Colossal Orbital Current Induced by Gradient Oxidation for High-Efficiency Magnetization Switching.

Orbital angular momentum flow can be used to develop a low-dissipation electronic information device by manipulating the orbital current. However, efficiently generating and fully harnessing orbital currents is a formidable challenge. In this study, an approach is presented that induces a colossal orbital current by gradient oxidation in Pt/Ta to enhance spin-orbit torque (SOT) and achieve high-efficiency magnetization switching. The maximum efficiency of the SOT before and after the gradient oxidation of Ta is improved relative to that of Pt by ≈600 and 1200%, respectively. The large SOT originates from the colossal orbital current because of the orbital Rashba-Edelstein effect induced by the gradient oxidation of Ta. In addition, a large spin-to-charge conversion efficiency is observed in yttrium iron garnet/Pt/TaOx because of the inverse orbital Rashba-Edelstein effect. Harnessing the orbital current can help effectively minimize the critical current density of the current-induced magnetization switching to 2.26-1.08 × 106 A cm-2, marking a 12-fold reduction compared to that using Pt. This findings provide a new path for research on low-dissipation spin-orbit devices and improve the tunability of orbital current generation.

Enhanced Spin-Orbit Torque Efficiency in Platinum-Gadolinium Oxide Nanocomposite Films.

Spin-orbit torque (SOT) has emerged as an effective means of manipulating magnetization. However, the current energy efficiency of SOT operation is inefficient due to low damping-like SOT efficiency per unit current bias. In this work, we dope conventional rare earth oxides, GdOy, into highly conductive platinum by magnetron sputtering to form a new group of spin Hall materials. A large damping-like spin-orbit torque (DL-SOT) efficiency of about 0.35 ± 0.013 is obtained in Pt0.70(GdOy)0.30 measured by the spin-torque ferromagnetic resonance (ST-FMR) technique, which is about five times that of pure Pt under the same conditions. The substantial enhancement of the spin Hall effect is revealed by theoretical analysis to be attributed to the strong side jump induced by the rare earth oxide GdOy impurities. Moreover, this large DL-SOT efficiency contributes to a low critical switching current density (8.0 × 106 A·cm-2 in the Pt0.70(GdOy)0.30 layer) in current-induced magnetization switching measurements. This systematic study on SOT switching properties suggests that Pt1-x(GdOy)x is an attractive spin current source with large DL-SOT efficiency for future SOT applications and provides another idea to regulate the spin Hall angle.

The impact of boarding school on student development in primary and secondary schools: a meta-analysis.

As a long-established model of schooling, the boarding system is commonly practiced in countries around the world. Numerous scholars have conducted a great deal of research on the relationship between the boarding school and student development, but the results of the research are quite divergent. In order to clarify the real effects of boarding school on students' development, this study used meta-analysis to quantify 49 (91 effect sizes) experimental or quasi-experimental studies on related topics at home and abroad. The results find that: (1) Overall, boarding school has no significant predictive effect on student development, with a combined effect size of 0.002 (p > 0.05); (2) Specifically, boarding school has a significant positive predictive effect on students' cognitive development (g = 0.248, p < 0.001), a significant negative predictive effect on students' affective and attitudinal development (g = -0.159, p < 0.05), and no significant predictive effect on students' behavioral development (g = -0.115, p > 0.05) and physical development (g = -0.038, p > 0.05); (3) The relationship between the two is moderated by the school stage and the type of boarding school, but not by the instruments; (4) Compared with primary school students, senior high school students and urban boarding students, the negative predictive effect of boarding system on junior middle school students and rural boarding students is more significant. In addition, there are some limitations in the study, such as the limited number of moderator variables included, the results of the study are easily affected by the quality of the included literature, and the dimensionality of the core variable "student development" is not comprehensive enough. In the future, further validation should be conducted through in-depth longitudinal or experimental studies.

Cobalt catalyzed ethane dehydrogenation to ethylene with CO2: Relationships between cobalt species and reaction pathways.

