Publications by authors named "Jinfeng Yang"

121 Publications

Synergistically enhanced multienzyme catalytic nanoconjugates for efficient cancer therapy.

J Mater Chem B 2021 Jul;9(29):5877-5886

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, China.

Tumors are complex and highly variable, making it difficult for a single treatment strategy to be significantly effective for cancer therapy. Herein, we report a robust cascade biomimetic nanoplatform that integrates chemiluminescence-induced photodynamic therapy (CL-PDT), Fenton reaction-based chemodynamic therapy (CDT), and glucose oxidase (GOD)-mediated starvation therapy to synergistically enhance cancer treatment. For the nanoplatform of [email protected]@Cancer cell membrane-GOD ([email protected]@C2G), the ferric ion-linked porphyrin-MOF can trigger a Fenton reaction to reach CDT, the carried CPPO as an energy donor is used to excite a photo-sensitive porphyrin-MOF in situ to generate singlet oxygen (1O2) for PDT, GOD catalyzes glucose into H2O2 and gluconic acid to realize starvation therapy, and the cancer cell membrane wrapped onto the nanoparticle plays a key role in homologous targeting, which is conducive to achieving better therapeutic effects. Significantly, the porphyrin-MOF with catalase-like activity can generate O2 to effectively relieve tumor hypoxia, thereby enhancing the catalytic effect of GOD and the efficacy of PDT. Additionally, the produced H2O2 and gluconic acid can further improve the CPPO-H2O2-triggered CL-PDT and promote the low pH-dependence Fenton reaction-based CDT, respectively. Both in vitro and in vivo studies showed that the constructed nanoplatform displays an excellent cooperative anti-tumor performance, so we firmly believe that this simple nanoplatform broadens the pathway to fight against cancer through effective cascade catalysis.
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http://dx.doi.org/10.1039/d1tb00821hDOI Listing
July 2021

The Application of Nucleic Acid Probe-Based Fluorescent Sensing and Imaging in Cancer Diagnosis and Therapy.

Front Chem 2021 1;9:705458. Epub 2021 Jun 1.

Department of Anesthesiology and Pain Medicine, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China.

It is well known that cancer incidence and death rates have been growing, but the development of cancer theranostics and therapeutics has been a challenging work. Recently, nucleic acid probe-based fluorescent sensing and imaging have achieved remarkable improvements in a variety of cancer management techniques, credited to their high sensitivity, good tolerance to interference, fast detection, and high versatility. Herein, nucleic acid probe-based fluorescent sensing and imaging are labeled with advanced fluorophores, which are essential for fast and sensitive detection of aberrant nucleic acids and other cancer-relevant molecules, consequently performing cancer early diagnosis and targeted treatment. In this review, we introduce the characteristics of nucleic acid probes, summarize the development of nucleic acid probe-based fluorescent sensing and imaging, and prominently elaborate their applications in cancer diagnosis and treatment. In discussion, some challenges and perspectives are elaborated in the field of nucleic acid probe-based fluorescent sensing and imaging.
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http://dx.doi.org/10.3389/fchem.2021.705458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204288PMC
June 2021

Association of ACEi/ARB Use and Clinical Outcomes of COVID-19 Patients With Hypertension.

Front Cardiovasc Med 2021 31;8:577398. Epub 2021 May 31.

State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Evidence has shown that angiotensin-converting enzyme 2 (ACE2), which can be upregulated after angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, may play a dual role in the pathogenesis and progression of coronavirus disease 2019 (COVID-19). We aimed to assess the association between the use of ACEi/ARB and the outcome of COVID-19 patients with preexisting hypertension in non-endemic areas. From January 17, 2020, to February 19, 2020, 286 patients with hypertension were enrolled in this retrospective study out of 1,437 COVID-19 patients from 47 centers in Zhejiang and Jiangsu Province. The composite endpoints consisted of mechanical ventilation, intensive care unit (ICU) admission, or death. Cox proportional hazards analysis was performed to assess the association between ACEi/ARB and clinical outcomes of COVID-19 patients with hypertension. In the main analysis, 103 patients receiving ACEi/ARB were compared with 173 patients receiving other regimens. Overall, 44 patients (15.94%) had an endpoint event. The risk probability of crude endpoints in the ACEi/ARB group (12.62%) was lower than that in the non-ACEi/ARB group (17.92%). After adjusting for confounding factors by inverse probability weighting, the results showed that the use of ACEi/ARB reduced the occurrence of end events by 47% [hazard ratio (HR) = 0.53; 95% CI, 0.34-0.83]. Similar results were obtained in multiple sensitivity analyses. In this retrospective study, among COVID-19 patients with hypertension, the use of ACEi/ARB is not associated with an increased risk of disease severity compared with patients without ACEi/ARB. The trends of beneficial effects of ACEi/ARB need to be further evaluated in randomized clinical trials.
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http://dx.doi.org/10.3389/fcvm.2021.577398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202940PMC
May 2021

Design and Engineering of Hypoxia and Acidic pH Dual-Stimuli-Responsive Intelligent Fluorescent Nanoprobe for Precise Tumor Imaging.

Small 2021 Jul 12;17(28):e2100243. Epub 2021 Jun 12.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Institute of Chemical Biology and Nanomedicine (ICBN), Hunan University, Changsha, 410082, China.

