Publications by authors named "Jian Zhang"

7,993 Publications

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Membrane orthologs of TLR5 of tongue sole Cynoglossus semilaevis: Expression patterns, signaling pathway and antibacterial property.

Fish Shellfish Immunol 2022 May 23. Epub 2022 May 23.

School of Ocean, Yantai University, Yantai, China.

Mammalian toll-like receptor 5 (TLR5) is crucial for recognizing bacterial flagellin and initiating the inflammatory signaling cascades via myeloid differentiation factor 88 (MyD88) signaling pathway, which plays vital role in innate immune against pathogenic bacteria. Herein, we reported the signaling pathway and antibacterial property of tongue sole (Cynoglossus semilaevis) membrane forms of TLR5 (i.e. CsTLR5M1and CsTLR5M2). CsTLR5M1/M2 contain 936 and 885 amino acid residues respectively. CsTLR5M1 shares 86.7% overall sequence identities with CsTLR5M2. CsTLR5M1/M2 possess the same extracellular domain (ECD) and transmembrane domain (TMD), but the different toll-interleukin-1 receptor (TIR) domain. CsTLR5M1/M2 expression occurred constitutively in multiple tissues and regulated by bacterial stimulation. Recombinant CsTLR5M1/M2 (rCsTLR5M) could bind to flagellin and Gram-negative/positive bacteria, which could suppress bacterial growth. Stimulation of the CsTLR5M pathway by flagellin resulted in increased expression of MyD88-dependent signaling molecules and inflammatory cytokines. Blocking rCsTLR5M by antibody markedly reduced the phagocytosis and ROS production of peripheral blood leukocytes (PBLs), which in turn in vivo promoted the dissemination of bacteria. Overall, these observations add new insights into the signaling pathway and immune function of teleost TLR5M.
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http://dx.doi.org/10.1016/j.fsi.2022.05.031DOI Listing
May 2022

Phase I Trial of a Novel Anti-HER2 Antibody-drug Conjugate, ARX788, for the Treatment of HER2-positive Metastatic Breast Cancer.

Clin Cancer Res 2022 May 26. Epub 2022 May 26.

Fudan University Shanghai Cancer Center, Shanghai, China.

Purpose: ARX788 is a novel antibody-drug conjugate (ADC) comprised of an anti-HER2 monoclonal antibody and a potent tubulin inhibitor payload AS269 that is site-specifically conjugated to the antibody via a non-natural amino acid incorporated into the antibody. Herein, we present the results of a phase I study of the safety, pharmacokinetics, and antitumor activity of ARX788 in HER2-positive metastatic breast cancer (MBC) patients.

Experimental Design: Patients with HER2-positive MBC received ARX788 at doses of 0.33, 0.66, 0.88, 1.1, 1.3, or 1.5 mg/kg Q3W, or 0.88, 1.1, or 1.3 mg/kg Q4W. The dose-limiting toxicity (DLT) was assessed for 84 days for pulmonary toxicity and at a duration of one cycle (21 or 28 days) for other toxicities.

Results: In total, 69 patients were enrolled. No DLT or drug-related deaths occurred. Most patients (67/69; 97.1%) experienced at least one treatment-related adverse event (TRAE). Common ({greater than or equal to} 30%) TRAEs included an increase in aspartate aminotransferase, an increase in alanine aminotransferase, corneal epitheliopathy, alopecia, hypokalemia, interstitial lung disease (ILD)/pneumonitis, and an increase in aldosterone. While 34.8% of participants experienced ILD/pneumonitis, only two had a severity of grade 3. At 1.5 mg/kg Q3W, the recommended phase II dose, the objective response rate was 65.5% (19/29, 95% confidence interval [CI], 45.7-82.1), the disease control rate was 100% (95% CI, 81.2-100), and the median progression-free survival was 17.02 months (95% CI, 10.09 to not reached).

Conclusions: ARX788 demonstrated a manageable safety profile with promising preliminary signs of activity in HER2-positive MBC patients who progressed on prior anti-HER2 therapies.
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http://dx.doi.org/10.1158/1078-0432.CCR-22-0456DOI Listing
May 2022

A Shigella sp. variant is causally linked to intractable functional constipation.

J Clin Invest 2022 May 26. Epub 2022 May 26.

Model Animal Research Center, Nanjing University, Nanjing, China.

Functional constipation (FC) with intractable nature is the most severe form of constipation, but its etiology has long been unknown. In light of the intractable nature, we hypothesized that such intractable FC (IFC) sufferers were caused by intractable infection of a pathogenic bacterium. Here, we isolated a bacterium of Shigella sp. PIB from IFC patients that significantly inhibited the peristaltic contraction of colon by production of docosapentaenoic acid (DPA). PIB could colonize mice at least for six months. Oral administration of PIB was sufficient to induce constipation, which was reversed by PIB-specific phages. The mutated PIB with reduced DPA was incapable of inhibiting colonic function and inducing constipation, suggesting that DPA produced by PIB was the key mediator for the genesis of constipation. The PIB were detected in stools of 56% (38/68) of the IFC patients, but not in non-IFC or healthy populations (0/180). DPA levels in stools were elevated in 44.12% (30/68) of the IFC patients, but none of the healthy volunteers (0/97). Our results suggest Shigella sp. PIB may be the critical causative pathogen for IFC, and detections of fecal PIB bacteria plus DPA may be reliable methods for IFC diagnosis and classification.
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http://dx.doi.org/10.1172/JCI150097DOI Listing
May 2022

The superior response speed of table tennis players is associated with proactive inhibitory control.

PeerJ 2022 20;10:e13493. Epub 2022 May 20.

School of Physical Education and Coaching, Shanghai University of Sport, Shanghai, China.

Objective: To explore the mechanism behind the faster volitional reaction time (RT) of open skill sports athletes from the perspective of proactive inhibitory control, with the hypothesis that the superior response speed of athletes from open skill sports is related to their enhanced capacity for releasing inhibition.

Methods: Participants were divided into two groups, an experimental group of 27 table tennis players and a control group of 27 non-athletes. By manipulating cue-target onset asynchrony (CTOA) in a simple cue-target detection task, the timing of target presentation occurred in different phases of the disinhibition process. The time needed for disinhibition were compared between groups.

Results: For the experimental group, RT varied with CTOA at delays less than 200 ms; for CTOAs greater than 200 ms, RTs were not significantly different. For the control group, RT varied with CTOA for delays as long as 300 ms.

Conclusions: Table tennis players took less time (200 ms) than non-athletes (300 ms) to complete the disinhibition process, which might partly explain their rapid response speed measured in unpredictable contexts.

Significance: The study provided evidence for disinhibition speed as a new index to assess the capacity of proactive inhibitory control, and provided a new perspective to explore the superior RT of athletes from open skill sports. We also offered support for the fundamental cognitive benefits of table tennis training.
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http://dx.doi.org/10.7717/peerj.13493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126139PMC
May 2022

LCN2 is a new diagnostic biomarker and potential therapeutic target in idiopathic short stature.