TiO2, ZrO2 and a series of TiO2-ZrO2 (TxZ1, x means the atomic ratio of Ti/Zr = 10, 5, 1, 0.2 and 0.1) composite oxide supports were prepared through co-precipitation, and then 3 wt% Co was loaded through wetness impregnation methods. The obtained 3 wt% Co/TiO2 (3CT), 3 wt% Co/ZrO2 (3CZ) and 3 wt% Co/TxZ1 (3CTxZ1) catalysts were evaluated for the oxidative ethane dehydrogenation reaction with CO2 (CO2-ODHE) as a soft oxidant. 3CT1Z1 catalyst exhibits excellent catalytic properties, with C2H4 yield, C2H6 conversion and CO2 conversion about 24.5 %, 33.8 % and 18.0 % at 650 °C, respectively. X-Ray Diffraction (XRD), in-situ Raman, UV-vis diffuse reflectance spectra (UV-vis DRS), H2 temperature-programmed reduction (H2-TPR), Electron paramagnetic resonance (EPR) and quasi in-situ X-ray Photoelectron Spectroscopy (XPS) have been utilized to thoroughly characterize the investigated catalysts. The results revealed that 3CT1Z1 produced TiZrO4 solid solution with more metal defect sites and oxygen vacancies (Ov), promoting the formation of Co2+-TiZrO4 structure. Furthermore, the presence of Ov and Ti3+can facilitate the high dispersion and stabilization of Co2+, as well as suppressing the severe reduction of Co2+, leading to superior ethane oxidative dehydrogenation activity. Besides, less Co0 is beneficial to ODHE reaction, because of its promotion effects for reverse water gas shift reaction; however, more Co0 results in dry reforming reaction (DRE). This work will shed new lights for the design and preparation of highly efficient catalysts for ethylene production.

Tunable linear-to-circular terahertz polarization convertor enabled by a plasmonic nanocomposite metasurface.

We proposed and demonstrated a metasurface based terahertz polarizer consisting of an optically responsive nanocomposite and a flexible base body, which fulfilled the function of linear-to-circular polarization conversion in transmission mode. Meanwhile, as the dynamic and stretchable materials enable the active manipulation of conversion points, evident frequency shifts for circular polarization transformation were discovered by applying laser irradiation and tension. Hence the modulation of conversion points covered a broadband with combination of those two external excitations. This THz polarization convertor may find its applications in polarization controls and beam steering, which also provides a low-cost and large-scale manufacturable method to achieve versatile active THz devices.

Splitting phenomenon of ferromagnetic resonance spectra in NiFe films deposited on periodically rippled sapphire substrates.

The splitting phenomenon of ferromagnetic resonance (FMR) spectra of Ni80Fe20 (NiFe) films deposited on periodically rippled sapphire substrates is studied experimentally and with the help of micromagnetic simulation. The analyses show that the splitting of FMR spectra is related to the periodic ripple topography of films. When the applied magnetic field is perpendicular to the ripple direction, the effective field of periodically rippled films becomes inhomogeneous. The splitting of ferromagnetic resonance spectra originates from localized FMR peaks corresponding to different regions with different effective field intensities in the rippled structure. Furthermore, the relative intensity and position between the split mode and the main FMR mode can be changed by designing ripple topography. This work would help understand the splitting phenomenon of FMR spectra for these NiFe films deposited on the periodically rippled sapphire substrates.

The in vitro metabolism of GMDTC in liver microsomes of human, monkey, dog, rat and mouse: Metabolic stability assessment, metabolite identification and interspecies comparison.