Stimulus-responsive fluorescence imaging modality shows great promise for detection of tumor due to the advantages of high sensitivity, simplicity and noninvasiveness. However, some non-cancer regions including nodules and inflammation may also exhibit a stimulus-related characteristic, which cause the problem of nonspecific responsiveness and then cause "false positive" results for tumor recognition. Herein, hypoxia and acidic pH, two typical features strongly associated with tumor invasion, progression and metastasis in tumor microenvironment (TME), are chosen as dual stimuli to fabricate "dual lock-and-key" fluorescent nanoprobe for highly specific and precise imaging of tumor cells. Mesoporous silica coated gold nanorods ([email protected] ) are employed as nanocarrier and nanoquencher to load the pH-sensitive fluorescent reporter (Rho-TP). Azobenzene (azo) which can be reduced to amines by the highly expressed azoreductase under hypoxic conditions, is elected as the effective gatekeeper for [email protected] by forming complex with β-cyclodextrin polymer via host-guest interaction (azo/β-CDP). By elaborately combining the hypoxia-responsive gatekeeper and pH-responsive fluorescent signal reporter into one nanoprobe, sensitive and specific imaging of tumor cells can be realized. The fabricated dual lock-and-key fluorescent nanoprobe successfully further apply in tumor-bearing mice model, which indicate potential of early diagnosis and assessment of cancer treatment.
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http://dx.doi.org/10.1002/smll.202100243DOI Listing
July 2021

Interferon-α-2b aerosol inhalation is associated with improved clinical outcomes in patients with coronavirus disease-2019.

Br J Clin Pharmacol 2021 May 13. Epub 2021 May 13.

State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou City, 310003, China.

Aims: Type 1 interferon (IFN) is used to treat patients with coronavirus disease-2019 (COVID-19) but robust supporting evidence is lacking. We investigated the association between IFN-α-2b and the clinical outcomes of patients with COVID-19.

Methods: A total of 1401 patients were enrolled, with 852 (60.8%) patients receiving 5 000 000 U of IFN-α-2b via aerosol inhalation twice daily. The primary outcome was a composite measure consisting of mechanical ventilation, intensive care unit (ICU) admission and death. A subgroup analysis was performed to investigate the impact of the IFN-α-2b initiation schedule on symptom onset.

Results: The risk probability for crude endpoints was lower in the IFN-α-2b group (3.8%) than in the non-IFN-α-2b group (9.3%, P < .001). After adjusting the confounding factors, IFN-α-2b therapy achieved a reduction of 64% in occurrence of endpoint events (hazard ratio, 0.36; 95% confidence interval [CI], 0.21-0.62). In the subgroup analysis, compared with patients who received IFN-α-2b treatment 0-2 days after symptom onset, the hazard ratio for endpoints was 2.2 (95% CI, 0.43-11.13) in patients who received the therapy 3-5 days after symptom onset, 5.89 (95% CI, 0.99-35.05) in patients who received the therapy 6-8 days after symptom onset, and remained at a high level thereafter.

Conclusions: IFN-α-2b aerosol inhalation therapy may be associated with improved clinical outcomes in patients with COVID-19, and delayed IFN-α-2b intervention was associated with increased probabilities of risk events. Further randomized clinical trials are needed to validate the preliminary findings of this study.
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http://dx.doi.org/10.1111/bcp.14898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239515PMC
May 2021

PEGylated AIEgen molecular probe for hypoxia-mediated tumor imaging and photodynamic therapy.

Chem Commun (Camb) 2021 May;57(38):4710-4713

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, China.

We report a novel PEGylated aggregation-induced emission luminogen (AIEgen) molecular probe for hypoxia-mediated tumor imaging and photodynamic therapy by linking a PEG chain to the AIE-active photosensitizer via a hypoxia-sensitive azo group.
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http://dx.doi.org/10.1039/d1cc00967bDOI Listing
May 2021

Tablet Use Affects Preschoolers' Executive Function: fNIRS Evidence from the Dimensional Change Card Sort Task.

Brain Sci 2021 Apr 29;11(5). Epub 2021 Apr 29.

School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518061, China.

This study aims to examine the impact of heavy use of tablets on preschoolers' executive function during the Dimensional Change Card Sort (DCCS) task using the functional near-infrared spectroscopy (fNIRS). Altogether, 38 Chinese preschoolers ( = 5.0 years, = 0.69 years, 17 girls) completed the tasks before the COVID-19 lockdown. Eight children never used tablets, while 16 children were diagnosed as the 'heavy-user'. The results indicated that: (1) the 'non-user' outperformed the 'heavy-user' with a significantly higher correct rate in the DCCS task; (2) the two groups differed significantly in the activation of the prefrontal cortex (BA 9): the 'non-user' pattern is normal and healthy, whereas the 'heavy-user' pattern is not normal and needs further exploration.
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http://dx.doi.org/10.3390/brainsci11050567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146550PMC
April 2021

Synthesis of Desacyl Furanmonogones A and B.

Org Lett 2021 Jun 29;23(12):4532-4537. Epub 2021 Apr 29.

State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055, China.

A strategy for the stereoselective synthesis of desacyl furanmonogones A and B has been achieved. The key steps in this synthesis are (1) an Fe(ClO)-mediated oxidative radical cyclization for construction of a -fused [5-6]-bicyclic core with a bridged lactone substitute, (2) a phosphorane-mediated rearrangement to convert the -fused [5-6]-bicyclic core to the corresponding -fused [5-6]-bicyclic core, and (3) a Au-catalyzed cascade reaction for formation of the 4,5--3(2)-furanone motif.
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http://dx.doi.org/10.1021/acs.orglett.1c01157DOI Listing
June 2021

A CaO @Tannic Acid-Fe Nanoconjugate for Enhanced Chemodynamic Tumor Therapy.

ChemMedChem 2021 Jul 4;16(14):2278-2286. Epub 2021 May 4.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, China.

