 at 25 °C and low activation energy of 32.8 kJ mol−1. Cu0.45Ni0.55/TiO2–CdS catalyst showed good recycle performance, maintaining 99.3% and 85.6% of the original hydrogen evolution rate even after five and ten recycles, respectively. Strong absorption of visible light, improved electron–hole separation efficiency, and metal synergy between Cu and Ni elements played a crucial role in improving the catalytic hydrolysis performance of AB. The catalyst prepared in this study provides a new strategy for the application of photocatalysts.

Quick identification of the active sites on the surfaces of nanomaterials is rather critical for disclosing their exact interaction mechanism with various adsorbates in the general adsorption and catalysis processes. In this work, we propose that the local aromaticity of the surface sites (bonds or atoms) of different heterocyclic nanostructures (fullerenes, nanotubes, and nanosheets) could be easily evaluated by averaging the nucleus-independent chemical shifts at the centers of the surrounding rings. Significantly, almost all the sites exhibiting the weakest aromaticity or the strongest antiaromaticity are optimal active sites for adsorbing common small molecules. The underlying driving force is further clarified to be the maximum preservation of the global aromaticity of the system.

The design and synthesis of bifunctional heterostructure catalysts is significant to achieve excellent water electrolysis performance. Nevertheless, it remains a challenge to explore the exact active centers of the bifunctional catalysts in the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). Herein, a bifunctional catalyst of ultra-thin porous δ-FeOOH modified Ni3S2 nanosheets exhibits a relatively low overpotential of 187 mV for the OER and 106 mV for the HER at a current density of 10 mA cm−2, respectively. In addition, the overall water splitting unit provides a potential of 1.525 V at 10 mA cm−2 and maintains a performance of 96.85% after 24 h continuous testing. Multispectral analysis and density functional theory (DFT) calculations disclose that the constructed interface between δ-FeOOH and Ni3S2 has two functional groups of Ni–O–Fe and Fe–S bonds to boost the OER and HER performance, respectively, thereby accelerating the overall electrochemical water splitting process in alkaline solution.

Acute myeloid leukaemia (AML) is an aggressive and mostly incurable haematological malignancy with frequent relapse after an initial response to standard chemotherapy. Therefore, novel therapies are urgently required to improve AML clinical outcome. Here, we aim to study the dysregulation of a particular transcription factor, E2F4, and its role in the progression of AML. In this study, human clinical data from the Gene Expression Profiling Interactive Analysis (GEPIA) revealed that increased E2F4 expression was associated with poor prognosis in AML patients. Moreover, the experimental results showed that E2F4 was aberrantly overexpressed in human AML patients and cell lines. Depletion of E2F4 inhibited the proliferation, induced the differentiation and suppressed the growth of AML cells in a nude mouse model. By contrast, overexpression of E2F4 promoted the proliferation and inhibited the differentiation of AML cells in vitro. Additionally, E2F4 expression not only is positively correlated with EZH2 but also can bind to EZH2. RNA microarray results also showed that E2F4 can regulate MAPK signalling pathway. EZH2 can reverse the inhibitory effect of E2F4 silencing on MAPK signaling pathway. In summary, our data suggest that E2F4 may be a potential therapeutic target for AML therapy.

Drug-induced tissue injury has become a growing public health problem. Gastrointestinal injury and liver dysfunction are the most common side effects related to drug therapies, resulting in high morbidity and mortality in recent years. The overproduction of reactive oxygen species (ROS) is critically involved in the pathogenesis of drug-induced tissue injury. Consequently, antioxidant therapy represents a very promising strategy for the treatment of drug-induced tissue injury. Herein, a multifunctional antioxidant nanotherapy (TON) is engineered from a cyclodextrin-derived ROS-responsive material and a radical scavenger tempol, and is capable of eliminating a broad spectrum of ROS. After oral administration, TON can passively accumulate in the inflamed gastrointestinal tissues in mice with indomethacin-induced gastrointestinal injury. Correspondingly, TON shows superior efficacy in two representative murine models of indomethacin-induced gastrointestinal injury and acetaminophen-induced hepatic injury via attenuating oxidative stress and mitigating inflammatory responses. Additionally, preliminary in vitro and in vivo experiments demonstrate the good safety profile of TON. Consequently, the ROS-responsive antioxidant nanotherapy TON is promising for the treatment of drug-induced tissue and organ injury.

