Publications by authors named "Zewen Zhang"

27 Publications

  • Page 1 of 1

Dual-Solvent Li-Ion Solvation Enables High-Performance Li-Metal Batteries.

Adv Mater 2021 May 9:e2008619. Epub 2021 May 9.

Department of Materials Science and Engineering, Stanford University, Stanford, CA, 94305, USA.

Novel electrolyte designs to further enhance the lithium (Li) metal battery cyclability are highly desirable. Here, fluorinated 1,6-dimethoxyhexane (FDMH) is designed and synthesized as the solvent molecule to promote electrolyte stability with its prolonged -CF - backbone. Meanwhile, 1,2-dimethoxyethane is used as a co-solvent to enable higher ionic conductivity and much reduced interfacial resistance. Combining the dual-solvent system with 1 m lithium bis(fluorosulfonyl)imide (LiFSI), high Li-metal Coulombic efficiency (99.5%) and oxidative stability (6 V) are achieved. Using this electrolyte, 20 µm Li||NMC batteries are able to retain ≈80% capacity after 250 cycles and Cu||NMC anode-free pouch cells last 120 cycles with 75% capacity retention under ≈2.1 µL mAh lean electrolyte conditions. Such high performances are attributed to the anion-derived solid-electrolyte interphase, originating from the coordination of Li-ions to the highly stable FDMH and multiple anions in their solvation environments. This work demonstrates a new electrolyte design strategy that enables high-performance Li-metal batteries with multisolvent Li-ion solvation with rationally optimized molecular structure and ratio.
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http://dx.doi.org/10.1002/adma.202008619DOI Listing
May 2021

Preliminary Investigation about the Expression of G Protein-Coupled Receptors in Platelets from Patients with Chronic Immune Thrombocytopenic Purpura.

Acta Haematol 2021 Apr 13:1-9. Epub 2021 Apr 13.

Department of Clinical Laboratory Medicine, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China.

Objective: The objective of this study was to determine the expression of G protein-coupled receptors (GPCRs) in platelets from adult patients with chronic immune thrombocytopenic purpura (ITP).

Methods: Peripheral blood samples were collected from 40 patients with chronic ITP in the Second Affiliated Hospital of Shantou University Medical College, and 40 peripheral blood samples from healthy volunteers were collected; expressions of the adenosine diphosphate receptors (P2Y1 and P2Y12), alpha-2A adrenergic receptor (α2A-AR), and thromboxane A2 receptor (TP) in platelets were detected by flow cytometry. Gα protein, protease-activated receptor 1 (PAR1), and protease-activated receptor 4 (PAR4) were analyzed by Western blot and analyzed statistically.

Results: Flow cytometry measurements of mean fluorescence intensities showed platelets from patients with chronic ITP, compared to healthy individuals, had significantly higher levels of P2Y1 (31.4 ± 2.2 vs. 7.8 ± 0.8), P2Y12 (29.6 ± 2.1 vs. 7.2 ± 1.3), α2A-AR (25.8 ± 2.9 vs. 9.8 ± 0.9), and TP (39.8 ± 3.1 vs. 4.7 ± 0.6) (all p < 0.01). Similarly, integrated optical density analysis of Western blots showed that platelets from patients with chronic ITP had significantly higher levels of Gα (1046.3 ± 159.96 vs. 254.49 ± 39.51), PAR1 (832.98 ± 98.81 vs. 203.92 ± 27.47), and PAR4 (1518.80 ± 272.45 vs. 431.27 ± 41.86) (all p < 0.01).

Conclusion: Expression of GPCRs is increased in platelets from patients with chronic ITP, suggesting that platelets of chronic ITP may participate in the complicated biological process by means of GPCR-mediated signaling pathways.
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http://dx.doi.org/10.1159/000514907DOI Listing
April 2021

Characteristics of the gut microbiome in patients with prediabetes and type 2 diabetes.

PeerJ 2021 24;9:e10952. Epub 2021 Mar 24.

School of Public Health, Xinjiang Medical University, Urumqi, China.

Background: Gut microbiome has recently been identified as a new potential risk factor in addition to well-known diabetes risk factors. The aim of this study was to analyze the differences in the composition of gut microbiome in prediabetes(PreDM), type 2 diabetes mellitus (T2DM) and non-diabetic controls.

Methods: A total of 180 participants were recruited for this study: 60 with T2DM, 60 with PreDM and 60 non-diabetics (control group). Fecal samples were collected from the participants and genomic DNA was extracted. The composition and diversity of gut microbiome were investigated in fecal DNA samples using Illumina sequencing of the V3∼V4 regions of 16sRNA.

Results: There were significant differences in the number of bacteria among patients with PreDM and T2DM and the control group. Compared with the control group, Proteobacteria bacteria were significantly higher in the PreDM group ( = 0.006). On the genus level, Compared with the control group, the relative abundance of Prevotella and Alloprevotella was significantly higher in the T2DM group ( = 0.016, = 0.018), and the relative abundance of Paraprevotella in T2DM and PreDM groups was lower than that in the control group ( = 0.011, = 0.045). Compared with the PreDM group and the control group, the relative abundance of Bacteroides in the T2DM group was significantly lower ( = 0.019, = 0.002).

