The Parkinson's disease-associated protein α-synuclein inhibits hepatoma by exosome delivery.

Numerous epidemiological studies suggest a link between Parkinson's disease (PD) and cancer. However, their relevant pathogenesis is not clear. In the present study, we investigated the potential role of exosome-delivered α-synuclein (α-syn) in the regulation between PD and liver cancer. We cultured hepatocellular carcinoma (HCC) cells with exosomes derived from conditioned medium of the PD cellular model, and injected exosomes enriched with α-syn into the striatum of a liver cancer rat model. We found that α-syn-contained exosomes from the rotenone-induced cellular model of PD suppressed the growth, migration, and invasion of HCC cells. Integrin αVß5 in exosomes from the rotenone-induced PD model was higher than that in the control, resulting in more α-syn-contained exosomes being taken up by HCC cells. Consistently, in vivo experiments with rat models also confirmed exosome-delivered α-syn inhibited liver cancer. These findings illustrate the important role of PD-associated protein α-syn inhibiting hepatoma by exosome delivery, suggesting a new mechanism underlying the link between these two diseases and therapeutics of liver cancer.

Improving the repopulation capacity of elderly human hepatocytes by decoding aging-associated hepatocyte plasticity.

BACKGROUND AND AIMS: The loss of liver regenerative capacity is the most dramatic age-associated alteration. Because of an incomplete mechanistic understanding of the liver aging process, a successful therapeutic strategy to improve liver regeneration in the elderly has not been developed so far. Hepatocyte plasticity is a principal mechanism for producing new hepatocytes and cholangiocytes during regeneration. This study aims to promote the repopulation capacity of elderly hepatocytes by decoding the underlying mechanism about the regulation of aging on human hepatocyte plasticity. APPROACH AND RESULTS: To understand the age-related mechanisms, we established a hepatocyte aging model from human-induced pluripotent stem cells and developed a method for ex vivo characterization of hepatocyte plasticity. We found that hepatocyte plasticity was gradually diminished with aging, and the impaired plasticity was caused by age-induced histone hypoacetylation. Notably, selective inhibition of histone deacetylases could markedly restore aging-impaired plasticity. Based on these findings, we successfully improved the plasticity of elderly primary human hepatocytes that enhanced their repopulation capacity in the liver injury model. CONCLUSIONS: This study suggests that age-induced histone hypoacetylation impairs hepatocyte plasticity, and hepatocyte plasticity might be a therapeutic target for promoting the regenerative capacity of the elderly liver.

Upregulation of Parkinson's disease-associated protein alpha-synuclein suppresses tumorigenesis via interaction with mGluR5 and gamma-synuclein in liver cancer.

Numerous epidemiological studies suggest a link between Parkinson's disease (PD) and cancer, indicating that PD-associated proteins may mediate the development of cancer. Here, we investigated a potential role of PD-associated protein α-synuclein in regulating liver cancer progression in vivo and in vitro. We found the negative correlation of α-synuclein with metabotropic glutamate receptor 5 (mGluR5) and γ-synuclein by analyzing the data from The Cancer Genome Atlas database, liver cancer patients and hepatoma cells with overexpressed α-synuclein. Moreover, upregulated α-synuclein suppressed the growth, migration, and invasion. α-synuclein was found to associate with mGluR5 and γ-synuclein, and the truncated N-terminal of α-synuclein was essential for the interaction. Furthermore, overexpressed α-synuclein exerted the inhibitory effect on hepatoma cells through the degradation of mGluR5 and γ-synuclein via α-synuclein-dependent autophagy-lysosomal pathway (ALP). Consistently, in vivo experiments with rotenone-induced rat model of PD also confirmed that, upregulated α-synuclein in liver cancer tissues through targeting on mGluR5/α-synuclein/γ-synuclein complex inhibited tumorigenesis involving in ALP-dependent degradation of mGluR5 and γ-synuclein. These findings give an insight into an important role of PD-associated protein α-synuclein accompanied by the complex of mGluR5/α-synuclein/γ-synuclein in distant communications between PD and liver cancer, and provide a new strategy in therapeutics for the treatment of liver cancer.