J Cell Mol Med 2022 May 24. Epub 2022 May 24.

Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Idiopathic short stature (ISS) is the most common paediatric endocrine disease. However, the underlying pathology of ISS remains unclear. Currently, there are no effective diagnostic markers or therapeutic strategies available for ISS. In this study, we aimed to identify differential plasma protein expression and novel biomarkers in patients with ISS, and elucidate the biological functions of candidate proteins in ISS pathogenesis. Four specimen pairs from four ISS children and age-/sex-matched control individuals were subjected to proteomics analysis, and 340 samples of children with a mean age 9.73 ± 0.24 years were utilized to further verify the differentially expressed proteins by enzyme-linked immunosorbent assay (ELISA). The receiver-operating characteristic (ROC) curve and the area under the ROC curve (AUC) were plotted. A total of 2040 proteins were identified, of which 84 were differentially expressed. In vitro and in vivo experiments confirmed the biological functions of these candidate proteins. LCN2 overexpression in ISS was verified using ELISA. Meanwhile, LCN2 showed high sensitivity and specificity in discriminating children with ISS from those with growth hormone deficiency, precocious puberty and normal control individuals. The upregulated expression of LCN2 not only suppressed food intake but also impaired chondrocyte proliferation and bone growth in chondrocytes and rats. As a result, the rats presented a short-stature phenotype. Subsequently, we found that bone growth inhibition recovered after LCN2 overexpression was stopped in immature rats. To our knowledge, this is the first study to report that LCN2 may be a significant target for ISS diagnosis and treatment.
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http://dx.doi.org/10.1111/jcmm.17408DOI Listing
May 2022

Cyclocarya paliurus triterpenoids suppress hepatic gluconeogenesis via AMPK-mediated cAMP/PKA/CREB pathway.

Phytomedicine 2022 May 16;102:154175. Epub 2022 May 16.

Department of Endocrinology, Nanjing Lishui District Hospital of Traditional Chinese Medicine, Nanjing, 211200, China; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China. Electronic address:

Background: Abnormal enhancement of hepatic gluconeogenesis is a vital mechanism of the pathogenesis of Type 2 diabetes mellitus (T2DM); thus, its suppression may present an efficient therapeutic strategy for T2DM. Cyclocarya paliurus (CP), a plant species native to China, has been reported to have anti-hyperglycemia activity. Our previous studies have revealed that Cyclocarya paliurus triterpenic acids (CPT) exert the favorable glucose-lowering activity, but the regulatory effect of CPT on hepatic gluconeogenesis is still unclarified.

Purpose: This study aimed to investigate the potential role and mechanism of CPT in gluconeogenesis.

Study Design: In this study, the ameliorative effect and underlying mechanism of CPT on gluconeogenesis were investigated: high-fat diet and streptozotocin-induced T2DM mice and glucagon-challenged mouse primary hepatocytes.

Methods: T2DM model mice with or without oral administration of CPT for 4 weeks were monitored for body weight, glucose and lipid metabolism. Hematoxylin and eosin staining was used to observe liver lipid deposition. Real-time PCR assays were performed to examine the mRNA expression of glucose-6-phosphate (G6Pase), and phosphoenolpyruvate carboxykinase (PEPCK), two key enzymes involved in liver gluconeogenesis. Western blotting was used to determine AMP-dependent protein kinase (AMPK) expression and induction of the glucagon signaling pathway. The possible mechanism of CPT on liver gluconeogenesis was further explored in glucagon-induced mouse primary hepatocytes.

Results: In vivo and in vitro experiments revealed that CPT treatment significantly reduced fasting blood glucose, total cholesterol and triglyceride levels, and improved insulin resistance. Furthermore, CPT could obviously decreased the mRNA and protein expression of G6Pase and PEPCK, the cyclic AMP content, the phosphorylation level of protein kinase A and cyclic AMP response element-binding protein. But CPT promoted the phosphorylation of AMP-dependent protein kinase (AMPK) and activation of phosphodiesterase 4B. Mechanistically, intervention with Compound C (an AMPK inhibitor) partially blocked the suppressive effect of CPT on hepatic gluconeogenesis.

Conclusion: These findings suggested that CPT may inhibit hepatic gluconeogenesis against T2DM by activating AMPK.
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http://dx.doi.org/10.1016/j.phymed.2022.154175DOI Listing
May 2022

A rapid and quantitative detection method for plasma soluble growth stimulating gene protein 2 based on time resolved fluorescence immunochromatography.

Anal Methods 2022 May 24. Epub 2022 May 24.

Wuxi Children's Hospital, Wuxi, China.

: plasma soluble growth stimulating gene protein 2 (sST2) is a new generation biomarker in heart failure (HF), which is an independent predictor of adverse outcomes of heart failure. Thus, the establishment of a rapid and sensitive method for detecting sST2 is urgently needed. : lanthanide element Eu coated fluorescent nanometer microspheres ([email protected]) can be used as markers to label monoclonal mouse anti-human sST2 antibody ST-01 ([email protected]). When the immune sandwich complex formed between the monoclonal mouse anti-human sST2 antibody ST-02 and [email protected] on the test band with the appearance of target object sST2, we can detect the fluorescence intensity of Eu on the test band and the quality control band using a dry fluorescence analyzer. We calculated the / value (/ = fluorescence intensity of the test band/fluorescence intensity of the quality control band), fitted to the calibration curve, and measured the concentration value of sST2 in the corresponding sample. : the best reaction time was 15 min after condition exploration, and the optimal sample volume was 80 μL. The detection sensitivity of the scheme was 2.14 ng mL. The calibration curve of the assay was = 0.0113 + 0.0033, and the linear range was 5-200 ng mL. No cross reaction was found when the samples contained BNP, NT-proBNP, and galectin-3, indicating a good specificity. The precision was good with a relative deviation < 15%. The coefficient of variation of detection results of low-concentration samples and high-concentration samples was 4.20% and 3.30% respectively in the same batch of strip tests, so the intra-assay CV was set as <10%; when different batches of strips were used for testing, the coefficient of variation of detection results of low-concentration samples and high-concentration samples was 10.06% and 8.38% respectively, so the inter-assay CV was set as <15%. Stability test results showed that the relative deviation of test results at each time node was <15%, indicating good stability of the assay strips. The correlation coefficient between the [email protected] based time-resolved fluorescence immunochromatography analysis and sST2 ELISA kit was 0.98. To confirm the usage of our proposed TRF-ICA for clinical samples, it was used to determine the concentration of sST2 in samples obtained from 34 patients with heart insufficiency, acute and chronic heart failure. As a result, we successfully detected a minimal concentration of 5.21 ng mL and a maximum concentration of 184.26 ng mL for sST2. : this technique provides a rapid, simple and quantitative detection method for sST2 in clinics. It can help clinicians to predict the incidence of adverse events in patients with HF.
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http://dx.doi.org/10.1039/d2ay00120aDOI Listing
May 2022

Peroxynitrite (ONOO) Redox Signaling Molecule-Responsive Polymersomes.

