Publications by authors named "Shiyu Liu"

233 Publications

Inhibition of NLRC5 attenuates the malignant growth and enhances the sensitivity of gastric cancer cells to 5-FU chemotherapy by blocking the carcinogenic effect of YY1.

Exp Ther Med 2022 Sep 28;24(3):601. Epub 2022 Jul 28.

College of Modern Agriculture and Bioengineering, Yangtze Normal University, Chongqing 408000, P.R. China.

Gastric cancer (GC) is one of the commonest malignant tumors of the digestive system, characterized by high morbidity and mortality rates. It has been reported that NOD like receptor (NLR) family, CARD domain containing 5 (NLRC5) serves an important role in the occurrence and development of GC. Therefore, the current study aimed to investigate the role of NLRC5 in GC. The mRNA and protein expression levels of NLRC5 in GC cell lines were determined by reverse transcription-quantitative PCR and western blot analysis, respectively. Additionally, following NLRC5 knockdown, cell proliferation, invasion and migration were evaluated using Cell Counting Kit 8, colony formation, wound healing and Transwell assays, and western blot analysis. The NLRC and Yin Yang 1 (YY1) expression in the AGS cells with 5-FU resistance were detected by western blotting. The sensitivity of GC cells to 5-fluorouracil (5-FU) was detected by flow cytometry and western blot analysis. Additionally, the binding capacity of YY1 on NLRC5 promoter was predicted using JASPAR database and it was further verified by chromatin immunoprecipitation and luciferase reporter assays. Finally, to elucidate the mechanism underlying the effect of NLRC5 on GC, YY1 was overexpressed and NLRC5 was silenced in GC cell lines. The results showed that NLRC5 was abnormally upregulated in GC cells. In addition, NLRC5 knockdown significantly attenuated the proliferation, invasion and migration abilities of GC cells, while it enhanced the sensitivity of GC cells to 5-FU. The above effects were regulated by the YY1 transcription factor. Overall, the results of the present study indicated that NLRC5 silencing could reduce the malignant growth and enhance the sensitivity of GC cells to 5-FU chemotherapy via inhibiting the carcinogenic effect of YY1.
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http://dx.doi.org/10.3892/etm.2022.11538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353549PMC
September 2022

Anti-Inflammatory Effects and Molecular Mechanisms of Shenmai Injection in Treating Acute Pancreatitis: Network Pharmacology Analysis and Experimental Verification.

Drug Des Devel Ther 2022 2;16:2479-2495. Epub 2022 Aug 2.

Pancreatitis Centre, Department and Laboratory of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, People's Republic of China.

Background: Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas without specific treatment. Shenmai injection (SMI) was reported to eliminate the severity of experimental AP. This study aimed to explore the mechanisms underlying the synergistic protective effects of SMI on AP based on network pharmacology and experimental validation.

Methods: Network pharmacology analysis and molecular docking based on identified components were performed to construct the potential therapeutic targets and pathways. The principal components of SMI were detected via ultra-high-performance liquid chromatography-coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Effect of SMI and the identified components on cellular injury and IL6/STAT3 signaling was assessed on mouse pancreatic acinar cell line 266-6 cells. Finally, 4% sodium taurocholate (NaT) was used to induce AP model to assess the effects of SMI in treating AP and validate the potential molecular mechanisms.

Results: By searching the TCMSP and ETCM databases, 119 candidate components of SMI were obtained. UHPLC-QTOF/MS analysis successfully determined the representative components of SMI: ginsenoside Rb1, ginsenoside Rg1, ginsenoside Re, and ophiopogonin D. Fifteen hub targets and eight related pathways were obtained to establish the main pharmacology network. Subnetwork analysis and molecular docking indicated that the effects of these four main SMI components were mostly related to the interleukin (IL) 6/STAT3 pathway. In vitro, SMI, ginsenoside Rb1, ginsenoside Rg1, ginsenoside Re, and ophiopogonin D increased the cell viability of NaT-stimulated mouse pancreatic acinar 266-6 cells and decreased IL6 and STAT3 expression. In vivo, 10 mL/kg SMI significantly alleviated the pancreatic histopathological changes and the expression of IL6 and STAT3 in the AP mice.

Conclusion: This study demonstrated SMI may exert anti-inflammatory effects against AP by suppressing IL6/STAT3 activation, thus providing a basis for its potential use in clinical practice and further study in treating AP.
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http://dx.doi.org/10.2147/DDDT.S364352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356589PMC
August 2022

Potential targets and treatments affect oxidative stress in gliomas: An overview of molecular mechanisms.

Front Pharmacol 2022 22;13:921070. Epub 2022 Jul 22.

Jilin Provincial Key Laboratory of Radiation Oncology and Therapy, The First Hospital of Jilin University, Changchun, China.

Oxidative stress refers to the imbalance between oxidation and antioxidant activity in the body. Oxygen is reduced by electrons as part of normal metabolism leading to the formation of various reactive oxygen species (ROS). ROS are the main cause of oxidative stress and can be assessed through direct detection. Oxidative stress is a double-edged phenomenon in that it has protective mechanisms that help to destroy bacteria and pathogens, however, increased ROS accumulation can lead to host cell apoptosis and damage. Glioma is one of the most common malignant tumors of the central nervous system and is characterized by changes in the redox state. Therapeutic regimens still encounter multiple obstacles and challenges. Glioma occurrence is related to increased free radical levels and decreased antioxidant defense responses. Oxidative stress is particularly important in the pathogenesis of gliomas, indicating that antioxidant therapy may be a means of treating tumors. This review evaluates oxidative stress and its effects on gliomas, describes the potential targets and therapeutic drugs in detail, and clarifies the effects of radiotherapy and chemotherapy on oxidative stress. These data may provide a reference for the development of precise therapeutic regimes of gliomas based on oxidative stress.
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http://dx.doi.org/10.3389/fphar.2022.921070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355528PMC
July 2022

Erratum: Human Umbilical Cord MSCs as New Cell Sources for Promoting Periodontal Regeneration in Inflammatory Periodontal Defect: Errautm.

Theranostics 2022 8;12(12):5332-5333. Epub 2022 Jul 8.

State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.

[This corrects the article DOI: 10.7150/thno.19888.].
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http://dx.doi.org/10.7150/thno.74942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330535PMC
July 2022

Correction: Composite cell sheet for periodontal regeneration: crosstalk between different types of MSCs in cell sheet facilitates complex periodontal-like tissue regeneration.

Stem Cell Res Ther 2022 Jul 27;13(1):363. Epub 2022 Jul 27.

State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.