The transcription factor Friend leukemia virus integration 1 (Fli-1) belonging to the E26 Transformation-Specific (ETS) transcription factor family is not only expressed in normal cells such as hematopoietic stem cells and vascular endothelial cells, but also abnormally expressed in various malignant tumors including Ewing sarcoma, Merkel cell sarcoma, small cell lung carcinoma, benign or malignant hemangioma, squamous cell carcinoma, adenocarcinoma, bladder cancer, leukemia, and lymphoma. Fli-1 binds to the promoter or enhancer of the target genes and participates in a variety of physiological and pathological processes of tumor cells, including cell growth, proliferation, differentiation, and apoptosis. The expression of Fli-1 gene is related to the specific biological functions and characteristics of the tissue in which it is located. In tumor research, Fli-1 gene is used as a specific marker for the occurrence, metastasis, efficacy, and prognosis of tumors, thus, a potential new target for tumor diagnosis and treatment. These studies indicated that Fli-1 may be a specific candidate for antitumor drug development. Recent studies identified small molecules regulating Fli-1 thanks to our screened strategy of natural products and their derivatives. Therefore, in this review, the advanced research on Fli-1 as a target for antitumor drug development is analyzed in different cancers. The inhibitors and agonists of Fli-1 that regulate its expression are introduced and their clinical applications in the treatment of cancer, thus providing new therapeutic strategies.

Our previous study showed that ENSMUST00000147869 was abnormally low expressed in the early stage of diabetic nephropathy (DN). ENSMUST00000147869 could inhibit the fibrosis and proliferation of mouse mesangial cells (MMCs), but the mechanism is still unclear. This study aims to explore the specific mechanism underline ENSMUST00000147869 regulates the proliferation and fibrosis of MMCs in DN. Nucleocytoplasmic fractionation was applied to define the location of ENSMUST00000147869 in MMCs. RNA-protein pulldown, RNA immunoprecipitation and mass spectrometry were used to identify upregulated Hspa9 directly interacting with ENSMUST00000147869. SiRNA and lentivirus packaging were used to clarify the role of Hspa9 downregulated by ENSMUST00000147869 in promoting proliferation and fibrosis in MMCs. CHX and MG132 were used to clarify the regulatory role of ENSMUST00000147869 to Hspa9. Immunoprecipitation confirmed the binding of Hspa9 and HMGB1. HSPA9 was a direct binding protein of ENSMUST00000147869, and ENSMUST00000147869 could inhibit proliferation and fibrosis of MMCs by down-regulating HSPA9 through ubiquitination process. HMGB1 was the downstream binding protein of Hspa9, and ENSMUST00000147869 could inhibit the interaction between Hspa9 and HMGB1. Our data showed that ENSMUST00000147869 regulates Hspa9 through the ubiquitin proteasome pathway and inhibits the binding of Hspa9 and HMGB1. The ENSMUST00000147869/Hspa9/HMGB1 axis may act as a diagnostic molecular marker and an effective therapeutic target for DN.

As an emerging industry, cultural and creative industry is an external manifestation of cultural materialization and dissemination. It is an industry that uses technology, economy, creativity, and industrial clusters to combine mainstream culture or certain cultural factors to develop and sell intellectual property. The Belt and Road initiative is China’s move to the world’s frontier after parting ways with modern Western thought. Realizing a community with a shared future for mankind is China’s great goal. The continuous enrichment and sublimation of the “Belt and Road” in connotation and extension conform to the common interests of the international community. This is of great significance for actively exploring new forms of global governance and promoting world peace and development. In the context of the way along the way, combined with the further development of economic globalization, we will create a new creative industry with creativity as the core through new methods such as artificial intelligence, cloud services, and cross-border e-commerce.

