Publications by authors named "Xiaomeng Hu"

41 Publications

Impact of different enzymes on biofilm formation and mussel settlement.

Sci Rep 2022 03 18;12(1):4685. Epub 2022 Mar 18.

International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, China.

Enzymes have been known to impact the biofilm forming capacity. However, how the enzymes mediate the biofilm formation and macrofouling remains little known. Here, we investigated the effects of the three kinds of proteases, four kinds of glycosidases and one kind of lipase on the detachment of biofilms of Shewanella marisflavi ECSMB14101, identified biofilm total proteins response to enzyme treatments, and then tested the effects of biofilms treated with enzymes on the settlement of the mussel Mytilus coruscus plantigrades. The results showed that the cell density of bacteria in biofilms formed at different initial bacterial density were noticeably reduced after treating with all tested enzymes, and Neutrase and α-Amylase exhibited best removing efficiency of > 90%. Bacterial total proteins in S. marisflavi biofilm noticeably reduced or disappeared after treated by Alcalase. For the settlements of the mussel M. coruscus plantigrades, inducing capacities of S. marisflavi biofilm were noticeably suppressed and downregulation was > 75% at the initial density of 5 × 10 cells/cm. Thus, the tested enzymes could effectively remove the adhered bacterial cell, inhibit the biofilm formation and finally suppress the mussel settlement. Our findings extend novel knowledge to developing eco-friendly approach to control micro- and macro-fouling.
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http://dx.doi.org/10.1038/s41598-022-08530-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8933495PMC
March 2022

Dialectical Thinking Is Linked With Smaller Left Nucleus Accumbens and Right Amygdala.

Front Psychol 2022 10;13:760489. Epub 2022 Feb 10.

Department of Psychology, Renmin University of China, Beijing, China.

Our current work examined the interface between thinking style and emotional experience at both the behavioral and neuropsychological levels. Thirty-nine Chinese participants completed the triad task, and we calculated the rate of individually selected relationship pairings to overall selections to represent their holistic thinking tendencies. In addition, participants in the top one-third of the ratio score were classified into the high holistic thinking group, while those in the bottom one-third of the ratio score were classified into the low holistic thinking group. We used the sensitivity to punishment and sensitivity to reward questionnaire (SPSRQ) to examine how people elicit positive and negative affective behaviors. Additionally, we examined the volume of the amygdala and nucleus accumbens and their functional connectivity in the resting-state. We found that high holistic thinkers were much less sensitive to rewards than low holistic thinkers. In other words, individuals with high holistic thinking are less likely to pursue behaviors that have positive emotional outcomes. Furthermore, their bilateral nucleus accumbens and right amygdala volumes were smaller than those of low holistic thinkers. Hierarchical regression analysis showed that holistic thinking tendency can negatively predict the volume of the left nucleus accumbens and right amygdala. Finally, resting-state functional connectivity results showed increased functional connectivity FC between left nucleus accumbens and bilateral amygdala in high holistic thinkers. These findings provide emotion-related manifestations of thinking styles at the behavioral and neural levels.
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http://dx.doi.org/10.3389/fpsyg.2022.760489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866571PMC
February 2022

Autonomic behavioral impairment induced by simazine exposure during early life of male mouse is mediated by Lmx1a/Wnt1 pathway.

Environ Toxicol 2022 Apr 22;37(4):776-788. Epub 2021 Dec 22.

Department of Hygienic Toxicology, College of Public Health, Harbin Medical University, Harbin, China.

Simazine is a widely used herbicide and known as an environmental estrogen. Multiple studies have proved simazine can induced the degeneration of dopaminergic neuron resulting in a degenerative disease-like syndrome. Herein, we explored the neurotoxicity of simazine on the dopaminergic nervous system of embryos and weaned offspring during the maternal gestation period or the maternal gestation and lactation periods. We found that simazine disturbed the crucial components expression involved in Lmx1a/Wnt1 pathway of dopaminergic neuron in embryonic and weaned offspring. Furthermore, morphological and behavioral tests performed on weaned male offspring treated by simazine suggested that the grip strength, autonomic exploring, and the space sense ability were weakened, as well as the pathological damage of dopaminergic neuron was clearly observed. But, the same neurotoxicity of simazine is less significantly observed in female offspring. Our findings will provide reliable reference for the determination of environmental limits and new insight into the pathogenesis of nonfamilial neurodegenerative diseases related to environmental risk factors.
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http://dx.doi.org/10.1002/tox.23442DOI Listing
April 2022

Bioconversion of Food Waste to produce Industrial-scale Sophorolipid Syrup and Crystals: dynamic Life Cycle Assessment (dLCA) of Emerging Biotechnologies.

Bioresour Technol 2021 Oct 27;337:125474. Epub 2021 Jun 27.

School of Energy and Environment, City University of Hong Kong, Kowloon, Hong Kong. Electronic address:

Bioconversion of food waste into sophorolipid-based biosurfactants is a promising emerging technology. It is important to evaluate the environmental impacts associated with the latest advancements in sophorolipid production as it matures to maximize sustainability on scale-up. This study takes a dynamic Life Cycle Assessment (dLCA) approach to address the inherent uncertainties and evaluate the environmental performances. It demonstrates the dLCA framework by conducting the new traversal of food waste-derived industrial-scale sophorolipid production, with the combination of Techno-Economic Analysis (TEA). A systematic investigation of the environmental-economic implications of the two pathways to produce SL crystals and syrup. The global warming potential (GWP) for 1 kg of SL crystals and syrup was 7.9 kg CO eq. and 5.7 kg CO eq., respectively. The Ashby-like charts based on the LCA and TEA results at the pilot plant highlighted the trade-offs between systemic environmental costs and economic benefits for design decisions.
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http://dx.doi.org/10.1016/j.biortech.2021.125474DOI Listing
October 2021

Hypoimmune induced pluripotent stem cell-derived cell therapeutics treat cardiovascular and pulmonary diseases in immunocompetent allogeneic mice.