Chemodynamic therapy (CDT) is an effective tumor treatment strategy in which Fe reacts with hydrogen peroxide (H O ) in tumor cells to produce highly toxic hydroxyl radical ( OH) through the Fenton reaction. However, the content of endogenous H O in cells is limited, and the reaction between Fe and H O is inefficient, greatly limiting the efficiency of the Fenton reaction and reducing the effectiveness of tumor treatment. Therefore, in this work, we designed and synthesized a new type of nano-system (CaO @TA-Fe ) for the enhanced CDT of tumors, in which the polyphenolic compound- tannic acid (TA) and Fe formed a TA-Fe nano-coating on the surface of calcium peroxide (CaO ) nanospherical aggregates. When the CaO @TA-Fe nanoconjugates reach the tumor site, the CaO contained in the nanoconjugates produces H O after disintegration in tumor cells, and the carried TA rapidly reduces Fe to Fe , solving the two major shortcomings in CDT of (1) insufficient content of H O in cancer cells, and (2) low catalytic efficiency of the Fenton reaction. Additionally, the OH produced in the Fenton reaction induces oxidative stress for the tumor cells, promoting the occurrence of the "calcium overload" process, and thereby accelerating the death of tumor cells. Experimental results in vitro and in vivo showed that CaO @TA-Fe nanoconjugates can effectively kill cancer cells and display an excellent tumor therapeutic effect. We believe that the CaO @TA-Fe nanoconjugates are a promising new nano-platform for highly effective tumor treatment.
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http://dx.doi.org/10.1002/cmdc.202100108DOI Listing
July 2021

Human placenta mesenchymal stem cell-derived exosomes delay HO-induced aging in mouse cholangioids.

Stem Cell Res Ther 2021 03 22;12(1):201. Epub 2021 Mar 22.

State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou City, 310003, China.

Background: Cholangiocyte senescence is an important pathological process in diseases such as primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC). Stem cell/induced pluripotent stem cell-derived exosomes have shown anti-senescence effects in various diseases. We applied novel organoid culture technology to establish and characterize cholangiocyte organoids (cholangioids) with oxidative stress-induced senescence and then investigated whether human placenta mesenchymal stem cell (hPMSC)-derived exosomes exerted a protective effect in senescent cholangioids.

Methods: We identified the growth characteristics of cholangioids by light microscopy and confocal microscopy. Exosomes were introduced concurrently with HO into the cholangioids. Using immunohistochemistry and immunofluorescence staining analyses, we assessed the expression patterns of the senescence markers p16, p21, and senescence-associated β-galactosidase (SA-β-gal) and then characterized the mRNA and protein expression levels of chemokines and senescence-associated secretory phenotype (SASP) components.

Results: Well-established cholangioids expressed cholangiocyte-specific markers. Oxidative stress-induced senescence enhanced the expression of the senescence-associated proteins p16, p21, and SA-β-gal in senescent cholangioids compared with the control group. Treatment with hPMSC-derived exosomes delayed the cholangioid aging progress and reduced the levels of SASP components (i.e., interleukin-6 and chemokine CC ligand 2).

Conclusions: Senescent organoids are a potential novel model for better understanding senescence progression in cholangiocytes. hPMSC-derived exosomes exert protective effects against senescent cholangioids under oxidative stress-induced injury by delaying aging and reducing SASP components, which might have therapeutic potential for PSC or PBC.
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http://dx.doi.org/10.1186/s13287-021-02271-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983269PMC
March 2021

Effect of Long-Term Fertilization on Ammonia-Oxidizing Microorganisms and Nitrification in Brown Soil of Northeast China.

Front Microbiol 2020 4;11:622454. Epub 2021 Feb 4.

College of Land and Environment, Shenyang Agricultural University, Shenyang, China.

The objective of this study was to find out changes in ammonia oxidation microorganisms with respect to fertilizer as investigated by real-time polymerase chain reaction and high-throughput sequencing. The treatments included control (CK); chemical fertilizer nitrogen low (N) and high (N); nitrogen and phosphorus (NP); nitrogen phosphorus and potassium (NPK) and organic manure fertilizer (M); MN; MN; MNPK. The results showed that long-term fertilization influenced soil fertility and affected the abundance and community of ammonia-oxidizing microorganisms by changing the physical and chemical properties of the soil. The abundance and community structure of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) was influenced by soil organic carbon, total nitrogen, total soil phosphorus, available phosphorus, available potassium, and soil nitrate. Soil environmental factors affected the nitrification potential by affecting the structure of ammonia-oxidizing microorganisms; specific and rare AOA and AOB rather than the whole AOA or AOB community played dominant role in nitrification.
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http://dx.doi.org/10.3389/fmicb.2020.622454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890093PMC
February 2021

Gut Escherichia coli expressing Pb-adsorption protein reduces lead accumulation in grass carp, Ctenopharyngodon idellus.

Environ Pollut 2021 May 2;276:116634. Epub 2021 Feb 2.

Gansu Key Laboratory of Biomonitoring and Bioremediation for Environment Pollution, School of Life Science, Lanzhou University, 222 South Tianshui Rd, Lanzhou, Gansu, 730000, PR China. Electronic address:

Lead (Pb) is easy to accumulate in fish which become a major source of Pb exposure to humans. In this study, a recombinant Escherichia coli strain expressing Pb-specific surface-binding protein anchored by the ice nucleation protein was introduced into grass carp (Ctenopharyngodon idellus) gut to investigate its protective effect against dietary Pb exposure. Pb mostly precipitated on the surface of the engineered strain through Pb-specific surface-binding protein, with a maximum adsorption efficiency of 73% and an adsorption capacity of 163 μmol/g dry cells. The Pb concentration in engineered bacteria-fed grass carp was reduced significantly, and the residual level of Pb in feces was increased by 76%, compared with the control group. Meantime, the engineered bacteria were able to mitigate the oxidative stress and histological alterations of intestines and dysbiosis of gut microbiota induced by Pbexposure. Thus, the engineered bacterium that can effectively reduce Pb residue in grass carp might be a useful tool for decontamintion of lead in aquatic organisms.
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http://dx.doi.org/10.1016/j.envpol.2021.116634DOI Listing
May 2021

A Functional Near-Infrared Spectroscopy Examination of the Neural Correlates of Cognitive Shifting in Dimensional Change Card Sort Task.

Front Hum Neurosci 2020 21;14:561223. Epub 2021 Jan 21.

School of Biomedical Engineering, Shenzhen University, Shenzhen, China.

