Publications by authors named "Yun Lu"

566 Publications

[Study of the root position of palatally malposed maxillary lateral incisor based on cone-beam CT images].

Shanghai Kou Qiang Yi Xue 2021 Apr;30(2):129-134

Department of Orthodontics, Shanghai Stomatological Hospital; Oral Biomedical Engineering Laboratory, Fudan University. Shanghai 200001, China.

Purpose: The goal of this investigation was to measure and analyze the root position of palatally malposed maxillary lateral incisor based on cone-beam CT(CBCT)images, in order to provide references for orthodontists to move this kind of teeth scientifically.

Methods: CBCT data from 200 patients meeting the selection criteria with palatally malposed maxillary lateral incisor were investigated in this study. The root was divided into eight equal parts by length, then T1 to T8 were orderly pointed from root apex to alveolar ridge crest. The labial and palatal bone thickness at each point was measured; meanwhile, the angle between the long axis of the tooth and that of the alveolar bone was measured.The data was analyzed using SPSS 19.0 software package.

Results: The mean labial bone thicknesses at all researched points were less than 1.00 mm, except for point T1,T7 and T8. The mean labial bone thicknesses at point T3, T4 and T5 were the thinnest, which were all less than 0.5 mm(P<0.05). The mean thicknesses of labial bone gradually increased from T4 to T8(P<0.05). The mean palatal bone thicknesses were all more than 1.00 mm at the eight points,the mean thicknesses of palatal bone gradually increased from T8 to T1(P<0.05). All the angulations between the long axes of teeth and those of the alveolar bone were negative, indicating the root was close to the labial alveolar wall. The average angulation was minus 31.06 degrees.

Conclusions: Results suggest that the root of palatally malposed maxillary lateral incisor is close to the labial wall of the alveolar bone, its labial alveolar bone is frequently quite thin or even deficient, especially in the zone between 1/4 root length to the root apex and the mid-root. If we move the palatally malposed maxillary lateral incisor labially, it is better to choose tipping movement, instead of bodily movement, in order to avoid serious bone fenestration and dehiscence or root absorption.
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April 2021

Trace endotoxin in reclaimed water is only one of the risk sources in subchronic inhalation exposure.

Environ Pollut 2021 May 29;285:117479. Epub 2021 May 29.

School of Life Science, Tsinghua University, Beijing, 100084, China.

Pulmonary injury and inflammation have been detected in cases of subchronic inhalation exposure to reclaimed water, but the mechanism remains unclear. Endotoxin has been verified as the key risk factor in acute inhalation exposure through the TLR4 (Toll-like receptor 4) signalling pathway. In long-term exposure, endotoxin may also be a risk factor in reclaimed water, but the contribution of other health risk factors should not be underestimated. Wild-type C57BL/6J and TLR4-signalling-pathway-defective mice were used in this study to assess the risk of subchronic inhalation exposure to reclaimed water. Two types of reclaimed water, i.e., secondary effluent and MBR (membrane bioreactor) effluent, were found to induce pulmonary injury and inflammation in the wild-type mice and Tlr4 mutants. However, when both mice were exposed to the same concentrations of pure endotoxin in reclaimed water, only the wild-type mice that were treated with high-dose endotoxin showed pulmonary injury. In summary, non-TLR4 signalling pathways are related to lung inflammation caused by long-term exposure to reclaimed water. It is highly possible that pollutants in addition to endotoxin in the reclaimed water can induce chronic inflammation in the lung.
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http://dx.doi.org/10.1016/j.envpol.2021.117479DOI Listing
May 2021

Association of Positive Fluid Balance at Discharge After Sepsis Management With 30-Day Readmission.

JAMA Netw Open 2021 Jun 1;4(6):e216105. Epub 2021 Jun 1.

The Permanente Medical Group, Oakland, California.

Importance: Although early fluid administration has been shown to lower sepsis mortality, positive fluid balance has been associated with adverse outcomes. Little is known about associations in non-intensive care unit settings, with growing concern about readmission from excess fluid accumulation in patients with sepsis.

Objective: To evaluate whether positive fluid balance among non-critically ill patients with sepsis was associated with increased readmission risk, including readmission for heart failure.

Design, Setting, And Participants: This multicenter retrospective cohort study was conducted between January 1, 2012, and December 31, 2017, among 57 032 non-critically ill adults hospitalized for sepsis at 21 hospitals across Northern California. Kaiser Permanente Northern California is an integrated health care system with a community-based population of more than 4.4 million members. Statistical analysis was performed from January 1 to December 31, 2019.

Exposures: Intake and output net fluid balance (I/O) measured daily and cumulatively at discharge (positive vs negative).

Main Outcomes And Measures: The primary outcome was 30-day readmission. The secondary outcomes were readmission stratified by category and mortality after living discharge.

Results: The cohort included 57 032 patients who were hospitalized for sepsis (28 779 women [50.5%]; mean [SD] age, 73.7 [15.5] years). Compared with patients with positive I/O (40 940 [71.8%]), those with negative I/O (16 092 [28.2%]) were older, with increased comorbidity, acute illness severity, preexisting heart failure or chronic kidney disease, diuretic use, and decreased fluid administration volume. During 30-day follow-up, 8719 patients (15.3%) were readmitted and 3639 patients (6.4%) died. There was no difference in readmission between patients with positive vs negative I/O (HR, 1.00; 95% CI, 0.95-1.05). No association was detected between readmission and I/O using continuous, splined, and quadratic function transformations. Positive I/O was associated with decreased heart failure-related readmission (HR, 0.80 [95% CI, 0.71-0.91]) and increased 30-day mortality (HR, 1.23 [95% CI, 1.15-1.31]).

Conclusions And Relevance: In this large observational study of non-critically ill patients hospitalized with sepsis, there was no association between positive fluid balance at the time of discharge and readmission. However, these findings may have been limited by variable recording and documentation of fluid intake and output; additional studies are needed to examine the association of fluid status with outcomes in patients with sepsis to reduce readmission risk.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.6105DOI Listing
June 2021

Association Between Troponin I Levels During Sepsis and Post-Sepsis Cardiovascular Complications.