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http://dx.doi.org/10.1186/s13287-022-03077-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327228PMC
July 2022

Peroxydisulfate activation by sulfur-doped ordered mesoporous carbon: Insight into the intrinsic relationship between defects and O generation.

Water Res 2022 Aug 30;221:118797. Epub 2022 Jun 30.

College of Environmental Science and Engineering, Hunan University, Changsha, 410082, PR China; Key Laboratory of Environmental Biology and Pollution Control, Hunan University, Ministry of Education, Changsha 410082, PR China.

The carbon-catalyzed persulfate-based advanced oxidation process (PS-AOP) has recently received much focus owing to the green, economical, and sustainable nature of carbon catalysts. In this study, sulfur-doped ordered mesoporous carbons (S-OMCs) were utilized to activate peroxydisulfate (PDS) for ciprofloxacin (CIP) removal. A synthesis temperature gradient was set to regulate the defect level of S-OMCs, since the thermal decomposition of oxygen- and sulfur-containing groups at different temperatures could release S and O and then create defects. In all S-OMCs/PDS systems, O dominated CIP degradation. Interestingly, a high linear correlation (R = 0.9091) between defect level and O yield was found, confirming the structure-activity relationship between defects and O generation. Moreover, the impacts of several important reaction conditions and water matrix on S-OMC-1000/PDS activation system were surveyed. In the S-OMC-1000/PDS activation system, CIP removal could attain 85.84% under the condition of unadjusted pH (pH = 5.3) and small amount of S-OMC-1000 (50 mg/L). The S-OMC-1000/PDS activation system also exhibited relatively stable or even better performance in the presence of common inorganic anions and natural organic matter (NOM), manifesting its good potential for practical applications. In addition, the reusability of S-OMC-1000 was investigated. This study provides a practical and high-efficiency way for decontaminating antibiotic-polluted water, and gives an alternative approach for identifying the active site of catalysts.
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http://dx.doi.org/10.1016/j.watres.2022.118797DOI Listing
August 2022

An armed oncolytic virus enhances the efficacy of tumor-infiltrating lymphocyte therapy by converting tumors to artificial antigen-presenting cells in situ.

Mol Ther 2022 Jun 17. Epub 2022 Jun 17.

State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300350, PR China; CNBG-Nankai University Joint Research and Development Center, Nankai University, Tianjin 300350, PR China; Frontiers Science Center for Cell Responses, Nankai University, Tianjin 300350, PR China. Electronic address:

The full potential of tumor-infiltrating lymphocyte (TIL) therapy has been hampered by the inadequate activation and low persistence of TILs, as well as inefficient neoantigen presentation by tumors. We transformed tumor cells into artificial antigen-presenting cells (aAPCs) by infecting them with a herpes simplex virus 1 (HSV-1)-based oncolytic virus encoding OX40L and IL12 (OV-OX40L/IL12) to provide local signals for optimum T cell activation. The infected tumor cells displayed increased expression of antigen-presenting cell-related markers and induced enhanced T cell activation and killing in coculture with TILs. Combining OV-OX40L/IL12 and TIL therapy induced complete tumor regression in patient-derived xenograft and syngeneic mouse tumor models and elicited an antitumor immunological memory. In addition, the combination therapy produced aAPC properties in tumor cells, activated T cells, and reprogrammed macrophages to a more M1-like phenotype in the tumor microenvironment. This combination strategy unleashes the full potential of TIL therapy and warrants further evaluation in clinical studies.
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http://dx.doi.org/10.1016/j.ymthe.2022.06.010DOI Listing
June 2022

Application of vancomycin-impregnated calcium sulfate hemihydrate/nanohydroxyapatite/carboxymethyl chitosan injectable hydrogels combined with BMSC sheets for the treatment of infected bone defects in a rabbit model.

BMC Musculoskelet Disord 2022 Jun 9;23(1):557. Epub 2022 Jun 9.

Department of Orthopaedics, Second affiliated hospital, Air Force Medical University, Xi'an, 710038, Shaanxi, China.

Background: The choice of bone substitutes for the treatment of infected bone defects (IBDs) has attracted the attention of surgeons for years. However, single-stage bioabsorbable materials that are used as carriers for antibiotic release, as well as scaffolds for BMSC sheets, need further exploration. Our study was designed to investigate the effect of vancomycin-loaded calcium sulfate hemihydrate/nanohydroxyapatite/carboxymethyl chitosan (CSH/n-HA/CMCS) hydrogels combined with BMSC sheets as bone substitutes for the treatment of IBDs.

Methods: BMSCs were harvested and cultured into cell sheets. After the successful establishment of an animal model with chronic osteomyelitis, 48 New Zealand white rabbits were randomly divided into 4 groups. Animals in Group A were treated with thorough debridement as a control. Group B was treated with BMSC sheets. CSH/n-HA/CMCS hydrogels were implanted in the treatment of Group C, and Group D was treated with CSH/n-HA/CMCS+BMSC sheets. Gross observation and micro-CT 3D reconstruction were performed to assess the osteogenic and infection elimination abilities of the treatment materials. Histological staining (haematoxylin and eosin and Van Gieson) was used to observe inflammatory cell infiltration and the formation of collagen fibres at 4, 8, and 12 weeks after implantation.

Results: The bone defects of the control group were not repaired at 12 weeks, as chronic osteomyelitis was still observed. HE staining showed a large amount of inflammatory cell infiltration around the tissue, and VG staining showed no new collagen fibres formation. In the BMSC sheet group, although new bone formation was observed by gross observation and micro-CT scanning, infection was not effectively controlled due to unfilled cavities. Some neutrophils and only a small amount of collagen fibres could be observed. Both the hydrogel and hydrogel/BMSCs groups achieved satisfactory repair effects and infection control. Micro-CT 3D reconstruction at 4 weeks showed that the hydrogel/BMSC sheet group had higher reconstruction efficiency and better bone modelling with normal morphology. HE staining showed little aggregation of inflammatory cells, and VG staining showed a large number of new collagen fibres.

Conclusions: Our preliminary results suggested that compared to a single material, the novel antibiotic-impregnated hydrogels acted as superior scaffolds for BMSC sheets and excellent antibiotic vectors against infection, which provided a basis for applying tissue engineering technology to the treatment of chronic osteomyelitis.
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http://dx.doi.org/10.1186/s12891-022-05499-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9185966PMC
June 2022

Direct lactic acid production from household food waste by lactic acid bacteria.

Sci Total Environ 2022 Sep 6;840:156479. Epub 2022 Jun 6.