Proc Natl Acad Sci U S A 2021 07;118(28)

Division of Cardiothoracic Surgery, Department of Surgery, Transplant and Stem Cell Immunobiology Laboratory, University of California, San Francisco, CA 94143;

The emerging field of regenerative cell therapy is still limited by the few cell types that can reliably be differentiated from pluripotent stem cells and by the immune hurdle of commercially scalable allogeneic cell therapeutics. Here, we show that gene-edited, immune-evasive cell grafts can survive and successfully treat diseases in immunocompetent, fully allogeneic recipients. Transplanted endothelial cells improved perfusion and increased the likelihood of limb preservation in mice with critical limb ischemia. Endothelial cell grafts transduced to express a transgene for alpha1-antitrypsin (A1AT) successfully restored physiologic A1AT serum levels in mice with genetic A1AT deficiency. This cell therapy prevented both structural and functional changes of emphysematous lung disease. A mixture of endothelial cells and cardiomyocytes was injected into infarcted mouse hearts, and both cell types orthotopically engrafted in the ischemic areas. Cell therapy led to an improvement in invasive hemodynamic heart failure parameters. Our study supports the development of hypoimmune, universal regenerative cell therapeutics for cost-effective treatments of major diseases.
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http://dx.doi.org/10.1073/pnas.2022091118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285900PMC
July 2021

Do Experiences Studying Abroad Promote Dialectical Thinking? Empirical Evidence From Chinese International Students.

Front Psychol 2021 28;12:595935. Epub 2021 May 28.

Department of Psychology, Tsinghua University, Beijing, China.

Our current work seeks to provide direct empirical evidence on whether Chinese international students' experiences studying abroad promote dialectical thinking. We collected behavioral data from 258 Chinese international students studying in multiple regions. We found that there was a main effect among the four conditions (i.e., studying abroad, exposure to foreign culture, hometown, and typical day). More specifically, when primed with studying abroad or typical day (relative to hometown culture), participants were more likely to show tolerance for contradiction by deeming both sides of contradictory scientific statements as convincing and rating them more favorably. Therefore, it is plausible that Chinese international students' experiences studying abroad promote their dialectical thinking. More work is needed to further this line of research by (1) extending these effects with other measures of dialectical thinking such as perception of interconnectedness and prediction of change, (2) adopting differing paradigms to provide more robust findings, and (3) probing the underlying processes as to why experiences studying abroad promote dialectical thinking.
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http://dx.doi.org/10.3389/fpsyg.2021.595935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195590PMC
May 2021

PNO1 regulates autophagy and apoptosis of hepatocellular carcinoma via the MAPK signaling pathway.

Cell Death Dis 2021 05 28;12(6):552. Epub 2021 May 28.

Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, 300060, Tianjin, China.

Some studies have reported that activated ribosomes are positively associated with malignant tumors, especially in hepatocellular carcinoma (HCC). The RNA-binding protein PNO1 is a critical ribosome rarely reported in human tumors. This study aimed to explore the molecular mechanisms of PNO1 in HCC. Using 150 formalin-fixed and paraffin-embedded samples and 8 fresh samples, we found high PNO1 expression in HCC tumor tissues through Western blotting and RT-PCR. Moreover, the higher PNO1 expression was associated with poor HCC prognosis patients. In vitro and in vivo experiments indicated that PNO1 overexpression promoted the proliferation and depressed the apoptosis of HCC cells. High PNO1 expression also increased the autophagy of HCC cells. The molecular mechanisms underlying PNO1 were examined by RNA-seq analysis and a series of functional experiments. Results showed that PNO1 promoted HCC progression through the MAPK signaling pathway. Therefore, PNO1 was overexpressed in HCC, promoted autophagy, and inhibited the apoptosis of HCC cells through the MAPK signaling pathway.
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http://dx.doi.org/10.1038/s41419-021-03837-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163843PMC
May 2021

Interim Effectiveness and Safety Comparison of Bedaquiline-Containing Regimens for Treatment of Diabetic Versus Non-Diabetic MDR/XDR-TB Patients in China: A Multicenter Retrospective Cohort Study.

Infect Dis Ther 2021 Mar 30;10(1):457-470. Epub 2021 Jan 30.

Clinical Center on TB, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, China.

Introduction: Diabetes mellitus (DM), a common tuberculosis (TB) comorbidity, is associated with delayed bacillary clearance during anti-TB treatment and unfavorable outcomes. Bedaquiline (BDQ), when used as part of multidrug regimen for multidrug-resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB), has been shown to be effective and safe although treatment outcome and risks for patients with MDR/XDR-TB and DM are unknown. A multicenter retrospective study was conducted to compared the safety and effectiveness of 24-week BDQ-containing anti-TB treatment for patients with MDR/XDR-TB with and without DM.

Methods: The study of patients with MDR/XDR-TB with or without DM (enrolled February 2018-September 2019, 21 Chinese hospitals) was supervised by the New Drug Introduction and Protection Program (NDIP). Of 640 patients with MDR/XDR-TB receiving BDQ-containing anti-TB treatments, two propensity score-matched groups (107 DM/107 non-DM) were compared for cumulative culture conversion rate, time to culture conversion, adverse events, and corrected QT interval.

