Publications by authors named "Hao Tian"

278 Publications

Explore Protein Conformational Space With Variational Autoencoder.

Front Mol Biosci 2021 12;8:781635. Epub 2021 Nov 12.

Center for Research Computing, Center for Drug Discovery, Design, and Delivery (CD4), Department of Chemistry, Southern Methodist University, Dallas, TX, United States.

Molecular dynamics (MD) simulations have been actively used in the study of protein structure and function. However, extensive sampling in the protein conformational space requires large computational resources and takes a prohibitive amount of time. In this study, we demonstrated that variational autoencoders (VAEs), a type of deep learning model, can be employed to explore the conformational space of a protein through MD simulations. VAEs are shown to be superior to autoencoders (AEs) through a benchmark study, with low deviation between the training and decoded conformations. Moreover, we show that the learned latent space in the VAE can be used to generate unsampled protein conformations. Additional simulations starting from these generated conformations accelerated the sampling process and explored hidden spaces in the conformational landscape.
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http://dx.doi.org/10.3389/fmolb.2021.781635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633506PMC
November 2021

Regulation of epigenetic homeostasis in uveal melanoma and retinoblastoma.

Prog Retin Eye Res 2021 Nov 30:101030. Epub 2021 Nov 30.

Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, PR China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, 200025, PR China. Electronic address:

Uveal melanoma (UM) and retinoblastoma (RB), which cause blindness and even death, are the most frequently observed primary intraocular malignancies in adults and children, respectively. Epigenetic studies have shown that changes in the epigenome contribute to the rapid progression of both UM and RB following classic genetic changes. The loss of epigenetic homeostasis plays an important role in oncogenesis by disrupting the normal patterns of gene expression. The targetable nature of epigenetic modifications provides a unique opportunity to optimize treatment paradigms and establish new therapeutic options for both UM and RB with these aberrant epigenetic modifications. We aimed to review the research findings regarding relevant epigenetic changes in UM and RB. Herein, we 1) summarize the literature, with an emphasis on epigenetic alterations, including DNA methylation, histone modifications, RNA modifications, noncoding RNAs and an abnormal chromosomal architecture; 2) elaborate on the regulatory role of epigenetic modifications in biological processes during tumorigenesis; and 3) propose promising therapeutic candidates for epigenetic targets and update the list of epigenetic drugs for the treatment of UM and RB. In summary, we endeavour to depict the epigenetic landscape of primary intraocular malignancy tumorigenesis and provide potential epigenetic targets in the treatment of these tumours.
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http://dx.doi.org/10.1016/j.preteyeres.2021.101030DOI Listing
November 2021

Effect of combined treatment with lobaplatin and osthole on inducing apoptosis and inhibiting proliferation in human breast cancer MDA-MB-231 cells.

Med Oncol 2021 Nov 27;39(1):16. Epub 2021 Nov 27.

College of Traditional Chinese Medicine, Chongqing Medical University, #1 Yixueyuan Road, Yuzhong District, 400016, Chongqing, People's Republic of China.

The present study investigates the underlying mechanisms of treatment with osthole (OST) combined with lobaplatin in human triple-negative MDA-MB-231 breast cancer cells. Human triple-negative MDA-MB-231 breast cancer cells were treated with different concentrations of OST (0.1, 1, 5, 10, 20, 50, and 100 μM) alone or in combination with 10 μM lobaplatin for 48 h. Cell viability was determined and compared between the treatment groups with the Cell Counting Kit-8 assay. Transcriptome sequencing (Project Number: M-GSGC0250521) was employed to elucidate the gene expression profile of the control group and the OST treatment group, and differentially expressed genes (DEGs) were identified based on the following criteria: logFC > 0, P < 0.05. KEGG enrichment analysis was employed to determine the biological functions of these DEGs and the related signaling pathways. Finally, flow cytometry and western blotting were used to assess differences in the apoptosis rate and protein expression in MDA-MB-231 cells subjected to different treatments. The findings showed that OST inhibited the growth of MDA-MB-231 cells in a concentration-dependent manner and cell proliferation was significantly inhibited (as indicated by a decrease of 40%) at the OST concentration of 50 μM (P < 0.05). Transcriptome sequencing identified 4712 DEGs, including 2169 upregulated DEGs and 2543 downregulated DEGs. Enrichment analysis indicated that the DEGs played a role in apoptosis, p53 signaling, DNA replication, and cell cycle. In vitro experiments showed that OST and lobaplatin could significantly induce apoptosis in the MDA-MB-231 cells (P < 0.05), as indicated by elevation in the translation level of p53/Bax/caspase-3 p17 and downregulation of the Bcl-2 protein. Finally, combined treatment with OST and lobaplatin had an enhanced anti-tumor effect (P < 0.05) on proliferation and apoptosis, as well as more obvious effects on the related proteins (p53, Bax, Bcl-2, and caspase-3 p17). Thus, OST enhanced the apoptosis-mediated growth inhibitory effect of lobaplatin on breast cancer cells and has potential for the treatment of breast cancer in the future.
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http://dx.doi.org/10.1007/s12032-021-01609-4DOI Listing
November 2021

Emerging Applications of Silica Nanoparticles as Multifunctional Modifiers for High Performance Polyester Composites.

Nanomaterials (Basel) 2021 Oct 22;11(11). Epub 2021 Oct 22.

National Center of International Research for Hybrid Materials Technology, Institute of Hybrid Materials, National Base of International Science & Technology Cooperation, Qingdao University, Qingdao 266071, China.