State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China. Electronic address:

China is vigorously promoting garbage classification, but the treatment of classified waste, especially household food waste (HFW) has yet to be studied. Lactic acid (LA), a high value-added platform molecule has broad market prospects. Although there have been many studies on the production of LA from food waste, open fermentation often produces lots of by-products, while the traditional fermentation under a pure bacteria system often requires the saccharification process, which increases the production cost. We sought to analyze the comprehensive properties of classified HFW in Shanghai, then to produce LA by inoculating lactic acid bacteria (LAB) directly. The effects of strains, temperature, sterilized or not, initial pH, inoculum size, and substrate concentration on LA production were investigated. HFW was rich in nutrients and growth factors which provided the possibility for direct LA production from HFW by inoculating LAB. The results showed that Lactobacillus rhamnosus ATCC 7469, Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus all could be used as the inoculum, however, no significant synergistic effect of the three strains on LA production was found. LA concentration of 30.25 g/L at 37 °C, pH 6.8 could be obtained by inoculating Lactobacillus rhamnosus ATCC 7469 from sterilized HFW. High inoculum size and substrate concentration resulted in high LA concentration, but not high LA yield. The result of ANOVA indicated that there was a significantly positive relationship between substrate concentration and LA concentration (r = 0.942, p < 0.01), while no statistically significant difference between these groups at different inoculum size was evident (p = 0.318). In addition, an average LA concentration of 26.8 g/L, LA yield of 0.20 g/g TCOD was obtained by repeated batch fermentation for 32 d.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156479DOI Listing
September 2022

Hemostatic biomaterials to halt non-compressible hemorrhage.

J Mater Chem B 2022 Jun 8. Epub 2022 Jun 8.

Department of Mechanical Engineering, McGill University, Montreal, Quebec, Canada.

Non-compressible hemorrhage is an unmet clinical challenge, which occurs in inaccessible sites in the body where compression cannot be applied to stop bleeding. Current treatments reliant on blood transfusion are limited in efficacy and complicated by blood supply (short shelf-life and high cost), immunogenicity and contamination risks. Alternative strategies based on hemostatic biomaterials exert biochemical and/or mechanical cues to halt hemorrhage. The biochemical hemostats are built upon native coagulation cascades, while the mechanical hemostats use mechanical efforts to stop bleeding. This review covers the design principles and applications of such hemostatic biomaterials, following an overview of coagulation mechanisms and clot mechanics. We present how biochemical strategies modulate coagulation and fibrinolysis, and also mechanical mechanisms such as absorption, agglutination, and adhesion to achieve hemostasis. We also outline the challenges and immediate opportunities to provide comprehensive guidelines for the rational design of hemostatic biomaterials.
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http://dx.doi.org/10.1039/d2tb00546hDOI Listing
June 2022

Molecular Cytogenetic Identification of a New Wheat-Rye 6R Addition Line and Physical Localization of Its Powdery Mildew Resistance Gene.

Front Plant Sci 2022 12;13:889494. Epub 2022 May 12.

Center for Agricultural Resources Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Shijiazhuang, China.

Rye ( L.), a naturally cross-pollinating relative of wheat, is a tertiary gene donor and of substantial value in wheat improvement. Wheat powdery mildew is caused by f. sp. (), which seriously affects yield and quality worldwide. Identifying and transferring new, effective resistance genes against powdery mildew from rye is important for wheat breeding. The current study developed a wheat-rye line YT2 resistant to powdery mildew by crossing, backcrossing, and self-pollination for multiple generations between octoploid triticale 09R2-100 and common wheat cultivar Shixin 616. YT2 was confirmed to be a 6R disomic addition and T1RS⋅1BL translocation line by genomic hybridization (GISH), multicolor fluorescence hybridization (mc-FISH), multicolor-GISH (mc-GISH), and molecular marker analyses. Disease responses to different isolates and genetic analysis showed that the powdery mildew resistance gene of YT2 was derived from the rye chromosome 6R of 09R2-100, which differed from the previously reported genes from rye including on 6RL. Resistance phenotype of different translocation lines and deletion lines derived from YT2 combined with newly developed 6RL-specific markers analysis suggested that the powdery mildew resistance gene of YT2 was localized to the region in chromosome 6RL: 890.09-967.51 Mb and flanked by markers and , corresponding to the reference genome of Weining rye. Therefore, YT2 could be used as a promising bridging parent for wheat disease resistance improvement.
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http://dx.doi.org/10.3389/fpls.2022.889494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134188PMC
May 2022

Hybrid Biomaterial Initiates Refractory Wound Healing via Inducing Transiently Heightened Inflammatory Responses.

Adv Sci (Weinh) 2022 07 23;9(21):e2105650. Epub 2022 May 23.

State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China.

Inflammation plays a crucial role in triggering regeneration, while inadequate or chronic inflammation hinders the regenerative process, resulting in refractory wounds. Inspired by the ideal regeneration mode in lower vertebrates and the human oral mucosa, realigning dysregulated inflammation to a heightened and acute response provides a promising option for refractory wound therapy. Neutrophils play important roles in inflammation initiation and resolution. Here, a hybrid biomaterial is used to stimulate transiently heightened inflammatory responses by precise tempospatial regulation of neutrophil recruitment and apoptosis. The hybrid biomaterial ([email protected]/SiO -FasL) is constructed by loading of formyl-met-leu-phe (fMLP) and FasL-conjugated silica nanoparticles (SiO -FasL) into a pH-responsive hydrogel matrix. This composition enables burst release of fMLP to rapidly recruit neutrophils for heightened inflammation initiation. After neutrophils act to produce acids, the pH-responsive hydrogel degrades to expose SiO -FasL, which induces activated neutrophils apoptosis via FasL-Fas signaling triggering timely inflammation resolution. Apoptotic neutrophils are subsequently cleared by macrophages, and this efferocytosis activates key signalings to promote macrophage anti-inflammatory phenotypic transformation to drive regeneration. Ultimately, [email protected]/SiO -FasL successfully promotes tissue regeneration by manipulating inflammation in critical-sized calvarial bone defects and diabetic cutaneous wound models. This work provides a new strategy for refractory wound therapy via inducing transiently heightened inflammatory responses.
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http://dx.doi.org/10.1002/advs.202105650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313498PMC
July 2022

Apoptotic vesicles activate autophagy in recipient cells to induce angiogenesis and dental pulp regeneration.

Mol Ther 2022 May 10. Epub 2022 May 10.