A Composite Flexible Sensor for Direct Ventricular Assist Device.

A direct ventricular assist device is one of the effective means to treat patients with heart failure; the key point of the problem is the flexible sensor that can measure the drive pressure and shape variable of the heart auxiliary device. This study was based on the high-voltage electric field guidance process and the porous foaming process, and designed an implantable resistance/capacitive composite flexible sensor that can effectively detect the pressure and deformation signal caused by fine surface contact and pneumatic muscle expansion. Experiments showed the performance of composite sensors with special structure design was greatly improved compared with the control group-the strain measurement sensitivity was 22, pressure measurement sensitivity was up to 0.19 Kpa-1. Stable strain measurements were made up to 35 times and pressure measurements over 100 times. In addition, we solved the interference problem of resistance/capacitance flexible sensors through an optimized common substrate process. Finally, we tested a pneumatic muscle direct ventricular assist device with a composite flexible sensor on a model heart; the experiment showed that this resistance/capacitive composite flexible sensor can effectively detect surface contact with pneumatic muscle and the displacement signals.

[Active ingredients and in vitro anti-inflammatory effects of Polygoni Cuspidati Rhizoma et Radix decoction pieces by integrated processing and traditional processing: a comparative analysis].

The present study explored the differences in active ingredients and in vitro anti-inflammatory effects of the decoction pieces by integrated processing(IPDP) and traditional processing(TPDP) of Polygoni Cuspidati Rhizoma et Radix(PCRER).The content of polydatin, resveratrol, emodin-8-O-ß-D-glucoside, emodin, and physcion in IPDP and TPDP was determined by high-performance liquid chromatography(HPLC).The inflammation model was induced by lipopolysaccharide(LPS) in RAW264.7 cells.The mRNA levels of inflammatory cytokines tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1ß(IL-1ß) in 60% ethanol extracts of IPDP and TPDP of different concentrations(5 and 10 µg·mL~(-1)) were determined by PCR.The results showed that the content of polydatin and emodin-8-O-ß-D-glucoside in IPDP was significantly higher than that in TPDP, while the content of resveratrol, emodin, and physcion was higher in TPDP.The anti-inflammatory results showed that ethanol extracts of IPDP of different concentrations(5 and 10 µg·mL~(-1)) significantly inhibited the increase in the mRNA levels of IL-1ß and TNF-α induced by LPS, whereas TPDP only had a significant inhibitory effect on IL-1ß.This study preliminarily showed that the total content of five active ingredients in IPDP was higher than that in TPDP, and IPDP was superior to TPDP in anti-inflammatory activity in vitro, which provided an experimental basis for the production and application of IPDP.

[Identification, biological characteristics, and screening of effective fungicides of Phoma rhei causing leaf spot on Polygonum cuspidatum].

Severe leaf spot on Polygonum cuspidatum was found in the planting base of P. cuspidatum in Fangxian county, Shiyan of Hubei province. To clarify the types of pathogens and their pathogenesis, the present study isolated and purified the pathogen of leaf spot disease of P. cuspidatum according to Koch's postulates, determined the pathogenicity of the pathogen, and investigated its biological characteristics. Meanwhile, the inhibitory effects of 11 types of fungicides on the bacteria were determined according to the mycelium growth rate, and suitable prevention and control drugs were selected. The results showed that the pathogen isolated from the diseased leaves of P. cuspidatum was Phoma rhei by morphological and molecular identification. The colony morphology and microscopic characteristics were the same as those of Ph. rhei. The homology of rDNA-ITS and TEF gene sequences with Ph. rhei reached 99.96% and 99.43%, respectively. The optimal growth temperature of Ph. rhei was 25 ℃, and the optimal pH was 7-10. Furthermore, Ph. rhei grew faster under dark or light conditions. In fungicides, 0.3% eugenol, 250 g·L~(-1) propiconazole, and 33.5% quinoline copper had significant inhibitory effects on the pathogen with EC_(50) values of 57.54, 59.58, 88.69 µg·mL~(-1), respectively. Eugenol is a botanical fungicide, which can be used as a green and environmentally friendly fungicide in the prevention and control of P. cuspidatum. This study reported for the first time that the pathogen of P. cuspidatum leaf spot was Ph. rhei. investigated the biological characteristics of the pathogen, and screened the indoor chemicals, which provided a theoretical basis for the prevention and control of P. cuspidatum leaf spot in production.