Am J Respir Crit Care Med 2021 May 26. Epub 2021 May 26.

Boston University School of Medicine, 12259, Pulmonary Center, Boston, Massachusetts, United States.

Rationale: Sepsis commonly results in elevated serum troponin I levels and increased risk for post-sepsis cardiovascular complications; however, the association between troponin I level during sepsis and cardiovascular complications after sepsis is unclear.

Objectives: To evaluate the association between serum troponin levels during sepsis and 1-year post-sepsis cardiovascular risks.

Methods: We included patients aged >40 years without a prior diagnosis of cardiovascular disease within 5-years, admitted with sepsis across 21 hospitals from 2011 to 2017. Peak serum troponin I levels during sepsis were grouped as normal (<0.04ng/mL) or tertiles of abnormal (>0.04 to <0.09ng/mL, >0.09 to <0.42ng/mL, or >0.42ng/mL). Multivariable adjusted, cause-specific, Cox proportional hazards models that treated death as a competing risk were used to assess associations between peak sepsis troponin I levels and a composite cardiovascular outcome (atherosclerotic cardiovascular disease, atrial fibrillation, and heart failure) in the year following sepsis. Models were adjusted for pre-sepsis and intra-sepsis factors considered potential confounders.

Measurements And Main Results: Among 14,046 patients with troponin I measured during sepsis, 2,012 (14.3%) patients experienced the composite cardiovascular outcome in the year following sepsis hospitalization. Compared with patients with normal troponin levels, those with elevated troponins had increased risks of adverse cardiovascular events (adjusted Hazard Ratiotroponin 0.04-0.09=1.37 (95% CI 1.20-1.55), aHRtroponin 0.09-0.42=1.44 (95% CI 1.27-1.63), and aHRtroponin > 0.42=1.77 (95% CI 1.56-2.00)).

Conclusions: Among patients without pre-existing cardiovascular disease, troponin elevation during sepsis identified patients at increased risk for post-sepsis cardiovascular complications. Strategies to mitigate cardiovascular complications among this high-risk subset of patients is warranted.
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http://dx.doi.org/10.1164/rccm.202103-0613OCDOI Listing
May 2021

Direct Correlation between Donor-Acceptor Distance and Temperature Dependence of Kinetic Isotope Effects in Hydride-Tunneling Reactions of NADH/NAD Analogues.

J Org Chem 2021 Jun 26;86(11):7500-7507. Epub 2021 May 26.

Department of Chemistry, Southern Illinois University Edwardsville, Edwardsville, Illinois 62026, United States.

Recent study of structural effects on primary kinetic isotope effects (1° KIEs) of H-transfer reactions in enzymes and solution revealed that a more rigid reaction system gave rise to a weaker temperature dependence of 1° KIEs, i.e., a smaller isotopic activation energy difference (Δ = - ). This has been explained within the contemporary vibrationally assisted activated H-tunneling (VA-AHT) model in which rigidity is defined according to the density of donor-acceptor distance (DAD) populations at the tunneling ready state (TRS) sampled by heavy atom motions. To test the relationship between DAD and Δ in the model, we developed a computational method to obtain the TRS structures for H-transfer reactions. The method was applied to three hydride transfer reactions of NADH/NAD analogues for which the Δ's as well as secondary (2°) KIEs have been reported. The 2° KIEs computed from each TRS structure were fitted to the observed values to obtain the optimal TRSs/DAD's. It was found that a shorter DAD does correspond with a smaller Δ. This appears to support the VA-AHT model. Moreover, an analysis of hybridizations at the bent TRS structures shows that rehybridizations at the donor-acceptor centers are much more advanced than predicted from the classical mechanism. This implies that more orbital preparations are required for the nonclassical H-tunneling to take place.
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http://dx.doi.org/10.1021/acs.joc.1c00497DOI Listing
June 2021

[Key Problems and Novel Strategy of Controlling Emerging Trace Organic Contaminants During Municipal Wastewater Reclamation].

Huan Jing Ke Xue 2021 Jun;42(6):2573-2582

State Key Joint Laboratory of Environmental Simulation and Pollution Control, Beijing Laboratory for Environmental Frontier Technologies, School of Environment, Tsinghua University, Beijing 100084, China.

Emerging trace organic contaminants (TOrCs) have been ubiquitously detected in municipal wastewater. TOrCs show low concentrations but are usually harmful to aquatic biota and recalcitrant to treatments. The advanced treatment of TOrCs is challenged by four main aspects. First, it is hard to qualify the chemical structure and concentrations of TOrCs, which are typically very low. Second, risk assessment results vary with the selection of target-species and toxicity-endpoints, which makes it hard to regulate priority lists and concentration limits. Third, TOrCs account for less than 0.01% of the total organics in wastewater. Thus, TOrCs cannot be selectively and efficiently removed by conventional treatments. Fourth, it is hard to optimize and manage the treatment trains of TOrCs. In this manuscript, a new strategy combing non-targeting TOrC screening and TOrC "fingerprinting" are proposed to overcome the difficulties of quantification and treatment optimization. Based on this, the standards and regulations to control the TOrCs in reclaimed water should be developed on the basis of elimination efficiency rather than concentration.
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http://dx.doi.org/10.13227/j.hjkx.202009251DOI Listing
June 2021

A Universal Method for Enhancing the Structural Stability of Ni-Rich Cathodes Via the Synergistic Effect of Dual-Element Cosubstitution.

ACS Appl Mater Interfaces 2021 Jun 20;13(21):24925-24936. Epub 2021 May 20.

School of Materials Science and Engineering, Beijing Institute of Technology, Beijing Key Laboratory of Environmental Science and Engineering, Beijing 100081, P. R. China.