State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China. Electronic address:

Extracellular vesicles (EVs) derived from living cells play important roles in donor cell-induced recipient tissue regeneration. Although numerous studies have found that cells undergo apoptosis after implantation in an ischemic-hypoxic environment, the roles played by the EVs released by apoptotic cells are largely unknown. In this study, we obtained apoptotic vesicles (apoVs) derived from human deciduous pulp stem cells and explored their effects on the dental pulp regeneration process. Our work showed that apoVs were ingested by endothelial cells (ECs) and elevated the expression of angiogenesis-related genes, leading to pulp revascularization and tissue regeneration. Furthermore, we found that, at the molecular level, apoV-carried mitochondrial Tu translation elongation factor was transported and regulated the angiogenic activation of ECs via the transcription factor EB-autophagy pathway. In a beagle model of dental pulp regeneration in situ, apoVs recruited endogenous ECs and facilitated the formation of dental-pulp-like tissue rich in blood vessels. These findings revealed the significance of apoptosis in tissue regeneration and demonstrated the potential of using apoVs to promote angiogenesis in clinical applications.
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http://dx.doi.org/10.1016/j.ymthe.2022.05.006DOI Listing
May 2022

Odontogenic MSC Heterogeneity: Challenges and Opportunities for Regenerative Medicine.

Front Physiol 2022 19;13:827470. Epub 2022 Apr 19.

State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China.

Cellular heterogeneity refers to the genetic and phenotypic differences among cells, which reflect their various fate choices, including viability, proliferation, self-renewal probability, and differentiation into different lineages. In recent years, research on the heterogeneity of mesenchymal stem cells has made some progress. Odontogenic mesenchymal stem cells share the characteristics of mesenchymal stem cells, namely, good accessibility, low immunogenicity and high stemness. In addition, they also exhibit the characteristics of vasculogenesis and neurogenesis, making them attractive for tissue engineering and regenerative medicine. However, the usage of mesenchymal stem cell subgroups differs in different diseases. Furthermore, because of the heterogeneity of odontogenic mesenchymal stem cells, their application in tissue regeneration and disease management is restricted. Findings related to the heterogeneity of odontogenic mesenchymal stem cells urgently need to be summarized, thus, we reviewed studies on odontogenic mesenchymal stem cells and their specific subpopulations, in order to provide indications for further research on the stem cell regenerative therapy.
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http://dx.doi.org/10.3389/fphys.2022.827470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9061943PMC
April 2022

Novel roles of RTN4 and CLIMP-63 in regulating mitochondrial structure, bioenergetics and apoptosis.

Cell Death Dis 2022 May 4;13(5):436. Epub 2022 May 4.

Departments of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 3GE, UK.

The recruitment of DRP1 to mitochondrial membranes prior to fission is facilitated by the wrapping of endoplasmic reticulum (ER) membranes around the mitochondria. To investigate the complex interplay between the ER membranes and DRP1 in the context of mitochondrial structure and function, we downregulate two key ER shaping proteins, RTN4 and CLIMP-63, and demonstrate pronounced mitochondrial hyperfusion and reduced ER-mitochondria contacts, despite their differential regulation of ER architecture. Although mitochondrial recruitment of DRP1 is unaltered in cells lacking RTN4 or CLIMP-63, several aspects of mitochondrial function, such as mtDNA-encoded translation, respiratory capacity and apoptosis are significantly hampered. Further mechanistic studies reveal that CLIMP-63 is required for cristae remodeling (OPA1 proteolysis) and DRP1-mediated mitochondrial fission, whereas both RTN4 and CLIMP-63 regulate the recruitment of BAX to ER and mitochondrial membranes to enable cytochrome c release and apoptosis, thereby performing novel and distinct roles in the regulation of mitochondrial structure and function.
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http://dx.doi.org/10.1038/s41419-022-04869-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068774PMC
May 2022

Apoptotic extracellular vesicles alleviate Pg-LPS induced inflammation of macrophages via AMPK/SIRT1/NF-κB pathway and inhibit adjacent osteoclast formation.

J Periodontol 2022 May 2. Epub 2022 May 2.

State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Air Force Medical University, Xi'an, Shaanxi, People's Republic of China.

Background: Periodontitis is caused by the imbalance of anti-bacteria immune response and excessive inflammation whereas macrophages play an important role in inflammation. Thus, it is critical for finding efficient anti-inflammatory strategies to alleviate periodontal inflammation and prevent bone destruction. Apoptosis of mesenchymal stem cells (MSCs) exerts immune silencing effects, however, using these effects to develop anti-inflammatory strategies remains unknown. In our study, we extracted apoptotic extracellular vesicles (ApoEVs) from bone marrow MSCs (BMMSCs) and found ApoEVs inhibited macrophages polarizing into proinflammatory condition via AMPK/SIRT1/NF-κB pathway. Besides that, we also found ApoEVs inhibited adjacent osteoclast formation by suppressing the secretion of TNF-α of proinflammatory macrophages.

Methods: BMMSCs derived ApoEVs were extracted by gradient centrifugation. Protein expression level and secreted cytokines of ApoEVs treated macrophages were examined by western blot and ELISA, respectively. Besides, the change of NF-κB pathway and related molecules were examined by immunofluorescence and western blot. The osteoclast formation under the different conditioned mediums from macrophages was measured by TRAP staining, MMP-9 expression, and pit assay.

Results: ApoEVs were extracted from staurosporine-induced apoptotic BMMSCs and were in sphere shapes whose diameters are between 100 and 1000 nm. ApoEVs could be phagocyted by macrophages and in turn reduce the expression of COX2 in proinflammatory macrophages. Besides that, ApoEVs suppressed the secretions of TNF-α and IL-6 while elevating the secretion of IL-10 in a dose-dependent manner. Further studies revealed that ApoEVs inhibited macrophages polarizing into proinflammatory phenotypes via AMPK/SIRT1/NF-κB pathway. In addition, ApoEVs inhibited osteoclasts differentiation and bone resorption measured by TRAP staining, MMP-9 expression, and pit resorption area by downregulating the secretion of TNF-α of proinflammatory macrophages.

Conclusions: The results suggest that ApoEVs inhibited macrophages to skew into proinflammatory phenotypes via AMPK/SIRT1/NF-κB pathway and suppress adjacent osteoclasts formation by reducing the secretion of TNF-α. Our findings shed a light on the treatment for periodontitis based on EVs therapy.
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http://dx.doi.org/10.1002/JPER.21-0657DOI Listing
May 2022

Rapid and accurate determination of diesel multiple properties through NIR data analysis assisted by machine learning.

Spectrochim Acta A Mol Biomol Spectrosc 2022 Sep 13;277:121261. Epub 2022 Apr 13.