This study aims to examine the neural correlates of cognitive shifting during the task with functional near-infrared spectroscopy. Altogether 49 children completed the tasks, and 25 children (M = 68.66, SD = 5.3) passing all items were classified into the Switch group. Twenty children (M = 62.05, SD = 8.13) committing more than one perseverative errors were grouped into the Perseverate group. The Switch group had Brodmann Area (BA) 9 and 10 activated in the pre-switch period and BA 6, 9, 10, 40, and 44 in the post-switch period. In contrast, the Perseverate group had BA 9 and 10 activated in the pre-switch period and BA 8, 9, 10 in the post-switch period. The general linear model results afford strong support to the "V-shape curve" hypothesis by identifying a significant decrease-increase cycle in BA 9 and 44, the neural correlations of cognitive shifting.
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http://dx.doi.org/10.3389/fnhum.2020.561223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859114PMC
January 2021

Neural Correlates of Mental Rotation in Preschoolers With High or Low Working Memory Capacity: An fNIRS Study.

Front Psychol 2020 10;11:568382. Epub 2020 Dec 10.

Macquarie University, Sydney, NSW, Australia.

This study explored the differentiated neural correlates of mental rotation (MR) in preschoolers with high and low working memory capacity using functional near-infrared spectroscopy (fNIRS). Altogether 38 Chinese preschoolers ( = 5.0 years, = 0.69 years) completed the (WMC) test, the (MR), and its Control tasks (without MR). They were divided into High-WMC ( = 9) and Low-WMC ( = 18) groups based on the WMC scores. The behavioral and fNIRS results indicated that: (1) there were no significant differences in MR task performance between the High-WMC ( = 23.44, = 0.88) and Low-WMC group ( = 23.67, = 0.59); (2) the Low-WMC group activated BA6, BA8, BA 9, and BA 44, whereas the High-WMC group activated BA8, BA10 and BA 44 during mental rotation; (3) significant differences were found in the activation of BA44 and BA9 between the High-WMC and Low-WMC groups during mental rotation; and (4) the High-WMC and Low-WMC groups differed significantly in the activation of BA 9 and BA10 during the control tasks, indicating that both areas might be responsible for the group differences in working memory.
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http://dx.doi.org/10.3389/fpsyg.2020.568382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758205PMC
December 2020

Th1/Th2 Cells and Associated Cytokines in Acute Hepatitis E and Related Acute Liver Failure.

J Immunol Res 2020 17;2020:6027361. Epub 2020 Nov 17.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China.

Background And Aims: The involvement of cellular immunity in the development of hepatitis E virus (HEV) infection is rare. We aimed to study the roles of viral load and Th cell responses in acute hepatitis E (AHE) and HEV-related acute liver failure (HEV-ALF).

Methods: We evaluated viral load and Th1/Th2 cytokine levels in 34 patients with HEV infection, including 17 each with AHE or HEV-ALF. Seventeen healthy controls (HCs) were also included who were negative for anti-HEV IgM and IgG.

Results: There was no significant difference in viral load and HEV RNA in the AHE and HEV-ALF groups (both > 0.05). The Th lymphocyte levels (CD3+, CD4+) in the AHE and HEV-ALF groups were significantly higher than those in the HC group (both < 0.05), but there was no significant difference between the AHE and HEV-ALF groups ( > 0.05). Both IFN- and IL-10 showed gradual upward trend from the HC group to the AHE (both < 0.01), but IFN- showed a sharp downward trend from the AHE group to the HEV-ALF group ( < 0.01) and IL-4 showed gradual upward trend from the AHE group to the HEV-ALF group ( < 0.01).There was no significant difference in Th1 and Th2 cytokines between the HEV RNA(+) group and HEV RNA(-) group (all > 0.05). Th2 bias was observed from the AHE (ratio = 58.65) to HEV-ALF (ratio = 1.20) groups. The level of IFN- was associated with the outcome of HEV-ALF patients.

Conclusions: HEV viral load was not associated with aggravation of AHE, and the HEV-ALF patients showed significant Th2 bias, which may be involved in the aggravation of AHE.
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http://dx.doi.org/10.1155/2020/6027361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691005PMC
November 2020

ICOSL plasmacytoid dendritic cells as inducer of graft-versus-host disease, responsive to a dual ICOS/CD28 antagonist.

Sci Transl Med 2020 10;12(564)

Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Acute graft-versus-host disease (aGVHD) remains a major complication of allogeneic hematopoietic cell transplantation (HCT). CD146 and CCR5 are proteins that mark activated T helper 17 (Th17) cells. The Th17 cell phenotype is promoted by the interaction of the receptor ICOS on T cells with ICOS ligand (ICOSL) on dendritic cells (DCs). We performed multiparametric flow cytometry in a cohort of 156 HCT recipients and conducted experiments with aGVHD murine models to understand the role of ICOSL DCs. We observed an increased frequency of ICOSL plasmacytoid DCs, correlating with CD146CCR5 T cell frequencies, in the 64 HCT recipients with gastrointestinal aGVHD. In murine models, donor bone marrow cells from ICOSL-deficient mice compared to those from wild-type mice reduced aGVHD-related mortality. Reduced aGVHD resulted from lower intestinal infiltration of pDCs and pathogenic Th17 cells. We transplanted activated human ICOSL pDCs along with human peripheral blood mononuclear cells into immunocompromised mice and observed infiltration of intestinal CD146CCR5 T cells. We found that prophylactic administration of a dual human ICOS/CD28 antagonist (ALPN-101) prevented aGVHD in this model better than did the clinically approved belatacept (CTLA-4-Fc), which binds CD80 (B7-1) and CD86 (B7-2) and interferes with the CD28 T cell costimulatory pathway. When started at onset of aGVHD signs, ALPN-101 treatment alleviated symptoms of ongoing aGVHD and improved survival while preserving antitumoral cytotoxicity. Our data identified ICOSL-pDCs as an aGVHD biomarker and suggest that coinhibition of the ICOSL/ICOS and B7/CD28 axes with one biologic drug may represent a therapeutic opportunity to prevent or treat aGVHD.
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http://dx.doi.org/10.1126/scitranslmed.aay4799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811191PMC
October 2020

Letter: gastrointestinal symptoms pre-admission are associated with greater severity of COVID-19.