Sodium (S)- 2-(dithiocarboxylato((2 S,3 R,4 R,5 R)- 2,3,4,5,6-pentahydroxyhexyl)amino)- 4(methylthio)butanoate (GMDTC) is a compound that removes cadmium from kidney cells. This study aims to investigate the metabolic stability and metabolite identification of GMDTC in various liver microsomes, including those from human, monkey, dog, rat and mouse. The results show that the T1/2 values of GMDTC in human, monkey, dog, rat and mouse liver microsomes were 16.54, 18.14, 16.58, 15.16 and 16.00 min, respectively. While the hepatic extraction ratios (ERh) of GMDTC measured after 60 min incubation in these liver microsomes were 0.82, 0.70, 0.80, 0.75 and 0.79, respectively, indicating that GMDTC exhibits rapid hepatic metabolism and high hepatic clearance with no significant interspecies differences. Subsequent metabolite identification by high-resolution mass spectrometry revealed the presence of three metabolites, designated M1∼M3. The major metabolite products of GMDTC were found to be M1 and M2. The relative abundances of the hydrolysis products (M1 and M2) in human, monkey, dog, rat and mouse liver microsomes were found to be 97.18%, 97.99%, 95.94%, 96.31% and 93.43%, respectively, indicating that hydrolysis is the primary metabolic pathway of GMDTC in liver microsomes in vitro, and with no significant interspecies differences.

A multicenter prospective study on the management of hepatoblastoma in children: a report from the Chinese Children's Cancer Group.

BACKGROUND: This study aimed to identify survival risk factors in Chinese children with hepatoblastoma (HB) and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group (CCCG) in 2016. METHODS: A multicenter, prospective study that included 399 patients with HB from January 2015 to June 2020 was conducted. Patient demographics, treatment protocols, and other related information were collected. Cox regression models and Kaplan-Meier curve methods were used. RESULTS: The 4-year event-free survival (EFS) and overall survival (OS) were 76.9 and 93.5%, respectively. The 4-year EFS rates for the very-low-risk, low-risk, intermediate-risk, and high-risk groups were 100%, 91.6%, 81.7%, and 51.0%, respectively. The 4-year OS was 100%, 97.3%, 94.4%, and 86.8%, respectively. Cox regression analysis found that age, tumor rupture (R +), and extrahepatic tumor extension (E +) were independent prognostic factors. A total of 299 patients had complete remission, and 19 relapsed. Patients with declining alpha-fetoprotein (AFP) > 75% after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those ≤ 75%. CONCLUSIONS: The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 therapy. Age ≥ 8 years, R + , and E + were independent risk factors for prognosis. Patients with a declining AFP > 75% after the first two cycles of neoadjuvant chemotherapy had better EFS and OS.

Renal glucose transporters play a role in removal of cadmium from kidney cells mediated by GMDTC - A novel metal chelator.

Cadmium (Cd) is a toxic heavy metal, exposure to which leads to adverse health effects including chronic kidney damage. Tremendous efforts have been explored in identifying safe chelating agents for removing accumulated Cd from kidney, but with limited success owing to their associated side effects and the ineffectiveness in eliminating Cd. A newly developed chelating agent, sodium (S)-2-(dithiocarboxylato((2S,3 R,4R,5 R)-2,3,4,5,6-pentahydroxyhexyl) amino)-4(methylthio)butanoate (GMDTC), has been shown to effectively mobilize Cd from kidney. However, the mechanism(s) of removal are unclear, while it has been hypothesized that renal glucose transporters potentially play key roles mainly because GMDTC contains an open chain glucose moiety. To test this hypothesis, we utilized the CRISPR/Cas9 technology and human kidney tubule HK-2 cells, and constructed sodium-dependent glucose transporter 2 (SGLT2) or glucose transporter 2 (GLUT2) gene knockout cell lines. Our data showed that GMDTC's ability in removing Cd from HK-2 cells was significantly reduced both in GLUT2-/- or SGLT2-/- cells, with a removal ratio reduced from 28.28% in the parental HK-2 cells to 7.37% in GLUT2-/- cells and 14.6% in SGLT2-/- cells. Similarly, knocking out the GLUT2 or SGLT2 led to a compromised protective effect of GMDTC in reducing cytotoxicity of HK-2 cells. This observation was further observed in animal studies, in which the inhibition of GLUT2 transporter by phloretin treatment resulted in reduced efficiency of GMDTC in removing Cd from the kidney. Altogether, our results show that GMDTC is safe and highly efficient in removing Cd from the cells, and this effect is mediated by renal glucose transporters.

Metamaterials-based broadband absorption in long-wave infrared frequency enabled by multilayered ENZ films on metal-coated patterned silicon.