Ni-rich layered cathodes suffer detrimental structural changes due to irreversible phase transformation (IPT). Precisely surface structural reconstruction through foreign element doping is a potential method to alleviate IPT propagation. The structure of surface reconstructed layer is greatly determined by the foreign element content and species. Herein, small doses of Ti and Al were co-substituted in LiNiCoO to synergistically regulate the surface reductive Ni distribution, consequently constructing thin rock salt phase at the particle surface. This homogeneous rock salt phase combined with the strong Ti-O and Al-O bonds generated a reversible H2-H3 phase transition and further eliminated IPT propagation. Moreover, the suppressed IPT propagation converted the two-phase (H2 and H3) coexistence to a quasi-single-phase transition. This eliminated the strong internal strains caused by a significant lattice mismatch. The Ti and Al co-substituted LiNiCoO exhibited outstanding capacity retention and excellent structural stability. Similar improvements were observed with W or Zr and Al cosubstitution in Ni-rich layered cathodes. This study proposes a universal method for comprehensive improvement of structural stability based on the synergistic effect of dual-element cosubstitution in Ni-rich layered oxide cathodes, which is being explored for production of high-cycle-stability lithium-ion batteries.
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http://dx.doi.org/10.1021/acsami.1c05486DOI Listing
June 2021

Study on the influence of operational and management processes of a water reclamation plant since COVID-19 situation.

Environ Pollut 2021 Apr 28;285:117257. Epub 2021 Apr 28.

Xi'an High-Tech Institute, Shaanxi, Xi'an, 710025, China.

Reusing treated wastewater can effectively alleviate water shortages and water contamination problems but depends on ensuring the safety of the reclaimed water that is produced. The operating and management conditions for water reclamation plants in China have been changed since the outbreak of the COVID-19 epidemic in China at the end of 2019 to prevent emerging viruses being spread through wastewater treatment processes and the reclaimed water that is produced. Removal of pathogens and trace organic compounds (e.g., pharmaceuticals and personal care products and endocrine disrupting chemicals) in a real water reclamation plant after the start of COVID-19 epidemic was studied. Disinfection byproduct formation caused by chlorine being added to meet disinfection requirements was also assessed. The pathogenic microorganism concentrations in effluent were <2 (most probable number)/L, and the removal rates for most trace organic compounds were >80% when advanced treatments were performed using ozone, ultraviolet light, and chlorine doses of 2 mg/L, 20.5 mJ/cm, and 2-3 mg/L, respectively. The main disinfection byproduct produced at a chlorine dose of 2 mg/L and a residence time of 1 h was chloroform (at concentrations <15 μg/L). The results indicated that the water reclamation processes with modified conditions gave high pathogen and trace organic compound removal rates and reasonably well-controlled disinfection byproduct concentrations.
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http://dx.doi.org/10.1016/j.envpol.2021.117257DOI Listing
April 2021

Ecological Barrier Deterioration Driven by Human Activities Poses Fatal Threats to Public Health due to Emerging Infectious Diseases.

Engineering (Beijing) 2021 Jan 5. Epub 2021 Jan 5.

School of Environment, Tsinghua University, Beijing 100084, China.

The recent outbreak of coronavirus disease 2019 (COVID-19) and concerns about several other pandemics in the 21st century have attracted extensive global attention. These emerging infectious diseases threaten global public health and raise urgent studies on unraveling the underlying mechanisms of their transmission from animals to humans. Although numerous works have intensively discussed the cross-species and endemic barriers to the occurrence and spread of emerging infectious diseases, both types of barriers play synergistic roles in wildlife habitats. Thus far, there is still a lack of a complete understanding of viral diffusion, migration, and transmission in ecosystems from a macro perspective. In this review, we conceptualize the ecological barrier that represents the combined effects of cross-species and endemic barriers for either the natural or intermediate hosts of viruses. We comprehensively discuss the key influential factors affecting the ecological barrier against viral transmission from virus hosts in their natural habitats into human society, including transmission routes, contact probability, contact frequency, and viral characteristics. Considering the significant impacts of human activities and global industrialization on the strength of the ecological barrier, ecological barrier deterioration driven by human activities is critically analyzed for potential mechanisms. Global climate change can trigger and expand the range of emerging infectious diseases, and human disturbances promote higher contact frequency and greater transmission possibility. In addition, globalization drives more transmission routes and produces new high-risk regions in city areas. This review aims to provide a new concept for and comprehensive evidence of the ecological barrier blocking the transmission and spread of emerging infectious diseases. It also offers new insights into potential strategies to protect the ecological barrier and reduce the wide-ranging risks of emerging infectious diseases to public health.
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http://dx.doi.org/10.1016/j.eng.2020.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060651PMC
January 2021

[Discussion of Microbial Control Standards of Water Reclamation and Formulation Methods].

Huan Jing Ke Xue 2021 May;42(5):2558-2564

State Key Joint Laboratory of Environmental Simulation and Pollution Control, State Environmental Protection Key Laboratory of Microorganism Application and Risk Control, School of Environment, Tsinghua University, Beijing 100084, China.

The key to water reclamation and reuse is water quality safety insurance and risk control. Microbial risk control is an important issue that requires priority during the safe reuse of reclaimed water. This paper systematically summarizes the control requirements for microbial indicators in China's current water reuse standards, focusing on the necessity and deficiencies of water quality targets and microbial indicator concentration control. The performance targets based on the removal requirements of microorganisms together with the methodology and implementation strategies are introduced in detail for the first time. In the future, it is necessary to further explore the microbial control method of water reclamation based on the combination of water quality targets and performance targets, which could provide support for the safe reuse of reclaimed water in China.
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http://dx.doi.org/10.13227/j.hjkx.202010024DOI Listing
May 2021

Fabrication of novel AgBiO towards excellent photocatalytic oxidation of gaseous toluene under visible light irradiation.

Environ Res 2021 Jun 13;197:111130. Epub 2021 Apr 13.