Results: Body mass index was higher in patients with DM than patients without DM (23.29 ± 3.9 vs. 20.5 ± 3.6, P < 0.001); lung cavity prevalence (86.9% vs. 72.9%, P = 0.037) was also higher in patients with DM; the non-DM group had higher hepatitis prevalence (29.0% vs. 15.9%, P = 0.022). No significant intergroup differences were found for sputum culture conversion rate at week 8 (80.0% vs. 81.4%, P = 0.884), at week 24 (95.6% vs. 98.2%, P = 0.629), or for median time to sputum culture conversion [56 days (IQR 28-63) vs. 56 days (IQR 28-84) (P = 0.687)]. Favorable post-24-week treatment outcomes were presented by 90.7% and 93.5% in the DM group and non-DM group, respectively, without significant intergroup differences (P = 0.448). The DM adverse event rate exceeded non-DM rate (77.6% vs. 64.5%, P = 0.035).

Conclusion: Despite some differences in baseline characteristics, Chinese patients with MDR/XDR-TB with or without DM had similar sputum culture conversion rates and favorable treatment outcomes post-24-week BDQ-containing anti-TB treatment. Low BMI but not DM is risk factor associated with unfavorable outcome of patients with MDR/XDR-TB.
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http://dx.doi.org/10.1007/s40121-021-00396-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954881PMC
March 2021

The SIRPα-CD47 immune checkpoint in NK cells.

J Exp Med 2021 03;218(3)

Department of Surgery, Division of Cardiothoracic Surgery, Transplant and Stem Cell Immunobiology Lab, University of California, San Francisco, San Francisco, CA.

Here we report on the existence and functionality of the immune checkpoint signal regulatory protein α (SIRPα) in NK cells and describe how it can be modulated for cell therapy. NK cell SIRPα is up-regulated upon IL-2 stimulation, interacts with target cell CD47 in a threshold-dependent manner, and counters other stimulatory signals, including IL-2, CD16, or NKG2D. Elevated expression of CD47 protected K562 tumor cells and mouse and human MHC class I-deficient target cells against SIRPα+ primary NK cells, but not against SIRPα- NKL or NK92 cells. SIRPα deficiency or antibody blockade increased the killing capacity of NK cells. Overexpression of rhesus monkey CD47 in human MHC-deficient cells prevented cytotoxicity by rhesus NK cells in a xenogeneic setting. The SIRPα-CD47 axis was found to be highly species specific. Together, the results demonstrate that disruption of the SIRPα-CD47 immune checkpoint may augment NK cell antitumor responses and that elevated expression of CD47 may prevent NK cell-mediated killing of allogeneic and xenogeneic tissues.
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http://dx.doi.org/10.1084/jem.20200839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802363PMC
March 2021

Guiding environmental sustainability of emerging bioconversion technology for waste-derived sophorolipid production by adopting a dynamic life cycle assessment (dLCA) approach.

Environ Pollut 2021 Jan 23;269:116101. Epub 2020 Nov 23.

School of Energy and Environment, City University of Hong Kong, Kowloon, SAR, Hong Kong. Electronic address:

Microbial biosurfactants are surface-active molecules that are naturally produced by a range of microorganisms. They have certain advantages over chemical surfactants, such as lower toxicity, higher biodegradability, anti-tumor, and anti-microbial properties. Sophorolipids (SLs) in particular are one of the most promising biosurfactants, as they hold the largest share of the biosurfactant market. Currently, researchers are developing novel approaches for SL production that utilize renewable feedstocks and advanced separation technologies. However, challenges still exist regarding consumption of materials, enzymes, and electricity, that are primarily fossil based. Researchers lack a clear understanding of the associated environmental impacts. It is imperative to quantify and optimize the environmental impacts associated with this emerging technology very early in its design phase to guide a sustainable scale-up. It is necessary to take a collaborative perspective, wherein life cycle assessment (LCA) experts work with experimentalists, to quantify environmental impacts and provide recommendations for improvements in the novel waste-derived SL production pathways. Studies that have analyzed the environmental sustainability of microbial biosurfactant production are very scarce in literature. Hence, in this work, we explore the possibility of applying LCA to evaluate the environmental sustainability of SL production. A dynamic LCA (dLCA) framework that quantifies the environmental impacts of a process in an iterative manner, is proposed and applied to evaluate SL production. The first traversal of the dLCA was associated with the selection of an optimal feedstock, and results identified food waste as a promising feedstock. The second traversal compared fermentation coupled with alternative separation techniques, and highlighted that the fed-batch fermentation of food waste integrated with the in-situ separation technique resulted in less environmental impacts. These results will guide experimentalists to further optimize those processes, and improve the environmental sustainability of SL production. Resultant datasets can be iteratively used in subsequent traversals to account for technological changes and mitigate the corresponding impacts before scaling up.
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http://dx.doi.org/10.1016/j.envpol.2020.116101DOI Listing
January 2021

Knowledge is money: Do people think cultural capital can be transformed into economic value?

Psych J 2021 Feb 9;10(1):87-95. Epub 2020 Aug 9.

Department of Psychology, Renmin University of China, Beijing, China.