Large-scale, and high-throughput produced devices with strong ultrabroadband absorption and high angular tolerance are in demand for applications such as thermal imaging, energy harvesting, and radiative cooling. Despite long-standing efforts in design and fabrication, it has been challenging to achieve all these desired properties simultaneously. Here, we create a metamaterial-based infrared absorber fabricated from thin films of epsilon-near-zero (ENZ) materials grown on metal-coated patterned silicon substrates that exhibit ultrabroadband infrared absorption in both p- and s-polarization at angles ranging from 0° to 40°. The results show that the structured multilayered ENZ films exhibit high absorption (> 0.9) covering the entire 8∼14 µm wavelengths. In addition, the structured surface can be realized via scalable, low-cost methods on large-area substrates. Overcoming the limitations on angular and polarized response improves performance for applications such as thermal camouflage, radiative cooling for solar cell, thermal image and et., al.

Establishment of LC-MS/MS Method for Determination of GMDTC in Rat Plasma and Its Application in Preclinical Pharmacokinetics.

Sodium (S)-2-(dithiocarboxylato((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)-4(methylthio)butanoate (GMDTC) is the first compound to use cadmium repellent as an indication. In this paper, we established and validated a bioanalytical method for the determination of GMDTC in rat plasma, and used it to determine the drug concentrations in the plasma of rats after intravenous dosing in different genders and dosages. After pretreating the plasma samples with an acetonitrile-water-ammonia solution (70:30:1.25, v/v/v), liquid chromatographic separations were efficiently achieved with a XBridge C18 column using a 5 min gradient system of aqueous ammonium bicarbonate and 95% acetonitrile-water solution (95:5, v/v) as the eluent. The GMDTC and metolazone (internal standard, IS) detection were carried out using high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (LC-MS/MS), monitored at m/z 390.06-324.1 (for the GMDTC, tR: 2.03 min) and m/z 366.0-259.2 (for IS, tR: 3.88 min). The GMDTC was stable under various testing conditions, and this analytical method conforms to the verification standard of biological analysis methods. The half-life (t1/2) was determined to be 0.54-0.65 h for the intravenous, mean distribution volume and clearances were 1.08-2.08 L/kg and 1-3 L/h/kg, respectively. The AUC0-t and AUC0-∞ found after increasing the dosage exhibited a linear relationship with the administered dose. There were no statistically significant differences in the values obtained for the different genders at dosages of 50, 100 and 250 mg/kg, respectively (p > 0.05). This is the first report of a bioanalytical method to quantify GMDTC in rat plasma using LC-MS/MS, which provides useful information for the study of its pharmacological effects and clinical applications.

Factors associated with the high susceptibility to depression of women during the perimenopause.

OBJECTIVE: This study investigated the factors associated with the high susceptibility of perimenopausal women to depression. METHODS: A total of 66 perimenopausal women participated in this study. The Zung self-rating depression scale (SDS) was used to evaluate the intensity of depressive symptoms. The modified Kupperman index (KI) was used to assess common perimenopausal symptoms. Psychosocial factors were assessed via the Eysenck Personality Questionnaire, attitudes toward menopause checklist, and metacognition questionnaire (MCQ). Levels of serum estradiol, testosterone, and progesterone were determined. RESULTS: There were statistically significant associations between SDS standard score and the KI scale score (ß = .361, p = .001), years of education (ß = -.309, p = .005), and F3 cognitive self-consciousness score of MCQ (ß = -.234, p = .032; adjusted R2  = .264, F = 8.759, p < .001). CONCLUSIONS: High susceptibility to depression of perimenopausal women may be related to lower educational level, more severe perimenopausal symptoms, and altered metacognition.

Executive functions and mathematical competence in Chinese preschool children: A meta-analysis and review.