Nano-modification of polyester has become a research hotspot due to the growing demand for high-performance polyester. As a functional carrier, silica nanoparticles show large potential in improving crystalline properties, enhancing strength of polyester, and fabricating fluorescent polyester. Herein, we briefly traced the latest literature on synthesis of silica modifiers and the resultant polyester nanocomposites and presented a review. Firstly, we investigated synthesis approaches of silica nanoparticles for modifying polyester including sol-gel and reverse microemulsion technology, and their surface modification methods such as grafting silane coupling agent or polymer. Then, we summarized processing technics of silica-polyester nanocomposites, like physical blending, sol-gel processes, and in situ polymerization. Finally, we explored the application of silica nanoparticles in improving crystalline, mechanical, and fluorescent properties of composite materials. We hope the work provides a guideline for the readers working in the fields of silica nanoparticles as well as modifying polyester.
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http://dx.doi.org/10.3390/nano11112810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8622537PMC
October 2021

Integrated endotoxin-adsorption and antibacterial properties of platelet-membrane-coated copper silicate hollow microspheres for wound healing.

J Nanobiotechnology 2021 Nov 22;19(1):383. Epub 2021 Nov 22.

Department of Radiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510005, China.

Serious infection caused by drug-resistant gram-negative bacteria and their secreted toxins (e.g., lipopolysaccharide) is a serious threat to human health. Thus, treatment strategies that efficiently kill bacteria and reducing the impact of their toxins simultaneously are urgently required. Herein, a novel antibacterial platform composed of a mesoporous copper silicate microsphere (CSO) core and a platelet membrane (PM) shell was prepared ([email protected]). [email protected] specifically targets bacteria owing to formyl peptide receptors on the PM and, combined with photothermal therapy (PTT), exhibits highly effective bacter icidal activity. Importantly, [email protected] can adsorb lipopolysaccharide secreted by gram-negative bacteria, resulting in inflammation reduction. Thus, [email protected] stimulates re-epithelialization and granulation-tissue formation, promoting wound healing. Moreover, this antibacterial platform exhibits no obvious toxicity at all the test concentrations in vitro and in vivo. Thus, [email protected] exhibits a robust antibacterial effect and a strong toxin-adsorption capacity, facilitating the clinical treatment of many bacterial infections and the development of next-generation antibacterial nanoagents.
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http://dx.doi.org/10.1186/s12951-021-01130-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607565PMC
November 2021

Influence of geometric parameters on partial compressive force and pushing performance of flow diverter.

Int J Numer Method Biomed Eng 2021 Nov 15:e3553. Epub 2021 Nov 15.

Shanghai Engineering Research Center of Interventional Medical Device, University of Shanghai for Science and Technology, Shanghai, China.

Research on flow diverter (FD) has progressed over the past decades; however, the relationships between parameters such as stent diameter, porosity, and number of wires and the properties of FDs, such as partial compressive force and push resistance, are not well understood. In this study, the partial compressive force and push resistance of braided FDs with varying porosity (61%-75%), diameter (2.5-5.0 mm), and number of wires (48 or 64) were evaluated using finite element analysis (FEA) and bench tests. At a small compression ratio, the 48-wire stents exhibited a larger partial compressive force than 64-wire stents of the same diameter. But when the compression ratio was 50%, the 64-wire stents had better resistance to pressure. The partial compressive force decreased as the stent diameter increased when all other parameters were equal. However, the influence of the diameter decreased as the stent porosity increased. The push resistance decreased as the porosity and diameter increased, and increased with the number of wires. These results provide useful information for FD design. Decreasing the number of wires can reduce the push resistance, while the push resistance is mainly influenced by the porosity and number of wires, and almost has no relationship with the partial compressive force. The FEA model proved very reliable, and corresponded well to the bench test results, which indicates that this model can be utilized to guide the design of FDs.
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http://dx.doi.org/10.1002/cnm.3553DOI Listing
November 2021

ADAM17 Mediates Hypoxia-Induced Keratinocyte Migration via the p38/MAPK Pathway.

Biomed Res Int 2021 28;2021:8328216. Epub 2021 Oct 28.

Department of Plastic and Aesthetic Surgery, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, The Third Military Medical University (Army Medical University), Chongqing 400038, China.

Although hypoxia has been shown to promote keratinocyte migration and reepithelialization, the underlying molecular mechanisms remain largely unknown. ADAM17, a member of the metalloproteinase superfamily, has been implicated in a variety of cellular behaviors such as proliferation, adhesion, and migration. ADAM17 is known to promote cancer cell migration under hypoxia, and whether or how ADAM17 plays a role in hypoxia-induced keratinocyte migration has not been identified. Here, we found that ADAM17 expression and activity were significantly promoted in keratinocytes under hypoxic condition, inhibition of ADAM17 by TAPI-2, or silencing of ADAM17 using small interfering RNA which suppressed the hypoxia-induced migration of keratinocytes significantly, indicating a pivotal role for ADAM17 in keratinocyte migration. Further, we showed that p38/MAPK was activated by hypoxia. SB203580, an inhibitor of p38/MAPK, significantly attenuated the upregulation of ADAM17 as well as the migration of keratinocytes induced by hypoxia. Activation of p38/MAPK by MKK6 (Glu) overexpression, however, had adverse effects. Taken together, our study demonstrated that hypoxia-induced keratinocyte migration requires the p38/MAPK-ADAM17 signal axis, which sheds new light on the regulatory mechanisms of keratinocyte migration. Our study might also help in developing therapeutic strategies to facilitate wound healing in vivo, where cells are migrated in a hypoxic microenvironment.
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http://dx.doi.org/10.1155/2021/8328216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568513PMC
October 2021

Computational characterization of domain-segregated 3D chromatin structure and segmented DNA methylation status in carcinogenesis.