Cultural capital is defined as the accumulation of knowledge, behaviors, and skills that a person can tap into to demonstrate one's cultural competence and social status (Bourdieu, 1986). Cultural capital has been well-understood in social sciences such as sociology and economics for the past decades. Little research has examined the psychological antecedences and consequences of cultural capital at the individual level. Our current work seeks to provide empirical evidence to support the claim that cultural capital (embodied, objective, and institutionalized) can be transformed into economic value. Using a 3 × 3 × 2 (Cultural Capital Conditions × Behavioral Agents × Frames) mixed experimental design, our data showed that under the gain frame rather than the loss frame, the property of people with cultural capital was judged higher than those pretending to have cultural capital, but without real knowledge. Interestingly, this pattern of results only holds true under the embodied cultural capital condition, but did not hold true under the objectified and institutionalized cultural capital conditions.
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http://dx.doi.org/10.1002/pchj.387DOI Listing
February 2021

The H-Y Antigen in Embryonic Stem Cells Causes Rejection in Syngeneic Female Recipients.

Stem Cells Dev 2020 09 25;29(18):1179-1189. Epub 2020 Aug 25.

Transplant and Stem Cell Immunobiology Lab, Department of Surgery, University of California, San Francisco, California, USA.

Pluripotent stem cells are promising candidates for cell-based regenerative therapies. To avoid rejection of transplanted cells, several approaches are being pursued to reduce immunogenicity of the cells or modulate the recipient's immune response. These include gene editing to reduce the antigenicity of cell products, immunosuppression of the host, or using major histocompatibility complex-matched cells from cell banks. In this context, we have investigated the antigenicity of H-Y antigens, a class of minor histocompatibility antigens encoded by the Y chromosome, to assess whether the gender of the donor affects the cell's antigenicity. In a murine transplant model, we show that the H-Y antigen in undifferentiated embryonic stem cells (ESCs), as well as ESC-derived endothelial cells, provokes T- and B cell responses in female recipients.
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http://dx.doi.org/10.1089/scd.2019.0299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482111PMC
September 2020

Machine learning of serum metabolic patterns encodes early-stage lung adenocarcinoma.

Nat Commun 2020 07 16;11(1):3556. Epub 2020 Jul 16.

State Key Laboratory for Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, 200030, Shanghai, P. R. China.

Early cancer detection greatly increases the chances for successful treatment, but available diagnostics for some tumours, including lung adenocarcinoma (LA), are limited. An ideal early-stage diagnosis of LA for large-scale clinical use must address quick detection, low invasiveness, and high performance. Here, we conduct machine learning of serum metabolic patterns to detect early-stage LA. We extract direct metabolic patterns by the optimized ferric particle-assisted laser desorption/ionization mass spectrometry within 1 s using only 50 nL of serum. We define a metabolic range of 100-400 Da with 143 m/z features. We diagnose early-stage LA with sensitivity~70-90% and specificity~90-93% through the sparse regression machine learning of patterns. We identify a biomarker panel of seven metabolites and relevant pathways to distinguish early-stage LA from controls (p < 0.05). Our approach advances the design of metabolic analysis for early cancer detection and holds promise as an efficient test for low-cost rollout to clinics.
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http://dx.doi.org/10.1038/s41467-020-17347-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366718PMC
July 2020

Redox-Responsive Polycondensate Neoepitope for Enhanced Personalized Cancer Vaccine.

ACS Cent Sci 2020 Mar 3;6(3):404-412. Epub 2020 Feb 3.

Institute of Materials Science and Engineering, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.

A versatile and highly effective platform remains a major challenge in the development of personalized cancer vaccines. Here, we devised a redox-responsive polycondensate neoepitope (PNE) through a reversible polycondensation reaction of peptide neoantigens and adjuvants together with a tracelessly responsive linker-monomer. Peptide-based neoantigens with diverse sequences and structures could be copolymerized with molecular adjuvants to form PNEs of high loading capacity for vaccine delivery without adding any carriers. The redox-responsive PNEs with controlled molecular weights and sizes efficiently targeted and accumulated in draining lymph nodes and greatly promoted the antigen capture and cross-presentation by professional antigen presenting cells. Mice immunized with PNEs showed markedly enhanced antigen-specific T cell response and the protective immunity against the tumor cell challenge.
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http://dx.doi.org/10.1021/acscentsci.9b01174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099592PMC
March 2020

Understanding traditional and modern eating: the TEP10 framework.

BMC Public Health 2019 Dec 2;19(1):1606. Epub 2019 Dec 2.

Department of Psychology, University of Konstanz, Konstanz, Germany.

Across the world, there has been a movement from traditional to modern eating, including a movement of traditional eating patterns from their origin culture to new cultures, and the emergence of new foods and eating behaviors. This trend toward modern eating is of particular significance because traditional eating has been related to positive health outcomes and sustainability. Yet, there is no consensus on what constitutes traditional and modern eating. The present study provides a comprehensive compilation of the various facets that seem to make up traditional and modern eating. Specifically, 106 facets were mentioned in the previous literature and expert discussions, combining international and interdisciplinary perspectives. The present study provides a framework (the TEP10 framework) systematizing these 106 facets into two major dimensions, what and how people eat, and 12 subdimensions. Hence, focusing only on single facets of traditional and modern eating is an oversimplification of this complex phenomenon. Instead, the multidimensionality and interplay between different facets should be considered to gain a comprehensive understanding of the trends, consequences, and underlying factors of traditional and modern eating.
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http://dx.doi.org/10.1186/s12889-019-7844-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889524PMC
December 2019

A cross-cultural examination on global orientations and moral foundations.

Psych J 2020 Feb 19;9(1):108-117. Epub 2019 Nov 19.