Numerous studies have been conducted on the correlation between preschool children's executive functions and mathematical competence, the findings of those studies are inconsistent. This study used meta-analysis to investigate the correlation between executive functions and mathematical competence of preschool children in China, and then explored the moderating effects of age, gender, and instruments. The researchers conducted an extensive search of CNKI, Web of Science, Google Scholar and used screening criteria to identify 22 studies of Chinese preschoolers aged 3-7 years from 2007 to 2021. The findings indicated that there was a positive correlation between Chinese preschool children's executive functions and mathematical competence (r = 0496), of which the effect size between mathematical competence and inhibition control was 0.347, and the effect size for working memory was 0.432, with an effect size of 0.370 for cognitive flexibility. Furthermore, Moderation analysis suggests that the preschoolers' age, gender, and instruments affected the association between the executive functions and mathematical competence. The implications of these findings for theory and practice deserve further discussion.

Tune the resonance of VO2 joined metamaterial dimers by adjacent cut wires.

Two terahertz metamaterials were joined by a conductivity variable VO2 patch to obtain a metamaterial dimer. By applying voltage or heat to the VO2 patches, active modulation of terahertz wave could be achieved. A cut-wire metamaterial was placed adjacent to the VO2 joined dimer to affect its electromagnetic response. It was found that the cut wire could heavily impact the resonance mode of the VO2 joined dimer, which gives dual resonance dips in transmission spectrum for both insulating and conducting states of VO2 patches. As a result, by tuning the conductivity of VO2, active dual band phase modulation could be achieved with high transmission window by this dimer-cut wire coupling system.

Hypoxia drives hematopoiesis with the enhancement of T lineage through eliciting arterial specification of hematopoietic endothelial progenitors from hESC.

BACKGROUND: Hematopoietic stem cells are able to self-renew and differentiate into all blood cell lineages. Hematopoietic stem cell transplantation is a mainstay of life-saving therapy for hematopoietic malignancies and hypoproliferative disorders. In vitro hematopoietic differentiation of human pluripotent stem cells (hPSCs) is a promising approach for modeling hematopoietic development and cell replacement therapies. Although using hPSCs to derive hematopoietic progenitor cells has achieved some successes in the past, differentiation from hPSCs to produce all hematopoietic cells which can provide robust long-term multilineage engraftment is still very difficult. Here, we reported a novel culture system for hematopoietic differentiation from human embryonic stem cells (hESCs) with optimal cytokines combinations under hypoxia condition. METHODS: In vitro production of T lineage hematopoietic stem/progenitor cells from hESCs by using hypoxia differentiation system, the effects and the potential mechanism of hypoxia promoting T lineage hematopoiesis were investigated by RT-qPCR validation, cell cycle assay and flow cytometry analysis. RESULTS: Using our differentiation system, almost 80% CD45+ cells generated from hESCs were hematopoietic cells and particularly could be further induced into CD3+TCRαß+ T cells in vitro. We detected more CD34+CD144+ hematopoietic endothelial progenitors (HEPs) induced from hESCs than those in normoxia conditions, and the early HEPs-related gene DLL4 was upregulated by enhancing the hypoxia signaling via potential HIF-1α/NOTCH1/DLL4 axis to enhance arterial feature, thus drove T lineage during the hematopoiesis. Strikingly, hematopoietic cells generated in our system exhibited the potential for all multilineage reconstruction including lymphoid, myeloid and erythroid lineages in vivo by transplantation assay. CONCLUSION: Our results demonstrated that hypoxia plays an important role in T lineage hematopoiesis by promoting the expression of arterial endothelial gene DLL4 and upregulation of NOTCH1 through the activation of the HIF-1α signaling pathway. These results provide a significant approach for in vitro and in vivo production of fully functional hematopoietic stem/progenitor cells from hESCs.

Dextran sulfate prevents excess aggregation of human pluripotent stem cells in 3D culture by inhibiting ICAM1 expression coupled with down-regulating E-cadherin through activating the Wnt signaling pathway.