Flow Measurement Technology Key Lab of Zhejiang Province, College of Metrology & Measurement Engineering, China Jiliang University, Hangzhou, Zhejiang 310018, China.

The rapid and accurate detection of diesel multiple properties is an important research topic in petrochemical industry that is conducive to diesel quality assessment and environmental pollution mitigation. To that end, this paper developed a new machine learning model for near infrared (NIR) spectroscopy capable of simultaneously determining diesel density, viscosity, freezing point, boiling point, cetane number and total aromatics. The model combined improved XY co-occurrence distance (ISPXY) and differential evolution-gray wolf optimization support vector machine (DEGWO-SVM) to attain the goal of rapidity and accuracy. Experimental results indicated that the average recovery, mean square error, mean absolute percentage error and determination coefficient of the presented method outperformed those of the existing machine learning methods. The proposed hybrid model provides superior solution to the problem of low efficiency and high cost of diesel quality detection, and has the potential to be utilized as a promising tool for diesel routine monitoring.
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http://dx.doi.org/10.1016/j.saa.2022.121261DOI Listing
September 2022

Rapid Detection of Multi-Resistance Strains Carrying -1 Gene Using Recombinase-Aided Amplification Directly on Clinical Samples.

Front Microbiol 2022 31;13:852488. Epub 2022 Mar 31.

Department of Bacteriology, Capital Institute of Pediatrics, Beijing, China.

With the increasingly severe problem of bacterial resistance, colistin, as the last line of defense, has attracted attention again. Mobile colistin resistance (-1) gene is involved in the horizontal transmission of colistin resistance in Gram-negative bacteria (GNB), which is a serious threat to human health. Therefore, rapid detection of -1 gene presence in clinical samples is crucial. In this study, a Recombinase-aided amplification(RAA) method for -1 was successfully constructed, with sensitivity of 20 copies/reaction. In addition, amplification signal could only be detected in the strain containing -1 gene among 14 different bacterial species. The method was then used to test a total of 672 clinical samples from a pediatric hospital in Beijing. Five strains harbored -1 genes were isolated from -1-positive clinical samples and identified as . Multi-locus sequence typing (MLST) analysis showed that the five belonged to different ST types. Notably, the -1 gene from the isolates could be transferred conjugately to the recipient strain J53, with highest transfer efficiency up to 57-58%, suggesting that the -1 gene was located on the plasmid. These findings showed that the RAA assay has potential to be a rapid and sensitive -1 gene screening test for clinical samples, and -1 could be transmitted vertically and horizontally between and within bacterial species in a plasmid-mediated manner.
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http://dx.doi.org/10.3389/fmicb.2022.852488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009391PMC
March 2022

Genetic Diversity and Pathogenic Features in Klebsiella pneumoniae Isolates from Patients with Pyogenic Liver Abscess and Pneumonia.

Microbiol Spectr 2022 04 30;10(2):e0264621. Epub 2022 Mar 30.

Department of Bacteriology, Capital Institute of Pediatricsgrid.418633.b, Beijing, China.

While Klebsiella pneumoniae is a common cause of nosocomial and community-acquired infections, including pneumonia and pyogenic liver abscess, little is known about the population structure of this bacterium. In this study, we investigated the prevalence and molecular characteristics of K. pneumoniae isolates from carriers, pyogenic liver abscess patients, and pneumonia patients, and genomic and phenotypic assays were used to determine the differences among the isolates. A total of 232 K. pneumoniae isolates were subtyped into 74 sequence types (STs). The isolates from different sources had their own STs, and the predominant subtypes in liver abscess and pneumonia patients were ST23 and ST11, respectively. Pangenome analysis also distinguished three phylogroups that were consistent with the isolate sources. The isolates collected from liver abscess patients carried significantly more virulence factors, and those from pneumonia patients harbored significantly more resistance genes and replicons. Almost all isolate STs (93/97 [95.88%]) from liver abscesses strongly correlated with the virulence factor salmochelin, while most pneumonia isolate STs (52/53 [98.11%]) from pneumonia did not correlate with salmochelin. The isolates collected from liver abscesses showed higher virulence in the cytotoxicity and mouse models. These data provide genomic support for the proposal that isolates collected from carriers, liver abscess patients, and pneumonia patients have distinct genomic features. Isolates from the different sources are largely nonoverlapping, suggesting that different patients may be infected via different sources. Further studies on the pathogenic mechanisms of salmochelin and other virulence factors will be required. While Klebsiella pneumoniae is a common cause of nosocomial and community-acquired infections, including pneumonia and pyogenic liver abscess, little is known about the population structure of this bacterium. We collected 232 isolates from carriers, pyogenic liver abscess patients, and pneumonia patients, and the isolates from different sources had their own sequence types. Pangenome analysis also distinguished three phylogroups that were consistent with the isolate sources. The isolates collected from liver abscess patients carried significantly more virulence factors, and those from pneumonia patients harbored significantly more resistance genes and replicons. Besides, there was a strong link between salmochelin and liver abscess. The isolates collected from liver abscesses also showed higher virulence in the cytotoxicity and mouse models. Isolates collected from different sources have distinct genomic features, suggesting that different patients may be infected via different sources.
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http://dx.doi.org/10.1128/spectrum.02646-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045331PMC
April 2022

Ketogenesis acts as an endogenous protective programme to restrain inflammatory macrophage activation during acute pancreatitis.

EBioMedicine 2022 Apr 25;78:103959. Epub 2022 Mar 25.

State Key Laboratory of Oncogenes and Related Genes, Stem Cell Research Centre, Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Rd, Shanghai 200127 China. Electronic address:

Background: Innate immunity and metabolites link to the pathogenesis and severity of acute pancreatitis (AP). However, liver metabolism and its role in immune response and AP progression remain elusive. We investigated the function of liver metabolism in the pathogenesis of AP.

Methods: Circulating ketone body β-hydroxybutyrate (βOHB) levels were determined in AP clinical cohorts and caerulein-induced AP (CER-AP) mouse models receiving seven (Cer*7) or twelve (Cer*12) injection regimens at hourly intervals. Liver transcriptomics and metabolomics were compared between CER-AP (Cer*7) and CER-AP (Cer*12). Inhibition of fatty acid β-oxidation (FAO)-ketogenesis, or supplementation of βOHB was performed in mouse models of AP. The effect and mechanism of βOHB were examined in vitro.