Department of Psychology, Tsinghua University, Beijing, China.

Although there is a flourishing literature on the psychology of globalization and the psychology of morality, respectively, the moral dimension has been largely absent in the discourse of globalization psychology. Our current work attempts to fill this gap by establishing a conceptual and empirical link between global orientations and moral foundations. Our results indicated that (1) multicultural acquisition was positively linked with both individualizing and binding values; (2) ethnic protection was positively linked with only binding values; and (3) the relation patterns between global orientations and moral foundations were essentially congruent across cultures albeit with some cultural variations. Our findings provide direct evidence to map out the relation patterns between how people mentally cope with globalization and their explicit moral matrices.
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http://dx.doi.org/10.1002/pchj.315DOI Listing
February 2020

A Cryoinjury Model to Study Myocardial Infarction in the Mouse.

J Vis Exp 2019 09 19(151). Epub 2019 Sep 19.

Transplant and Stem Cell Immunobiology Lab, University Heart Center; Department of Surgery, Transplant and Stem Cell Immunobiology Lab, University of California San Francisco; Cardiovascular Research Center (CVRC) and DZHK German Center for Cardiovascular Research; Cardiovascular Surgery, University Heart Center;

The use of animal models is essential for developing new therapeutic strategies for acute coronary syndrome and its complications. In this article, we demonstrate a murine cryoinjury infarct model that generates precise infarct sizes with high reproducibility and replicability. In brief, after intubation and sternotomy of the animal, the heart is lifted from the thorax. The probe of a handheld liquid nitrogen delivery system is applied onto the myocardial wall to induce cryoinjury. Impaired ventricular function and electrical conduction can be monitored with echocardiography or optical mapping. Transmural myocardial remodeling of the infarcted area is characterized by collagen deposition and loss of cardiomyocytes. Compared to other models (e.g., LAD-ligation), this model utilizes a handheld liquid nitrogen delivery system to generate more uniform infarct sizes.
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http://dx.doi.org/10.3791/59958DOI Listing
September 2019

Targeting of EZH2 inhibits epithelial‑mesenchymal transition in head and neck squamous cell carcinoma via regulating the STAT3/VEGFR2 axis.

Int J Oncol 2019 Nov 18;55(5):1165-1175. Epub 2019 Sep 18.

Department of Maxillofacial and Otorhinolaryngology Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute, National Clinical Research Center of Cancer, Tianjin 300060, P.R. China.

Tumor metastasis regulated by epithelial‑mesenchymal transition (EMT) plays a significant role in the development of human cancers, whereas the molecular mechanisms of this process in head and neck squamous cell carcinoma (HNSCC) remain elusive. In this study, we found that inhibition of enhancer of zeste homolog 2 (EZH2) resulted in suppressed EMT in HNSCC in vitro and in vivo. We reported that signal transducer and activator of transcription factor 3 (STAT3)/vascular endothelial growth factor receptor 2 (VEGFR2) axis served as the downstream signaling of EZH2 and mediated EMT in HNSCC. EZH2 inhibition downregulated the expression of key molecules of the STAT3/VEGFR2 axis and EMT‑related markers, while the expression of E‑cadherin was upregulated in HNSCC cells. Targeting the EZH2/STAT3/VEGFR2 axis significantly reduced motility of HNSCC cells. Furthermore, EZH2 knockdown reduced the growth of xenograft HNSCC tumors via inhibiting the EZH2/STAT3/VEGFR2 axis. In conclusion, we proposed that EZH2 regulates EMT and tumor invasion and metastasis in HNSCC by governing the STAT3/VEGFR2 axis. These findings provide a rationale for developing novel strategies to treat invasive and metastatic HNSCC via targeting the EZH2/STAT3/VEGFR2 pathway.
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http://dx.doi.org/10.3892/ijo.2019.4880DOI Listing
November 2019

De novo mutations in mitochondrial DNA of iPSCs produce immunogenic neoepitopes in mice and humans.

Nat Biotechnol 2019 10 19;37(10):1137-1144. Epub 2019 Aug 19.

Department of Surgery, Division of Cardiothoracic Surgery, Transplant and Stem Cell Immunobiology Lab, University of California, San Francisco, San Francisco, CA, USA.

The utility of autologous induced pluripotent stem cell (iPSC) therapies for tissue regeneration depends on reliable production of immunologically silent functional iPSC derivatives. However, rejection of autologous iPSC-derived cells has been reported, although the mechanism underlying rejection is largely unknown. We hypothesized that de novo mutations in mitochondrial DNA (mtDNA), which has far less reliable repair mechanisms than chromosomal DNA, might produce neoantigens capable of eliciting immune recognition and rejection. Here we present evidence in mice and humans that nonsynonymous mtDNA mutations can arise and become enriched during reprogramming to the iPSC stage, long-term culture and differentiation into target cells. These mtDNA mutations encode neoantigens that provoke an immune response that is highly specific and dependent on the host major histocompatibility complex genotype. Our results reveal that autologous iPSCs and their derivatives are not inherently immunologically inert for autologous transplantation and suggest that iPSC-derived products should be screened for mtDNA mutations.
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http://dx.doi.org/10.1038/s41587-019-0227-7DOI Listing
October 2019

Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients.

Nat Biotechnol 2019 03 18;37(3):252-258. Epub 2019 Feb 18.

Department of Surgery, Division of Cardiothoracic Surgery, Transplant and Stem Cell Immunobiology-Lab, University of California San Francisco, San Francisco, CA, USA.