Aliment Pharmacol Ther 2020 Oct;52(7):1229-1230

State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou City, China.

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http://dx.doi.org/10.1111/apt.15985DOI Listing
October 2020

Immunosuppressive effects of mesenchymal stem cells on lung B cell gene expression in LPS-induced acute lung injury.

Stem Cell Res Ther 2020 09 25;11(1):418. Epub 2020 Sep 25.

State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Rd, Hangzhou City, 310003, China.

Background: Immune system disorders play important roles in acute lung injury (ALI), and mesenchymal stem cell (MSC) treatment can reduce inflammation during ALI. In this study, we compared the changes in lung B cells during MSC treatment.

Methods: We investigated the effects of MSCs on lung B cells in a mouse model of lipopolysaccharide (LPS)-induced ALI. MSCs were administered intratracheally 4 h after LPS. As vehicle-treated controls, mice were treated with phosphate-buffered saline (PBS) containing 2% C57BL/6 (PBS group). Histopathological changes, survival rate, inflammatory factor levels, and the number of neutrophils in bronchoalveolar lavage fluid (BALF) were determined. Single-cell RNA sequencing (scRNA-Seq) analysis was performed to evaluate the transcriptional changes in lung B cells between the PBS, LPS, and LPS/MSC groups on days 3 and 7.

Results: MSC treatment ameliorated LPS-induced ALI, as indicated by the reductions in mortality, the levels of chemokines and cytokines in BALF, and the severity of lung tissue histopathology in ALI mice. Lung B cells in the PBS group remained undifferentiated and had an inhibitory phenotype. Based on our scRNA-Seq results, the differentially expressed genes (DEGs) in lung B cells in both the PBS group and LPS group were involved in chemotaxis processes and some proinflammatory pathways. MSC treatment inhibited the expression of chemokine genes that were upregulated by LPS and were related to the recruitment of neutrophils into lung tissues. Immunoglobulin-related gene expression was decreased in lung B cells of mice treated with LPS/MSC for 7 days. The DEGs regulated by MSCs were enriched in biological processes, including humoral immune response and apoptotic signaling.

Conclusions: Lung B cells played an important role in the effects of treatment of ALI with MSCs. These observations provide new insights into the mechanisms underlying the effects of MSC treatment for ALI.
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http://dx.doi.org/10.1186/s13287-020-01934-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517809PMC
September 2020

Manure application increased crop yields by promoting nitrogen use efficiency in the soils of 40-year soybean-maize rotation.

Sci Rep 2020 09 10;10(1):14882. Epub 2020 Sep 10.

College of Land and Environment, Shenyang Agricultural University, Shenyang, 110866, China.

It is great of importance to better understand the effects of the long-term fertilization on crop yields, soil properties and nitrogen (N) use efficiency in a rotation cropping cultivation system under the conditions of frequent soil disturbance. Therefore, a long-term field experiment of 40 years under soybean-maize rotation was performed in a brown soil to investigate the effects of inorganic and organic fertilizers on crop yields, soil properties and nitrogen use efficiency. Equal amounts of N-labelled urea with 20.8% of atom were used and uniformly applied into the micro-plots of the treatments with N, NPK, MNPK, MNPK before soybean sowing, respectively. Analyses showed that a total of 18.3-32.5% of applied N fertilizer was taken up by crops in the first soybean growing season, and that the application of manure combining with chemical fertilizer MNPK demonstrated the highest rate of N recovery and increased soil organic matter (SOM) and Olsen phosphorus (Olsen P), thereby sustaining a higher crop yield and alleviating soil acidification. Data also showed that no significant difference was observed in the N recovery from residue N in the second maize season plant despite of showing a lower N recovery compared with the first soybean season. The recovery rates of N in soils were ranged from 38.2 to 49.7% by the end of the second cropping season, and the residuals of N distribution in soil layers revealed significant differences. The MNPK treatment demonstrated the highest residual amounts of N, and a total of 50% residual N were distributed in a soil layer of 0-20 cm. Our results showed that long-term application of organic fertilizers could effectively promote N use efficiency by increasing SOM and improving soil fertility, and thus leading to an increase in crop yields. This study will provide a scientific reference and guidance for improving soil sustainable productivity by manure application.
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http://dx.doi.org/10.1038/s41598-020-71932-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483704PMC
September 2020

Sufentanil postoperative analgesia reduce the increase of T helper 17 (Th17) cells and FoxP3 regulatory T (Treg) cells in rat hepatocellular carcinoma surgical model: A randomised animal study.

BMC Anesthesiol 2020 08 26;20(1):212. Epub 2020 Aug 26.

Department of Anesthesiology, Perioperative Medicine and Pain Management, University of Miami-Miller School of Medicine, Miami, FL, 33136, USA.

Background: Surgery-related pain and opioids might exacerbate immune defenses in immunocompromised cancer patients which might affect postoperativd overall survival. Sufentanil is a good postoperative pain control drug,the present study aimed to figure out whether it effect T cell immunity in rat hepatocellular carcinoma surgical model.

Methods: A rat hepatocellular carcinoma (HCC) models was established by N-nitrosodiethylamine. Forty-eight of them were randomly divided into 3 equal groups: surgery without postoperative analgesia (Group C), surgery with morphine postoperative analgesia (Group M), surgery with sufentanil postoperative analgesia (Group S). Each animal underwent a standard left hepatolobectomy, and intraperitoneally implanted with osmotic minipumps filled with sufentanil, morphine or normal saline according to the different group. The food and water consumptions, body weight changes, locomotor activity and mechanical pain threshold (MPT) were observed. The ratio of CD4/CD8, proportions of Th1, Th2, Th17 and Treg cells in blood were detected using flow cytometry. The liver function and the rats' survival situation of each group were observed.