Conclusions: The present study found significant differences in the gut microbiome between PreDM, T2DM and non-diabetic individuals, specifically at the genus level, suggesting that early intervention in PreDM patients could have implications for gut flora transitioning to T2DM. In addition, these results may be valuable for developing strategies to control T2DM by modifying the gut microbiome.
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http://dx.doi.org/10.7717/peerj.10952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000457PMC
March 2021

Consecutive Hypoalbuminemia Predicts Inferior Outcome in Patients With Diffuse Large B-Cell Lymphoma.

Front Oncol 2020 27;10:610681. Epub 2021 Jan 27.

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

The prognostic value of albumin changes between diagnosis and end-of-treatment (EoT) in diffuse large B-cell lymphoma (DLBCL) remains unknown. We retrospectively analyzed 574 DLBCL patients treated with R-CHOP from our and two other centers. All patients were divided into a training cohort (n = 278) and validation cohort (n = 296) depending on the source of the patients. Overall survival (OS) and progression-free survival (PFS) were analyzed by the method of Kaplan-Meier and Cox proportional hazard regression model. In the training cohort, 163 (58.6%) patients had low serum albumin at diagnosis, and 80 of them were present with consecutive hypoalbuminemia at EoT. Patients with consecutive hypoalbuminemia showed inferior OS and PFS ( = 0.010 and  = 0.079, respectively). Similar survival differences were also observed in the independent validation cohort ( = 0.006 and = 0.030, respectively). Multivariable analysis revealed that consecutive hypoalbuminemia was an independent prognostic factor OS [relative risk (RR), 2.249; 95% confidence interval (CI), 1.441-3.509, < 0.001] and PFS (RR, 2.001; 95% CI, 1.443-2.773, < 0.001) in all DLBCL patients independent of IPI. In conclusion, consecutive hypoalbuminemia is a simple and effective adverse prognostic factor in patients with DLBCL, which reminds us to pay more attention to patients with low serum albumin at EoT during follow-up.
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http://dx.doi.org/10.3389/fonc.2020.610681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873605PMC
January 2021

Designing a Nanoscale Three-phase Electrochemical Pathway to Promote Pt-catalyzed Formaldehyde Oxidation.

Nano Lett 2020 12 17;20(12):8719-8724. Epub 2020 Nov 17.

Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States.

Gas-phase heterogeneous catalysis is a process spatially constrained on the two-dimensional surface of a solid catalyst. Here, we introduce a new toolkit to open up the third dimension. We discovered that the activity of a solid catalyst can be dramatically promoted by covering its surface with a nanoscale-thin layer of liquid electrolyte while maintaining efficient delivery of gas reactants, a strategy we call three-phase catalysis. Introducing the liquid electrolyte converts the original surface catalytic reaction into an electrochemical pathway with mass transfer facilitated by free ions in a three-dimensional space. We chose the oxidation of formaldehyde as a model reaction and observed a 25000-times enhancement in the turnover frequency of Pt in three-phase catalysis as compared to conventional heterogeneous catalysis. We envision three-phase catalysis as a new dimension for catalyst design and anticipate its applications in more chemical reactions from pollution control to the petrochemical industry.
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http://dx.doi.org/10.1021/acs.nanolett.0c03560DOI Listing
December 2020

Underpotential lithium plating on graphite anodes caused by temperature heterogeneity.

Proc Natl Acad Sci U S A 2020 Nov 9;117(47):29453-29461. Epub 2020 Nov 9.

Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305;

Rechargeability and operational safety of commercial lithium (Li)-ion batteries demand further improvement. Plating of metallic Li on graphite anodes is a critical reason for Li-ion battery capacity decay and short circuit. It is generally believed that Li plating is caused by the slow kinetics of graphite intercalation, but in this paper, we demonstrate that thermodynamics also serves a crucial role. We show that a nonuniform temperature distribution within the battery can make local plating of Li above 0 V vs. Li/Li (room temperature) thermodynamically favorable. This phenomenon is caused by temperature-dependent shifts of the equilibrium potential of Li/Li Supported by simulation results, we confirm the likelihood of this failure mechanism during commercial Li-ion battery operation, including both slow and fast charging conditions. This work furthers the understanding of nonuniform Li plating and will inspire future studies to prolong the cycling lifetime of Li-ion batteries.
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http://dx.doi.org/10.1073/pnas.2009221117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703581PMC
November 2020

IL‑27 suppresses airway inflammation, hyperresponsiveness and remodeling via the STAT1 and STAT3 pathways in mice with allergic asthma.

Int J Mol Med 2020 Aug 29;46(2):641-652. Epub 2020 May 29.

Department of Respiratory Medicine and Critical Care, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250014, P.R. China.