School of Environmental Science and Engineering, Huazhong University of Science and Technology, Luoyu Road 1037#, Wuhan, 430074, China. Electronic address:

In this work, a novel oxide combined with bismuth (Bi) and silver (Ag) was prepared via simple ball milling. This substance was optimized by adjusting the amount of pre-source. Preliminary characterization results confirmed the successful synthesis of AgBiO. Subsequently, gaseous toluene was selected as model compound to evaluate the photocatalytic activity of AgBiO photocatalyst. According to the degradation results, AgBiO performed excellent visible light-driven photocatalytic activity with high stability. For the oxidation process of gaseous compound, reactive oxygen species (ROS) were responsible for the achievement, and the formation of oxygen vacancies on AgBiO were involved in the generation of ROS to promote the transfer of photogenerated electrons, and improving photocatalytic activity. DFT calculations revealed the theoretical band gap of AgBiO bulk is 1.758 eV. And the work function of AgBiO (112)ov was ca. at 4.447 eV. The material was easily fabricated and a reliable path was provided for the synthesis of new and efficient photocatalyst for the remediation of polluted indoor air.
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http://dx.doi.org/10.1016/j.envres.2021.111130DOI Listing
June 2021

Monascus pilosus YX-1125: An efficient digester for directly treating ultra-high-strength liquor wastewater and producing short-chain fatty acids under multiple-stress conditions.

Bioresour Technol 2021 Jul 26;331:125050. Epub 2021 Mar 26.

College of Environment and Ecology, Chongqing University, Chongqing 400044, China; State Key Laboratory of Coal Mine Disaster Dynamics and Control, Chongqing University, Chongqing, 400044, China. Electronic address:

Ultra-high-strength liquor wastewater (UHS-LWW) is rich in organic matter, and the required treatment is expensive. Here, an extremophilic strain Monascus pilosus YX-1125 was isolated for the direct conversion of UHS-LWW to short-chain fatty acids (SCFAs). Strain YX-1125 is an efficient SCFA producer with carbohydrate metabolic flexibility under multiple-stress conditions. Moreover, strain YX-1125 could tolerate up to 75 g/L, 100 g/L, and 50 g/L of ethanol, organic acids, and salt, respectively, without inhibition. In repeated-cycle fermentations, 17.8 g/L of butyric acid and 2.0 g/L of propionic acid were produced from UHS-LWW at the fifth cycle, which are the highest concentrations of wastewater-derived SCFAs reported to date. After SCFA recovery, a 98.9% COD reduction was achieved, which is estimated to reduce treatment costs by 91.7%. Results indicate that M. pilosus YX-1125 is a promising strain for the direct treatment of UHS-LWW, and for converting it into valuable biochemicals without any pre-treatment.
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http://dx.doi.org/10.1016/j.biortech.2021.125050DOI Listing
July 2021

[Zr]-Pertuzumab PET Imaging Reveals Paclitaxel Treatment Efficacy Is Positively Correlated with HER2 Expression in Human Breast Cancer Xenograft Mouse Models.

Molecules 2021 Mar 12;26(6). Epub 2021 Mar 12.

Department of Radiology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.

Paclitaxel (PTX) treatment efficacy varies in breast cancer, yet the underlying mechanism for variable response remains unclear. This study evaluates whether human epidermal growth factor receptor 2 (HER2) expression level utilizing advanced molecular positron emission tomography (PET) imaging is correlated with PTX treatment efficacy in preclinical mouse models of HER2+ breast cancer. HER2 positive (BT474, MDA-MB-361), or HER2 negative (MDA-MB-231) breast cancer cells were subcutaneously injected into athymic nude mice and PTX (15 mg/kg) was administrated. In vivo HER2 expression was quantified through [Zr]-pertuzumab PET/CT imaging. PTX treatment response was quantified by [F]-fluorodeoxyglucose ([F]-FDG) PET/CT imaging. Spearman's correlation, Kendall's tau, Kolmogorov-Smirnov test, and ANOVA were used for statistical analysis. [Zr]-pertuzumab mean standard uptake values (SUV) of BT474 tumors were 4.9 ± 1.5, MDA-MB-361 tumors were 1.4 ± 0.2, and MDA-MB-231 (HER2-) tumors were 1.1 ± 0.4. [F]-FDG SUV changes were negatively correlated with [Zr]-pertuzumab SUV (r = -0.5887, = 0.0030). The baseline [F]-FDG SUV was negatively correlated with initial [Zr]-pertuzumab SUV (r = -0.6852, = 0.0002). This study shows PTX treatment efficacy is positively correlated with HER2 expression level in human breast cancer mouse models. Molecular imaging provides a non-invasive approach to quantify biological interactions, which will help in identifying chemotherapy responders and potentially enhance clinical decision-making.
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http://dx.doi.org/10.3390/molecules26061568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001650PMC
March 2021

Establishment and clinical application value of an automatic diagnosis platform for rectal cancer T-staging based on a deep neural network.

Chin Med J (Engl) 2021 Feb 25;134(7):821-828. Epub 2021 Feb 25.

Department of General Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China.

Background: Colorectal cancer is harmful to the patient's life. The treatment of patients is determined by accurate preoperative staging. Magnetic resonance imaging (MRI) played an important role in the preoperative examination of patients with rectal cancer, and artificial intelligence (AI) in the learning of images made significant achievements in recent years. Introducing AI into MRI recognition, a stable platform for image recognition and judgment can be established in a short period. This study aimed to establish an automatic diagnostic platform for predicting preoperative T staging of rectal cancer through a deep neural network.

Methods: A total of 183 rectal cancer patients' data were collected retrospectively as research objects. Faster region-based convolutional neural networks (Faster R-CNN) were used to build the platform. And the platform was evaluated according to the receiver operating characteristic (ROC) curve.

Results: An automatic diagnosis platform for T staging of rectal cancer was established through the study of MRI. The areas under the ROC curve (AUC) were 0.99 in the horizontal plane, 0.97 in the sagittal plane, and 0.98 in the coronal plane. In the horizontal plane, the AUC of T1 stage was 1, AUC of T2 stage was 1, AUC of T3 stage was 1, AUC of T4 stage was 1. In the coronal plane, AUC of T1 stage was 0.96, AUC of T2 stage was 0.97, AUC of T3 stage was 0.97, AUC of T4 stage was 0.97. In the sagittal plane, AUC of T1 stage was 0.95, AUC of T2 stage was 0.99, AUC of T3 stage was 0.96, and AUC of T4 stage was 1.00.