Autologous induced pluripotent stem cells (iPSCs) constitute an unlimited cell source for patient-specific cell-based organ repair strategies. However, their generation and subsequent differentiation into specific cells or tissues entail cell line-specific manufacturing challenges and form a lengthy process that precludes acute treatment modalities. These shortcomings could be overcome by using prefabricated allogeneic cell or tissue products, but the vigorous immune response against histo-incompatible cells has prevented the successful implementation of this approach. Here we show that both mouse and human iPSCs lose their immunogenicity when major histocompatibility complex (MHC) class I and II genes are inactivated and CD47 is over-expressed. These hypoimmunogenic iPSCs retain their pluripotent stem cell potential and differentiation capacity. Endothelial cells, smooth muscle cells, and cardiomyocytes derived from hypoimmunogenic mouse or human iPSCs reliably evade immune rejection in fully MHC-mismatched allogeneic recipients and survive long-term without the use of immunosuppression. These findings suggest that hypoimmunogenic cell grafts can be engineered for universal transplantation.
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http://dx.doi.org/10.1038/s41587-019-0016-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419516PMC
March 2019

Tumor Lysate-Loaded Lipid Hybrid Nanovaccine Collaborated with an Immune Checkpoint Antagonist for Combination Immunotherapy.

Adv Healthc Mater 2019 01 3;8(1):e1800837. Epub 2018 Dec 3.

Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, 430030, China.

Cancer vaccines have shown great potential for treating different types of cancer. However, the application of vaccination still presents two major challenges. One is efficiency of antigen delivery, and the other is dealing with immune tolerance accompanied with tumor development. Lipid zinc phosphate hybrid nanoparticles (LZnP NPs) with a unique material structure can realize efficient delivery of antigens to dendritic cells (DCs) and also serve as an adjuvant to promote immune responses. Herein, ZnP NPs are introduced to load toll-like receptor 4 agonist (monophosphoryl lipid A) and B16F10 melanoma cell-derived tumor lysate (TLS) for vaccination. To regulate immune tolerance, the immune checkpoint antagonist, d-peptide antagonist ( PPA-1), is involved in treatment. TLS-loaded LZnP nanovaccine can efficiently prime DCs and induce cytotoxic T lymphocytes response. The explored combination treatment further exhibits the anticipated tumor inhibition on therapeutic and prophylactic melanoma models with extended survival time. It demonstrates the possibility to combine TLS-loaded LZnP nanovaccine with PPA-1 against melanoma and provides support to optimize the combination treatment based on nanovaccine and immune checkpoint therapy.
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http://dx.doi.org/10.1002/adhm.201800837DOI Listing
January 2019

Fake science: The impact of pseudo-psychological demonstrations on people's beliefs in psychological principles.

PLoS One 2018 27;13(11):e0207629. Epub 2018 Nov 27.

Department of Psychology, Goldsmiths University of London, London, United Kingdom.

Magicians use deception to create effects that allow us to experience the impossible. More recently, magicians have started to contextualize these tricks in psychological demonstrations. We investigated whether witnessing a magic demonstration alters people's beliefs in these pseudo-psychological principles. In the classroom, a magician claimed to use psychological skills to read a volunteer's thoughts. After this demonstration, participants reported higher beliefs that an individual can 1) read a person's mind by evaluating micro expressions, psychological profiles and muscle activities, and 2) effectively prime a person's behaviour through subtle suggestions. Whether he was presented as a magician or psychologist did not influence people's beliefs about how the demonstration was achieved, nor did it influence their beliefs in pseudo-psychological principles. Our results demonstrate that pseudo-psychological demonstrations can have a significant impact on perpetuating false beliefs in scientific principles and raise important questions about the wider impact of scientific misinformation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0207629PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258475PMC
April 2019

Do Chinese Traditional and Modern Cultures Affect Young Adults' Moral Priorities?

Front Psychol 2018 6;9:1799. Epub 2018 Nov 6.

Beijing Key Lab of Applied Experimental Psychology, School of Psychology, Beijing Normal University, Beijing, China.

Dramatic cultural change has occurred in Mainland China over the past four decades, yet little is known about how this cultural shift impacts Chinese peoples' moral values. The present research aims to fill this gap by examining whether Chinese traditional and modern cultures influence young adults' moral judgments. Study 1 investigated the relation between psychological traditionality/modernity and moral concerns. Results indicated that participants who strongly endorsed Chinese traditional culture prioritize relationship concern rather than justice concern. Study 2 used the cultural priming method and tested the effects of traditional and modern icons on moral concerns. Results suggested that participants who were primed with traditional or modern or neutral icons did not give priority to relationship or justice concern. Together, our findings provide initial empirical evidence on whether Chinese traditional and modern cultures shift the moral mindsets of bicultural young Chinese among alternative (and even competing) moral codes.
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http://dx.doi.org/10.3389/fpsyg.2018.01799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232185PMC
November 2018

Heterogeneous mutation pattern in tumor tissue and circulating tumor DNA warrants parallel NGS panel testing.

Mol Cancer 2018 08 28;17(1):131. Epub 2018 Aug 28.

State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China.