Human Pluripotent Stem Cell-Derived Hepatocyte-Like Cells and Organoids for Liver Disease and Therapy.

Liver disease is a global health issue that has caused an economic burden worldwide. Organ transplantation is the only effective therapy for end-stage liver disease; however, it has been hampered by a shortage of donors. Human pluripotent stem cells (hPSCs) have been widely used for studying liver biology and pathology as well as facilitating the development of alternative therapies. hPSCs can differentiate into multiple types of cells, which enables the generation of various models that can be applied to investigate and recapitulate a range of biological activities in vitro. Here, we summarize the recent development of hPSC-derived hepatocytes and their applications in disease modeling, cell therapy, and drug discovery. We also discuss the advantages and limitations of these applications and critical challenges for further development.

Generation of a hypoxia-sensing mouse model.

Oxygen (O2 ) homeostasis is essential to the metazoan life. O2 -sensing or hypoxia-regulated molecular pathways are intimately involved in a wide range of critical cellular functions and cell survival from embryogenesis to adulthood. In this report, we have designed an innovative hypoxia sensor (O2 CreER) based on the O2 -dependent degradation domain of the hypoxia-inducible factor-1α and Cre recombinase. We have further generated a hypoxia-sensing mouse model, R26-O2 CreER, by targeted insertion of the O2 CreER-coding cassette in the ROSA26 locus. Using the ROSAmTmG mouse strain as a reporter, we have found that this novel hypoxia-sensing mouse model can specifically identify hypoxic cells under the pathological condition of hind-limb ischemia in adult mice. This model can also label embryonic cells including vibrissal follicle cells in E13.5-E15.5 embryos. This novel mouse model offers a valuable genetic tool for the study of hypoxia and O2 sensing in mammalian systems under both physiological and pathological conditions.

[Chemical constituents and their biosynthesis mechanisms of Polygonum cuspidatum].

This article reviews the research progress of the chemical constituents and biosynthesis mechanisms of Polygonum cuspidatum. The chemistry components isolated from P. cuspidatum are mainly anthraquinones, naphthoquinones, stilbenes, flavonoids, and other compounds. The synthase genes involved in the biosynthesis process were summarized. The biosynthesis mechanism of stilbenes and anthraquinones was discussed. This article hopefully to provide a reference for further research, development and utilization of P. cuspidatum.

The Parallelogram Effect of Degenerative Structures Around the Apical Vertebra in Patients with Adult Degenerative Scoliosis: The Influence of Asymmetric Degeneration and Diagonal Degeneration on the Severity of Deformity.