BACKGROUND: Human pluripotent stem cells (hPSCs) have great potential in applications for regenerative medicine and drug development. However, 3D suspension culture systems for clinical-grade hPSC large-scale production have been a major challenge. Accumulating evidence has demonstrated that the addition of dextran sulfate (DS) could prevent excessive adhesion of hPSCs from forming larger aggregates in 3D suspension culture. However, the signaling and molecular mechanisms underlying this phenomenon remain elusive. METHODS: By using a cell aggregate culture assay and separating big and small aggregates in suspension culture systems, the potential mechanism and downstream target genes of DS were investigated by mRNA sequence analysis, qRT-PCR validation, colony formation assay, and interference assay. RESULTS: Since cellular adhesion molecules (CAMs) play important roles in hPSC adhesion and aggregation, we assumed that DS might prevent excess adhesion through affecting the expression of CAMs in hPSCs. As expected, after DS treatment, we found that the expression of CAMs was significantly down-regulated, especially E-cadherin (E-cad) and intercellular adhesion molecule 1 (ICAM1), two highly expressed CAMs in hPSCs. The role of E-cad in the adhesion of hPSCs has been widely investigated, but the function of ICAM1 in hPSCs is hardly understood. In the present study, we demonstrated that ICAM1 exhibited the capacity to promote the adhesion in hPSCs, and this adhesion was suppressed by the treatment with DS. Furthermore, transcriptomic analysis of RNA-seq revealed that DS treatment up-regulated genes related to Wnt signaling resulting in the activation of Wnt signaling in which SLUG, TWIST, and MMP3/7 were highly expressed, and further inhibited the expression of E-cad. CONCLUSION: Our results demonstrated that DS played an important role in controlling the size of hPSC aggregates in 3D suspension culture by inhibiting the expression of ICAM1 coupled with the down-regulation of E-cad through the activation of the Wnt signaling pathway. These results represent a significant step toward developing the expansion of hPSCs under 3D suspension condition in large-scale cultures.

Giant Extrinsic Spin Hall Effect in Platinum-Titanium Oxide Nanocomposite Films.

Although the spin Hall effect provides a pathway for efficient and fast current-induced manipulation of magnetization, application of spin-orbit torque magnetic random access memory with low power dissipation is still limited to spin Hall materials with low spin Hall angles or very high resistivities. This work reports a group of spin Hall materials, Pt1 -x (TiO2 )x nanocomposites, that combines a giant spin Hall effect with a low resistivity. The spin Hall angle of Pt1 -x (TiO2 )x in an yttrium iron garnet/Pt1 -x (TiO2 )x double-layer heterostructure is estimated from a combination of ferromagnetic resonance, spin pumping, and inverse spin Hall experiments. A giant spin Hall angle 1.607 ± 0.04 is obtained in a Pt0.94 (TiO2 )0.06 nanocomposite film, which is an increase by an order of magnitude compared with 0.051 ± 0.002 in pure Pt thin film under the same conditions. The great enhancement of spin Hall angle is attributed to strong side-jump induced by TiO2 impurities. These findings provide a new nanocomposite spin Hall material combining a giant spin Hall angle, low resistivity and excellent process compatibility with semiconductors for developing highly efficiency current-induced magnetization switching memory devices and logic devices.

Vacancy tuned coupling in terahertz metamaterial arrays.

Metamaterials have shown great potential for modulation on the amplitude, phase and polarization of the terahertz wave. Here vacancies were introduced into the metamaterial arrays to tune the mutual interaction between the constituent resonators, which could heavily affect the electromagnetic response of the whole metamaterial arrays. We show that the introduced vacancies in the metamaterial arrays can effectively affect the resonance mode of the metamaterial arrays. Based upon the vacancy mediated coupling, a silicon-metal hybrid metamaterial arrays were designed to achieve active modulation of propagating terahertz waves.

3D hESC exosomes enriched with miR-6766-3p ameliorates liver fibrosis by attenuating activated stellate cells through targeting the TGFßRII-SMADS pathway.