Conclusion: Faster R-CNN AI might be an effective and objective method to build the platform for predicting rectal cancer T-staging.

Trial Registration: chictr.org.cn: ChiCTR1900023575; http://www.chictr.org.cn/showproj.aspx?proj=39665.
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http://dx.doi.org/10.1097/CM9.0000000000001401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104246PMC
February 2021

Establishment and Clinical Application of an Artificial Intelligence Diagnostic Platform for Identifying Rectal Cancer Tumor Budding.

Front Oncol 2021 8;11:626626. Epub 2021 Mar 8.

Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.

Tumor budding is considered a sign of cancer cell activity and the first step of tumor metastasis. This study aimed to establish an automatic diagnostic platform for rectal cancer budding pathology by training a Faster region-based convolutional neural network (F-R-CNN) on the pathological images of rectal cancer budding. Postoperative pathological section images of 236 patients with rectal cancer from the Affiliated Hospital of Qingdao University, China, taken from January 2015 to January 2017 were used in the analysis. The tumor site was labeled in Label image software. The images of the learning set were trained using Faster R-CNN to establish an automatic diagnostic platform for tumor budding pathology analysis. The images of the test set were used to verify the learning outcome. The diagnostic platform was evaluated through the receiver operating characteristic (ROC) curve. Through training on pathological images of tumor budding, an automatic diagnostic platform for rectal cancer budding pathology was preliminarily established. The precision-recall curves were generated for the precision and recall of the nodule category in the training set. The area under the curve = 0.7414, which indicated that the training of Faster R-CNN was effective. The validation in the validation set yielded an area under the ROC curve of 0.88, indicating that the established artificial intelligence platform performed well at the pathological diagnosis of tumor budding. The established Faster R-CNN deep neural network platform for the pathological diagnosis of rectal cancer tumor budding can help pathologists make more efficient and accurate pathological diagnoses.
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http://dx.doi.org/10.3389/fonc.2021.626626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982570PMC
March 2021

F-fluorodeoxyglucose positron emission tomography for the detection of inflammatory lesions of the arterial vessel walls in Wistar rats.

Exp Ther Med 2021 Apr 19;21(4):370. Epub 2021 Feb 19.

Internal Medicine, Jiangsu Provincial Research Center for Health Assessment and Intervention, Jiangsu Provincial Taihu Sanatorium, Wuxi, Jiangsu 214086, P.R. China.

The present study aimed to evaluate the use of F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET) for detection of high-fat and high-salt diet-induced inflammatory lesions of the arterial vessel walls in Wistar rats. A total of 20 healthy, 8-week-old, male Wistar rats were randomly assigned to the high-fat diet group and the normal diet group. After 16 and 24 weeks of feeding, Wistar rats in the normal diet group and the high-fat diet group (five rats in each group) were injected with F-FDG through the tail vein at a dose of 1 mCi/kg after fasting for 12 h. After 1 h, the rats were anesthetized with 2% isoflurane, followed by micro-PET imaging with a 10-min image capture duration and immunohistochemical staining. The standardized uptake values (SUVs) of F-FDG were significantly higher in the iliac artery in the high-fat diet group compared with those in the normal diet group at 16 weeks (1.53±0.08 vs. 1.04±0.03; P<0.05) and at 24 weeks (1.96±0.17 vs. 1.12±0.07; P<0.05). The SUVs of F-FDG were also significantly greater in the abdominal aorta in the high-fat diet group compared with those in the normal diet group at 16 weeks (1.35±0.08 vs. 1.02±0.02; P<0.05) and at 24 weeks (1.54±0.09 vs. 1.04±0.02; P<0.05). In addition, the SUVs of F-FDG in the iliac artery and abdominal aorta were significantly higher at 24 weeks compared with those at 16 weeks in the high-fat diet group (P<0.05). As determined by immunohistochemistry, the percentage of CD68-positive cells in the total number of cells per unit area in each group was 3.20±1.80% in the 24-week normal diet group, 4.70±2.02% in the 16-week high-fat diet group and 6.94±2.02% in the 24-week high-fat diet group; the percentage of CD68-positive cells in the high-fat diet group at 24 weeks was significantly higher than that in the high-fat diet group at 16 weeks and in the normal diet group at 24 weeks (P<0.05). In conclusion, F-FDG PET is a noninvasive imaging tool that can continuously monitor inflammatory lesions of the arterial vessel walls in Wistar rats. Further improvement of the Wistar rat atherosclerosis model may provide data to support the early assessment of and intervention in atherosclerosis.
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http://dx.doi.org/10.3892/etm.2021.9801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903450PMC
April 2021

[Treatment of osteonecrosis of the femoral head with vascularized bone grafting].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Mar;35(3):381-386

Department of Hand and Foot Surgery and Reparative and Reconstructive, Tianjin Union Medical Center, Tianjin, 300121, P.R.China.

Objective: To summarize the current progress of vascularized bone grafting in the treatment of osteonecrosis of the femoral head (ONFH), and to provide reference for treatment of ONFH.

Methods: The literature at home and abroad on the treatment of ONFH with vascularized bone grafting was reviewed, and the mechanism, operating methods and effectiveness, indications, and complications were summarized.

Results: Vascularized bone grafting is a commonly used clinical hip-preserving operation. By replacing necrotic bone tissue with vascularized bone, it can rebuild the blood circulation system, promote the healing of the necrotic area, and provide biomechanical support for the necrotic area of the femoral head, prevent the joint surface collapse. The main operations include the vascularized iliac bone flap grafting, the vascularized greater trochanter bone flap grafting, and the vascularized fibular grafting. The clinical application has achieved certain effectiveness, and the different procedures are suitable for different types of patients. The procedures need to be selected based on the patient's overall condition, the cause of ONFH, the necrosis stage, and the degree of the evaluation.