ACS Macro Lett 2016 Aug 15;5(8):919-924. Epub 2016 Jul 15.

Department of Macromolecular Science, State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200433, China.

Designing specific-responsive polymer nanocapsules toward a definite cell signaling molecule for targeted therapy faces a great challenge. Here we demonstrate that new block copolymer appended trifluoromethyl ketone side groups can chemoselectively respond to an endogenous redox biosignal, peroxynitrite (ONOO), but shield the interference of other biogenic reactive oxygen, nitrogen, and sulfur species (ROS/RNS/RSS). The ONOO signaling molecule is capable of triggering cascade oxidation-elimination reactions to cleave the side functionalities from the polymer chain, which induces a large alteration of the polymer amphiphilicity and further leads to controllable disassembly of their self-assembled vesicular structure. Modulating the ONOO stimulus concentrations could readily control the vesicle dissociation rates for desirable drug delivery. We envisage that this polymer model would provide a new scenario to construct bioresponsive macromolecular systems for future biomedical nanotechnologies.
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http://dx.doi.org/10.1021/acsmacrolett.6b00474DOI Listing
August 2016

Controlled Formation of Microgels/Nanogels from a Disulfide-Linked Core/Shell Hyperbranched Polymer.

ACS Macro Lett 2012 Nov 19;1(11):1295-1299. Epub 2012 Oct 19.

Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.

A general approach to controlled formation of microgels/nanogels is developed for producing hydrogel particles with customizable structures and properties, especially for fabricating multilayered hydrogel particles with flexibly designable structures and properties of each layer. An inverse emulsion technique is adopted to obtain micro- or nanodroplets of a disulfide-linked core/shell hyperbranched polymer. Then pH of the droplets is manipulated to trigger and control in situ core/shell separation of the polymer, dissociation of the shells, and cross-linking of the cores, in the confined space at micro/nanoscales. Loose and compact microgels/nanogels with diverse properties like particle size and swelling capacity are yielded via adjusting the gelation time. Multilayered hydrogel particles with each tailor-made layer are further prepared using the controlled in situ gelation method in association with a seed emulsion technique.
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http://dx.doi.org/10.1021/mz300489nDOI Listing
November 2012

Iron ore or manganese ore filled constructed wetlands enhanced removal performance and changed removal process of nitrogen under sulfamethoxazole and trimethoprim stress.

Environ Sci Pollut Res Int 2022 May 23. Epub 2022 May 23.

Shandong Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science & Engineering, Shandong University, Qingdao, 266237, China.

Iron ore and manganese ore were used as substrate of constructed wetlands (CWs) to enhance nitrogen (N) removal. However, the N purification performance in CWs filled with iron or manganese ore under antibiotics stress needs further study. In this study, three groups of CWs filled with river sand, limonite (a kind of iron ore), and manganese ore sand were constructed, which were named as C-CWs, Fe-CWs, and Mn-CWs, respectively. The effect and mechanism of the composite antibiotics sulfamethoxazole (SMX) and trimethoprim (TMP) on N removal in CWs were investigated. While the addition of SMX and TMP inhibited about 40% nitrification and promoted about 25% denitrification in all CWs, Fe-CWs and Mn-CWs always had better N removal performance than C-CWs. Changes in microbial community structure in CWs indicated that the better N removal performance in Fe-CWs and Mn-CWs was attributed to the presence of more abundant and diverse N-associated bacteria, especially Fe- and Mn-driven autotrophic denitrifying bacteria. What's more, the addition of iron ore or manganese ore contributed to the better N removal performance with highest relative abundance of N-transferring bacteria under antibiotics stress.
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http://dx.doi.org/10.1007/s11356-022-20103-6DOI Listing
May 2022

Machine-learning-assisted spontaneous Raman spectroscopy classification and feature extraction for the diagnosis of human laryngeal cancer.

Comput Biol Med 2022 May 18;146:105617. Epub 2022 May 18.

Division of Electrical and Computer Engineering, College of Engineering, Louisiana State University, Baton Rouge, LA, 70803, USA. Electronic address:

The early detection of laryngeal cancer significantly increases the survival rates, permits more conservative larynx sparing treatments, and reduces healthcare costs. A non-invasive optical form of biopsy for laryngeal carcinoma can increase the early detection rate, allow for more accurate monitoring of its recurrence, and improve intraoperative margin control. In this study, we evaluated a Raman spectroscopy system for the rapid intraoperative detection of human laryngeal carcinoma. The spectral analysis methods included principal component analysis (PCA), random forest (RF), and one-dimensional (1D) convolutional neural network (CNN) methods. We measured the Raman spectra from 207 normal and 500 tumor sites collected from 10 human laryngeal cancer surgical specimens. Random Forest analysis yielded an overall accuracy of 90.5%, sensitivity of 88.2%, and specificity of 92.8% on average over 10 trials. The 1D CNN demonstrated the highest performance with an accuracy of 96.1%, sensitivity of 95.2%, and specificity of 96.9% on average over 50 trials. In predicting the first three principal components (PCs) of normal and tumor data, both RF and CNN demonstrated high performances, except for the tumor PC2. This is the first study in which CNN-assisted Raman spectroscopy was used to identify human laryngeal cancer tissue with extracted feature weights. The proposed Raman spectroscopy feature extraction approach has not been previously applied to human cancer diagnosis. Raman spectroscopy, as assisted by machine learning (ML) methods, has the potential to serve as an intraoperative, non-invasive tool for the rapid diagnosis of laryngeal cancer and margin detection.
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http://dx.doi.org/10.1016/j.compbiomed.2022.105617DOI Listing
May 2022

Effect of Acupoint Hot Compress on Postpartum Urinary Retention After Vaginal Delivery: A Randomized Clinical Trial.

JAMA Netw Open 2022 May 2;5(5):e2213261. Epub 2022 May 2.

Department of Obstetrics, Zhejiang Xiaoshan Hospital, Hangzhou, China.

Importance: Acupoint hot compress during the early postpartum period may benefit patients after a vaginal delivery, but the evidence of this effect is limited.

Objective: To assess whether acupoint hot compress involving the abdominal, lumbosacral, and plantar regions could reduce the incidence of postpartum urinary retention, relieve postpartum uterine contraction pain, prevent emotional disorders, and promote lactation.

Design, Setting, And Participants: This multicenter randomized clinical trial was conducted at 12 hospitals in China. Pregnant patients were screened for eligibility (n = 13 949) and enrolled after vaginal delivery (n = 1200) between January 17 and August 15, 2021; data collection was completed on August 18, 2021. After vaginal delivery, these participants were randomized 1:1 to either the intervention group or control group. Statistical analysis was based on per-protocol population.

Interventions: Participants in the control group received routine postpartum care. Participants in the intervention group received routine postpartum care plus 3 sessions of a 4-hour acupoint hot compress involving the abdominal, lumbosacral, and plantar regions within 30 minutes, 24 hours, and 48 hours after delivery.