Findings: Elevated circulating βOHB was observed in patients with non-severe AP (SAP) but not SAP. These findings were replicated in CER-AP (Cer*7) and CER-AP (Cer*12), which manifested as limited and hyperactive immune responses, respectively. FAO-ketogenesis was activated in CER-AP (Cer*7), while impaired long-chain FAO and mitochondrial function were observed in the liver of CER-AP (Cer*12). Blockage of FAO-ketogenesis (Cpt1a antagonism or Hmgcs2 knockdown) worsened, while supplementation of βOHB or its precursor 1,3-butanediol alleviated the severity of CER-AP. Mechanistically, βOHB had a discernible effect on pancreatic acinar cell damage, instead, it greatly attenuated the activation of pancreatic and systemic proinflammatory macrophages via class I histone deacetylases.

Interpretation: Our findings reveal that hepatic ketogenesis is activated as an endogenous protective programme to restrain AP progression, indicating its potential therapeutic value.

Funding: This work was supported by the National Natural Science Foundation of China, Shanghai Youth Talent Support Programme, and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant.
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http://dx.doi.org/10.1016/j.ebiom.2022.103959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8960978PMC
April 2022

Body Dissatisfaction and Disordered Eating Behaviors: The Mediation Role of Smartphone Addiction and Depression.

Nutrients 2022 Mar 17;14(6). Epub 2022 Mar 17.

Faculty of Psychology, Southwest University, Chongqing 400715, China.

This study aimed to determine whether smartphone addiction and depression sequentially mediate the relationship between body dissatisfaction and disordered eating behaviors (e.g., restrained eating, emotional eating and external eating). A total of 5986 participants (54.1% females, average age = 19.8 years, age range = 17-32) completed the Satisfaction and Dissatisfaction with Body Parts Scale, the Three-Factor Eating Questionnaire, the Smartphone Addiction Scale and the Patient Health Questionnaire-9. Mediational analysis showed that, after controlling for age, sex and body mass index, body dissatisfaction was related to disordered eating behaviors through (a) the mediating effect of smartphone addiction, (b) the mediating effect of depression, and (c) the serial mediating effect of smartphone addiction and depression. In conclusion, our study showed for the first time that smartphone addiction and depression can be sequential mediator variables in the association between body dissatisfaction and disordered eating. However, this study is a cross-sectional study; future longitudinal studies could further test the causal associations between these study variables.
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http://dx.doi.org/10.3390/nu14061281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955505PMC
March 2022

Yunpi Heluo decoction reduces ectopic deposition of lipids by regulating the SIRT1-FoxO1 autophagy pathway in diabetic rats.

Pharm Biol 2022 Dec;60(1):579-588

Department of Endocrinology, Ningbo Municipal Hospital of TCM, Affliated Hospital of Zhejiang Chinese Medical University, Ningbo, China.

Context: Yunpi Heluo (YPHL) decoction is a Chinese herbal formula with particular advantages for treating type 2 diabetes. Yet, its exact mechanism of action is not fully understood.

Objective: To examine the therapeutic effect of YPHL on ectopic lipid deposition (EDL) in Zucker diabetic fatty (ZDF) rats and the underlying mechanism.

Materials And Methods: The ZDF Rats were randomized into five groups, including model, YPHL (200 mg/kg/d for 10 weeks), SIRT1-overexpression (injected with HBAAV2/9-r-SIRT1-3'-flag-GFP), NC (injected with HBAAV2/9-CMV-GFP as blank control) and control group. Pancreatic β-cells obtained from high-lipid-high-glucose fed rats were treated with YPHL (10 mg/mL) for 48 h. Lipid deposition and autophagosomes were analyzed by transmission electron microscopy. Intracellular HO and ROS concentrations were measured by flow cytometry. SIRT1, FOXO1, LC3 and P62 mRNA and protein levels were analyzed using qRT-PCR and Western blots.

Results: Compared with the model group, blood glucose levels in YPHL and si-SIRT1 groups were reduced by 19.3% and 27.9%, respectively. In high-lipid-high-glucose cells treated with YPHL, lipid droplets were reduced and decrease in apoptosis rate (38.6%), HO (31.2%) and ROS (44.5%) levels were observed. After YPHL intervention or SIRT1 overexpression, LC3 and p62 expression increased. Protein expression of SIRT1 and LC3 in model, si-SIRT1, si-NC and si-SIRT1 + YPHL groups was lower than those in control group, while FoxO1 expression was increased. All of these protein level alterations were reversed in the si-NC + YPHL group.

Discussion And Conclusions: YPHL reduced EDL by regulating the SIRT1-FoxO1 autophagy pathway in diabetic rats, which could lead to future perspectives for the treatment of diabetes.
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http://dx.doi.org/10.1080/13880209.2022.2042567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8916783PMC
December 2022

Enhancing hydrogen peroxide activation of CuCo layered double hydroxide by compositing with biochar: Performance and mechanism.

Sci Total Environ 2022 Jul 28;828:154188. Epub 2022 Feb 28.

College of Environmental Science and Engineering and Key Laboratory of Environmental Biology and Pollution Control (Ministry of Education), Hunan University, Changsha 410082, PR China. Electronic address:

In this study, CuCo layered double hydroxide/biochar composite (CuCo LDH/BC) was prepared and employed for activating HO to degrade ciprofloxacin (CIP), a common fluroquinolone antibiotic detected in water environment. The as-synthesized catalysts were also comprehensively characterized to study the physiochemical properties. For the catalytic activity, the degradation rate of CuCo LDH/BC to CIP was approximately 1.5 times higher than that of CuCo LDH. The improved catalytic activity can be ascribed to the synergistic effect between CuCo LDH and BC, such as more functional groups, accelerated electron transfer, and varied charge distribution. Meanwhile, CuCo LDH/BC/HO could degrade CIP efficiently in a wider pH range comparing with CuCo LDH/HO, and the efficiency was approximately 84.7% at neutral pH within 90 min. The generation of OH, O and O in CuCo LDH/BC/HO system were then verified by electron spin resonance (ESR) technology. The quenching experiments indicated that both non-radical pathway (O) and radical pathway (OH, O) led to CIP degradation, in which O and O made major contribution. Then, the intermediate products of CIP during catalytic reaction were monitored by high-performance liquid chromatography-mass spectrometry (HPLC-MS), and the environmental risk of these degradation intermediates was tested through seed germination experiments. This study tends to provide valuable information for LDH/BC application in heterogeneous Fenton-like reaction.
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http://dx.doi.org/10.1016/j.scitotenv.2022.154188DOI Listing
July 2022

A Novel Wheat-Rye 2R (2D) Disomic Substitution Line Pyramids Two Types of Resistance to Powdery Mildew.