Conclusion: Vascularized bone grafting has a definite effectiveness in the treatment of ONFH in the young and middle-aged. It can significantly improve hip joint function, control the further development of the disease to a great extent, effectively delay or even avoid hip arthroplasty. It is a reliable hip-preserving operation worthy of promotion.
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http://dx.doi.org/10.7507/1002-1892.202006053DOI Listing
March 2021

Roles of Fast-Ion Conductor LiTaO Modifying Ni-rich Cathode Material for Li-Ion Batteries.

ChemSusChem 2021 Apr 18;14(8):1955-1961. Epub 2021 Mar 18.

School of Materials Science & Engineering, Beijing Key Laboratory of Environmental Science and Engineering, Beijing Institute of Technology, Beijing, 100081, P.R. China.

Limited cycling stability hampers the commercial application of Ni-rich materials, which are regarded as one of the most promising cathode materials for Li-ion batteries. Ni-rich LiNi Co Mn O layered cathode was modified with different amounts of LiTaO , and the influences of fast-ion conductor material on cathode materials were explored. Detailed analysis of the materials revealed the formation of a uniformly epitaxial LiTaO coating layer and a little Ta doping into the lattice structure of Ni-rich materials. The coating-layer thickness increased with the amount of LiTaO added, protecting the electrode from erosion by electrolyte and suppressing undesired parasitic reactions on the cathode-electrolyte interface. Meanwhile, the doped Ta increased the interplanar spacing of materials, accelerating Li transfer. Using the positive synergistic effects of LiTaO -coating and Ta -doping, improved capacity retentions of the modified materials, especially for 0.25 and 0.5 wt%-coated Ni-rich materials, were obtained after long-term cycling, showing the potential applications of LiTaO modification. Further, the relations between one excessively thick coating layer and transfer of Li /electron between the cathode and electrolyte was established, proving that very thick coating layers, even layers containing Li ions, have adverse effects on electrochemical performances. This finding may help to understand the roles of the coating layer better.
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http://dx.doi.org/10.1002/cssc.202100156DOI Listing
April 2021

An analytical study of drug utilization, disease progression, and adverse events among 165 COVID-19 patients.

Ann Transl Med 2021 Feb;9(4):306

Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, China.

Background: The coronavirus disease 2019 (COVID-19) epidemic has lasted for nearly 4 months by this study was conducted. We aimed to describe drug utilization, disease progression, and adverse drug events of COVID-19.

Methods: A retrospective, single-center case series study enrolled 165 consecutive hospitalized COVID-19 patients who were followed up until March 25, 2020, from a designated hospital in Wuhan. Patients were grouped by a baseline degree of severity: non-severe and severe. An analytical study of drug utilization, disease progression, and adverse events (AEs) of COVID-19 was conducted.

Results: Of the 165 COVID-19 cases, antivirals, antibacterials, glucocorticoids, and traditional Chinese medicine (TCM) were administered to 92.7%, 98.8%, 68.5%, and 55.2% of patients, respectively. The total kinds of drugs administered to the severe subgroup [26, interquartile range (IQR) 18-39] were 11 more than the non-severe subgroup (15, IQR 10-24), regardless of comorbidities. The 2 most common combinations of medications in the 165 cases were 'antiviral therapy + glucocorticoids + TCM' (81, 49.1%) and 'antiviral therapy + glucocorticoids' (23, 13.9%). Compared with non-severe cases, severe cases received more glucocorticoids (88.5% . 66.2%, P=0.02), but less TCM (50.0% . 63.3%, P=0.20), and suffered a higher percentage of death (34.6% . 7.2%, P=0.001). At the end of the follow-up, 130 (78.8%) patients had been discharged, and 24 (14.5%) died. There were 13 patients (7.9%) who had elevated liver enzymes, and 49 patients (29.7%) presented with worsening kidney function during the follow-up.

Conclusions: Of the 165 COVID-19 patients, the fatality rate remained high (14.5%). Drug utilization for COVID-19 was diverse and generally complied with the existing guidelines. Combination regimens containing antiviral drugs might be beneficial to assist COVID-19 recovery. Additionally, liver and kidney AEs should not be ignored.
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http://dx.doi.org/10.21037/atm-20-4960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944318PMC
February 2021

Efficacy and safety of PEG-asparaginase versus L-asparaginase in Chinese children with acute lymphoblastic leukemia: a meta-analysis.

Transl Pediatr 2021 Feb;10(2):244-255

Center for Health Care Policy Research, School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, China.

Background: Multiagent chemotherapy is the primary treatment for acute lymphoblastic leukemia (ALL), of which asparaginases including L-asparaginase ( L-Asp) and pegylated-asparaginase (PEG-Asp), are cornerstone components. The study aimed to conduct a meta-analysis to compare the efficacy and safety of PEG-Asp with L-Asp in Chinese children with ALL.

Methods: A systematic literature search was conducted to collect randomized controlled trials (RCTs) on PEG-Asp versus L-Asp in Chinese children with ALL. Two reviewers independently selected articles and extracted data. Risk-of-bias assessment was conducted with Cochrane recommendation tool. Pooled estimates and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for all outcomes in Review Manager 5.3.

Results: Out of the 470 publications screened, 15 studies were included, involving 1,194 patients. Pooled estimates showed that there were no significant differences in complete responses (CR), overall response rate (ORR), gastrointestinal symptoms, and coagulation abnormalities rate between the PEG-Asp and L-Asp groups (all P>0.05). Hypersensitivity (RR =0.63; 95% CI, 0.40-1.01; Ρ=0.05) and hepatic injury rate (RR =0.45; 95% CI, 0.27-0.75; Ρ=0.002) were lower in the PEG-Asp group. The frequency of administration and length of hospital stay of patients in the PEG-Asp group were less than those in the L-Asp group (both Ρ<0.0001).

Conclusions: Current evidence pointed out a similar efficacy in the two groups. The PEG-Asp group showed a lower hypersensitivity and hepatic injury rate. In addition, using PEG-Asp decreased the frequency of administration and the length of hospital stay, which, to some extent, might reduce patients' burden caused by medical resource consumption.
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http://dx.doi.org/10.21037/tp-20-178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944179PMC
February 2021

First-line atezolizumab plus chemotherapy in advanced non-squamous non-small cell lung cancer: a cost-effectiveness analysis from China.