Type 2 cytokine‑associated immunity may be involved in the pathogenesis of allergic asthma. Although interleukin 27 (IL‑27) has been reported as an initiator and suppressor of T‑helper 1 (Th1) and T‑helper 2 (Th2) responses, respectively, its effects on the development of asthma remain unclear. In the present study, mice were induced and challenged with ovalbumin and received subsequent intranasal administration of IL‑27. Total and differential cell counts were determined from Wright‑Giemsa‑stained cytospins, whereas the cytokine levels were detected using ELISA. In addition, the expression levels of signal transducer and activator of transcription (STAT) 1, STAT3, GATA‑binding protein‑3 (GATA3) and T‑bet (T‑box transcription factor) were analyzed in T cells by western blot analysis. Their corresponding mRNA expression levels were determined by quantitative PCR. Airway remodeling was assessed by conventional pathological techniques. The results indicated that intranasal administration of IL‑27 ameliorated airway inflammation and hyperresponsiveness in an acute model of asthma. Furthermore, IL‑27 prevented airway remodeling in a chronic model of asthma. Following administration of IL‑27, the mRNA expression levels of STAT1 and T‑bet were upregulated, while those of GATA3 were downregulated. Moreover, the phosphorylation levels of STAT1 and STAT3 were increased. Taken together, these findings demonstrated that intranasal administration of IL‑27 ameliorated Th2‑related allergic lung inflammation and remodeling in mouse models of asthma by repairing both the STAT1 and STAT3 pathways.
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http://dx.doi.org/10.3892/ijmm.2020.4622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307842PMC
August 2020

Incorporating the Nanoscale Encapsulation Concept from Liquid Electrolytes into Solid-State Lithium-Sulfur Batteries.

Nano Lett 2020 Jul 15;20(7):5496-5503. Epub 2020 Jun 15.

Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States.

Solid-state Li-S batteries are attractive due to their high energy density and safety. However, it is unclear whether the concepts from liquid electrolytes are applicable in the solid state to improve battery performance. Here, we demonstrate that the nanoscale encapsulation concept based on LiS@TiS core-shell particles, originally developed in liquid electrolytes, is effective in solid polymer electrolytes. Using in situ optical cell and sulfur K-edge X-ray absorption, we find that polysulfides form and are well-trapped inside individual particles by the nanoscale TiS encapsulation. This TiS encapsulation layer also functions to catalyze the oxidation reaction of LiS to sulfur, even in solid-state electrolytes, proven by both experiments and density functional theory calculations. A high cell-level specific energy of 427 W·h·kg is achieved by integrating the LiS@TiS cathode with a poly(ethylene oxide)-based electrolyte and a lithium metal anode. This study points to the fruitful direction of borrowing concepts from liquid electrolytes into solid-state batteries.
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http://dx.doi.org/10.1021/acs.nanolett.0c02033DOI Listing
July 2020

Mesoporous Polymer-Derived Ceramic Membranes for Water Purification via a Self-Sacrificed Template.

ACS Omega 2020 May 5;5(19):11100-11105. Epub 2020 May 5.

Engineering Laboratory of Advanced Energy Materials, Ningbo Institute of Materials Technology & Engineering, Chinese Academy of Sciences, No. 1219 Zhongguan West Road, Zhenhai District, Ningbo, Zhejiang 315201, P. R. China.

Membrane separation has been widely used in water purification, and mesoporous ceramic membranes show a high potential in the future because of their high stability and resistance to harsh environments. In the current study, a novel polymer-derived ceramic silicon oxycarbide (SiOC) membrane was developed via a preceramic reactive self-sacrificed method and was further applied in a homemade dead-end system for water purification. A cyclosiloxane hybrid polymer was selected as the precursor and polydimethylsiloxane (PDMS) was used as the sacrificial template. Membrane pores were formed because of template removal during the sintering process, creating channels for water transportation. The pore size and porosity could be readily adjusted by changing the amounts and types of PDMS used in the fabrication process. The as-prepared SiOC membrane showed a high water permeability (140 LMH@2.5 bar) and high removal rate of rhodamine B (RhB), demonstrating its potential applications in water treatment. This work would provide an easy and scalable method to prepare ceramic membranes with a controlled pore size, which could be used for different water treatment applications.
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http://dx.doi.org/10.1021/acsomega.0c01021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241006PMC
May 2020

Prevalence of, and risk factors for underweight or excess weight in patients with chronic obstructive emphysema from a multiethnic region of Xinjiang, China.

Expert Rev Respir Med 2020 08 13;14(8):851-858. Epub 2020 May 13.

School of Public Health, Xinjiang Medical University , Urumqi, P. R. China.

Background: The purpose of this study is to assess the basic nutritional status (body metabolic index, BMI) and its risk factors in the patients suffering from chronic obstructive emphysema.

Methods: We described their demographic characteristics and comorbidity distribution of 2812 obstructive emphysema participants. Comparative analyzes were conducted on BMI with different demographic characteristics and comorbidities status, and comprehensive analysis on risk factors of excess weight and underweight in patients with different characters.

Results: The prevalence of underweight and excess weight was 17.57% and 31.54% respectively. There were differences in the distribution of three types of body mass index among patients with different demographic characteristics and different comorbidities. The study found that age of 50 ~ 64 (odds ratio, OR: 2.99), tuberculosis (OR: 2.41), and low TG (OR: 2.32) were the risk factors about underweight. Low HDL-C (OR: 4.15), nonalcoholic fatter liver (NAFLD) (OR: 3.96), and age of 50 ~ 64 (OR: 2.72) were closely related to the excess weight of participants.

Conclusions: This study highlighted the prevalence of underweight and excess weight in patients among emphysema. Comorbidities were important risk factors of underweight or excess weight among chronic emphysema patients. These findings were important for the prevention and treatment of chronic obstructive emphysema in the future.
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http://dx.doi.org/10.1080/17476348.2020.1762491DOI Listing
August 2020

Improving Lithium Metal Composite Anodes with Seeding and Pillaring Effects of Silicon Nanoparticles.

ACS Nano 2020 Apr 14;14(4):4601-4608. Epub 2020 Apr 14.

Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States.

Metallic lithium (Li) anodes are crucial for the development of high specific energy batteries yet are plagued by their poor cycling efficiency. Electrode architecture engineering is vital for maintaining a stable anode volume and suppressing Li corrosion during cycling. In this paper, a reduced graphene oxide "host" framework for Li metal anodes is further optimized by embedding silicon (Si) nanoparticles between the graphene layers. They serve as Li nucleation seeds to promote Li deposition within the framework even without prestored Li. Meanwhile, the LiSi alloy particles serve as supporting "pillars" between the graphene layers, enabling a minimized thickness shrinkage after full stripping of metallic Li. Combined with a Li compatible electrolyte, a 99.4% Coulombic efficiency over ∼600 cycles is achieved, and stable cycling of a Li||NMC532 full cell for ∼380 cycles with negligible capacity decay is realized.
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http://dx.doi.org/10.1021/acsnano.0c00184DOI Listing
April 2020

Amide proton transfer-weighted magnetic resonance imaging of human brain aging at 3 Tesla.

Quant Imaging Med Surg 2020 Mar;10(3):727-742

Department of MR, Shandong Medical Imaging Research Institute, Shandong University, Jinan 250021, China.

Background: Amide proton transfer-weighted (APTw) imaging has been revealed to hold great potential in the diagnosis of several brain diseases. The purpose of this proof-of-concept study was to evaluate the feasibility and value of APTw magnetic resonance imaging (MRI) in characterizing normal brain aging.

Methods: A total of 106 healthy subjects were recruited and scanned at 3.0 Tesla, with APTw and conventional magnetization transfer (MT) sequences. Quantitative image analyses were performed in 12 regions of interest (ROIs) for each subject. The APTw or MT ratio (MTR) signal differences among five age groups (young, mature, middle-aged, young-old, and middle-old) were assessed using the one-way analysis of variance, with the Benjamini-Hochberg correction for multiple comparisons. The relationship between APTw and MTR signals and the age dependencies of APTw and MTR signals were assessed using the Pearson correlation and non-linear regression.

Results: There were no significant differences between the APTw or MTR values for males and females in any of the 12 ROIs analyzed. Among the five age groups, there were significant differences in the three white matter regions in the temporal, occipital, and frontal lobes. Overall, the mean APTw values in the older group were higher than those in the younger group. Positive correlations were observed in relation to age in most brain regions, including four with significant positive correlations (r=0.2065-0.4182) and five with increasing trends. As a comparison, the mean MTR values did not appear to be significantly different among the five age groups. In addition, the mean APTw and MTR values revealed significant positive correlations in 10 ROIs (r=0.2214-0.7269) and a significant negative correlation in one ROI (entorhinal cortex, r=-0.2141).

Conclusions: Our early results show that the APTw signal can be used as a promising and complementary imaging biomarker with which normal brain aging can be evaluated at the molecular level.
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http://dx.doi.org/10.21037/qims.2020.02.22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136735PMC
March 2020

Potential Antifungal Targets Based on Glucose Metabolism Pathways of .

Front Microbiol 2020 17;11:296. Epub 2020 Mar 17.

Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.

In recent years, fungal infections have become a serious health problem. are considered as the fourth most common isolates associated with approximately 40% mortality in bloodstream infections among hospitalized patients. Due to various limitations of classical antifungals used currently, such as limited kinds of drugs, inevitable toxicities, and high price, there is an urgent need to explore new antifungal agents based on novel targets. Generally, nutrient metabolism is involved with fungal virulence, and glucose is one of the important nutrients in . can obtain and metabolize glucose through a variety of pathways; in theory, many enzymes in these pathways can be potential targets for developing new antifungal agents, and several studies have confirmed that compounds which interfere with alpha-glucosidase, acid trehalase, trehalose-6-phosphate synthase, class II fructose bisphosphate aldolases, and glucosamine-6-phosphate synthase in these pathways do have antifungal activities. In this review, the glucose metabolism pathways in , the potential antifungal targets based on these pathways, and some compounds which have antifungal activities by inhibiting several enzymes in these pathways are summarized. We believe that our review will be helpful to the exploration of new antifungal drugs with novel antifungal targets.
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http://dx.doi.org/10.3389/fmicb.2020.00296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093590PMC
March 2020

The Risk Ratio of Immune-Related Colitis, Hepatitis, and Pancreatitis in Patients With Solid Tumors Caused by PD-1/PD-L1 Inhibitors: A Systematic Review and Meta-Analysis.

Front Oncol 2020 28;10:261. Epub 2020 Feb 28.

Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.

The meta-analysis was put into practice in evaluating the risk ratio of immune-related digestive system inflammation in patients with solid tumors caused by PD-1/PD-L1 inhibitors. The process of the meta-analysis was performed by us according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. After screening and eligibility assessment, a total of 26 clinical trials involving 16,409 patients were selected for the final quantitative synthesis. Immune-related digestive system inflammations, including colitis, hepatitis, pancreatitis, were evaluated separately. Compared with chemotherapy, PD-1/PD-L1 inhibitors led to an increase in the incidence risk of all grade colitis (RR = 2.43, 95% CI: [1.23, 4.82], = 0.01). Similar incidence trend could also be seen when PD-1/PD-L1 inhibitors were combined with chemotherapy (RR = 2.62, 95% CI: [1.25, 5.48], = 0.01). Whether compared with Nivolumab plus Ipilimumab or Ipilimumab alone, the incidence risk of colitis in the Nivolumab group was significantly lower than that of the control group. Similar analysis results could also be seen in the incidence risk of hepatitis. We did not find a statistically significant effect on the incidence of immune-related pancreatitis after the use of PD-1/PD-L1 inhibitors. The use of PD-1/PD-L1 inhibitors increased the incidence risk of immune-related colitis and hepatitis, but this potential to increase the incidence risk of the disease was weaker than Ipilimumab.
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http://dx.doi.org/10.3389/fonc.2020.00261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059308PMC
February 2020

IL-27 alleviates airway remodeling in a mouse model of asthma via PI3K/Akt pathway.