Plant Dis 2022 Jun 19:PDIS12212765RE. Epub 2022 Jun 19.

Center for Agricultural Resources Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Shijiazhuang, Hebei 050022, China.

Powdery mildew, caused by f. sp. , is a devastating disease of wheat that seriously affects yield and quality worldwide. Because of the extensive growth of wheat cultivars with homogeneous genetic background, exploring novel resistant resources from wheat relatives has become important for increasing the genetic diversity of wheat. Rye () is a wheat relative possessing abundant resistance genes because of its high variation. Wheat line AL69, resistant to powdery mildew, was developed by crossing, backcrossing, and self-pollination for multiple generations between hexaploid triticale Zhongsi 237 and common wheat cultivar Zimai 17. Through genomic in situ hybridization (GISH) and multicolor fluorescence in situ hybridization (FISH), nondenaturing FISH, multicolor GISH, and selection with specific molecular markers, AL69 was determined to be a wheat-rye 2R (2D) disomic substitution line. Testing with different f. sp. isolates and genetic analysis showed that the all-stage resistance (also called seedling resistance) of AL69 was conferred by the cataloged powdery mildew resistance gene derived from Zimai 17, and its adult-plant resistance was derived from the alien chromosome 2R of Zhongsi 237, which was found to be different from the previously reported rye-derived genes, including on 2RL. In addition, AL69 showed improved spike number per plant, spike length, fertile spikelet number per spike, kernel number per spike, and grain yield per plant compared with its wheat parent Zimai 17. An elite line S251 combining powdery mildew resistance with excellent agronomic performance was selected from the progenies of AL69 and wheat cultivar Jimai 22. Therefore, AL69 has two types of resistance genes to powdery mildew and improved agronomic traits through pyramiding and thus can be used as a promising genetic stock for wheat breeding.
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http://dx.doi.org/10.1094/PDIS-12-21-2765-REDOI Listing
June 2022

CO Absorption Mechanism by the Deep Eutectic Solvents Formed by Monoethanolamine-Based Protic Ionic Liquid and Ethylene Glycol.

Int J Mol Sci 2022 Feb 8;23(3). Epub 2022 Feb 8.

School of Science, China University of Geosciences, Beijing 100083, China.

Deep eutectic solvents (DESs) have been widely used to capture CO in recent years. Understanding CO mechanisms by DESs is crucial to the design of efficient DESs for carbon capture. In this work, we studied the CO absorption mechanism by DESs based on ethylene glycol (EG) and protic ionic liquid ([MEAH][Im]), formed by monoethanolamine (MEA) with imidazole (Im). The interactions between CO and DESs [MEAH][Im]-EG (1:3) are investigated thoroughly by applying H and C nuclear magnetic resonance (NMR), 2-D NMR, and Fourier-transform infrared (FTIR) techniques. Surprisingly, the results indicate that CO not only binds to the amine group of MEA but also reacts with the deprotonated EG, yielding carbamate and carbonate species, respectively. The reaction mechanism between CO and DESs is proposed, which includes two pathways. One pathway is the deprotonation of the [MEAH] cation by the [Im] anion, resulting in the formation of neutral molecule MEA, which then reacts with CO to form a carbamate species. In the other pathway, EG is deprotonated by the [Im], and then the deprotonated EG, HO-CH-CH-O, binds with CO to form a carbonate species. The absorption mechanism found by this work is different from those of other DESs formed by protic ionic liquids and EG, and we believe the new insights into the interactions between CO and DESs will be beneficial to the design and applications of DESs for carbon capture in the future.
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http://dx.doi.org/10.3390/ijms23031893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836646PMC
February 2022

Scavenging ROS to Alleviate Acute Liver Injury by [email protected]

Adv Sci (Weinh) 2022 04 9;9(11):e2103982. Epub 2022 Feb 9.

Central Laboratory and Department of Laboratory Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200070, China.

Currently, the incidence of acute liver injury (ALI) is increasing year by year, and infection with coronavirus disease 2019 (COVID-19) can also induce ALI, but there are still no targeted therapeutic drugs. ZnO-NiO particles is mainly used to clean up reactive oxygen species (ROS) in industrial wastewater, and it is insoluble in water. Its excellent properties are discovered and improved by adding shuttle-based bonds to make it more water-soluble. [email protected] particles are synthetically applied to treat ALI. The p-n junction in [email protected] increases the surface area and active sites, thereby creating large numbers of oxygen vacancies, which can quickly adsorb ROS. The content in tissues and serum levels of L-glutathione (GSH) and the GSH/oxidized GSH ratio are measured to assess the capacity of [email protected] particles to absorb ROS. The [email protected] particles significantly reduce the expression levels of inflammatory factors (i.e., IL-1, IL-6, and TNF-α), macrophage infiltration, and granulocyte activation. [email protected] rapidly adsorb ROS in a short period of time to block the generation of inflammatory storms and gain time for the follow-up treatment of ALI, which has important clinical significance.
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http://dx.doi.org/10.1002/advs.202103982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008431PMC
April 2022

Social Media for Health Campaign and Solidarity Among Chinese Fandom Publics During the COVID-19 Pandemic.

Front Psychol 2021 19;12:824377. Epub 2022 Jan 19.

School of Journalism and Communication, Peking University, Beijing, China.

Background: As a highly contagious disease, the COVID-19 pandemic has become a serious health threat and psychological burden for the global communities. From the conceptual perspective of affordances, this research examined the role of social media for health campaign and psychological support during the global crisis.

Methods: Data from both social media and a nationwide survey were collected and analyzed. Face mask-related posts on Sina Weibo from January 1, 2020, to June 30, 2020, were retrieved and studied. Face mask wearing as a well-established preventive measure was identified and examined from hashtag topics. A nationwide survey with a randomized experiment embedded was conducted to further investigate the mobilizing dynamics.

Results: During the escalation phase in the first half of 2020, the hashtag topic "#national mask campaign#," initiated by a celebrity, topped the ranking of mask-related topics on Weibo. The findings indicated that prevention activities, solidarity expression, and names of celebrity idols were frequently discussed. With celebrity idols as opinion leaders, millions of fandom publics actively participated in this hashtag health campaign. Results of the nationwide survey show the popularity of fan identity, and the experiment results demonstrate the strong mobilizing power of celebrity idol and fandom community in civic engagement and participation among young Chinese.

Conclusions: The research demonstrates how the affordances of social media, such as liking, commenting, reposting, and hashtagging can be influential in promoting health behaviors and expressing solidarity. Implications for public health professionals and policymakers to raise awareness and understanding about health campaigns social media are discussed.
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http://dx.doi.org/10.3389/fpsyg.2021.824377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8815027PMC
January 2022

Blood clot behaves as a poro-visco-elastic material.