BACKGROUND This is the first published study assessing the parallelogram effect of degenerative structures around the apical vertebra. We evaluated the effect of degenerative structures around the apical vertebra and spinopelvic parameters on the severity of ADS. MATERIAL AND METHODS We retrospectively reviewed data on 144 patients with ADS. The coronal (coronal Cobb angle, CA) and sagittal (thoracic kyphosis, TK; sagittal vertical axis, SVA; pelvic incidence, PI; lumbar lordosis, LL; sacral slope, SS; pelvic tilt, PT) parameters, lumbar multifidus muscle atrophy (LMA), and facet joint osteoarthritis (FJOA) were evaluated. Multiple linear regression was used to assess the correlations. RESULTS LL and PT were negatively correlated with CA (P<0.001), and the correlation between LL and SVA was positive (P<0.001), as was the correlation between PI and CA (P<0.001). The correlation between SS and SVA was negative (P<0.001). The correlation between CA and concave LMA at upper or lower intervertebral level of the apical vertebra was positive (P≤0.001). The convex LMA at upper and lower intervertebral levels was negatively correlated with CA (P<0.001). Convex LMA at the upper intervertebral level and concave LMA at the lower intervertebral level of the apical vertebra were negatively correlated with the SVA (P≤0.001). FJOA works similar to LMA (P<0.05). CONCLUSIONS Spinopelvic parameters are correlated with severity of ADS. The structures around the apical vertebra are very important to maintain global alignment of the spine via the parallelogram effect.

The hypoxic tumor microenvironment in vivo selects the cancer stem cell fate of breast cancer cells.

BACKGROUND: Tumor hypoxia is an independent prognostic factor associated with poor patient survival. Emerging evidence suggests that hypoxia can potentially maintain or enhance the stem cell phenotype of both normal stem cells and cancer cells. However, it remains to be determined whether cell fate is regulated in vivo by the hypoxic tumor microenvironment (TME). METHODS: We established a hypoxia-sensing xenograft model to identify hypoxic tumor cell in vivo primarily using human breast cancer cell lines MDA-MB-231 and MCF7. Hypoxic tumor cells were identified in situ by fluorescence of green fluorescence protein. They were further isolated from xenografts, purified and sorted by flow cytometry for detailed analysis of their stem cell characteristics. RESULTS: We have found that hypoxic tumor cells freshly isolated from xenografts contain increased subpopulations of tumor cells with cancer stem cell (CSC)-like characteristics. The CSC characteristics of the hypoxic tumor cells are further enhanced upon re-implantation in vivo, whereas secondary xenografts derived from the non-hypoxic tumor cells remain similar to the primary xenografts. Interestingly, the phenotypes exhibited by the hypoxic tumor cells are stable and remain distinctively different from those of the non-hypoxic tumor cells isolated from the same tumor mass even when they are maintained under the same ambient culture conditions. Mechanistically, the PI3K/AKT pathway is strongly potentiated in the hypoxic tumor cells and is required to maintain the CSC-like phenotype. Importantly, the differential cell fates between hypoxic and non-hypoxic tumor cells are only found in tumor cells isolated from the hypoxic TME in vivo and are not seen in tumor cells treated by hypoxia in vitro alone. CONCLUSIONS: These previously unknown observations suggest that the hypoxic TME may promote malignant progression and therapy resistance by coordinating induction, selection and/or preferential maintenance of the CSC-like phenotype in tumor cells.

Role of GPR30 in estrogen-induced prostate epithelial apoptosis and benign prostatic hyperplasia.

Several studies have implicated estrogen and the estrogen receptor (ER) in the pathogenesis of benign prostatic hyperplasia (BPH); however, the mechanism underlying this effect remains elusive. In the present study, we demonstrated that estrogen (17ß-estradiol, or E2)-induced activation of the G protein-coupled receptor 30 (GPR30) triggered Ca2+ release from the endoplasmic reticulum, increased the mitochondrial Ca2+ concentration, and thus induced prostate epithelial cell (PEC) apoptosis. Both E2 and the GPR30-specific agonist G1 induced a transient intracellular Ca2+ release in PECs via the phospholipase C (PLC)-inositol 1, 4, 5-triphosphate (IP3) pathway, and this was abolished by treatment with the GPR30 antagonist G15. The release of cytochrome c and activation of caspase-3 in response to GPR30 activation were observed. Data generated from the analysis of animal models and human clinical samples indicate that treatment with the GPR30 agonist relieves testosterone propionate (TP)-induced prostatic epithelial hyperplasia, and that the abundance of GPR30 is negatively associated with prostate volume. On the basis of these results, we propose a novel regulatory mechanism whereby estrogen induces the apoptosis of PECs via GPR30 activation. Inhibition of this activation is predicted to lead to abnormal PEC accumulation, and to thereby contribute to BPH pathogenesis.