Health empowerment can be an effective way to reduce health inequities. This prospective cohort study evaluated the 5 year impact of a health empowerment program (HEP) on health outcomes among adults from low-income families. The Patient Enablement Instrument version 2 (PEI-2), Depression, Anxiety and Stress Scale 21 (DASS-21), and 12 item Short-Form Health Survey version 2 (SF-12v2) were administered at baseline and follow-up for both intervention and comparison groups. A total of 289 participants (n = 162 for intervention group, n = 127 for comparison group) were included in the analysis. Most of the participants were female (72.32%), and aged from 26 to 66 years old (M = 41.63, SD = 6.91). Linear regressions weighted by inverse probability weighting using the propensity score showed that, after follow-up of 5 years, the intervention group demonstrated significantly greater increases in all items and total scores for the PEI-2 (all B > 0.59, p < 0.001), greater decreases in the DASS depression score (B = −1.98 p = 0.001), and greater increases in the Mental Component Summary score of the SF-12v2 (B = 2.99, p = 0.027) than the comparison group. The HEP may be an effective intervention enabling adults from low-income families to manage their health-related issues and improve their mental health, as evidenced by our study.

IntroductionHypertension (HTN) is the leading cause of disease and death on a global scale. Diet’s sodium and potassium levels may synergistically affect blood pressure. Currently, the sodium-to-potassium (Na/K) ratio is becoming a more reliable indicator. There has not been a systematic investigation of the dose–response relationship between dietary sodium, potassium, the Na/K ratio and the incidence of HTN based on the same study criteria. This study will conduct a thorough dose–response meta-analysis of cohort studies to estimate the effects of dietary sodium, potassium, and the Na/K ratio on the incidence of HTN to provide the most accurate reference for sodium and potassium intake.Methods and analysisWe will identify all relevant prospective and retrospective cohort studies by searching PubMed, Embase and Web of Science (from inception until December 2022). Exposures are 24 hours urinary excretions, and the outcome is the incidence of HTN. Two researchers will perform the literature selection and data extraction separately. The Newcastle-Ottawa Scale will be used to evaluate the quality of the included studies. We will use both linear and non-linear regression models to investigate the dose–response relationship among different levels (≥3) of sodium, potassium, Na/K ratio intake and the incidence of HTN (OR/RR/HR). Subgroup and sensitivity analyses will be applied to assess the potential heterogeneity sources and examine the stability of the results. We will also evaluate heterogeneity across studies and publication bias. Stata V.15.0 and RevMan V.5.0 will be used for statistical analyses.Ethics and disseminationAccording to the Institutional Review Board/Independent Ethics Committee of the Guang'anmen Hospital of the China Academy of Chinese Medical Science, this systematic meta-analysis protocol does not require ethical approval or informed consent. This meta-analysis will be published in a scientific journal with peer reviews.PROSPERO registration numberCRD42022331203.

Our previous study showed that oscillatory shear stress (OSS) induces endothelial progenitor cells (EPCs) to undergo endothelial to mesenchymal transition (EndoMT), which may contribute to the onset and progression of atherosclerosis (AS). However, the underlying mechanisms have not been elucidated. A recent study showed that exosomes (Exos) released from EPCs played a key role in various cardiovascular diseases. The purpose of this study was to identify the role and mechanism of Exos released by EPCs exposed to OSS in EPC EndoMT.EPCs derived from the human umbilical cord blood were cultured and characterized. The Flexcell flow STR-4000 parallel plate flow chamber system was employed to apply OSS (±3.5 dyne/cmOSS-Exos inhibited angiogenesis, promoted the proliferation of EPCs both in vivo and in vitro, and induced EPC EndoMT. In addition, the expression of circ-1199 in OSS-Exos was higher than that in Static-Exos. Moreover, circ-1199 induced EPC EndoMT. The dual-luciferase reporter gene assay showed that let-7g-5p was the direct target of circ-1199. Furthermore, OSS-Exos upregulated the expression of circ-1199 and then downregulated let-7g-5p, upregulating HMGA2, which activated p-Smad3/Smad3 and Snail.OSS-Exos played an important role in the EndoMT of EPCs, which was mediated by the circ-1199/let-7g-5p/HMGA2 signaling pathway. These studies would have a high probability of revealing the mechanism of EPC EndoMT.