Liquid biopsy by genotyping circulating tumor DNA (ctDNA) has provided a non-invasive approach in assessing tumor genomic alterations in clinical oncology. However, emerging evidence in clinical settings has shown significant discordance in the genomic alterations between matched tumor tissue and blood ctDNA samples, and even between the same set of blood samples analyzed on different testing platforms. Thus, it is necessary to study underlying causes of discrepancies in these studies by genotyping tumor tissue and ctDNA in parallel using next generation sequencing (NGS) panels based on the same technology. Here we enrolled 56 non-small-cell lung cancer (NSCLC) patients and evaluated tumor tissue genotyping and ctDNA based liquid biopsy by parallel NGS panel testing and compared different sample preparation conditions. Somatic mutations in plasma cell-free DNA (cfDNA) were detected in 63.6% patients with early-stage NSCLC and 60% patients with advanced-stage NSCLC. The overall concordance between matched formalin-fixed paraffin-embedded sample and cfDNA was 54.6% in early-stage NSCLC patients and 80% in advanced-stage NSCLC patients. The positive concordance rate was 44.4% and 71.4% in early-stage and advanced-stage patients, respectively. Using fresh frozen tumor samples did not improve the overall concordance rate between matched tumor tissue and cfDNA. Processing blood samples beyond 4 h after blood draw significantly decreased the detection rate of somatic mutations in cfDNA. Thus, the concordance rate between tumor tissue-based and ctDNA-based genotyping in clinical samples can be affected by multiple pre-analytical, analytical and biologic factors. Parallel NGS panel testing on both sample types for each patient may be warranted for effective guidance of cancer targeted therapies and possible early detection of cancer.
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http://dx.doi.org/10.1186/s12943-018-0875-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6114875PMC
August 2018

When money meets morality: Human universals and cultural differences.

Psych J 2018 06;7(2):105-106

Department of Psychology, School of Social Sciences, Tsinghua University, Beijing, China.

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http://dx.doi.org/10.1002/pchj.213DOI Listing
June 2018

EGFRwt/vIII-PKM2-β-catenin cascade affects proliferation and chemo-sensitivity in head and neck squamous cell carcinoma.

Am J Cancer Res 2017 1;7(12):2491-2502. Epub 2017 Dec 1.

Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and HospitalTianjin 300060, China.

Patients suffered from head and neck squamous cell carcinoma (HNSCC) have an overall poor prognosis owing to proliferation and resistance to treatment. Hence, mining the underlying mechanism of malignancies above and translating the bench outcomes to clinical practice are in urgent need. Previous studies found that the epidermal growth factor receptor (EGFR) increases and co-expresses with EGFRvIII in HNSCC tissues, which indicates poor prognosis of HNSCC patients. Here, we clarify that compared with EGFRwt, EGFRwt/vIII enhances the capability of proliferation and colony formation in HNSCC cells , and reduces the sensitivity to cisplatin. Furthermore, EGFRwt/vIII induces nuclear translocation of the M2 isoform of pyruvate kinase (PKM2) in a time-dependent manner. The aberrant expression of PKM2 in HNSCC suggests unfavorable outcome. Especially, nuclear PKM2 determines the activation of β-catenin signaling and regulates the proliferation and chemo-sensitivity of HNSCC cells. Together, our findings demonstrate that EGFRwt/vIII-PKM2-β-catenin cascade controls the proliferation and chemo-sensitivity of HNSCC, thereby providing a promising strategy for diagnosis and therapy of HNSCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752689PMC
December 2017

Immunochemotherapy mediated by thermosponge nanoparticles for synergistic anti-tumor effects.

J Control Release 2018 01 22;269:322-336. Epub 2017 Nov 22.

Tongji School of Pharmacy, China; National Engineering Research Center for Nanomedicine, China; Hubei Engineering Research Center for Novel Drug Delivery System, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

The efficacy of immunotherapy was demonstrated to be compromised by reduced immunogenicity of tumor cells and enhanced suppressive properties of the tumor microenvironment in cancer treatment. There is growing evidence that low-dose chemotherapy can modulate the immune system to improve the anti-tumor effects of immunotherapy through multiple mechanisms, including the enhancement of tumor immunogenicity and reversal of the immunosuppressive tumor microenvironment. Here, we fabricated thermosponge nanoparticles (TSNs) for the co-delivery of chemotherapeutic drug paclitaxel (PTX) and immunostimulant interleukin-2 (IL-2) to explore the synergistic anti-tumor effects of chemotherapy and immunotherapy. The distinct temperature-responsive swelling/deswelling character facilitated the effective post-entrapment of cytokine IL-2 in nanoparticles by a facile non-solvent mild incubation method with unaffected bioactivity and favorable pharmacokinetics. PTX and IL-2 co-loaded TSNs exhibited significant inhibition on tumor growth and metastasis, and prolonged overall survival for tumor-bearing mice compared with the corresponding monotherapies. The synergistic effect was evidenced from the remodeled tumor microenvironment in which low-dose chemotherapeutics disrupted the immunosuppressive tumor microenvironment and enhanced tumor immunogenicity, and immunostimulant cytokine promoted the anti-tumor immune response of immune effector cells. The immunochemotherapy mediated by this thermosponge nanoplatform may provide a promising treatment strategy against cancer.
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http://dx.doi.org/10.1016/j.jconrel.2017.11.037DOI Listing
January 2018

Quantification of plasma EGFR mutations in patients with lung cancers: Comparison of the performance of ARMS-Plus and droplet digital PCR.

Lung Cancer 2017 12 20;114:31-37. Epub 2017 Oct 20.

Department of Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Objectives: EGFR mutation is a key factor to predict EGFR-TKI efficacy. However, a significant number of advanced patients do not have sufficient tumor specimens for molecular testing. Also, there is a lack of quantitative assay to analyze the mutant abundance. This study aims to evaluate the detection efficiency and clinical feasibility of a new platform, namely ARMS-Plus, for the detection and quantification of EGFR mutations in plasma.