Main Outcomes And Measures: The primary outcome was the incidence of postpartum urinary retention, defined as the first urination occurring more than 6.5 hours after delivery and/or use of an indwelling catheter within 72 hours after delivery. The secondary outcomes were postpartum uterine contraction pain intensity (assessed with the visual analog scale [VAS]), depressive symptoms (assessed with the Edinburgh Postnatal Depression Scale), and lactation conditions (including lactation initiation time, breastfeeding milk volume, feeding mood and times, and newborn weight).

Results: Of the 1200 participants randomized, 1085 completed the study (537 in the intervention group and 548 in the control group, with a median [IQR] age of 26.0 [24.0-29.0] years). Participants in the intervention group compared with the control group had significantly decreased incidence of postpartum urinary retention (relative risk [RR], 0.58; 95% CI, 0.35-0.98; P = .03); improved postpartum uterine contraction pain when measured at 6.5 hours (median [IQR] VAS score, 1 [1-2] vs 2 [1-2]; P < .001), 28.5 hours (median [IQR] VAS score, 1 [0-1] vs 1 [1-2]; P < .001), 52.5 hours (median [IQR] VAS score, 1 [0-1] vs 1 [0-1]; P < .001), and 76.5 hours (median [IQR] VAS score, 0 [0-1] vs 0 [0-1]; P = .01) after delivery; reduced depressive symptoms (RR, 0.73; 95% CI, 0.54-0.98; P = .01); and increased breastfeeding milk volume measured at 28.5, 52.5, and 76.5 hours after delivery. No adverse events occurred in either of the 2 groups.

Conclusions And Relevance: Results of this trial showed that acupoint hot compress after vaginal delivery decreased postpartum urinary retention, uterine contraction pain, and depressive symptoms and increased breastfeeding milk volume. Acupoint hot compress may be considered as an adjunctive intervention in postnatal care that meets patient self-care needs.

Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000038417.
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http://dx.doi.org/10.1001/jamanetworkopen.2022.13261DOI Listing
May 2022

A Zero-Strain Insertion Cathode Material for Room-Temperature Fluoride-Ion Batteries.

ACS Appl Mater Interfaces 2022 May 21. Epub 2022 May 21.

State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, P. R. China.

A fluoride-ion battery (FIB) is a novel type of energy storage system that has a higher volumetric energy density and low cost. However, the high working temperature (>150 °C) and unsatisfactory cycling performance of cathode materials are not favorable for their practical application. Herein, fluoride ion-intercalated CoFe layered double hydroxide (LDH) (CoFe-F LDH) was prepared by a facile co-precipitation approach combined with ion-exchange. The CoFe-F LDH shows a reversible capacity of ∼50 mAh g after 100 cycles at room temperature. Although there is still a big gap between FIBs and lithium-ion batteries, the CoFe-F LDH is superior to most cathode materials for FIBs. Another important advantage of CoFe-F LDH FIBs is that they can work at room temperature, which has been rarely achieved in previous reports. The superior performance stems from the unique topochemical transformation property and small volume change (∼0.82%) of LDH in electrochemical cycles. Such a tiny volume change makes LDH a zero-strain cathode material for FIBs. The 2D diffusion pathways and weak interaction between fluoride ions and host layers facilitate the de/intercalation of fluoride ions, accompanied by the chemical state changes of Co/Co and Fe/Fe couples. First-principles calculations also reveal a low F diffusion barrier during the cyclic process. These findings expand the application field of LDH materials and propose a novel avenue for the designs of cathode materials toward room-temperature FIBs.
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http://dx.doi.org/10.1021/acsami.2c06376DOI Listing
May 2022

Editorial: HFpEF and HFmrEF: Different Sides of the Same Coin?

Front Cardiovasc Med 2022 5;9:916534. Epub 2022 May 5.

Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong (CUHK), Shatin, Hong Kong SAR, China.

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http://dx.doi.org/10.3389/fcvm.2022.916534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117743PMC
May 2022

Water properties and marinade uptake in broiler pectoralis major with the woody breast condition.

Food Chem 2022 May 17;391:133230. Epub 2022 May 17.

USDA, Agricultural Research Service, U.S. National Poultry Research Center, 950 College Station Road, Athens, GA 30605, USA. Electronic address:

To provide insight into the mechanisms by which the woody breast (WB) condition reduces marinade uptake, water properties of normal (NOR) and WB meat were investigated using TD-NMR. Broiler Pectoralis major was marinated with either water, 0.625% sodium tripolyphosphate, 5% NaCl, or 5% NaCl + 0.625% sodium tripolyphosphate (SP). Targeted final concentrations were 4% NaCl and 0.5% SP. WB reduced meat marinade uptake but did not affect relationships between marinade ingredients and water mobility. WB inhibited increases in extra-myofibrillar water mobility induced by marinade ingredients. Marination increased intra-myofibrillar water (Amp) regardless of marinade ingredients or muscle condition; however, WB resulted in reduced Amp. Additionally, NaCl- or phosphate-induced extra-myofibrillar water (Amp) gain in WB was greater than that in NOR. Our data suggest changes in both Amp and Amp are related to the difference in marinade uptake between NOR and WB meat marinated with NaCl-phosphate marinade.
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http://dx.doi.org/10.1016/j.foodchem.2022.133230DOI Listing
May 2022

The role of demographic compensation in stabilising marginal tree populations in North America.

Ecol Lett 2022 May 22. Epub 2022 May 22.

Zhejiang Tiantong Forest Ecosystem National Observation and Research Station, Research Center of Global Change and Complex Ecosystems, School of Ecological and Environmental Sciences, East China Normal University, Shanghai, P. R. China.

Demographic compensation-the opposing responses of vital rates along environmental gradients-potentially delays anticipated species' range contraction under climate change, but no consensus exists on its actual contribution. We calculated population growth rate (λ) and demographic compensation across the distributional ranges of 81 North American tree species and examined their responses to simulated warming and tree competition. We found that 43% of species showed stable population size at both northern and southern edges. Demographic compensation was detected in 25 species, yet 15 of them still showed a potential retraction from southern edges, indicating that compensation alone cannot maintain range stability. Simulated climatic warming caused larger decreases in λ for most species and weakened the effectiveness of demographic compensation in stabilising ranges. These findings suggest that climate stress may surpass the limited capacity of demographic compensation and pose a threat to the viability of North American tree populations.
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http://dx.doi.org/10.1111/ele.14028DOI Listing
May 2022

Impact of π-Conjugation Length on the Excited-State Dynamics of Star-Shaped Carbazole-π-Triazine Organic Chromophores.

J Phys Chem A 2022 May 20. Epub 2022 May 20.

Department of Chemistry, Marquette University, Milwaukee, Wisconsin 53201, United States.