Exp Lung Res 2020 Apr - May;46(3-4):98-108. Epub 2020 Mar 12.

Department of Respiratory Medicine, Shandong Provincial Qianfoshan Hospital affiliated to Shandong University, Jinan, Shandong, China.

Airway remodeling is one of the features of severe asthma. Previous study shows that IL-27 inhibits airway inflammation in asthmatic mice. However, the role of IL-27 on airway remodeling in OVA-induced asthmatic mice and its possible mechanism remain unclear. We established an ovalbumin (OVA)-induced asthmatic mice model. IL-27 were preventative administered to OVA-induced asthmatic mice. The total cells in Bronchoalveolar lavage fluid (BALF) and Airway hyperresponsiveness (AHR) were measured. The lung tissues were performed by Hematoxylin and eosin (HE) staining to estimate the pathological changes. Masson staining was used to observe the collagen deposition area. The expression of α-smooth muscle actin (α-SMA) and Type I collagen was measured by immunohistochemistry, western blot, and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Additionally, western blot was also used to measure the expression of phosphorylated-Akt (p-Akt) in each group. IL-27 group showed significant inhibitory effect on the α-SMA and Type I collagen. The expression of p-Akt in the tissues of asthma model was increased and inhibited by IL-27. IL-27 can alleviate airway remodeling in OVA-induced asthmatic mice, and the mechanism may relate to PI3K/Akt pathway.
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http://dx.doi.org/10.1080/01902148.2020.1740356DOI Listing
March 2020

Protein-based amide proton transfer-weighted MR imaging of amnestic mild cognitive impairment.

Neuroimage Clin 2020 27;25:102153. Epub 2019 Dec 27.

Department of MR, Shandong Medical Imaging Research Institute, Shandong University, Jinan, Shandong, China. Electronic address:

Amide proton transfer-weighted (APTw) MRI is a novel molecular imaging technique that can noninvasively detect endogenous cellular proteins and peptides in tissue. Here, we demonstrate the feasibility of protein-based APTw MRI in characterizing amnestic mild cognitive impairment (aMCI). Eighteen patients with confirmed aMCI and 18 matched normal controls were scanned at 3 Tesla. The APTw, as well as conventional magnetization transfer ratio (MTR), signal differences between aMCI and normal groups were assessed by the independent samples t-test, and the receiver-operator-characteristic analysis was used to assess the diagnostic performance of APTw. When comparing the normal control group, aMCI brains typically had relatively higher APTw signals. Quantitatively, APTw intensity values were significantly higher in nine of 12 regions of interest in aMCI patients than in normal controls. The largest areas under the receiver-operator-characteristic curves were 0.88 (gray matter in occipital lobe) and 0.82 (gray matter in temporal lobe, white matter in occipital lobe) in diagnosing aMCI patients. On the contrary, MTR intensity values were significantly higher in only three of 12 regions of interest in the aMCI group. Additionally, the age dependency analyses revealed that these cross-sectional APTw/MTR signals had an increasing trend with age in most brain regions for normal controls, but a decreasing trend with age in most brain regions for aMCI patients. Our early results show the potential of the APTw signal as a new imaging biomarker for the noninvasive molecular diagnosis of aMCI.
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http://dx.doi.org/10.1016/j.nicl.2019.102153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948365PMC
December 2020

Odds ratio of programmed cell death-1 or ligand 1 inhibitor-related endocrine dysfunction in patients with lung cancer: A systematic review and meta-analysis.

Medicine (Baltimore) 2019 Dec;98(50):e18310

Department of Radiotherapy oncology, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated with Shandong First Medical University.

Purpose: We designed the study to investigate the incidence risk of Programmed Cell Death-1 (PD-1) or Ligand 1 (PD-L1) inhibitor-related endocrine dysfunction in patients with lung cancer.

Method: All the data were collected by 1 primary reviewer and then independently reviewed by 2 secondary reviewers according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISM) guidelines. Incidence risk of all-grade and grade 3-5 PD-1/PD-L1 inhibitors related endocrine dysfunction in patients with lung cancer were taken into account.

Results: Overall, 12 clinical trials comprising 6108 patients were identified in this systematic review and meta-analysis. The incidence risk of hypothyroidism, hyperthyroidism and adrenal insufficiency was higher in NSCLC patients receiving combination treatments. The incidence rate of all-grade of hypothyroidism was lower in PD-1/PD-L1 inhibitor subgroup compared to chemotherapy (OR = 22.62, 95%CI:9.79-52.25), while the similar result was seen in another treatment regimen (PD-1 + platinum-based chemotherapy vs platinum-based chemotherapy) (OR = 2.93, 95%CI: [2.08, 4.11). The different result can be seen in the group related to the other treatment regimen (1PD-1/PD-L1 inhibitor vs 2 PD-1/PD-L1 inhibitors) (OR = 0.40, 95%CI:0.21-0.76). All the results of the above analysis were considered to be statistical significant. Similar result could also be seen in meta-analysis related to hyperthyroidism and adrenal insufficiency.