J Mech Behav Biomed Mater 2022 04 29;128:105101. Epub 2022 Jan 29.

Department of Mechanical Engineering, McGill University, Montreal, Quebec, Canada. Electronic address:

Mechanical properties of blood clots play a crucial role in hemostasis and embolization. They are time-dependent and often described with viscoelastic models. But blood clots also exhibit some hallmark features of poroelasticity, as most biological tissues exhibit concurrent viscoelasticity and poroelasticity. In this study, we characterized the time-dependent behavior of blood clots, and developed an experimental-computational framework to decouple and model poroelastic and viscoelastic responses. Compression stress relaxation tests were conducted on bovine blood clots with different diameters to evaluate the influence of sample size on the relaxation time. In the compression tests, the mass of blood clots was measured to estimate fluid migration. To capture pure viscoelastic responses, rheological shear stress relaxation tests were carried out. A poroviscoelastic model was also proposed and calibrated to capture the complex multiaxial (compression and shear) relaxation behavior of blood clots. In unconfined compression tests, stresses relaxed markedly (average: 83%; range: 76-90%), and samples with larger diameters showed longer relaxation time. Blood clots lost about 24% of their initial masses, and the mass transport took place gradually in compression tests. Under shear deformation, blood clots relaxed in average 37% (range: 32-39%) which was much less than those under unconfined compression tests (in average 37% versus 83%). Unlike poroelastic and viscoelastic theories, the poroviscoelastic model accurately predicted multiaxial responses of blood clots under compression and shear; additionally, the estimated Darcy's coefficient (4.4×10 cm) was found within the reported physiological range (0.1×10 to 36 × 10 cm). The combination of size-dependent stress relaxation and mass loss under compression (due to poroelasticity) as well as substantial stress relaxation under shear deformation (due to viscoelasticity) demonstrate that blood clot behaves as a poroviscoelastic material; therefore, accurate interpretation of transient responses of blood clots requires a validated poroviscoelastic model. This work provides understanding and methodology on blood clot mechanics and will further motivate the development of clot-like biomaterials.
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http://dx.doi.org/10.1016/j.jmbbm.2022.105101DOI Listing
April 2022

Development of Loop-Mediated Isothermal Amplification Assay Targeting and Genes for Rapid and Visual Diagnosis of Pneumonia in Children.

Front Microbiol 2021 17;12:816997. Epub 2022 Jan 17.

Department of Bacteriology, Capital Institute of Pediatrics, Beijing, China.

() is a common major human pathogen associated with community-acquired pneumonia, septicemia, meningitis, and otitis media. It is difficult to isolate and identify form clinical samples. To evaluate a novel, rapid, sensitive, and specific loop-mediated isothermal amplification (LAMP) assay to detect pneumonia in children, we designed specific LAMP primers targeting and genes. We optimized the reaction time and reaction system, and evaluated its sensitivity and specificity of detection using real-time turbidity monitoring and visual observation. We also analyzed the molecular characteristics of the isolates obtained from the positive samples. The primer sets LytA-1 and PsaA-2 amplified the genes in the shortest times, and 63°C was confirmed as the optimum reaction temperature. The detection sensitivity of each reaction was 10 and 100 copies/μL with primer sets LytA-1 and PsaA-2, respectively. This LAMP assay showed no cross-reactivity with other 27 pathogens. To describe the availability of this method, we collected 748 clinical samples from children with pneumonia. Among them, 135 were confirmed to be positive by LAMP. The sensitivity was 100% (95% CI 96.4-100%), specificity 99.0% (95% CI 97.8-99.6%). Including them, 50 were co-infected with . This LAMP assay detected in 1 h and the results can be identified with visual naked eyes. Thus, it will be a powerful tool for early diagnosis and effective antibiotic therapy.
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http://dx.doi.org/10.3389/fmicb.2021.816997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803124PMC
January 2022

CD40L-armed oncolytic herpes simplex virus suppresses pancreatic ductal adenocarcinoma by facilitating the tumor microenvironment favorable to cytotoxic T cell response in the syngeneic mouse model.

J Immunother Cancer 2022 01;10(1)

Tianjin Key Laboratory of Protein Sciences, Department of Biochemistry and Molecular Biology, College of Life Sciences, Nankai University, Tianjin, China

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant cancers worldwide. Despite the promising outcome of immune checkpoint inhibitors and agonist antibody therapies in different malignancies, PDAC exhibits high resistance due to its immunosuppressive tumor microenvironment (TME). Ameliorating the TME is thus a rational strategy for PDAC therapy. The intratumoral application of oncolytic herpes simplex virus-1 (oHSV) upregulates pro-inflammatory macrophages and lymphocytes in TME, and enhances the responsiveness of PDAC to immunotherapy. However, the antitumor activity of oHSV remains to be maximized. The aim of this study is to investigate the effect of the CD40L armed oHSV on the tumor immune microenvironment, and ultimately prolong the survival of the PDAC mouse model.

Methods: The membrane-bound form of murine CD40L was engineered into oHSV by CRISPR/Cas9-based gene editing. oHSV-CD40L induced cytopathic effect and immunogenic cell death were determined by microscopy and flow cytometry. The expression and function of oHSV-CD40L was assessed by reporter cell assay. The oHSV-CD40L was administrated intratumorally to the immune competent syngeneic PDAC mouse model, and the leukocytes in TME and tumor-draining lymph node were analyzed by multicolor flow cytometry. Intratumoral cytokines were determined by ELISA.

Results: Intratumoral application of oHSV-CD40L efficiently restrained the tumor growth and prolonged the survival of the PDAC mouse model. In TME, oHSV-CD40L-treated tumor accommodated more maturated dendritic cells (DCs), which in turn activated T helper 1 and cytotoxic CD8 T cells in an interferon-γ-dependent and interleukin-12-dependent manner. In contrast, the regulatory T cells were significantly reduced in TME by oHSV-CD40L treatment. Repeated dosing and combinational therapy extended the lifespan of PDAC mice.

Conclusion: CD40L-armed oncolytic therapy endues TME with increased DCs maturation and DC-dependent activation of cytotoxic T cells, and significantly prolongs the survival of the model mice. This study may lead to the understanding and development of oHSV-CD40L as a therapy for PDAC in synergy with immune checkpoint blockade.
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http://dx.doi.org/10.1136/jitc-2021-003809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8796271PMC
January 2022
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