Expert Rev Pharmacoecon Outcomes Res 2021 Mar 19:1-7. Epub 2021 Mar 19.

School of International Pharmaceutical Business, China Pharmaceutical University, Jiangsu, China.

: To assess the cost-effectiveness of atezolizumab in combination with carboplatin plus nab-paclitaxel-based chemotherapy versus chemotherapy alone for first-line treatment of advanced non-squamous non-small cell lung cancer (NSCLC) from the Chinese healthcare system perspective.: A Markov model was developed based on the IMpower130 clinical trial. Drug costs and health state utility were obtained from the literature. Outcomes included life-years (LYs), quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to evaluate the model uncertainty.: When compared to chemotherapy alone, atezolizumab plus chemotherapy provides an additional 0.34 LY and 0.19 QALY, and has an ICER of $180,560.15 per additional LY gained and that of $325,328.71 per QALY gained. Sensitivity analysis revealed that the results were most sensitive to changes in atezolizumab cost. Probabilistic sensitivity analysis showed that there was a 0% probability that atezolizumab plus chemotherapy was cost-effective at willingness-to-pay values of $30,828 per QALY. If the WTP threshold increased to $325,000 per QALY, atezolizumab plus chemotherapy has a 50% chance to be cost-effective.: From the Chinese healthcare system perspective, atezolizumab combination is not cost-effective for first-line therapy of advanced non-squamous NSCLC.
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http://dx.doi.org/10.1080/14737167.2021.1899813DOI Listing
March 2021

FUBP1 mediates the growth and metastasis through TGFβ/Smad signaling in pancreatic adenocarcinoma.

Int J Mol Med 2021 05 2;47(5). Epub 2021 Mar 2.

Department of Gastroenterology, Anhui University of Science and Technology Affiliated Fengxian Hospital, Shanghai University of Medicine and Health Sciences Affiliated Sixth People's Hospital South Campus, Shanghai Fengxian District Central Hospital, Shanghai 201499, P.R. China.

Recent studies have reported that the expression levels of far upstream element‑binding protein 1 (FUBP1) were upregulated and served a crucial role in several types of cancer. However, the underlying molecular mechanisms and clinical significance of FUBP1 in pancreatic adenocarcinoma (PAAD) remain unclear. The present study aimed to determine the expression levels of FUBP1 in patients with PAAD and subsequently investigated the biological functions and mechanisms of FUBP1 using assays. FUBP1 expression levels and survival outcomes in patients with PAAD were analyzed using The Cancer Genome Atlas and starBase databases. Reverse transcription‑quantitative PCR was used to analyze the mRNA expression levels of FUBP1 in PAAD and adjacent normal tissues. In addition, the expression of FUBP1 was knocked down with small interfering RNA and overexpressed using FUBP1‑overexpressed plasmids, and the effects on biological functions, including cell proliferation, migration and invasion, were investigated. Western blotting and immunofluorescence assays were used to determine the role of FUBP1 in epithelial‑mesenchymal transition (EMT). The results of the present study revealed that the expression levels of FUBP1 were upregulated in PAAD tissues compared with adjacent normal tissues and the upregulated expression was significantly associated with poor survival. The knockdown of FUBP1 expression significantly inhibited the proliferative, migratory and invasive abilities of the PAAD PaTu8988 cell line, while the overexpression of FUBP1 promoted cell proliferation, migration and invasion in the PAAD SW1990 cell line. Furthermore, the knockdown of FUBP1 downregulated the expression levels of EMT‑related markers, including N‑cadherin, β‑catenin and vimentin, while the expression levels of E‑cadherin were upregulated. The knockdown of FUBP1 was also revealed to regulate the TGFβ/Smad signaling cascade by downregulating phosphorylated‑Smad2/3 and TGFβ1 expression levels. Conversely, the overexpression of FUBP1 reversed these effects. In conclusion, the findings of the present study indicated that FUBP1 may be a potential oncogene that mediates the EMT of PAAD via TGFβ/Smad signaling. These data suggested that FUBP1 may represent a potential biomarker for the diagnosis of PAAD or a target for the treatment of patients with PAAD.
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http://dx.doi.org/10.3892/ijmm.2021.4899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952245PMC
May 2021

Recombinant Zoster Vaccine (Shingrix) real-world effectiveness in the first two years post-licensure.

Clin Infect Dis 2021 Feb 13. Epub 2021 Feb 13.

Division of Viral Diseases, NCIRD, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Background: Shingrix™ (recombinant zoster vaccine) was licensed to prevent herpes zoster, dispensed as two doses given 2-6 months apart, among adults ages ≥50 years. Clinical trials yielded efficacy of >90% for confirmed herpes zoster,but post-market vaccine performance has not been evaluated. Efficacy of a single dose, delayed second dose, or among persons with autoimmune or general immunosuppressive conditions have also not been studied. We aimed to assess post-market vaccine effectiveness of Shingrix.

Methods: We conducted a cohort study among vaccinated and unvaccinated Medicare Part D community dwelling beneficiaries ages >65 years. Herpes zoster was identified using a medical office visit diagnosis with treatment, and postherpetic neuralgia using a validated algorithm. We used inverse probability of treatment weighting to improve cohort balance, and marginal structural models to estimate hazard ratios.

Results: We found a vaccine effectiveness of 70.1% (95% CI, 68.6-71.5) and 56.9% (95% CI, 55.0-58.8) for two and one doses, respectively. The two-dose vaccine effectiveness was not significantly lower for beneficiaries 80+ years, for second doses received at ≥180 days, or for individuals with autoimmune conditions. The vaccine was also effective among individuals with immunosuppressive conditions. Two-dose vaccine effectiveness against postherpetic neuralgia was 76.0% (95% CI, 68.4-81.8).