Conclusion: The incidence risk of endocrine dysfunctions, including hypothyroidism, hyperthyroidism and adrenal insufficiency, were higher for PD-1/PD-L1 inhibitors group.
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http://dx.doi.org/10.1097/MD.0000000000018310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6922418PMC
December 2019

The overall safety evaluation of programmed cell death/programmed cell death ligand 1 (PD-1/PD-L1) treatment for lung cancer patients: An updated systematic review and meta-analysis.

Medicine (Baltimore) 2019 Jul;98(30):e16439

Department of Radiotherapy Oncology, Shandong Provincial Qianfoshan Hospital, The First Hospital Affiliated with Shandong First Medical University.

Background: We performed the meta-analysis to evaluate the overall safety of programmed cell death-1 (PD-1) or ligand 1 (PD-L1) inhibitor treatment for lung cancer patients.

Method: Randomized controlled trials were collected according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Risk ratio (RR) of PD-1/PD-L1 inhibitor treatment-related death, treatment-related adverse events, any serious events, and any events leading to discontinuation were all taken into account for the final evaluation.

Results: Fourteen studies were collected for the meta-analysis. The RR of treatment-related death for PD-1/PD-L1 was significantly lower than that of the control group (RR = 0.37, 95% confidence interval, CI: [0.21, 0.66]). Similar analysis results could also be seen for the RR of treatment-related adverse events and adverse events leading to discontinuation. When PD-1/PD-L1 was combined with chemotherapy, it increased the RR of adverse events leading to discontinuation (RR = 1.68, 95% CI: [1.22, 3.32]). The RR of overall treatment-related adverse events was lower in nivolumab (PD-1) than that of the control group (nivolumab + ipilimumab) (RR = 0.77, 95% CI: [0.65, 0.90]). Similar analysis results could also be seen in the RR of treatment-related adverse events for grade 3 to 5 and adverse events leading to discontinuation.

Conclusion: Compared with chemotherapy, RR of the treatment-related deaths associated with PD-1/PD-L1 inhibitor was significantly lower than that of the chemotherapy group, while it did not increase the RR when they were combined with chemotherapy or other drugs. When PD-1/PD-L1 was combined with chemotherapy, it increased the RR of adverse events leading to discontinuation.
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http://dx.doi.org/10.1097/MD.0000000000016439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709159PMC
July 2019

Evolution of the Solid-Electrolyte Interphase on Carbonaceous Anodes Visualized by Atomic-Resolution Cryogenic Electron Microscopy.

Nano Lett 2019 Aug 23;19(8):5140-5148. Epub 2019 Jul 23.

Department of Materials Science and Engineering , Stanford University , Stanford , California 94305 , United States.

The stability of modern lithium-ion batteries depends critically on an effective solid-electrolyte interphase (SEI), a passivation layer that forms on the carbonaceous negative electrode as a result of electrolyte reduction. However, a nanoscopic understanding of how the SEI evolves with battery aging remains limited due to the difficulty in characterizing the structural and chemical properties of this sensitive interphase. In this work, we image the SEI on carbon black negative electrodes using cryogenic transmission electron microscopy (cryo-TEM) and track its evolution during cycling. We find that a thin, primarily amorphous SEI nucleates on the first cycle, which further evolves into one of two distinct SEI morphologies upon further cycling: (1) a compact SEI, with a high concentration of inorganic components that effectively passivates the negative electrode; and (2) an extended SEI spanning hundreds of nanometers. This extended SEI grows on particles that lack a compact SEI and consists primarily of alkyl carbonates. The diversity in observed SEI morphologies suggests that SEI growth is a highly heterogeneous process. The simultaneous emergence of these distinct SEI morphologies highlights the necessity of effective passivation by the SEI, as large-scale extended SEI growths negatively impact lithium-ion transport, contribute to capacity loss, and may accelerate battery failure.
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http://dx.doi.org/10.1021/acs.nanolett.9b01515DOI Listing
August 2019

Let-7a inhibits proliferation and promotes apoptosis of human asthmatic airway smooth muscle cells.

Exp Ther Med 2019 May 7;17(5):3327-3334. Epub 2019 Mar 7.

Department of Respiratory Disease, Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.