BACKGROUND: Exosomes secreted from stem cells exerted salutary effects on the fibrotic liver. Herein, the roles of exosomes derived from human embryonic stem cell (hESC) in anti-fibrosis were extensively investigated. Compared with two-dimensional (2D) culture, the clinical and biological relevance of three-dimensional (3D) cell spheroids were greater because of their higher regeneration potential since they behave more like cells in vivo. In our study, exosomes derived from 3D human embryonic stem cells (hESC) spheroids and the monolayer (2D) hESCs were collected and compared the therapeutic potential for fibrotic liver in vitro and in vivo. RESULTS: In vitro, PKH26 labeled-hESC-Exosomes were shown to be internalized and integrated into TGFß-activated-LX2 cells, and reduced the expression of profibrogenic markers, thereby regulating cellular phenotypes. TPEF imaging indicated that PKH26-labeled-3D-hESC-Exsomes possessed an enhanced capacity to accumulate in the livers and exhibited more dramatic therapeutic potential in the injured livers of fibrosis mouse model. 3D-hESC-Exosomes decreased profibrogenic markers and liver injury markers, and improved the level of liver functioning proteins, eventually restoring liver function of fibrosis mice. miRNA array revealed a significant enrichment of miR-6766-3p in 3D-hESC-Exosomes, moreover, bioinformatics and dual luciferase reporter assay identified and confirmed the TGFßRII gene as the target of miR-6766-3p. Furthermore, the delivery of miR-6766-3p into activated-LX2 cells decreased cell proliferation, chemotaxis and profibrotic effects, and further investigation demonstrated that the expression of target gene TGFßRII and its downstream SMADs proteins, especially phosphorylated protein p-SMAD2/3 was also notably down-regulated by miR-6766-3p. These findings unveiled that miR-6766-3p in 3D-hESC-Exosomes inactivated SMADs signaling by inhibiting TGFßRII expression, consequently attenuating stellate cell activation and suppressing liver fibrosis. CONCLUSIONS: Our results showed that miR-6766-3p in the 3D-hESC-Exosomes inactivates smads signaling by restraining TGFßRII expression, attenuated LX2 cell activation and suppressed liver fibrosis, suggesting that 3D-hESC-Exosome enriched-miR-6766-3p is a novel anti-fibrotic therapeutics for treating chronic liver disease. These results also proposed a significant strategy that 3D-Exo could be used as natural nanoparticles to rescue liver injury via delivering antifibrotic miR-6766-3p.

The combination of dextran sulphate and polyvinyl alcohol prevents excess aggregation and promotes proliferation of pluripotent stem cells in suspension culture.

OBJECTIVES: For clinical applications of cell-based therapies, a large quantity of human pluripotent stem cells (hPSCs) produced in standardized and scalable culture processes is required. Currently, microcarrier-free suspension culture shows potential for large-scale expansion of hPSCs; however, hPSCs tend to aggregate during culturing leading to a negative effect on cell yield. To overcome this problem, we developed a novel protocol to effectively control the sizes of cell aggregates and enhance the cell proliferation during the expansion of hPSCs in suspension. MATERIALS AND METHODS: hPSCs were expanded in suspension culture supplemented with polyvinyl alcohol (PVA) and dextran sulphate (DS), and 3D suspension culture of hPSCs formed cell aggregates under static or dynamic conditions. The sizes of cell aggregates and the cell proliferation as well as the pluripotency of hPSCs after expansion were assessed using cell counting, size analysis, real-time quantitative polymerase chain reaction, flow cytometry analysis, immunofluorescence staining, embryoid body formation, teratoma formation and transcriptome sequencing. RESULTS: Our results demonstrated that the addition of DS alone effectively prevented hPSC aggregation, while the addition of PVA significantly enhanced hPSC proliferation. The combination of PVA and DS not only promoted cell proliferation of hPSCs but also produced uniform and size-controlled cell aggregates. Moreover, hPSCs treated with PVA, or DS or a combination, maintained the pluripotency and were capable of differentiating into all three germ layers. mRNA-seq analysis demonstrated that the combination of PVA and DS significantly promoted hPSC proliferation and prevented cell aggregation through improving energy metabolism-related processes, regulating cell growth, cell proliferation and cell division, as well as reducing the adhesion among hPSC aggregates by affecting expression of genes related to cell adhesion. CONCLUSIONS: Our results represent a significant step towards developing a simple and robust approach for the expansion of hPSCs in large scale.