Mol Oncol 2021 Oct 27. Epub 2021 Oct 27.

Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.

The high-order chromatin structure, together with DNA methylation and other epigenetic marks, plays a vital role in gene regulation and displays abnormal status in cancer cells. Theoretical analyses are expected to provide a more unified understanding of the multi-omics data on the large variety of samples, and hopefully a common picture of carcinogenesis. In particular, we are interested in the question of whether an underlying origin DNA sequence exists for these epigenetic alterations. The human genome consists of two types of megabase-sized domain based on the distribution of CpG islands (CGIs) that show distinct structural, epigenetic, and transcriptional properties: CGI-rich and CGI-poor domains. Through an integrated analysis of chromatin structure, DNA methylation, and RNA sequencing data, we found that, in carcinogenesis, the two different types of domain display different structural changes and have an increased number of DNA methylation differences and transcriptional-level differences, compared with in noncancer cells. We also compared the structural features among carcinogenesis, senescence, and mitosis, showing the possible connection between chromatin structure and cell state, which could affect vital cancer-related properties. In summary, chromatin structure, DNA methylation, and gene expression, as well as their changes observed in several types of cancers, show a dependence on multiscale DNA sequence heterogeneity.
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http://dx.doi.org/10.1002/1878-0261.13127DOI Listing
October 2021

Synthesis and Design of a Highly Stable Platinum Nickel Electrocatalyst for the Oxygen Reduction Reaction.

ACS Appl Mater Interfaces 2021 Oct 27. Epub 2021 Oct 27.

State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan Provincial Key Lab of Fine Chemistry, School of Chemical Engineering and Technology, Hainan University, Haikou 570228, China.

Exploring effective, stable, and affordable oxygen reduction reaction (ORR) catalysts is very significant for the practical application of proton-exchange membrane fuel cells. In this work, a facile and expandable method is developed to prepare ultrathin PtNi nanowires (NWs) with various Pt/Ni contents, and the ORR performance of the synthesized samples is thoroughly investigated. PtNi NWs show the best ORR performance among the studied samples and, notably, exhibit much better ORR activity and stability than those of the Pt/C catalyst even after a 300,000-continuous cycling test. This work confirms that the initial Pt/Ni ratio plays a critical role in the ORR activity and stability of PtNi NWs, and the structure of the PtNi NWs can be well retained after the durability test. Additionally, the structure and performance of PtNi NWs are investigated in detail during various cycles, and the performance decay is attributed to the dealloying of Ni and the corrosion of the one-dimensional structure after a prolonged durability test. This work provides a desirable method for rationally synthesizing a highly efficient ORR electrocatalyst with remarkable stability.
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http://dx.doi.org/10.1021/acsami.1c16375DOI Listing
October 2021

Progressive Domain Segregation in Early Embryonic Development and Underlying Correlation to Genetic and Epigenetic Changes.

Cells 2021 09 23;10(10). Epub 2021 Sep 23.

Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

Chromatin undergoes drastic structural organization and epigenetic reprogramming during embryonic development. We present here a consistent view of the chromatin structural change, epigenetic reprogramming, and the corresponding sequence-dependence in both mouse and human embryo development. The two types of domains, identified earlier as forests (CGI-rich domains) and prairies (CGI-poor domains) based on the uneven distribution of CGI in the genome, become spatially segregated during embryonic development, with the exception of zygotic genome activation (ZGA) and implantation, at which point significant domain mixing occurs. Structural segregation largely coincides with DNA methylation and gene expression changes. Genes located in mixed prairie domains show proliferation and ectoderm differentiation-related function in ZGA and implantation, respectively. The chromatin of the ectoderm shows the weakest and the endoderm the strongest domain segregation in germ layers. This chromatin structure difference between different germ layers generally enlarges upon further differentiation. The systematic chromatin structure establishment and its sequence-based segregation strongly suggest the DNA sequence as a possible driving force for the establishment of chromatin 3D structures that profoundly affect the expression profile. Other possible factors correlated with or influencing chromatin structures, including transcription, the germ layers, and the cell cycle, are discussed for an understanding of concerted chromatin structure and epigenetic changes in development.
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http://dx.doi.org/10.3390/cells10102521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534146PMC
September 2021

Metal-Phenolic Network-Enabled Lactic Acid Consumption Reverses Immunosuppressive Tumor Microenvironment for Sonodynamic Therapy.

ACS Nano 2021 10 18;15(10):16934-16945. Epub 2021 Oct 18.

Cancer Center and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR 999078, China.

Nanomedicine has revolutionized cancer therapeutic strategies but has not completely changed the outcomes of tricky tumors that evolve a sophisticated immunosuppressive tumor microenvironment (TME) such as acidification. Here, a metal-phenolic network-based nanocomplex embedded with lactate oxidase (LOX) and a mitochondrial respiration inhibitor atovaquone (ATO) was constructed for immunosuppressive TME remodeling and sonodynamic therapy (SDT). In this nanocomplex, the sonosensitizer chlorin e6-conjugated polyphenol derivative can induce the generation of tumor lethal reactive oxygen species upon ultrasound irradiation. LOX served as a catalyst for intracellular lactic acid exhaustion, and ATO led to mitochondrial dysfunction to decrease oxygen consumption. This nanocomplex reversed the tumor immunosuppressive status by alleviating tumor hypoxia and acidic TME, achieving the characteristic enhancement of SDT and the inhibition of tumor proliferation and metastasis.
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http://dx.doi.org/10.1021/acsnano.1c08026DOI Listing
October 2021

A metal-polyphenolic nanosystem with NIR-II fluorescence-guided combined photothermal therapy and radiotherapy.