Results: The food and water consumption, locomotor activity and MPT of group C declined than those of group S and M on d1, d2, d3 (P < 0.05). The CD4/CD8 ratio and the proportion of Th1 cells were significantly higher while the proportion of Th2, Th17 and Treg cells were significantly lower in group S and group M compared with group C. The rats of group S have higher CD4/CD8 ratio on d3, while lower proportion of Treg cells on d7 compared with group M. The plasma ALT and AST values in group C were significantly higher than that of group S and group M on both d3 and d7. There were not significant differences in mortality rate between 3 groups.

Conclusions: Sufentanil and morphine postoperative analgesia in HCC rats accepted hepatectomy could relieve postoperative pain, promote the recovery of liver function after surgery, alleviate the immunosuppressive effect of pain. Furthermore, Compared to morphine, sufentanil might have a slighter effect on CD4/CD8 ratio and Treg frequencies. Therefore, sufentanil postoperative analgesia is better than morphine in HCC hepatectomy rats.
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http://dx.doi.org/10.1186/s12871-020-01129-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448519PMC
August 2020

Ternary multicomponent Ba/Mg/Si compounds with inherent bonding hierarchy and rattling Ba atoms toward low lattice thermal conductivity.

Phys Chem Chem Phys 2020 Sep 12;22(33):18556-18561. Epub 2020 Aug 12.

Institute for Computational Materials Science, School of Physics and Electronics, International Joint Research Laboratory of New Energy Materials and Devices of Henan Province, Henan University, Kaifeng, China.

Compositional tailoring externally enables the fine tuning of thermal transport parameters of materials using the dual modulation of electronic or thermal transport properties. Theoretically, we examined the lattice dynamics of three particularly ternary representatives with different stoichiometry, BaMgSi, BaMgSi, and BaMgSi, and identified the inherent bonding hierarchy and rattling Ba atoms, which were responsible for reducing the lattice thermal conductivity. BaMgSi and BaMgSi exhibited inherently ultra-low lattice thermal conductivity of 1.27-0.37 W m K in the range of 300-1000 K due to the bonding hierarchy and rattling Ba atoms. The low-energy optical phonons are overlapping with the acoustic phonons. This is associated with the intrinsic rattler-like vibration of Ba cations and leads to the characteristic in the localization of the propagative phonons and large anharmonicity. Although BaMgSi had a dumbbell-shaped Si-Si covalent and Ba-Si/Mg ionic bonding environment and intrinsic rattler-like vibration of Ba cations, the middle frequency optic phonon branches contribute considerably to the thermal conductivity of the lattice. At the same temperature, compared with BaMgSi and BaMgSi, the lattice thermal conductivity of BaMgSi almost doubles owing to the higher phonon lifetime and group velocities. Our findings highlight considerable potential for thermoelectric applications with a different stoichiometric ratio of Ba/Mg/Si systems due to their low lattice thermal conductivities via intrinsic modulating stoichiometry.
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http://dx.doi.org/10.1039/d0cp02792hDOI Listing
September 2020

Comparing post-operative analgesic effects of varying doses of dexmedetomidine as an adjuvant to ropivacaine for ultrasound-guided dual transversus abdominis plane block following laparotomy for gynecologic malignancies.

Exp Ther Med 2020 Aug 25;20(2):860-867. Epub 2020 May 25.

Department of Anesthesiology, Hunan Cancer Hospital, Changsha, Hunan 410013, P.R. China.

The aim of the present study was to determine the analgesic effects of ropivacaine combined with different doses of dexmedetomidine for ultrasound-guided transversus abdominis plane (TAP) block immediately following laparotomy in patients with gynecologic malignancies. A further aim was to determine the appropriate clinical dose of dexmedetomidine as an adjuvant for ropivacaine. Patients with gynecologic malignancies scheduled for laparotomy were randomly assigned to group R (TAP block with 0.3% ropivacaine), group RD1 (TAP block with ropivacaine and 0.5 µg/kg dexmedetomidine), group RD2 (TAP block with ropivacaine and 1 µg/kg dexmedetomidine) and group RD3 (TAP block with ropivacaine and 2 µg/kg dexmedetomidine). TAP blocks were performed post-operatively. The four groups all received patient-controlled intravenous analgesia (PCIA) after the operation. The numerical rating scale (NRS) as well as the Ramsay sedation scale (RSS) scores, the first request time for PCIA bolus, oxycodone hydrochloride consumption, the plasma concentration of ropivacaine, the incidence of post-operative complications and adverse events, and patient satisfaction were recorded. Post-operative NRS scores at rest exhibited significant differences between the R group and all the RD groups at 24 h after surgery (P<0.05). Compared with the other groups, the NRS score in the RD3 group was decreased (P<0.05). The RSS scores were higher in all of the RD groups compared with those in the R group at 2 h (P<0.05) and were highest in the RD3 group compared with those in all other groups at 4 h (P<0.05). The first request time for PCIA was significantly longer in the RD3 group compared with that in the RD2, RD1 and R groups (510.47±102.67, 595.47±100.11, 682.43±104.46 and 776.42±143.91 min, respectively; P<0.05). Cumulative opioid consumption based on the number of PCIA bolus requested at 24 and 48 h post-operatively indicated that the total number of PCIA boluses was significantly lower in the RD groups compared with those in the R group at 24 and 48 h (P<0.05). The ropivacaine concentration did not differ among the four groups. There was no significant difference between groups with respect to post-operative nausea and vomiting, bradycardia and hypotension; however, all RD groups had a higher patient satisfaction than group R (P<0.05). Compared with that in the other groups, the duration of post-anesthesia care unit stay in group RD3 was relatively longer due to excessive sedation (P<0.05). In conclusion, TAP blockade using 0.5-2 µg/kg dexmedetomidine combined with 0.3% ropivacaine is a safe and effective treatment for analgesia in laparotomy procedures for gynecologic malignancies. The study was registered in the Chinese Clinical Trial Registry (CHICTR; www.chictr.org.cn) on January 15th, 2019 (registration no. ChiCTR1900020995).
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http://dx.doi.org/10.3892/etm.2020.8787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388559PMC
August 2020

Compact low-voltage electro-optic Q-switch made of LiNbO.