Correlating star-shaped donor-bridge-acceptor (DBA) molecular structures with intramolecular charge transfer (ICT) and intersystem crossing (ISC) is essential to their application in photocatalysis, photovoltaics, and organic light-emitting diodes (OLEDs). In this work, we report a systematic photophysical study on a series of star-shaped triazine-phenylene-carbazole DBA molecules with 0, 1, and 2 bridging phenylene units (pTCT-0P, pTCT-1P, pTCT-2P). Using a combination of steady-state and time-resolved spectroscopy with time-dependent density functional theory (TDDFT), we find that the bridge length can strongly impact the structural conformation, ICT, and ISC. Global target analysis of the time-resolved spectroscopy reveals that pTCT-0P has the most favorable ISC rate of 1.96 × 10 ps, which is competitive with a singlet relaxation rate of 1.92 × 10 ps. TDDFT aligns with spectroscopic results within an order of magnitude, predicting an ISC rate of 2.1 × 10 ps and revealing that the donor/acceptor orthogonalization concomitantly suppresses singlet exciton recombination and lowers the singlet-triplet energy gap. The new fundamental insights gained from this work will help design the next generation of star-shaped DBA-type molecules for photocatalytic and photoelectronic applications.
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http://dx.doi.org/10.1021/acs.jpca.2c00682DOI Listing
May 2022

Automatic localization and identification of thoracic diseases from chest X-rays with deep learning.

Curr Med Imaging 2022 May 18. Epub 2022 May 18.

Department of Radiology, Drum Tower Hospital, Nanjing University, Nanjing, China.

Background: Automatic disease location and identification of chest X-rays (CXR) based on deep learning faces many challenges. The arguably most prevailing two are the lack of labeled data of disease locations and poor model transferability between different datasets. This study aims to tackle these problems.

Methods: We built a new form of bounding box dataset and developed a two-stage model for disease localization and identification of CXRs based on deep learning. The dataset marks anomalous regions in CXRs but not the corresponding diseases, different from all previous datasets. The advantages of this design are reduced labor of annotation and fewer possible errors associated with image labeling. The two-stage model combines the robustness of region proposal network, feature pyramid network, and multi-instance learning techniques. We trained and validated our model with the new bounding box dataset and the CheXpert dataset. Then, we tested its classification and localization performance on an external dataset, which is the official split test set of ChestX-ray14.

Results: For classification result, the mean area under the receiver operating characteristic curve (AUC) metrics of our model on the CheXpert validation dataset was 0.912, which was 0.021 superior to the baseline model. The mean AUC of our model on an external testing set was 0.784, whereas the state-of-the-art model got 0.773. The localization results showed comparable performance to the state-of-the-art models.

Conclusion: Our model exhibits a good transferability between datasets. And the new bounding box dataset is proven to be useful and shows an alternative technique of compiling disease localization datasets.
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http://dx.doi.org/10.2174/1573405618666220518110113DOI Listing
May 2022

The Preparation of Amorphous ZrC/Nanocrystalline Ni Multilayers and the Resistance to He Irradiation.

Materials (Basel) 2022 Apr 22;15(9). Epub 2022 Apr 22.

College of Energy, Xiamen University, Xiamen 361005, China.

The development of accident-tolerant materials is of great significance for preventing the zirconium-water reactions and improving the inherent safety of nuclear reactors. In this study, ZrC/Ni multilayers with average layer thicknesses of 5, 10, 20, 50, and 100 nm were designed and successfully fabricated by magnetron sputtering. The characterization results of GIXRD, SEM, AFM, TEM, etc., show that the series of films are mainly composed of alternately deposited Ni crystalline layers and ZrC amorphous layers, and the interface is clear. The films were irradiated with 50 keV He with a fluence of 1.0 × 10 ions/cm at room temperature, and the films with different layer thicknesses kept the original phase composition. It was found that an amorphous transition layer with a thickness of about 30 nm appeared between the amorphous and crystalline interface of the 100 nm film by TEM characterization. The analysis shows that this layer is formed by the mixing of Ni and Zr elements induced by irradiation, which is not conducive to He migration and produces large-sized helium bubbles. The appearance of the transition layer improves the irradiation stability of the amorphous/crystalline composite film, thus providing a theoretical basis for the application of this type of material in fuel cladding.
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http://dx.doi.org/10.3390/ma15093059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9101292PMC
April 2022

Identification and confirmation of key compounds causing cooked off-flavor in heat-treated tomato juice.

J Food Sci 2022 May 19. Epub 2022 May 19.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.

Cooked off-flavor produced by heat treatment greatly limited the acceptability of commercial tomato juice. To screen and identify the cooked off-flavor compounds, gas chromatography-mass spectrometry-olfactometry (GC-MS-O), aroma extract dilution analysis (AEDA), gas chromatography-mass spectrometry (GC-MS), and odor activity value (OAV) calculation were applied simultaneously. The results showed that there were 17 aroma-active compounds in tomato juice samples. Among them, three newly formed sulfur-containing compounds (dimethyl sulfide, dimethyl trisulfide, and methional) and 1-octen-3-one, which exhibited cooked corn/potato, onion, and mushroom odor, were proved to be responsible for the cooked off-flavor in heat-treated tomato juice (HTJ) by omission experiments and electronic nose analysis. The three newly formed sulfur-containing compounds were further confirmed to be the key compounds responsible for the cooked off-flavor in four different tomato cultivars that were commonly consumed in the market. PRACTICAL APPLICATION: Tomato is one of the most popular vegetables in the world and tomato juice is an important part of the tomato industry. However, the cooked off-flavor of tomato juice after sterilization severely restricts its industrial development. This study analyzed and compared the changes of aroma compounds before and after sterilization, and identified and confirmed the major off-flavor components. This work could provide fundamental information for the prevention of cooked off-flavor.
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http://dx.doi.org/10.1111/1750-3841.16168DOI Listing
May 2022

Influence of abdominal aortic calcification on the distal extent and branch blood supply of acute aortic dissection.

Ann Vasc Surg 2022 May 16. Epub 2022 May 16.

Department of Vascular Surgery, First Affiliated Hospital of China Medical University, Shenyang, China. Electronic address:

Objective: This study aimed to investigate the influence of abdominal aortic calcification on the distal extent, blood supply, and mid-term outcomes of acute aortic dissection (AAD).

Methods: This single-centre retrospective study was conducted from August 2014 to May 2021. The aortic calcification index (ACI) was used to evaluate abdominal aortic calcification. The standardized method provided by the Society for Vascular Surgery (SVS) was used to evaluate the distal extent of AAD. Patients were divided into three groups according to the degree of calcification: no calcification (NC), low calcification (LC), and high calcification (HC).

Results: In a cohort of 723 patients, abdominal aortic calcification was present in 424 (58.6%) patients. The prevalence of coronary heart disease increased with the degree of calcification (NC vs. LC vs. HC: 8.4% vs. 9.5% vs. 19.3%, P<0.001). The ACI of the distal extent at zone 9 was higher than that of the distal extent exceeding zone 9 (P=0.001). The proportions of the NC, LC and HC groups with distal extents exceeding zone 9 were 65.9% vs. 56.2% vs. 37.7%, P<0.001. In multivariate logistics analysis, the calcification grades was a protective factor of distal extents exceeding zone 9 (P<0.001, OR=0.592). Hypertension (P=0.019, OR=1.559) and D-dimer (P<.001, OR=1.045) were risk factors. There was a higher proportion of branch-vessels on the abdominal aorta supplied by the true lumen in the calcification group (NC vs. LC vs. HC: 27.8% vs. 43.8% vs. 51.1%, P<0.001). There were no significant differences in the mid-term outcomes among the groups.