Chem Commun (Camb) 2021 Nov 2;57(87):11473-11476. Epub 2021 Nov 2.

Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR 999078, China.

Photothermal therapy (PTT) achieves substantive therapeutic progress in certain tumor types without exogenous agents but is hampered by the over-activated inflammatory response or tumor recurrence in some cases. Herein, we technically developed the metal-polyphenolic nanosystem with precise NIR-II fluorescence-imaging guidance for combining hafnium (Hf)-sensitized radiotherapy with PTT to regress tumor growth.
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http://dx.doi.org/10.1039/d1cc04628dDOI Listing
November 2021

Investigation of the Geographical Environment Impact on the Chemical Components of L. through a Combined Analytical Method.

ACS Omega 2021 Oct 27;6(39):25497-25505. Epub 2021 Sep 27.

College of Chemistry and Chemical Engineering, Xinjiang Normal University, Urumqi 830054, China.

By implementing NMR, inductively coupled plasma-atomic emission spectrometry (ICP-AES), and the UV-vis spectroscopic techniques, metabolites, mineral elements, and antioxidant activities (DPPH) of L. samples from Manasi and Fuhai of Xinjiang were studied in this research to investigate the geographical environment impact at the molecular level. First of all, partial least squares discriminant analysis was conducted to explore differential endogenous metabolites. A total of 18 metabolites were identified, and 14 mineral element contents were calculated quantitatively, which displayed diverse changing trends from these two origins. Valine, succinic acid, betaine, sucrose, and vasicine exhibited significant differences between these two groups as well as mineral nutrient profiles (Mg, Cu, N, K, Na, P, Zn, C) and DPPH antioxidant activities (EC). The obvious different characteristics of chemical components and antioxidant activities in these two groups were further verified by heat map cluster analysis. Pearson correlation analysis also revealed the remarkable relationship of chemical components and antioxidant activities, which are strongly associated with the regional environment. This study showed that the combination of methodologies proposed will be highly useful in evaluating the environmental variation and diversity in terrestrial ecosystems.
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http://dx.doi.org/10.1021/acsomega.1c03420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495862PMC
October 2021

Pressure-induced reconstructive phase transitions, polarization with metallicity, and enhanced hardness in antiperovskite MgCNi.

Phys Chem Chem Phys 2021 Sep 17;23(33):18221-18226. Epub 2021 Aug 17.

School of Physics and Electronic Engineering, Zhengzhou Normal University, Zhengzhou 450044, China.

In general, hydrostatic pressure can suppress electrical polarization, instead of creating and/or enhancing polarization like strain engineering. Here, a combination of first-principles calculations and CALYPSO crystal structures prediction is used to point out that hydrostatic pressure applied on antiperovskite MgCNi can stabilize polarization with metallicity, and thus a polar metal can exist under high pressure. Strikingly, the metallic polar phase of MgCNi exhibits an original linear-cubic coupling between polar and nonpolar modes, resulting in an asymmetrical double-well when the polarization is switched. Moreover, another novel phase of MgCNi under high pressure possesses an enhanced hardness stemming from a robust s-s electrons interaction of an unexpected C-C bond, rather than typical sp orbital hybridization. These discoveries open new routes to design superhard materials and polar metals.
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http://dx.doi.org/10.1039/d1cp02742eDOI Listing
September 2021

Role of Fe Species of Ni-Based Catalysts for Efficient Low-Temperature Ethanol Steam Reforming.

JACS Au 2021 Sep 10;1(9):1459-1470. Epub 2021 Aug 10.

Key Laboratory for Green Chemical Technology of Ministry of Education, School of Chemical Engineering & Technology, Collaborative Innovation Center for Chemical Science & Engineering, Tianjin University, Tianjin 300072, China.

The suppression of methane and coke formation over Ni-based catalysts for low temperature ethanol steam reforming remains challenging. This paper describes the structural evolution of Fe-modified Ni/MgAlO catalysts and the influence of iron species on methane and coke suppression for low temperature ethanol steam reforming. Ni-Fe alloy catalysts are gradually oxidized by water to generate Ni-rich alloy and γ-FeO species at steam-to-carbon ratio of 4. The electron transfer from iron to nickel within Ni-Fe alloy weakens the CO adsorption and effectively alleviates the CO/CO methanation. The oxidation capacity of γ-FeO species promotes the transformation of ethoxy to acetate groups to avoid methane formation and the elimination of carbon deposits for anticoking. Ni10Fe10/MgAlO shows a superior performance with a highest H yield of 4.6 mol/mol ethanol at 400 °C for 15 h. This research could potentially provide instructions for the design of Ni-based catalysts for low-temperature ethanol steam reforming.
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http://dx.doi.org/10.1021/jacsau.1c00217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479767PMC
September 2021

A nanounit strategy reverses immune suppression of exosomal PD-L1 and is associated with enhanced ferroptosis.

Nat Commun 2021 09 30;12(1):5733. Epub 2021 Sep 30.

Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China.