Opt Express 2020 Jul;28(15):22287-22296

This work presents a compact LiNbO (lithium niobate, LN) electro-optic (EO) Q-switch with a lower driving voltage than the conventional LN Q-switches. By using non-direct cuts of a certain crystallographic orientation, a LN crystal is used both as a quarter-wave plate (QWP) and a pockels cell in a laser cavity. Through theoretical calculations and experiments, we have determined the optimized crystal orientations with low quarter-wave voltages (QWV). A set of compact LN EO Q-switches were prepared and used successfully in the pulse-on mode in a Nd:YAG laser. The Q-switched laser outputs are comparable to those obtained by using a conventional Z-cut LN Q-switch with a QWP. The QWV of the Q-switch with the optimized crystal orientation is 600V lower than that of the Z-cut LN Q-switch.
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http://dx.doi.org/10.1364/OE.393958DOI Listing
July 2020

Development and validation of a risk stratification model for screening suspected cases of COVID-19 in China.

Aging (Albany NY) 2020 07 29;12(14):13882-13894. Epub 2020 Jul 29.

State Key Laboratory for The Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.

How to quickly identify high-risk populations is critical to epidemic control. We developed and validated a risk prediction model for screening SARS-CoV-2 infection in suspected cases with an epidemiological history. A total of 1019 patients, ≥13 years of age, who had an epidemiological history were enrolled from fever clinics between January 2020 and February 2020. Among 103 (10.11%) cases of COVID-19 were confirmed. Multivariable analysis summarized four features associated with increased risk of SARS-CoV-2 infection, summarized in the mnemonic COVID-19-REAL: radiological evidence of pneumonia (1 point), eosinophils < 0.005 × 10/L (1 point), age ≥ 32 years (2 points), and leukocytes < 6.05 × 10 /L (1 point). The area under the ROC curve for the training group was 0.863 (95% CI, 0.813 - 0.912). A cut-off value of less than 3 points for COVID-19-REAL was assigned to define the low-risk population. Only 10 (2.70%) of 371 patients were proved to be SARS-CoV-2 positive, with a negative predictive value of 0.973. External validation was similar. This study provides a simple, practical, and robust screening model, COVID-19-REAL, able to identify populations at high risk for SARS-CoV-2 infection.
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http://dx.doi.org/10.18632/aging.103694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425460PMC
July 2020

Successful Treatment of Refractory Cancer Pain and Depression with Continuous Intrathecal Administration of Dexmedetomidine and Morphine: A Case Report.

Pain Ther 2020 Dec 12;9(2):797-804. Epub 2020 Jul 12.

Department of Anesthesiology and Pain Medicine, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, 410013, China.

Patients who have refractory cancer pain suffer both physically and psychologically. Cancer pain management has improved over the past few decades. However, the treatment of refractory cancer pain is still challenging all over the world. Intraspinal analgesia has become an effective strategy to treat refractory pain in patients with cancer. In this report, we present a patient receiving a large dose of intrathecal opioids for refractory cancer pain, and who is also afflicted with pain-induced depression. Dexmedetomidine (DEX) was used as part of a multimodal analgesic regimen that successfully alleviated both the patient's pain and depression. An intrathecal infusion of DEX may serve as an adjuvant drug in the treatment of cancer pain and pain-related depression.
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http://dx.doi.org/10.1007/s40122-020-00183-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648823PMC
December 2020

Cadmium toxicity reduction in rice (Oryza sativa L.) through iron addition during primary reaction of photosynthesis.

Ecotoxicol Environ Saf 2020 Sep 22;200:110746. Epub 2020 May 22.

National Engineering Laboratory for Efficient Utilization of Soil and Fertilizer Resources, College of Land and Environment, Shenyang Agricultural University, Shenyang, 110866, China. Electronic address:

Cadmium (Cd) pollution is a worldwide concern due to its biotoxicity. Because Cd and Fe are closely associated during plant photosynthesis, this study aims at investigating the mechanism governing Cd toxicity during photosynthetic primary reaction in rice by adjusting Fe concentration. The results show that moderate Fe concentration (1.0 g kg) added to soil can increase the stomatal conductance (Gs) and SPAD value by stimulating the stomatal opening and chlorophyll synthesis. Moderate Fe concentration can also improve the maximum fluorescence (Fm) and the maximal photochemical efficiency (Fv/Fm) to keep the high reaction center activity and electronic transfer efficiency in photosystems I and II. Thus, moderate Fe can eliminate Cd-induced decrease in Gs, intercellular CO concentration (Ci) and net photosynthetic rate (Pn) as well as the disorder of antioxidative system under Cd concentration of 2.0 mg kg in the soil. When its application is increased to 2.0 g kg, Fe can notably decrease Pn, and result in remarkable decrease in the biomass of shoots and grains. Decrease in Pn can be mainly attributed to high Fe concentration which can greatly destroy chloroplast structure and, meanwhile, inhibit the electron transfer between acceptor and donator in photosynthetic chain especially from quinone A (Q) to quinone B (Q). Unlike the situation under moderate Fe concentration, the high Fe application cannot mitigate the Cd-induced decrease in photosynthetic index. Our results indicate that the moderate Fe application is necessary to promote rice performance and production and, in the meantime, to inhibit Cd toxicity in the extensively polluted soils.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110746DOI Listing
September 2020

Noncovalently Caged Firefly Luciferins Enable Amplifiable Bioluminescence Sensing of Hyaluronidase-1 Activity in Vivo.

ACS Sens 2020 06 2;5(6):1726-1733. Epub 2020 Jun 2.