The present study aimed to examine the changes of let-7a expression in asthmatic airway smooth muscle cells (ASMCs) and to analyze its effect on the proliferation and apoptosis of ASMCs, as well as the potential mechanism of action. Let-7a expression levels in ASMCs from asthmatic and non-asthmatic subjects were detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. Furthermore, let-7a mimics were transfected into ASMCs isolated from asthmatic patients, and the effect of let-7a on ASMC proliferation was examined using a Cell Counting Kit-8. In addition, the influence of let-7a on ASMC apoptosis was detected using flow cytometry and a caspase-3/7 activity assay. Target genes of let-7a were predicted using bioinformatics software, and the direct regulatory effect of let-7a on the potential target gene signal transducer and activator of transcription 3 (STAT3) was verified through a dual-luciferase reporter gene assay combined with RT-qPCR and western blot analysis. The results demonstrated that let-7a expression was significantly lower in ASMCs of asthmatic subjects compared with that in ASMCs of normal subjects. Furthermore, upregulation of let-7a expression in asthmatic ASMCs markedly inhibited cell proliferation and promoted cell apoptosis. The results of the dual-luciferase reporter gene assay indicated that let-7a selectively binds with the 3'-untranslated region of the STAT3 mRNA. In addition, let-7a mimics evidently reduced the mRNA and protein expression levels of STAT3 in asthmatic ASMCs. In conclusion, the present study demonstrates that let-7a expression is downregulated in ASMCs from asthmatic patients. Furthermore, let-7a suppresses the proliferation and promotes apoptosis of human asthmatic ASMCs, which may, at least partially, be associated with the downregulation of STAT3 expression.
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http://dx.doi.org/10.3892/etm.2019.7363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447815PMC
May 2019

Wrinkled Graphene Cages as Hosts for High-Capacity Li Metal Anodes Shown by Cryogenic Electron Microscopy.

Nano Lett 2019 02 31;19(2):1326-1335. Epub 2019 Jan 31.

Department of Materials Science and Engineering , Stanford University , Stanford , California 94305 , United States.

Lithium (Li) metal has long been considered the "holy grail" of battery anode chemistry but is plagued by low efficiency and poor safety due to its high chemical reactivity and large volume fluctuation, respectively. Here we introduce a new host of wrinkled graphene cage (WGC) for Li metal. Different from recently reported amorphous carbon spheres, WGC show highly improved mechanical stability, better Li ion conductivity, and excellent solid electrolyte interphase (SEI) for continuous robust Li metal protection. At low areal capacities, Li metal is preferentially deposited inside the graphene cage. Cryogenic electron microscopy characterization shows that a uniform and stable SEI forms on the WGC surface that can shield the Li metal from direct exposure to electrolyte. With increased areal capacities, Li metal is plated densely and homogeneously into the outer pore spaces between graphene cages with no dendrite growth or volume change. As a result, a high Coulombic efficiency (CE) of ∼98.0% was achieved under 0.5 mA/cm and 1-10 mAh/cm in commercial carbonate electrolytes, and a CE of 99.1% was realized with high-concentration electrolytes under 0.5 mA/cm and 3 mAh/cm. Full cells using WGC electrodes with prestored Li paired with Li iron phosphate showed greatly improved cycle lifetime. With 10 mAh/cm Li metal deposition, the WGC/Li composite anode was able to provide a high specific capacity of ∼2785 mAh/g. With its roll-to-roll compatible fabrication procedure, WGC serves as a highly promising material for the practical realization of Li metal anodes in next-generation high energy density secondary batteries.
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http://dx.doi.org/10.1021/acs.nanolett.8b04906DOI Listing
February 2019

Biological significance and prognostic relevance of peripheral blood neutrophil-to-lymphocyte ratio in soft tissue sarcoma.

Sci Rep 2018 08 10;8(1):11959. Epub 2018 Aug 10.

Division of Medical Oncology, National Cancer Centre, Singapore, Singapore.

Peripheral blood indices of systemic inflammation such as the neutrophil-lymphocyte ratio (NLR) have been shown to be prognostic in various cancers. We aim to investigate the clinical significance of these indices in patients with soft tissue sarcoma (STS). Seven hundred and twelve patients with available blood counts at diagnosis and/or metastatic relapse were retrospectively examined. An optimal cutoff for NLR-high (>2.5) in predicting overall survival (OS) was determined using receiver operating curve analyses. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models. Our results show that NLR was significantly higher in patients with distant metastasis at diagnosis (n = 183) compared to those without (n = 529) (median: 4.36 vs 2.85, p < 0.0001). Progression of localized disease at diagnosis to metastatic relapse within the same patients was associated with an interval increase in NLR (median: 3.21 vs 3.74, p = 0.0003). In multivariate analysis, NLR-high was the only consistent factor independently associated with both worse OS (HR 1.53, 95% CI 1.10-2.13, p = 0.0112) and relapse-free survival (HR 1.41, 95% CI 1.08-1.85, p = 0.0125) in localized disease, as well as OS (HR 1.82, 95% CI 1.16-2.85, p = 0.0087) in metastatic/unresectable disease. In conclusion, high NLR is an independent marker of poor prognosis among patients with STS.
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http://dx.doi.org/10.1038/s41598-018-30442-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086886PMC
August 2018

ML-7 attenuates airway inflammation and remodeling via inhibiting the secretion of Th2 cytokines in mice model of asthma.

Mol Med Rep 2018 May 6;17(5):6293-6300. Epub 2018 Mar 6.

Department of Respiratory Diseases, Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, P.R. China.