Materials And Methods: The detection limit of ARMS-Plus was assessed by detecting spiked mutant plasmids which were serially diluted with normal human genomic DNA. The cutoff values were defined by examining the mutant copy numbers presented in 134 healthy controls. Plasma samples from 65 lung cancer patients were collected to evaluate the clinical performance of ARMS-Plus. EGFR mutations were concurrently tested by droplet digital PCR (ddPCR) for the plasma samples and conventional amplification refractory mutation system-PCR (ARMS-PCR) for the matched tumor tissue specimens to serve as a standard for comparison.

Results: In this study, the analytical sensitivity of ARMS-Plus was 0.015%. The cutoff values of EGFR 19Del, L858R, T790M mutations were defined as 2, 5, and 3 copies/mL, respectively. With tumor specimens as the standard, the sensitivity, specificity, and concordance rate of ARMS-Plus and ddPCR were 60.7%, 94.6%, and 80.0%; and 50.0%, 97.3%, and 76.9%, respectively. For quantification, the plasma 19Del and L858R mutant abundance detected by ARMS-Plus and ddPCR were consistent (Spearman R=0.7956 and 0.7710, P<0.0001).

Conclusion: ARMS-Plus is a reliable, convenient and cost-effective method for the detection and quantification of plasma EGFR mutations.
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http://dx.doi.org/10.1016/j.lungcan.2017.10.007DOI Listing
December 2017

DNA Methylation Analysis of the SHOX2 and RASSF1A Panel in Bronchoalveolar Lavage Fluid for Lung Cancer Diagnosis.

J Cancer 2017 30;8(17):3585-3591. Epub 2017 Sep 30.

Department of Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.

Currently the majority of lung cancer patients are diagnosed as advanced diseases for no sensitive and specific biomarkers exist, noninvasive biomarkers with high sensitivity and specificity are urgently needed in lung cancer diagnosis. Bronchoscopy is a standard procedure of the diagnostic work-up of patients with suspected lung cancer despite of the limited diagnostic accuracy. Besides, epigenetic changes through DNA methylation play an important role in tumorigenesis. Thus, we examined the aberrant methylation of the SHOX2 and RASSF1A in bronchoalveolar lavage fluid (BALF) in comparing with conventional cytology examination and serum CEA in order to evaluate the new diagnostic method. BALF and serum samples were collected from 322 patients at the time of diagnosis, 284 of them were pathologically confirmed lung cancer, 35 were benign lung diseases and 3 were malignancies in other systems. For all of the 322 patients, the methylation status of the SHOX2 and RASSF1A gene were detected by a new RT-PCR platform and then confirmed by sanger sequencing. Serum CEA were detected using electrochemiluminescence immunoassay. Profiling data showed the consistency of RT-PCR and sanger sequencing in detecting the methylation of the SHOX2 and RASSF1A. Besides, the combination of SHOX2 and RASSF1A methylation in BALF yielded a diagnostic sensitivity of 81.0% and specificity of 97.4%. When compared with established cytology examination (sensitivity: 68.3%, specificity: 97.4%) and serum biomarker carcinoembryonic antigen (CEA) (sensitivity: 30.6%, specificity: 100.0%), the SHOX2 and RASSF1A methylation panel showed the highest diagnostic efficiency. Notably, the combination of cytology and the SHOX2 and RASSF1A methylation panel could significantly improve the diagnostic efficacy. The methylation analysis of the SHOX2 and RASSF1A panel in BALF with RT-PCR achieved a satisfactory sensitivity and specificity in lung cancer diagnosis, especially in an early stage. It could be used as a promising noninvasive biomarker for auxiliary diagnosis of lung cancer.
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http://dx.doi.org/10.7150/jca.21368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687174PMC
September 2017

Thalidomide treatment prevents chronic graft rejection after aortic transplantation in rats - an experimental study.

Transpl Int 2017 Nov 14;30(11):1181-1189. Epub 2017 Aug 14.

Department of Pediatrics (Cardiology) and the Cardiovascular Institute, Stanford University, Stanford, CA, USA.

Cardiac allograft vasculopathy (CAV) affects approximately 30% of cardiac transplant patients at 5 years post-transplantation. To date, there are few CAV treatment or prevention options, none of which are highly effective. The aim of the study was to investigate the effect of thalidomide on the development of CAV. The effect of thalidomide treatment on chronic rejection was assessed in rat orthotopic aortic transplants in allogeneic F344 or syngeneic Lew rats (n = 6 per group). Animals were left untreated or received thalidomide for 30 days post-transplant, and evidence of graft CAV was determined by histology (trichrome and immunohistochemistry) and intragraft cytokine measurements. Animals that received thalidomide treatment post-transplant showed markedly reduced luminal obliteration, with concomitant rescue of smooth muscle cells (SMCs) in the aortic media of grafts. Thalidomide counteracted neointimal hyperplasia by preventing dedifferentiation of vascular SMCs. Measurement of intragraft cytokine levels after thalidomide treatment revealed downregulation of matrix metalloproteinase 8 and monocyte chemotactic protein 1, cytokines involved in tissue remodelling and inflammation, respectively. Importantly, no negative side effects of thalidomide were observed. Thalidomide treatment prevents CAV development in a rodent model and is therefore potentially useful in clinical applications to prevent post-transplant heart rejection.
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http://dx.doi.org/10.1111/tri.13004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5643223PMC
November 2017
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