Hunan Provincial Key Laboratory of Cytochemistry, School of Chemistry and Food Engineering, Changsha University of Science and Technology, Changsha 410114, P. R. China.

Hyaluronidase 1 (Hyal-1) is an important enzyme involved in intracellular hyaluronic acid (HA) catabolism for performing various physiological functions, and its aberrant level is closely associated with many malignant diseases. Bioluminescence imaging is advantageous for monitoring Hyal-1 activity in vivo, but it remains challenging to design an available probe for differentiating Hyal-1 from other isoforms by a traditional strategy that covalently masks the firefly luciferase substrate. Herein, we, for the first time, present a noncovalently caging approach to construct a Hyal-1-specific bioluminogenic nanosensor by entrapping d-luciferin (d-Luc) inside the cholesterylamine-modified HA (CHA) nanoassembly to inhibit the bioluminescence production. When encountered with intracellular Hyal-1, CHA could be fully dissembled to liberate multiple copies of the loaded d-Luc, thereby emitting light by the luciferase-catalyzed bioluminescence reaction. Because of its cascade signal amplification feature, [email protected] displayed a remarkable "turn-on" response (248-fold) to 5 μg/mL Hyal-1 with a detection limit of 0.07 ng/mL. Importantly, bioluminescence imaging results validated that [email protected] could be competent for dynamically visualizing endogenous Hyal-1 changes in living cells and animals and possessed the capability of discriminating between normal and cancer cells, thus offering a promising toolbox to evaluate Hyal-1 roles in biological processes as well as to diagnose Hyal-1-related diseases.
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http://dx.doi.org/10.1021/acssensors.0c00393DOI Listing
June 2020

ST2 as checkpoint target for colorectal cancer immunotherapy.

JCI Insight 2020 05 7;5(9). Epub 2020 May 7.

Department of Medical and Molecular Genetics.

Immune checkpoint blockade immunotherapy delivers promising clinical results in colorectal cancer (CRC). However, only a fraction of cancer patients develop durable responses. The tumor microenvironment (TME) negatively impacts tumor immunity and subsequently clinical outcomes. Therefore, there is a need to identify other checkpoint targets associated with the TME. Early-onset factors secreted by stromal cells as well as tumor cells often help recruit immune cells to the TME, among which are alarmins such as IL-33. The only known receptor for IL-33 is stimulation 2 (ST2). Here we demonstrated that high ST2 expression is associated with poor survival and is correlated with low CD8+ T cell cytotoxicity in CRC patients. ST2 is particularly expressed in tumor-associated macrophages (TAMs). In preclinical models of CRC, we demonstrated that ST2-expressing TAMs (ST2+ TAMs) were recruited into the tumor via CXCR3 expression and exacerbated the immunosuppressive TME; and that combination of ST2 depletion using ST2-KO mice with anti-programmed death 1 treatment resulted in profound growth inhibition of CRC. Finally, using the IL-33trap fusion protein, we suppressed CRC tumor growth and decreased tumor-infiltrating ST2+ TAMs. Together, our findings suggest that ST2 could serve as a potential checkpoint target for CRC immunotherapy.
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http://dx.doi.org/10.1172/jci.insight.136073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253019PMC
May 2020

Biomarkers for Allogeneic HCT Outcomes.

Front Immunol 2020 21;11:673. Epub 2020 Apr 21.

Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, United States.

Allogeneic hematopoietic cell transplantation (HCT) remains the only curative therapy for many hematological malignant and non-malignant disorders. However, key obstacles to the success of HCT include graft-versus-host disease (GVHD) and disease relapse due to absence of graft-versus-tumor (GVT) effect. Over the last decade, advances in "omics" technologies and systems biology analysis, have allowed for the discovery and validation of blood biomarkers that can be used as diagnostic test and prognostic test (that risk-stratify patients before disease occurrence) for acute and chronic GVHD and recently GVT. There are also predictive biomarkers that categorize patients based on their likely to respond to therapy. Newer mathematical analysis such as machine learning is able to identify different predictors of GVHD using clinical characteristics pre-transplant and possibly in the future combined with other biomarkers. Biomarkers are not only useful to identify patients with higher risk of disease progression, but also help guide treatment decisions and/or provide a basis for specific therapeutic interventions. This review summarizes biomarkers definition, omics technologies, acute, chronic GVHD and GVT biomarkers currently used in clinic or with potential as targets for existing or new drugs focusing on novel published work.
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http://dx.doi.org/10.3389/fimmu.2020.00673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186420PMC
March 2021

[Clinical study of concealed penis correction surgery based on principle of midline symmetry].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2020 Apr;34(4):505-508

Department of Pediatric Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong Sichuan, 637000, P.R.China.

Objective: To investigate the effectiveness of concealed penis correction surgery based on the principle of midline symmetry.

Methods: Between January 2016 and September 2018, 18 children with concealed penis were treated with correction surgery based on the principle of midline symmetry. All children were 3-12 years old, with an average age of 8.3 years. Physical examination showed that the penis was short; the penis body could not be exposed or be exposed too limited; the corpus cavernosum developed well. The pressure dressing was removed at 3 days after operation and the urethral tube was removed. The color of the glans, the swelling and congestion of penis and scrotum, and the blood supple of the prepuce flap were observed.

Results: The operation time ranged from 47 to 54 minutes, with an average of 50 minutes. All children were followed up 3 months after operation. There was no hemorrhage and necrosis of the glans and no infection or ischemic necrosis of the flap. All patients had different degree of prepuce edema at 3 days after operation, 5 patients still had prepuce edema at 2 weeks, and the prepuce edema in all patients subsided at 3 months. All penises were exposed well after midline symmetric anastomosis with no bulky prepuce and scrotum.

Conclusion: The correction surgery based on the principle of midline symmetry can be used to correct the appearance of the concealed penis effectively.
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http://dx.doi.org/10.7507/1002-1892.201909106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171519PMC
April 2020
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