Conclusions: Abdominal aortic calcification could limit the distal extent in patients with AAD and increase the proportion of branch-vessels on the abdominal aorta supplied by the true lumen.
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http://dx.doi.org/10.1016/j.avsg.2022.05.006DOI Listing
May 2022

A H9N2 Human Case and Surveillance of Avian Influenza Viruses in Live Poultry Markets - Huizhou City, Guangdong Province, China, 2021.

China CDC Wkly 2022 Jan;4(1):8-10

School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China.

What Is Already Known About This Topic?: An increasing number of human infected avian influenza A (H9N2) cases have been reported. In 2021, 11 human infections with influenza A virus subtype H9N2 (A/H9N2) have been reported in China.

What Is Added By This Report?: A new case of H9N2 that occurred in April 2021 in Huizhou City, Guangdong Province, China, was reported in this study. Epidemiological and laboratory information of the case and routine influenza surveillance data of avian influenza A were presented in this report.

What Are The Implications For Public Health Practice?: The emergence of a human infected with Avian Influenza Virus H9N2 demonstrates that there is an urgent need to strengthen the surveillance of influenza-like illness and live poultry market.
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http://dx.doi.org/10.46234/ccdcw2021.273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8796722PMC
January 2022

Combining multiparametric MRI features-based transfer learning and clinical parameters: application of machine learning for the differentiation of uterine sarcomas from atypical leiomyomas.

Eur Radiol 2022 May 18. Epub 2022 May 18.

State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.

Objectives: To explore the feasibility and effectiveness of machine learning (ML) based on multiparametric magnetic resonance imaging (mp-MRI) features extracted from transfer learning combined with clinical parameters to differentiate uterine sarcomas from atypical leiomyomas (ALMs).

Methods: The data of 86 uterine sarcomas between July 2011 and December 2019 and 86 ALMs between June 2013 and June 2017 were retrospectively reviewed. We extracted deep-learning features and radiomics features from T2-weighted imaging (T2WI) and diffusion weighted imaging (DWI). The two feature extraction methods, transfer learning and radiomics, were compared. Random forest was adopted as the classifier. T2WI features, DWI features, combined T2WI and DWI (mp-MRI) features, and combined clinical parameters and mp-MRI features were applied to establish T2, DWI, T2-DWI, and complex multiparameter (mp) models, respectively. Predictive performance was assessed with the area under the receiver operating characteristic curve (AUC).

Results: In the test set, the T2, DWI, T2-DWI and complex mp models based on transfer learning (AUCs range from 0.76 to 0.81, 0.80 to 0.88, 0.85 to 0.92, and 0.94 to 0.96, respectively) outperformed the models based on radiomics (AUCs of 0.73, 0.76, 0.79, and 0.92, respectively). Moreover, the complex mp model showed the best prediction performance, with the Resnet50-complex mp model achieving the highest AUC (0.96) and accuracy (0.87).

Conclusions: Transfer learning is feasible and superior to radiomics in the differential diagnosis of uterine sarcomas and ALMs in our dataset. ML models based on deep learning features of nonenhanced mp-MRI and clinical parameters can achieve good diagnostic efficacy.

Key Points: • The ML model combining nonenhanced mp-MRI features and clinical parameters can distinguish uterine sarcomas from ALMs. • Transfer learning can be applied to differentiate uterine sarcomas from ALMs and outperform radiomics. • The most accurate prediction model was Resnet50-based transfer learning, built with the deep-learning features of mp-MRI and clinical parameters.
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http://dx.doi.org/10.1007/s00330-022-08783-7DOI Listing
May 2022

Ocrelizumab for multiple sclerosis.

Cochrane Database Syst Rev 2022 05 18;5:CD013247. Epub 2022 May 18.

Department of Neurology, Second Affiliated Hospital of Guangxi Medical University, Nanning, China.

Background: Ocrelizumab is a humanised anti-CD20 monoclonal antibody developed for the treatment of multiple sclerosis (MS). It was approved by the Food and Drug Administration (FDA) in March 2017 for using in adults with relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS). Ocrelizumab is the only disease-modifying therapy (DMT) approved for PPMS. In November 2017, the European Medicines Agency (EMA) also approved ocrelizumab as the first drug for people with early PPMS. Therefore, it is important to evaluate the benefits, harms, and tolerability of ocrelizumab in people with MS.

Objectives: To assess the benefits, harms, and tolerability of ocrelizumab in people with RRMS and PPMS.

Search Methods: We searched MEDLINE, Embase, CENTRAL, and two trials registers on 8 October 2021. We screened reference lists, contacted experts, and contacted the main authors of studies.

Selection Criteria: All randomised controlled trials (RCTs) involving adults diagnosed with RRMS or PPMS according to the McDonald criteria, comparing ocrelizumab alone or associated with other medications, at the approved dose of 600 mg every 24 weeks for any duration, versus placebo or any other active drug therapy.

Data Collection And Analysis: We used standard methodological procedures expected by Cochrane.

Main Results: Four RCTs met our selection criteria. The overall population included 2551 participants; 1370 treated with ocrelizumab 600 mg and 1181 controls. Among the controls, 298 participants received placebo and 883 received interferon beta-1a. The treatment duration was 24 weeks in one study, 96 weeks in two studies, and at least 120 weeks in one study. One study was at high risk of allocation concealment and blinding of participants and personnel; all four studies were at high risk of bias for incomplete outcome data. For RRMS, compared with interferon beta-1a, ocrelizumab was associated with: 1. lower relapse rate (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.52 to 0.73; 2 studies, 1656 participants; moderate-certainty evidence); 2. a lower number of participants with disability progression (hazard ratio (HR) 0.60, 95% CI 0.43 to 0.84; 2 studies, 1656 participants; low-certainty evidence); 3. little to no difference in the number of participants with any adverse event (RR 1.00, 95% CI 0.96 to 1.04; 2 studies, 1651 participants; moderate-certainty evidence); 4. little to no difference in the number of participants with any serious adverse event (RR 0.79, 95% CI 0.57 to 1.11; 2 studies, 1651 participants; low-certainty evidence); 5. a lower number of participants experiencing treatment discontinuation caused by adverse events (RR 0.58, 95% CI 0.37 to 0.91; 2 studies, 1651 participants; low-certainty evidence); 6. a lower number of participants with gadolinium-enhancing T1 lesions on magnetic resonance imaging (MRI) (RR 0.27, 95% CI 0.22 to 0.35; 2 studies, 1656 participants; low-certainty evidence); 7. a lower number of participants with new or enlarging T2-hyperintense lesions on MRI (RR 0.63, 95% CI 0.57 to 0.69; 2 studies, 1656 participants; low-certainty evidence) at 96 weeks. For PPMS, compared with placebo, ocrelizumab was associated with: 1. a lower number of participants with disability progression (HR 0.75, 95% CI 0.58 to 0.98; 1 study, 731 participants; low-certainty evidence); 2. a higher number of participants with any adverse events (RR 1.06, 95% CI 1.01 to 1.11; 1 study, 725 participants; moderate-certainty evidence); 3. little to no difference in the number of participants with any serious adverse event (RR 0.92, 95% CI 0.68 to 1.23; 1 study, 725 participants; low-certainty evidence); 4. little to no difference in the number of participants experiencing treatment discontinuation caused by adverse events (RR 1.23, 95% CI 0.55 to 2.75; 1 study, 725 participants; low-certainty evidence) for at least 120 weeks. There were no data for number of participants with gadolinium-enhancing T1 lesions on MRI and number of participants with new or enlarging T2-hyperintense lesions on MRI.