In addition to increasing the expression of programmed death-ligand 1 (PD-L1), tumor cells can also secrete exosomal PD-L1 to suppress T cell activity. Emerging evidence has revealed that exosomal PD-L1 resists immune checkpoint blockade, and may contribute to resistance to therapy. In this scenario, suppressing the secretion of tumor-derived exosomes may aid therapy. Here, we develop an assembly of exosome inhibitor (GW4869) and ferroptosis inducer (Fe) via amphiphilic hyaluronic acid. Cooperation between the two active components in the constructed nanounit induces an anti-tumor immunoresponse to B16F10 melanoma cells and stimulates cytotoxic T lymphocytes and immunological memory. The nanounit enhances the response to PD-L1 checkpoint blockade and may represent a therapeutic strategy for enhancing the response to this therapy.
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http://dx.doi.org/10.1038/s41467-021-25990-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484261PMC
September 2021

A Review of Recent Advances in Nanomaterial-based Stem Cell Therapy and the Corresponding Risks.

Curr Stem Cell Res Ther 2021 Jul 18. Epub 2021 Jul 18.

Department of Breast Surgery, Southwest Hospital, Army Medical University, Chongqing 400038, China.

Stem cell therapy is widely regarded as a promising strategy in regenerative medicine, yet the therapeutic effects of stem cells in vivo are limited by many factors when applied without additional factors, such as poor cell engraftment, uncontrolled differentiation, and unclear cell fates and niches. The emergence of nanotechnology has provided several solutions for these problems. Nanomaterial-based cell labeling and tracking have been extensively investigated in recent decades, and many innovative and multifunctional nanomaterials have been used to reveal the fate of stem cells, allowing more efficient, sensitive, and accurate imaging/tracking strategies for stem cells to be achieved. Nanomaterials enhance stem cell therapy by incorporating or integrating with stem cells and, as scaffolds or substrates, nanomaterials with antioxidant properties that can be used as graft coatings show great promise for clinical transformation. However, current reviews on the subject tend to focus on the various effects of nanomaterials on stem cells and are less concerned with their application to stem cell therapy. Accordingly, we herein present a review of progress in the application of nanomaterials in stem cell therapy over the last three years, which we hope will be of benefit to a comprehensive understanding of nanomaterial-mediated stem cell therapy from lab to pre-clinical practice.
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http://dx.doi.org/10.2174/1574888X16666210719110436DOI Listing
July 2021

miR‑486‑5p suppresses gastric cancer cell growth and migration through downregulation of fibroblast growth factor 9.

Mol Med Rep 2021 11 7;24(5). Epub 2021 Sep 7.

Department of General Surgery, First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154002, P.R. China.

Non‑coding RNAs serve essential roles in regulating mRNA and protein expression and dysregulation of non‑coding RNAs participates in a variety of types of cancer. microRNAs (miRNAs/miRs), which are 21‑24 nucleotides non‑coding RNAs, have been shown to be important for the development of gastric cancer (GC). However, the role of miR‑486‑5p in GC remains to be elucidated. The present study found that miR‑486‑5p was downregulated in GC tissues. Comparing with gastric normal cells GES‑1, GC cells, including MKN‑45, AGS, HGC27 and MKN74, had reduced abundance of miR‑486‑5p transcript. CCK8 and colony formation assays demonstrated that GC cell growth and proliferation were enhanced by miR‑486‑5p inhibitors and were suppressed by miR‑486‑5p mimics. miR‑486‑5p also suppressed cell cycle process and migration and promoted apoptosis in GC cells, as verified by propidium iodide (PI) staining, Transwell assay and PI/Annexin V staining. miR‑486‑5p downregulated fibroblast growth factor 9 (FGF9) through combining to its 3'untranslated region. Overexpression of FGF9 accelerated the growth and proliferation of GC cells. The expression of miR‑486‑5p was negatively associated with FGF9 mRNA expression in GC samples. These results revealed that miR‑486‑5p was a tumor suppressor in GC. Downregulation of FGF9 contributed to the role of miR‑486‑5p in GC.
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http://dx.doi.org/10.3892/mmr.2021.12411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436225PMC
November 2021

Inhibition of Noncanonical Ca Oscillation/Calcineurin/GSK-3β Pathway Contributes to Anti-Inflammatory Effect of Sigma-1 Receptor Activation.

Neurochem Res 2021 Sep 1. Epub 2021 Sep 1.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221000, Jiangsu Province, China.

Further understanding the mechanism for microglia activation is necessary for developing novel anti-inflammatory strategies. Our previous study found that the activation of sigma-1 receptor can effectively inhibit the neuroinflammation, independent of the canonical mechanisms, such as NF-κB, JNK and ERK inflammatory pathways. Thus, it is reasonable that an un-identified, non-canonical pathway contributes to the activation of microglia. In the present study, we found that a sigma-1 receptor agonist of 2-morpholin-4-ylethyl 1-phenylcyclohexane-1-carboxylate (PRE-084) suppressed lipopolysaccharide (LPS) elevated nitric oxide (NO) content in BV-2 microglia culture supernatant and LPS-raised mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS) in BV-2 microglia. Moreover, PRE-084 alleviated LPS-increased Ser 9 de-phosphorylation of glycogen synthase kinase-3 beta (GSK-3β), LPS-elevated catalytic activity of calcineurin, and LPS-raised percent and frequency of Ca oscillatory BV-2 cells. We further found that the inhibitory effect of PRE-084 was reversed by a calcineurin activator of chlorogenic acid and a GSK-3β activator of pyrvinium. Moreover, an IP receptor inhibitor of 2-aminoethoxydiphenyl borate mimicked the anti-inflammatory activity of PRE-084. Thus, we identified a noncanonical pro-neuroinflammary pathway of Ca oscillation/Calcineurin/GSK-3β and the inhibition of this pathway is necessary for the anti-inflammatory activity of sigma-1 receptor activation.
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http://dx.doi.org/10.1007/s11064-021-03439-2DOI Listing
September 2021

Programmable dual responsive system reconstructing nerve interaction with small-diameter tissue-engineered vascular grafts and inhibiting intimal hyperplasia in diabetes.