[Analysis of Influence on Single Eythrocyte Injury Caused by Oscillating Boundary Flow Field].

The implantable axial blood pump, driven by external electromagnet, is studied recently. It oscillats when it is running because of the elastic implanted environment and driving force disequilibrium, etc. In this paper, a model of single erythrocyte in vibrated flow field was built to simulate the deformation and force of the erythrocyte. By using the mechanical injury principle of blood in blood pump, we studied the injury of a single erythrocyte resulted from oscillating boundary flow field. The research results indicated that the shape of the erythrocyte, force and velocity field nearby, which are affected by oscillating boundary flow field, all cause injury to the erythrocyte. All the researches shown in the present paper are expected to provide theoretical foundation for lightening hemolysis by the blood pump.

Prevalence and characterization of hepatitis B and C virus infections in a needle-sharing population in Northern China.

BACKGROUND: The epidemiologies of hepatitis C virus (HCV) and hepatitis B virus (HBV) infections in specific populations in certain areas of China are poorly understood. A pilot survey of HCV/HBV infections was carried out in villages in Kuancheng County, Heben Province, where injection of sodium benzoate or amphetamines using shared needles has been a common practice. The aims of this study were to analyze the endemicity and characterize HCV/HBV infections in this population. METHODS: Data on demographic characteristics and drug abuse were collected from individuals who signed informed consent forms. Serum HCV antibody (anti-HCV), hepatitis B surface antigen (HBsAg), and hepatitis B core antibody (anti-HBc) were measured in all participants. HCV RNA was measured in samples positive for anti-HCV using real-time polymerase chain reaction. RESULTS: Among 852 participants from 11 villages, 49.9% had used sodium benzoate or amphetamine at least once, by intravenous injection. The overall prevalence of anti-HCV, HCV RNA, anti-HBc, HBsAg, and HCV/HBV co-infection was 37.1%, 26.6%, 67.7%, 10.7%, and 30.0%, respectively. Two-hundred-twenty-three of 227 (98.2%) participants positive for HCV RNA were aged >40 years. Co-infection was related to sex, age, number of injections, and time from first injection. The rate of spontaneous HCV RNA clearance was 28.2% (89/316), and was related to the number of injections, time from first injection, and HBsAg positivity. However, HBsAg was related to the anti-HBc signal/cut-off ratio rather than to the above parameters. Trend tests demonstrated that the prevalence of anti-HCV, HCV RNA, and anti-HBc was related to the number of injections (P < 0.001), while HBsAg prevalence was not (P = 0.347). CONCLUSIONS: The prevalence of HCV and HBV infection is likely to be high among individuals older than 40 years in areas of needle sharing, and one-time screening for HCV infection should be offered to these populations.

[Efficacy of pegylated-interferon alpha-2a treatment in patients with HBeAg-positive chronic hepatitis B and partial viral response to nucleoside analogue therapy].