We proposed a novel deep learning-based radiomics (DLR) model to diagnose Parkinson's disease (PD) based on [In this two-center study, 255 normal controls (NCs) and 103 PD patients were enrolled from Huashan Hospital, China; 26 NCs and 22 PD patients were enrolled as a separate test group from Wuxi 904 Hospital, China. The proposed DLR model consisted of a convolutional neural network-based feature encoder and a support vector machine (SVM) model-based classifier. The DLR model was trained and validated in the Huashan cohort and tested in the Wuxi cohort, and accuracy, sensitivity, specificity and receiver operator characteristic (ROC) curve graphs were used to describe the model's performance. Comparative experiments were performed based on four other models including the scale model, radiomics model, standard uptake value ratio (SUVR) model and DLR model.The DLR model demonstrated superiority in differentiating PD patients and NCs in comparison to other models, with an accuracy of 95.17% [90.35%, 98.13%] (95% confidence intervals, CI) in the Huashan cohort. Moreover, the DLR model also demonstrated greater performance in diagnosing PD early than routine methods, with an accuracy of 85.58% [78.60%, 91.57%] in the Huashan cohort.We developed a DLR model based on [The DLR method on [

Mantle cell lymphoma (MCL) is a lymphoproliferative disorder that lacks reliable therapeutic options. Therefore, new treatment approaches for targeting novel biological pathways are required. 4-amino-2-trifluoromethyl-phenyl retinate (ATPR) synthesized by our group previously has been proven to have higher solubility and superior differentiation effects compared to those of conventional all-trans retinoic acid in acute myeloid leukemia. ATPR induces differentiation and inhibits the proliferation of acute promyelocytic leukemia. However, whether ATPR induces differentiation of MCL cells to normal immune cells has not been investigated. In this study, the proliferation of JEKO-1 cells was completely repressed, and differentiation was activated after ATPR treatment. The neural transcription factor SOX11 was further found to be highly expressed in MCL, but was downregulated by ATPR. After silencing SOX11 in vitro and in vivo, the malignant proliferation and inhibited differentiation of JEKO-1 cells were reversed, whereas the overexpression of SOX11 exacerbated the malignant phenotype of JEKO-1 cells. We also have added additional MCL cell lines (MINO) to complete the key pilot experiments. In addition, the CyclinD1/Rb/E2F1 axis was involved in MCL and was regulated by ATPR. In conclusion, ATPR promoted JEKO-1 cell differentiation via SOX11/CyclinD1/Rb/E2F1. This study provides experimental foundation for developing differentiation therapy for MCL with ATPR.

Studies have shown that resveratrol (Res) exerts significant antiproliferative effects in cancer, and regulating the expression of microRNAs (miRNAs) is one the underlying mechanisms of these effects. Overexpression of miR-155-5p leads to oncogenesis. However, it is unclear whether Res exerts antitumor effects by regulating the expression of miR-155-5p, and its specific mechanism in gastric cancer remains unknown. In this study, qRT-PCR was performed to assess the expression of miR-155-5p in gastric cells and clinical tissues, and the MTT assay, plate clone formation test, cell scratch test, Transwell assay, and flow cytometry were performed to investigate the functions of Res on the growth of gastric cancer cells after treatment with miR-155-5p. Western blot analysis was performed to detect the expression of claudin 1, c-Myc, cyclin D1, Bcl-2, and caspase-3 proteins in gastric cancer cell lines after treatment with miR-155-5p and Res. We found that miR-155-5p was overexpressed in gastric cancer cells and clinical tissues, while Res inhibited gastric cancer cell growth by regulating miR-155-5p expression. The results of MTT assay, plate clone formation test, cell scratch test, Transwell test, and flow cytometry showed that miR-155-5p promoted the proliferation, invasion, and metastasis of gastric cancer cell lines and inhibited apoptosis, while Res addition inhibited this effect ( P < 0.05 ). When miR-155-5p was overexpressed, the expressions of claudin 1, c-Myc, cyclin D1, and Bcl-2 were upregulated and that of caspase-3 was downregulated. Collectively, these results suggest that miR-155-5p may be a therapeutic target in gastric cancer, and Res may be a potential therapeutic agent based on its regulation of miR-155-5p.