Bioact Mater 2022 Jan 25;7:466-477. Epub 2021 Jun 25.

Department of Cell Biology, Third Military Army Medical University, Chongqing, 400038, China.

Small-diameter tissue-engineered vascular grafts (sdTEVGs) with hyperglycemia resistance have not been constructed. The intimal hyperplasia caused by hyperglycemia remains problem to hinder the patency of sdTEVGs. Here, inspired by bionic regulation of nerve on vascular, we found the released neural exosomes could inhibit the abnormal phenotype transformation of vascular smooth muscle cells (VSMCs). The transformation was a prime culprit causing the intimal hyperplasia of sdTEVGs. To address this concern, sdTEVGs were modified with an on-demand programmable dual-responsive system of ultrathin hydrogels. An external primary Reactive Oxygen Species (ROS)-responsive Netrin-1 system was initially triggered by local inflammation to induce nerve remolding of the sdTEVGs overcoming the difficulty of nerve regeneration under hyperglycemia. Then, the internal secondary ATP-responsive DENND1A (guanine nucleotide exchange factor) system was turned on by the neurotransmitter ATP from the immigrated nerve fibers to stimulate effective release of neural exosomes. The results showed nerve fibers grow into the sdTEVGs in diabetic rats 30 days after transplantation. At day 90, the abnormal VSMCs phenotype was not detected in the sdTEVGs, which maintained long-time patency without intima hyperplasia. Our study provides new insights to construct vascular grafts resisting hyperglycemia damage.
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http://dx.doi.org/10.1016/j.bioactmat.2021.05.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379357PMC
January 2022

Dehalogenative Cross-Coupling of -Difluoroalkenes with Alkyl Halides a Silyl Radical-Mediated Process.

J Org Chem 2021 09 30;86(18):12772-12782. Epub 2021 Aug 30.

State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, College of Chemistry, Frontiers Science Center for New Organic Matter, Nankai University, Tianjin 300071, People's Republic of China.

Herein, we describe a convenient general protocol for monofluoroalkenylation reactions of alkyl bromides involving cooperative visible-light photoredox catalysis and halogen abstraction. Mechanistic experiments showed that the products were generated by selective cross-coupling of aliphatic radicals with fluoroalkenyl radicals. Silyl radical-mediated halogen abstraction enabled the protocol to be used for the monofluoroalkenylation of a broad range of alkyl and heteroaryl halides. The protocol could be carried out on a gram scale and was applied to cholesterol, indicating its utility for late-stage monofluoroalkenylation reactions.
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http://dx.doi.org/10.1021/acs.joc.1c01363DOI Listing
September 2021

PASSer: Prediction of Allosteric Sites Server.

Mach Learn Sci Technol 2021 Sep 13;2(3). Epub 2021 May 13.

Department of Chemistry, Center for Research Computing, Center for Drug Discovery, Design, and Delivery (CD4), Southern Methodist University, Dallas, Texas, United States of America.

Allostery is considered important in regulating protein's activity. Drug development depends on the understanding of allosteric mechanisms, especially the identification of allosteric sites, which is a prerequisite in drug discovery and design. Many computational methods have been developed for allosteric site prediction using pocket features and protein dynamics. Here, we present an ensemble learning method, consisting of eXtreme gradient boosting (XGBoost) and graph convolutional neural network (GCNN), to predict allosteric sites. Our model can learn physical properties and topology without any information, and shows good performance under multiple indicators. Prediction results showed that 84.9% of allosteric pockets in the test set appeared in the top 3 positions. The PASSer: Protein Allosteric Sites Server (https://passer.smu.edu), along with a command line interface (CLI, https://github.com/smutaogroup/passerCLI) provide insights for further analysis in drug discovery.
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http://dx.doi.org/10.1088/2632-2153/abe6d6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360383PMC
September 2021

Pyrimidine-Functionalized Covalent Organic Framework and its Cobalt Complex as an Efficient Electrocatalyst for Oxygen Evolution Reaction.

ChemSusChem 2021 Oct 15;14(20):4556-4562. Epub 2021 Sep 15.

State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan Provincial Key Lab of Fine Chemistry, School of Chemical Engineering and Technology, Hainan University, Haikou, 570228, P. R. China.

A pyrimidine-modified covalent organic framework (COF-Pyr) was designed to be synthesized via the Povarov reaction. The nitrogen atom on the pyrimidine showed excellent coordination ability to metal ions. Their stable metal composite material ([email protected]) exhibited remarkable performance for electrocatalytic oxygen evolution reaction (OER) in 1.0 m KOH aqueous solution. The overpotential was 450 mV at 10 mA cm . The [email protected] with large specific surface area (392 m  g ) and regular crystal structure provided free passage for H O to move and make them fully contact with the uniformly dispersed cobalt ions on the surface. Thus, the turnover frequency of [email protected] was 0.1 s at the overpotential of 370 mV, which was higher than most reported OER catalysts. This work provided a new way to design and prepare nitrogen-containing heterocyclic functionalized COFs. They can be combined with metal ions to expand the application of COFs in the field of electrocatalysis.
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http://dx.doi.org/10.1002/cssc.202101434DOI Listing
October 2021

MnO-Based Nanomotors with Active Fenton-like Mn Delivery for Enhanced Chemodynamic Therapy.