OBJECTIVE: To investigate the efficacy and related factors of pegylated-interferon alpha-2a (PEG-IFN-2a) treatment in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) who achieved partial viral response with nucleoside analogue (NA) therapy. METHODS: Patients with HBeAg-positive CHB and partial viral response to NA treatment were administered a PEG-IFN-2a therapy regimen of 180 g subcutaneous injection once weekly for a personlized duration of time. The existing NA therapy was continued in combination with the new PEG-IFN-2a treatment for 12 weeks. Measurements of serum HBV DNA load, hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), HBeAg and hepatitis B e antibody (anti-HBe) were taken at baseline (prior to addition of the PEG-IFN-2a therapy) and every 3 months afterwards.For determining response to treatment, primary efficacy was defined as undetectable HBsAg and seroconversion, and secondary efficacy was defined as HBsAg less than 10 IU/mL and HBeAg seroconversion.Statistical analysis was carried out using SPSS statistical software. RESULTS: A total of 81 consecutive patients with an average of 12.0 months (range: 6.0-24.0 months) of NA therapy were included in the study and received an average of 19.6 months (range: 15.5-33.3 months) of PEG-IFN-2a treatment. At the end of PEG-IFN-2a therapy, 7 (8.6%) of the patients achieved undetectable HBsAg and seroconversion, and 14 (17.3%) showed HBsAg less than 10IU/mL. In addition, 40.7% achieved undetectable HBeAg and seroconversion, a rate that was slightly higher than that (38.3%) seen in treatment-naive patients who received PEG-IFN-2a. Statistical analyses suggest that baseline level of HBsAg at less than 1500 IU/mL may predict end of PEG-IFN-2a treatment response for HBsAg less than 10 IU/mL, as evidenced by the area under the curve measure of 0.747, sensitivity measure of 87.3%, specificity measure of 33.3%, positive predictive value of 82.1% and negative predictive value of 42.8%. CONCLUSION: Patients with HBeAg-positive CHB and partial viral response to NA therapy can achieve undetectable HBsAg and HBeAg seroconversion after switching to PEG-IFN-2a treatment. Baseline HBsAg level may be predictive of response to this therapeutic strategy.

Hypoxia and regulation of cancer cell stemness.

Spontaneous tumors often contain heterogeneous populations of tumor cells with different tumor-initiating potentials or cancer cell "stemness." Clonal heterogeneity can be traced to specific locations inside a tumor where clones with different metastatic capabilities are identified, suggesting that the tumor microenvironment can exert a significant effect on the evolution of different clonal populations. Hypoxia is a common feature of tumor microenvironments and has the potential to facilitate malignant progression. This chapter provides a synopsis of hypoxia-regulated pathways implicated in the maintenance of cancer stem cells.

Influence of rotor impeller structure on performance improvement of suspended axial flow blood pumps.

BACKGROUND: The hydrodynamic suspension structure design of the axial blood pump impeller can avoid the problems associated with using mechanical bearings. However, the particular impeller structure will impact the hydraulic performance and hemolysis of the blood pump. METHOD: This article combines computational fluid dynamics (CFD) with the Lagrange particle tracking method, aiming to improve the blood pump's hydraulic and hemolysis performance. It analyzes the flow characteristics and hemolysis performance inside the pump. It optimizes the taper of the impeller hub, the number of blades, and the inclination angle of the circumferential groove at the top of the blade. RESULTS: Under certain rotational speed conditions, an increase in the taper of the impeller hub or the number of blades can increase the pumping pressure of a blood pump, but an increase in the number of blades will reduce the flow rate. The design of circumferential grooves at the top of the blade can increase the pumping pressure to a certain extent, with little impact on the hemolysis performance. The impeller structure is optimized based on the estimated hemolysis of each impeller model blood pump. It could be seen that when the pump blood pressure and flow rate were reached, the optimized impeller speed was reduced by 11.4%, and the estimated hemolysis value was reduced by 10.5%. CONCLUSION: In this paper, the rotor impeller structure of the blood pump was optimized to improve the hydraulic and hemolytic performance effectively, which can provide a reference for the related research of the axial flow blood pump using hydraulic suspension.

Developing Humanized Animal Models with Transplantable Human iPSC-Derived Cells.