Post-transcriptional modifications of RNA, such as RNA methylation, can epigenetically regulate behavior, for instance learning and memory. However, it is unclear whether RNA methylation plays a critical role in the pathophysiology of major depression disorder (MDD). Here, we report that expression of the fat mass and obesity associated gene (FTO), an RNA demethylase, is downregulated in the hippocampus of patients with MDD and mouse models of depression. Suppressing Fto expression in the mouse hippocampus results in depression-like behaviors in adult mice, whereas overexpression of FTO expression leads to rescue of the depression-like phenotype. Epitranscriptomic profiling of N6-methyladenosine (m6A) RNA methylation in the hippocampus of Fto knockdown (KD), Fto knockout (cKO), and FTO-overexpressing (OE) mice allows us to identify adrenoceptor beta 2 (Adrb2) mRNA as a target of FTO. ADRB2 stimulation rescues the depression-like behaviors in mice and spine loss induced by hippocampal Fto deficiency, possibly via the modulation of hippocampal SIRT1 expression by c-MYC. Our findings suggest that FTO is a regulator of a mechanism underlying depression-like behavior in mice., Post-transcriptional modification of RNA can contribute to regulating behavior. Here, the authors show that modulating the expression of Fto results in epitranscriptomic changes in the mouse hippocampus associated with depression-like behavior.

Stroke is a primary cause of death and disability worldwide, while effective and safe drugs remain to be developed for its clinical treatment. Herein, we report bioactive nanoparticle-derived multifunctional nanotherapies for ischemic stroke, which are engineered from a pharmacologically active oligosaccharide material (termed as TPCD) prepared by covalently conjugating a radical-scavenging compound (Tempol) and a hydrogen-peroxide-eliminating moiety of phenylboronic acid pinacol ester (PBAP) on β-cyclodextrin. Of note, combined functional moieties of Tempol and PBAP on β-cyclodextrin contribute to antioxidative and anti-inflammatory activities of TPCD. Cellularly, TPCD nanoparticles (i.e., TPCD NPs) reduced oxygen-glucose deprivation-induced overproduction of oxidative mediators, increased antioxidant enzyme expression, and suppressed microglial-mediated inflammation, thereby inhibiting neuronal apoptosis. After intravenous (i.v.) delivery, TPCD NPs could efficiently accumulate at the cerebral ischemic injury site of mice with middle cerebral artery occlusion (MCAO), showing considerable distribution in cells relevant to the pathogenesis of stroke. Therapeutically, TPCD NPs significantly decreased infarct volume and accelerated recovery of neurological function in MCAO mice. Mechanistically, efficacy of TPCD NPs is achieved by its antioxidative, anti-inflammatory, and antiapoptotic effects. Furthermore, TPCD NPs can function as a reactive oxygen species labile nanovehicle to efficiently load and triggerably release an inflammation-resolving peptide Ac2-26, giving rise to an inflammation-resolving nanotherapy (i.e., ATPCD NP). Compared to TPCD NP, ATPCD NP demonstrated notably enhanced in vivo efficacies, largely resulting from its additional inflammation-resolving activity. Consequently, TPCD NP-derived nanomedicines can be further developed as promising targeted therapies for stroke and other inflammation-associated cerebrovascular diseases.