Previous studies have indicated that smooth muscle myosin light chain kinase (MLCK) has a prominent role in the regulation of smooth muscle contraction, which tends to be upregulated in asthma. In recent years, numerous studies have reported that MLCK is intimately connected with the immunoregulatory mechanism of T cells. The imbalance of T helper type 1 cells (Th1)/Th2 constitutes the immune‑associated pathological basis of chronic asthma. Th2‑associated cytokines, including interleukin‑4, ‑5, ‑13, ‑25 and ‑33, are involved in airway inflammation, hyperresponsiveness and remodeling, which leads to a progressive decline in lung function. The purpose of the present study was to verify whether inhibition of bronchial MLCK attenuated the expression Th2‑associated cytokines in asthmatic mice, including the above‑mentioned ones. Female BALB/c mice were used to establish an ovalbumin (OVA)‑induced model of asthma, of which one group was treated with the MLCK inhibitor (5-iodonaphthalene-1-sulfonyl) homopiperazine (ML‑7). The inhibitor of MLCK, ML‑7 attenuated airway inflammation and remodeling by reducing inflammatory cell infiltration and the secretion of Th2 cytokines in mice model of asthma, which may represent a promising therapeutic strategy for asthma.
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http://dx.doi.org/10.3892/mmr.2018.8683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928606PMC
May 2018

Specific mutation of transglutaminase gene from H197 and characterization of microbial transglutaminase.

J Biosci 2017 Dec;42(4):537-546

South-Central University for Nationalities, Wuhan 430070, People's Republic of China.

Microbial transglutaminase (MTG) gene (mtg) from H197 strain was cloned by PCR and mutated by deleting a specific 84 bp fragment using overlapping extension PCR. The mutant MTG and the wild MTG genes expressed by recombinant plasmid pET32a+- mutant mtg and pET32a+ -mtg, respectively, and were harvested by alternating freeze-thaw steps and purified by Ni column. The purified mutant MTG and the wild MTG exhibited 0.22 U/mg and 0.16 U/mg activity, respectively, and 0.69 U/mg and 0.54 U/mg activity, respectively, after activated by trypsin. The molecular weight of mutant MTG was estimated as 67 kDa by SDS-PAGE. Both MTGs showed optimum activity at pH 6-8 for hydroxamate formation from N-CBZ-Gln-Gly and hydroxylamine, and exhibited higher stability at 40°C and 1-3% salinity. The two types of MTG were not stable in the presence of Zn(II), Cu(II), Hg(II), Pb(II), Fe(III), and Ag(I), suggesting that they could possess a thiol group. In addition, the mutant MTG and the wild MTG were strongly affected by ethanol. Furthermore, the mutant MTG was obviously (P less than 0.05 or P less than 0.01) more stable than the wild MTG at 50°C and 60°C, at pH 4, 5, and 9, at 7 % and 9 % salinity, 30 % and 35 % ethanol concentration, and in the presence of Li(I) and Ag(I). The polyhydroxy compounds as protein stabilizers could elevate MTG stability.
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http://dx.doi.org/10.1007/s12038-017-9707-4DOI Listing
December 2017

Difference in hot carrier cooling rate between Langmuir-Blodgett and drop cast PbS QD films due to strong electron-phonon coupling.

Nanoscale 2017 Nov;9(43):17133-17142

School of Photovoltaic and Renewable Energy Engineering, UNSW Sydney, Sydney, NSW 2052, Australia.

The carrier dynamics of lead sulphide quantum dot (PbS QD) drop cast films and closely packed ordered Langmuir-Blodgett films are studied with ultra-fast femtosecond transient absorption spectroscopy. The photo-induced carrier temperature is extracted from transient absorption spectra and monitored as a function of time delay. The cooling dynamics of carriers in PbS QDs suggest a reduction of the carrier energy loss rate at longer time delays through the retardation of the longitudinal optical (LO) phonon decay due to partial heating of acoustic phonon modes. A slowed hot carrier cooling time up to 116 ps is observed in the drop cast film. A faster cooling rate was also observed in the highly compact Langmuir-Blodgett film due to the enhanced carrier-LO phonon coupling strength arising from the Coulombic interaction in neighboring QDs, which is verified by temperature dependent steady state PL measurements.
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http://dx.doi.org/10.1039/c7nr05247bDOI Listing
November 2017

Self-Templated Formation of Interlaced Carbon Nanotubes Threaded Hollow CoS Nanoboxes for High-Rate and Heat-Resistant Lithium-Sulfur Batteries.

J Am Chem Soc 2017 09 1;139(36):12710-12715. Epub 2017 Sep 1.

Key Laboratory of Mesoscopic Chemistry of MOE and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing, Jiangsu 210023, PR China.

Lithium-sulfur batteries (Li-S) have attracted soaring attention due to the particularly high energy density for advanced energy storage system. However, the practical application of Li-S batteries still faces multiple challenges, including the shuttle effect of intermediate polysulfides, the low conductivity of sulfur and the large volume variation of sulfur cathode. To overcome these issues, here we reported a self-templated approach to prepare interconnected carbon nanotubes inserted/wired hollow CoS nanoboxes (CNTs/CoS-NBs) as an efficient sulfur host material. Originating from the combination of three-dimensional CNT conductive network and polar CoS-NBs, the obtained hybrid nanocomposite of CNTs/CoS-NBs can offer ultrahigh charge transfer properties, and efficiently restrain polysulfides in hollow CoS-NBs via the synergistic effect of structural confinement and chemical bonding. Benefiting from the above advantages, the S@CNTs/CoS-NBs cathode shows a significantly improved electrochemical performance in terms of high reversible capacity, good rate performance, and long-term cyclability. More remarkably, even at an elevated temperature (50 °C), it still exhibits high capacity retention and good rate capacity.
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http://dx.doi.org/10.1021/jacs.7b06973DOI Listing
September 2017