ACS Appl Mater Interfaces 2021 Aug 9;13(32):38050-38060. Epub 2021 Aug 9.

School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou 510515, China.

Chemodynamic therapy (CDT) is an emerging strategy for cancer treatment based on Fenton chemistry, which can convert endogenous HO into toxic ·OH. However, the limited endocytosis of passive CDT nanoagents with low penetrating capability resulted in unsatisfactory anticancer efficacy. Herein, we propose the successful fabrication of a self-propelled biodegradable nanomotor system based on hollow MnO nanoparticles with catalytic activity for active Fenton-like Mn delivery and enhanced CDT. Compared with the passive counterparts, the significantly improved penetration of nanomotors with enhanced diffusion is demonstrated in both the 2D cell culture system and 3D tumor multicellular spheroids. After the intracellular uptake of nanomotors, toxic Fenton-like Mn is massively produced by consuming overexpressed intracellular glutathione (GSH), which has a strong scavenging effect on ·OH, thereby leading to enhanced cancer CDT. The as-developed MnO-based nanomotor system with enhanced penetration and endogenous GSH scavenging capability shows much promise as a potential platform for cancer treatment in the near future.
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http://dx.doi.org/10.1021/acsami.1c08926DOI Listing
August 2021

Urbanization-driven increases in summertime compound heat extremes across China.

Sci Total Environ 2021 Dec 20;799:149166. Epub 2021 Jul 20.

School of Geography and Planning, Sun Yat-sen University, Guangzhou 510275, China; Guangdong Key Laboratory for Urbanization and Geo-simulation, Guangdong Provincial Engineering Research Center for Public Security and Disaster, Sun Yat-sen University, Guangzhou 510275, China; Institute of Environment, Energy and Sustainability, The Chinese University of Hong Kong, Sha Tin, N.T., Hong Kong, China. Electronic address:

Summertime extreme heat events exert severe impacts on the natural environment and human society, especially in densely populated and highly urbanized regions. While previous studies have focused on independent heat day/night, there is a lack of attention to the changes in compound events with cooccurring daytime and nighttime extreme temperature on the same day. In this study, we examine the spatio-temporal changes of summertime compound heat extremes (including compound heat day and compound heatwave) across China, with a particular focus on 20 major urban agglomerations (UAs), and quantify the urbanization effects on these changes. We find that the frequency and fraction of compound heat events show obvious spatial disparities across China. The compound heat events occur more frequently in highly populated and urbanized areas such as the Pearl River Delta. Moreover, the frequency and fraction of compound heat events have significantly increased in recent decades in most parts of China, especially in more developed UAs. These intensifying trends have even accelerated in more recent decades. Our further investigations suggest that most UAs of China experienced an intensifying urbanization effect on compound heat events, and few UAs in northwestern and central China (e.g., UAs of the north Tianshan mountain and the middle reaches of the Yangtze River) display a weakening effect of urbanization. Our findings highlight the important role of urbanization in increasing compound heat extremes and suggest that the increasing threats of compound events in urban areas should be given more attention under the context of global warming and local urbanization.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149166DOI Listing
December 2021

Topological Constraints with Optimal Length Promote the Formation of Chromosomal Territories at Weakened Degree of Phase Separation.

J Phys Chem B 2021 08 5;125(32):9092-9101. Epub 2021 Aug 5.

Shenzhen Bay Laboratory, 5F, No. 9 Duxue Road, Nanshan District, 518055 Shenzhen, Guangdong, China.

It is generally agreed that the nuclei of eukaryotic cells at interphase are partitioned into disjointed territories, with distinct regions occupied by certain chromosomes. However, the underlying mechanism for such territorialization is still under debate. Here we model chromosomes as coarse-grained block copolymers and to investigate the effect of loop domains (LDs) on the formation of compartments and territories based on dissipative particle dynamics. A critical length of LDs, which depends sensitively on the length of polymeric blocks, is obtained to minimize the degree of phase separation. This also applies to the two-polymer system: The critical length not only maximizes the degree of territorialization but also minimizes the degree of phase separation. Interestingly, by comparing with experimental data, we find the critical length for LDs and the corresponding length of blocks to be respectively very close to the mean length of topologically associating domains (TADs) and chromosomal segments with different densities of CpG islands for human chromosomes. The results indicate that topological constraints with optimal length can contribute to the formation of territories by weakening the degree of phase separation, which likely promotes the chromosomal flexibility in response to genetic regulations.
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http://dx.doi.org/10.1021/acs.jpcb.1c03523DOI Listing
August 2021

Nitrate-functionalized patch confers cardioprotection and improves heart repair after myocardial infarction via local nitric oxide delivery.

Nat Commun 2021 07 23;12(1):4501. Epub 2021 Jul 23.

State key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials (Ministry of Education), College of Life Sciences, Nankai University, Tianjin, China.