Authors' Conclusions: For people with RRMS, ocrelizumab probably results in a large reduction in relapse rate and little to no difference in adverse events when compared with interferon beta-1a at 96 weeks (moderate-certainty evidence). Ocrelizumab may result in a large reduction in disability progression, treatment discontinuation caused by adverse events, number of participants with gadolinium-enhancing T1 lesions on MRI, and number of participants with new or enlarging T2-hyperintense lesions on MRI, and may result in little to no difference in serious adverse events (low-certainty evidence). For people with PPMS, ocrelizumab probably results in a higher rate of adverse events when compared with placebo for at least 120 weeks (moderate-certainty evidence). Ocrelizumab may result in a reduction in disability progression and little to no difference in serious adverse events and treatment discontinuation caused by adverse events (low-certainty evidence). Ocrelizumab was well tolerated clinically; the most common adverse events were infusion-related reactions and nasopharyngitis, and urinary tract and upper respiratory tract infections.
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http://dx.doi.org/10.1002/14651858.CD013247.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9115862PMC
May 2022

[Lipopolysaccharide induces inflammation and up-regulates the expression of methyltransferase-like 3 (METTL3) and METTL14 in human and mouse intestinal epithelial cells].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2022 Apr;38(4):308-315

Medical College,Yan'an University, Yan'an 716000, China. *Corresponding authors, E-mail:

Objective To investigate the changes of N-methyladenosine (mA) modification in the inflammatory status of HIEC-6 human intestinal epithelial cells and MODE-K mouse intestinal epithelial cells. Methods HIEC-6 cells and MODE-K cells were induced by different concentrations of lipopolysaccharide (LPS), interleukin-1β (IL-1β), IL-6 and tumor necrosis factor alpha (TNF-α) for 10 hours or the same concentration of LPS, IL-1β, IL-6 and TNF-α for 0, 3, 6, 12, 24 hours, respectively. The mRNA expression levels of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were detected by real-time quantitative PCR. The mRNA and protein expression levels of mA modification-related molecules methyltransferase-like 3 (METTL3), METTL14, METTL16, Wilm's tumor 1-associated protein (WTAP), alkylation repair homolog protein 5 (ALKBH5), fat-mass and obesity-associated protein (FTO), YTH domain-containing 1 (YTHDC1), YTHDC2 were detected through real-time quantitative PCR and Western blot, respectively. Results The mRNA expression levels of IL-1β, IL-6 and TNF-α were increased and the mRNA and protein expression levels of METTL3 and METTL14 were simultaneously up-regulated in time-dependent and concentration-dependent LPS-induced model in HIEC-6 cells and MODE-K cells. Conclusion LPS can induce inflammation and up-regulate the expression of METTL3 and METTL14 in intestinal epithelial cells.
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April 2022

Development of a FT3-related prognostic model for patients with hepatitis B virus-related acute-on-chronic liver failure.

Bioengineered 2022 May;13(5):12548-12557

Department of Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, China.

This study aimed to develop a prediction model for the prognosis of patients with Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). 122 patients were divided into survival group and death group according to 90-day prognosis after diagnosis. Risk factors affecting the prognosis were identified by the logistic regression analysis and then were used to establish an FT3-related prediction model. Age, proportion of liver cirrhosis, AST, TBil, INR, Cr, Na, WBC, and several scores (CTP, MELD, MELD-Na, CLIF-SOFA, CLIF-OF, and AARC scores) of the death group were significantly higher than that of the survival group on admission. FT3 and Na were protective factors for the prognosis of patients; Age, TBil, INR, HE grading, and Cr were risk factors. FT3 levels were (2.79 ± 0.34) (95%CI 2.73-2.87) pmol/L for the survival group and (2.20 ± 0.20) (95%CI 2.11-2.29) pmol/L for the death group. The level of FT3 in survival group was significantly higher than that of the death group in patients regardless of gender, initial liver disease, and liver failure stages (P < 0.05). The ROC curve for FT3-related prognostic model score was 0.923 (95%CI 0.809-0.947), significantly higher than that of the CTP, MELD, MELD-Na, CLIF-SOFA, CLIF-C OF, and AARC scores (P < 0.001). The FT3-related prediction model has good predictive value for 90-day prognosis.
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http://dx.doi.org/10.1080/21655979.2022.2077057DOI Listing
May 2022

Exosomal microRNAs shuttling between tumor cells and macrophages: cellular interactions and novel therapeutic strategies.

Cancer Cell Int 2022 May 16;22(1):190. Epub 2022 May 16.

Department of General Surgery, The First Affiliated Hospital With Nanjing Medical University, 300 Guanzhou Road, Nanjing, 210029, China.

Extracellular vesicles secreted by tumor microenvironment (TME) cells are vital players in tumor progression through transferring nucleic acids and proteins. Macrophages are the main immune cells in TME and tumor associated macrophages (TAM) express M2 phenotype, which induce tumor proliferation, angiogenesis, invasion, metastasis and immune elimination, resulting in the subsequent evolution of malignancies. There are a high number of studies confirmed that tumor cells and TAM interact with each other through extracellular vesicles in various cancers, like pancreatic ductal adenocarcinoma, gastric cancer, breast cancer, ovarian cancer, colon cancer, glioblastoma, hepatocellular cancer, and lung cancer. Herein, this review summarizes the current knowledge on mechanisms of communications between tumor cells and TAM via extracellular vesicles, mainly about microRNAs, and targeting these events might represent a novel approach in the clinical implications of this knowledge into successful anti-cancer strategies.
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http://dx.doi.org/10.1186/s12935-022-02594-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109313PMC
May 2022

Targeting SNORA38B attenuates tumorigenesis and sensitizes immune checkpoint blockade in non-small cell lung cancer by remodeling the tumor microenvironment via regulation of GAB2/AKT/mTOR signaling pathway.