Establishing reliable and reproducible animal models for disease modelling, drug screening and the understanding of disease susceptibility and pathogenesis is critical. However, traditional animal models differ significantly from humans in terms of physiology, immune response, and pathogenesis. As a result, it is difficult to translate laboratory findings into biomedical applications. Although several animal models with human chimeric genes, organs or systems have been developed in the past, their limited engraftment rate and physiological functions are a major obstacle to realize convincing models of humans. The lack of human transplantation resources and insufficient immune tolerance of recipient animals are the main challenges that need to be overcome to generate fully humanized animals. Recent advances in gene editing and pluripotent stem cell-based xenotransplantation technologies offer opportunities to create more accessible human-like models for biomedical research. In this article, we have combined our laboratory expertise to summarize humanized animal models, with a focus on hematopoietic/immune system and liver. We discuss their generation strategies and the potential donor cell sources, with particular attention given to human pluripotent stem cells. In particular, we discuss the advantages, limitations and emerging trends in their clinical and pharmaceutical applications. By providing insights into the current state of humanized animal models and their potential for biomedical applications, this article aims to advance the development of more accurate and reliable animal models for disease modeling and drug screening.

Human iPSC-liver organoid transplantation reduces fibrosis through immunomodulation.

Donor organ shortages for transplantation remain a serious global concern, and alternative treatment is in high demand. Fetal cells and tissues have considerable therapeutic potential as, for example, organoid technology that uses human induced pluripotent stem cells (hiPSCs) to generate unlimited human fetal-like cells and tissues. We previously reported the in vivo vascularization of early fetal liver-like hiPSC-derived liver buds (LBs) and subsquent improved survival of recipient mice with subacute liver failure. Here, we show hiPSC-liver organoids (LOs) that recapitulate midgestational fetal liver promote de novo liver generation when grafted onto the surface of host livers in chemical fibrosis models, thereby recovering liver function. We found that fetal liver, a hematopoietic tissue, highly expressed macrophage-recruiting factors and antifibrotic M2 macrophage polarization factors compared with the adult liver, resulting in fibrosis reduction because of CD163+ M2-macrophage polarization. Next, we created midgestational fetal liver-like hiPSC-LOs by fusion of hiPSC-LBs to induce static cell-cell interactions and found that these contained complex structures such as hepatocytes, vasculature, and bile ducts after transplantation. This fusion allowed the generation of a large human tissue suitable for transplantation into immunodeficient rodent models of liver fibrosis. hiPSC-LOs showed superior liver function compared with hiPSC-LBs and improved survival and liver function upon transplantation. In addition, hiPSC-LO transplantation ameliorated chemically induced liver fibrosis, a symptom of liver cirrhosis that leads to organ dysfunction, through immunomodulatory effects, particularly on CD163+ phagocytic M2-macrophage polarization. Together, our results suggest hiPSC-LO transplantation as a promising therapeutic option for liver fibrosis.

Low pressure reversibly driving colossal barocaloric effect in two-dimensional vdW alkylammonium halides.

Plastic crystals as barocaloric materials exhibit the large entropy change rivalling freon, however, the limited pressure-sensitivity and large hysteresis of phase transition hinder the colossal barocaloric effect accomplished reversibly at low pressure. Here we report reversible colossal barocaloric effect at low pressure in two-dimensional van-der-Waals alkylammonium halides. Via introducing long carbon chains in ammonium halide plastic crystals, two-dimensional structure forms in (CH3-(CH2)n-1)2NH2X (X: halogen element) with weak interlayer van-der-Waals force, which dictates interlayer expansion as large as 13% and consequently volume change as much as 12% during phase transition. Such anisotropic expansion provides sufficient space for carbon chains to undergo dramatic conformation disordering, which induces colossal entropy change with large pressure-sensitivity and small hysteresis. The record reversible colossal barocaloric effect with entropy change ΔSr ~ 400 J kg-1 K-1 at 0.08 GPa and adiabatic temperature change ΔTr ~ 11 K at 0.1 GPa highlights the design of novel barocaloric materials by engineering the dimensionality of plastic crystals.