Nitric oxide (NO) is a short-lived signaling molecule that plays a pivotal role in cardiovascular system. Organic nitrates represent a class of NO-donating drugs for treating coronary artery diseases, acting through the vasodilation of systemic vasculature that often leads to adverse effects. Herein, we design a nitrate-functionalized patch, wherein the nitrate pharmacological functional groups are covalently bound to biodegradable polymers, thus transforming small-molecule drugs into therapeutic biomaterials. When implanted onto the myocardium, the patch releases NO locally through a stepwise biotransformation, and NO generation is remarkably enhanced in infarcted myocardium because of the ischemic microenvironment, which gives rise to mitochondrial-targeted cardioprotection as well as enhanced cardiac repair. The therapeutic efficacy is further confirmed in a clinically relevant porcine model of myocardial infarction. All these results support the translational potential of this functional patch for treating ischemic heart disease by therapeutic mechanisms different from conventional organic nitrate drugs.
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http://dx.doi.org/10.1038/s41467-021-24804-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302626PMC
July 2021

Chiral nanomaterials for tumor therapy: autophagy, apoptosis, and photothermal ablation.

J Nanobiotechnology 2021 Jul 22;19(1):220. Epub 2021 Jul 22.

Department of Breast Surgery, Southwest Hospital, Army Medical University, Chongqing, 400038, China.

Chirality is a fundamental characteristic of natural molecules and a crucial factor in the biochemical reactions of living cells and organisms. Recently, researchers have successfully introduced chiral molecules to the surfaces of nanomaterials, creating chiral nanomaterials that exhibit an upscaling of chiral behavior from the molecular scale to the nanoscale. These chiral nanomaterials can selectively induce autophagy, apoptosis, and photothermal ablation in tumor cells based on their chirality, making them promising for application in anti-tumor therapy. However, these interesting and important phenomena have hitherto received little attention. Accordingly, we herein present a review of recent research progress in the field of chiral nanomaterials for tumor therapy along with brief looks at the mechanistic details of their actions. Finally, the current challenges and future perspectives of chiral nanomaterials in terms of maximizing their potential in tumor therapy are discussed. Thus, this review provides a helpful introduction to the design of chiral nanomaterials and will hopefully highlight the importance of chirality in tumor therapy.
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http://dx.doi.org/10.1186/s12951-021-00965-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299636PMC
July 2021

Single-atom catalysts for high-energy rechargeable batteries.

Chem Sci 2021 May 17;12(22):7656-7676. Epub 2021 May 17.

Centre for Clean Energy Technology, School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney Broadway Sydney NSW 2007 Australia

Clean and sustainable electrochemical energy storage has attracted extensive attention. It remains a great challenge to achieve next-generation rechargeable battery systems with high energy density, good rate capability, excellent cycling stability, efficient active material utilization, and high coulombic efficiency. Many catalysts have been explored to promote electrochemical reactions during the charge and discharge process. Among reported catalysts, single-atom catalysts (SACs) have attracted extensive attention due to their maximum atom utilization efficiency, homogenous active centres, and unique reaction mechanisms. In this perspective, we summarize the recent advances of the synthesis methods for SACs and highlight the recent progress of SACs for a new generation of rechargeable batteries, including lithium/sodium metal batteries, lithium/sodium-sulfur batteries, lithium-oxygen batteries, and zinc-air batteries. The challenges and perspectives for the future development of SACs are discussed to shed light on the future research of SACs for boosting the performances of rechargeable batteries.
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http://dx.doi.org/10.1039/d1sc00716eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188463PMC
May 2021

Effects of high-frequency temperature variabilities on the morbidity of chronic obstructive pulmonary disease: Evidence in 21 cities of Guangdong, South China.

Environ Res 2021 10 23;201:111544. Epub 2021 Jun 23.

School of Geography and Planning, Sun Yat-sen University, Guangzhou, China. Electronic address:

Background: While temperature changes have been confirmed as one of the contributory factors affecting human health, the association between high-frequency temperature variability (HFTV, i.e., temperature variation at short time scales such as 1, 2, and 5 days) and the hospitalization of chronic obstructive pulmonary disease (COPD) was rarely reported.

Objectives: To evaluate the associations between high-frequency temperature variabilities (i.e., at 1, 2, and 5-day scales) and daily COPD hospitalization.

Methods: We collected daily records of COPD hospitalization and meteorological variables from 2013 to 2017 in 21 cities of Guangdong Province, South China. A quasi-Poisson regression with a distributed lag nonlinear model was first employed to quantify the effects of two HFTV measures, i.e., the day-to-day (DTD) temperature change and the intraday-interday temperature variability (IITV), on COPD morbidity for each city. Second, we used multivariate meta-analysis to pool the city-specific estimates, and stratified analyses were performed by age and sex to identify vulnerable groups. Then, the meta-regression with city-level characteristics was employed to detect the potential sources of the differences among 21 cities.

Results: A monotonic increasing curve of the overall exposure-response association was observed, suggesting that positive HFTV (i.e., increased DTD and IITV) will significantly increase the risk of COPD admission. Negative DTD was associated with reduced COPD morbidity while positive DTD elevated the COPD risk. An interquartile range (IQR) increase in DTD was associated with a 24% (95% CI: 12-38%) increase in COPD admissions. An IQR increase in IITV was associated with 18% (95% CI: 7-27%) increase in COPD admissions. Males and people aged 0-64 years appeared to be more vulnerable to the DTD effect than others. Potential sources of the disparity among different cities include urbanization level, sex structure, industry structure, gross domestic product (GDP), health care services, and air quality.

Conclusions: The increases of DTD and IITV have significant adverse impacts on COPD hospitalization. As climate change intensifies, precautions need to be taken to mitigate the impacts of high-frequency temperature changes.
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http://dx.doi.org/10.1016/j.envres.2021.111544DOI Listing
October 2021
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