J Immunother Cancer 2022 05;10(5)

Department of Occupational and Environmental Health, Wuhan University, Wuhan, Hubei, People's Republic of China

Background: Non-coding RNAs (ncRNAs), including small nucleolar RNAs (snoRNAs), are widely involved in the physiological and pathological processes of human beings. While up to date, although considerable progress has been achieved in ncRNA-related pathogenesis of non-small cell lung cancer (NSCLC), the underlying mechanisms and biological significance of snoRNAs in NSCLC still need to be further clarified.

Methods: Quantitative real-time polymerase chain reaction or RNAscope was performed to verify the expression of Small Nucleolar RNA, H/ACA Box 38B (SNORA38B) in NSCLC cell lines or clinical samples. BALB/c nude mice xenograft model or C57BL/6J mice syngeneic tumor model were estimated to detect the effects of SNORA38B in tumor growth or tumor immune microenvironment in vivo. Cytometry by time of flight, enzyme-linked immunosorbent assay and flow cytometry assay were conducted to clarify the effects and mechanisms of SNORA38B-mediated tumor immunosuppressive microenvironment. The binding activity between SNORA38B and E2F transcription factor 1(E2F1) was detected by RNA immunoprecipitation and RNA pull-down assays. Then, bioinformatics analysis and chromatin immunoprecipitation were utilized to demonstrate the regulation of GRB2-associated-binding protein 2 (GAB2) by E2F1. Moreover, the combinatorial treatment of SNORA38B locked nucleic acid (LNA) and immune checkpoint blockade (ICB) was used to treat murine Lewis lung carcinoma-derived tumor burden C57BL/6J mice to clarify the effectiveness of targeting SNORA38B in NSCLC immunotherapy.

Results: SNORA38B was found highly expressed in NSCLC tissues and cell lines, and associated with worse prognosis. Further results showed that SNORA38B functioned as an oncogene via facilitating cell proliferation, migration, invasion, and inhibiting cell apoptosis in vitro and promoting tumorigenesis of NSCLC cells in vivo. SNORA38B could also recruit the CD4FOXP3 regulatory T cells by triggering tumor cells to secrete interleukin 10, which in turn reduced the infiltration of CD3CD8 T cells in NSCLC tumor microenvironment (TME), favoring tumor progression and poorer immune efficacy. Mechanistically, SNORA38B mainly distributed in the nucleus, and promoted NSCLC progression by regulating GAB2 transcription to activate protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway through directly binding with E2F1. Moreover, we found that SNORA38B LNAs were able to ameliorate CD3CD8 T cell infiltration in TME, which sensitized NSCLC to the treatment of ICB.

Conclusions: In conclusion, our data demonstrated that SNORA38B functioned as an oncogene in NSCLC both in vitro and in vivo at least in part by regulating the GAB2/AKT/mTOR pathway via directly binding to E2F1. SNORA38B could also sensitize NSCLC to immunotherapy, which may be a critical therapeutic target for NSCLC.
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http://dx.doi.org/10.1136/jitc-2021-004113DOI Listing
May 2022

Identification of Candidate Genes for Lint Percentage and Fiber Quality Through QTL Mapping and Transcriptome Analysis in an Allotetraploid Interspecific Cotton CSSLs Population.

Front Plant Sci 2022 29;13:882051. Epub 2022 Apr 29.

College of Agronomy and Biotechnology, Southwest University, Chongqing, China.

Upland cotton () has long been an important fiber crop, but the narrow genetic diversity of modern limits the potential for simultaneous improvement of yield and fiber quality. It is an effective approach to broaden the genetic base of through introgression of novel alleles from with excellent fiber quality. In the present study, an interspecific chromosome segment substitution lines (CSSLs) population was established using cultivar Pima S-7 as the donor parent and cultivar CCRI35 as the recipient parent. A total of 105 quantitative trait loci (QTL), including 85 QTL for fiber quality and 20 QTL for lint percentage (LP), were identified based on phenotypic data collected from four environments. Among these QTL, 25 stable QTL were detected in two or more environments, including four for LP, eleven for fiber length (FL), three for fiber strength (FS), six for fiber micronaire (FM), and one for fiber elongation (FE). Eleven QTL clusters were observed on nine chromosomes, of which seven QTL clusters harbored stable QTL. Moreover, eleven major QTL for fiber quality were verified through analysis of introgressed segments of the eight superior lines with the best comprehensive phenotypes. A total of 586 putative candidate genes were identified for 25 stable QTL associated with lint percentage and fiber quality through transcriptome analysis. Furthermore, three candidate genes for FL, (), (), and (), and one candidate gene for FM, (), were identified through RNA-Seq and qRT-PCR analysis. These results lay the foundation for understanding the molecular regulatory mechanism of fiber development and provide valuable information for marker-assisted selection (MAS) in cotton breeding.
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http://dx.doi.org/10.3389/fpls.2022.882051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100888PMC
April 2022

Prognostic value of thoracic tumor staging and volume parameters in non-small cell lung cancer patients with synchronous solitary bone metastasis.

J Thorac Dis 2022 Apr;14(4):1130-1138

Department of Orthopedic Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China.

Background: Non-small cell lung cancer (NSCLC) patients with synchronous solitary metastasis are a heterogeneous population. The analysis and evaluation of NSCLC patients with synchronous solitary bone metastases by cTN stage (thoracic tumor staging) and volume parameters have not yet been studied. The purpose of this study is to estimate the prognostic value of cTN stage and volume parameters obtained by fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in NSCLC patients with synchronous solitary bone metastasis.

Methods: A total of 157 NSCLC patients with synchronous solitary bone metastasis were retrospectively analyzed. Patients' cTN stage, metabolic tumor volume (MTV) parameters, and clinical data were collected. Kaplan-Meier survival analysis and a Cox regression model were performed to determine the association between each factor and overall survival (OS). Finally, time-dependent receiver operating characteristic (TDROC) curve analysis was used to assess the predictive capacity of the independent prognostic factors.

Results: Kaplan-Meier survival analysis showed significant differences between subgroups in terms of cTN stage. The median OS of group I was 44 months, and the 5-year survival rate was 39.6%. In the multivariate Cox regression analysis, cTN stage, MTV of the whole body (MTVwb), and MTV of thorax (MTVtho) were significantly associated with patient OS, even after adjusting for other clinical factors. However, MTV of bone (MTVbon) was not found to be an independent prognostic factor. TDROC curve analysis showed that cTN stage, MTVwb, and MTVtho had good predictive capacity for NSCLC patients with synchronous solitary bone metastasis. Compared with cTN stage and MTVtho, MTVwb had obviously better predictive specificity and sensitivity for the 5-year survival rate [5-year area under the curve (AUC) of MTVwb =0.844 cTN stage (P=0.035) MTVtho (P=0.052)]. The best cutoff value of MTVwb was 33.05.

Conclusions: The results of this study confirmed that cTN stage, MTVwb, and MTVtho were independent prognostic factors of NSCLC patients with synchronous solitary bone metastases. These factors can be used for risk stratification of these patients. TDROC curve analysis indicated that cTN stage, MTVtho, and MTVwb had good performance for survival prediction.
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http://dx.doi.org/10.21037/jtd-22-113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096287PMC
April 2022
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