Conclusions: This large real-world observational study of effectiveness of Shingrix demonstrates the benefit of completing the two-dose regimen. Second doses administered beyond the recommended 6 months did not impair vaccine effectiveness.Our effectiveness estimates were lower than the clinical trials estimates, likely due to differences in outcome specificity.
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http://dx.doi.org/10.1093/cid/ciab125DOI Listing
February 2021

Natural Host-Environmental Media-Human: A New Potential Pathway of COVID-19 Outbreak.

Engineering (Beijing) 2020 Oct 5;6(10):1085-1098. Epub 2020 Sep 5.

School of Environment, Tsinghua University, Beijing 100084, China.

Identifying the first infected case (patient zero) is key in tracing the origin of a virus; however, doing so is extremely challenging. Patient zero for coronavirus disease 2019 (COVID-19) is likely to be permanently unknown. Here, we propose a new viral transmission route by focusing on the environmental media containing viruses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or RaTG3-related bat-borne coronavirus (Bat-CoV), which we term the "environmental quasi-host." We reason that the environmental quasi-host is likely to be a key node in helping recognize the origin of SARS-CoV-2; thus, SARS-CoV-2 might be transmitted along the route of natural host-environmental media-human. Reflecting upon viral outbreaks in the history of humanity, we realize that many epidemic events are caused by direct contact between humans and environmental media containing infectious viruses. Indeed, contacts between humans and environmental quasi-hosts are greatly increasing as the space of human activity incrementally overlaps with animals' living spaces, due to the rapid development and population growth of human society. Moreover, viruses can survive for a long time in environmental media. Therefore, we propose a new potential mechanism to trace the origin of the COVID-19 outbreak.
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http://dx.doi.org/10.1016/j.eng.2020.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834166PMC
October 2020

Effect of Qizhitongluo capsule on lower limb rehabilitation after stroke: A randomized clinical trial.

Pharmacol Res 2021 Mar 27;165:105464. Epub 2021 Jan 27.

Luohe Hospital of Chinese Medicine, No. 649 Jiao Tong Road, Luohe, 462000 Henan, China.

Background: An individual's level of lower limb motor function is associated with his or her disability level after stroke, and motor improvement may lead to a better prognosis and quality of life. Data from animal models show that Qizhitongluo (QZTL) capsule facilitates recovery after focal brain injury. We aimed to validate the efficacy and safety of the QZTL capsule for promoting lower limb motor recovery in poststroke patients.

Methods: In this randomized, multicenter, double-blind, placebo- and active-controlled trial from 13 sites in China, participants with ischemic stroke and Fugl-Meyer motor scale (FMMS) scores of <95 were eligible for inclusion. Patients were randomly assigned in a 2:1:1 ratio to the QZTL group, Naoxintong (NXT) group or placebo group for 12 weeks at 15-28 days after the onset of stroke. The primary outcome was the change in the Lower Limb FMMS (FMMS-LL) score from baseline over the 12-week intervention period.

Results: 622 participants were randomly assigned to the QZTL group (309), NXT group (159), or placebo group (154). The FMMS-LL score increased by 4.81 points (95 % CI, 4.27-5.35) in the QZTL group, by 3.77 points (95 % CI, 3.03-4.51) in the NXT group and by 3.00 points (95 % CI, 3.03-4.51) in the placebo group at week 12. The QZTL group showed significantly larger improvements compared with the placebo group at each interview from weeks 4-12 (difference, 0.89 [0.30,1.49] at week 4, P = 0.0032; difference, 1.83[1.01,2.66] at 90 days poststroke, P < 0.0001; difference, 1.81[0.88,2.74] at week 12, P = 0.0001).

Conclusion: The QZTL capsule is an effective treatment for lower limb motor impairment. The finding indicates that the QZTL capsule may be used as a potential new strategy for stroke rehabilitation.
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http://dx.doi.org/10.1016/j.phrs.2021.105464DOI Listing
March 2021

The chromosome-level reference genome assembly for and insights into ginsenoside biosynthesis.

Plant Commun 2021 Jan 20;2(1):100113. Epub 2020 Sep 20.

School of Traditional Chinese Medicine, Capital Medical University, Beijing, China.

, a perennial herb of the genus in the family Araliaceae, has played an important role in clinical treatment in China for thousands of years because of its extensive pharmacological effects. Here, we report a high-quality reference genome of , with a genome size up to 2.66 Gb and a contig N50 of 1.12 Mb, produced with third-generation PacBio sequencing technology. This is the first chromosome-level genome assembly for the genus . Through genome evolution analysis, we explored phylogenetic and whole-genome duplication events and examined their impact on saponin biosynthesis. We performed a detailed transcriptional analysis of and explored gene-level mechanisms that regulate the formation of characteristic tubercles. Next, we studied the biosynthesis and regulation of saponins at temporal and spatial levels. We combined multi-omics data to identify genes that encode key enzymes in the terpenoid biosynthetic pathway. Finally, we identified five glycosyltransferase genes whose products catalyzed the formation of different ginsenosides in . The genetic information obtained in this study provides a resource for further exploration of the growth characteristics, cultivation, breeding, and saponin biosynthesis of .
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http://dx.doi.org/10.1016/j.xplc.2020.100113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816079PMC
January 2021

High-Temperature Storage Deterioration Mechanism of Cylindrical 21700-Type Batteries Using Ni-Rich Cathodes under Different SOCs.

ACS Appl Mater Interfaces 2021 Feb 27;13(5):6286-6297. Epub 2021 Jan 27.

School of Materials Science and Engineering, Beijing Key Laboratory of Environmental Science and Engineering, Beijing Institute of Technology, Beijing 100081, P. R. China.

The safety and energy density of lithium-ion batteries (LIBs) are important concerns. The use of high-capacity cathode materials, such as Ni-rich cathodes, can greatly improve the energy density of LIBs, but it also brings some safety hazards. Cylindrical 21700-type batteries using Ni-rich cathodes were employed here to investigate their high-temperature storage deterioration mechanism under different states of charge (SOCs). Electrolyte decomposition was identified as the main problem. It can be worsened by elevated storage temperatures and battery SOCs, with the latter having a more significant influence. Specifically, the decomposition of the LiPF solute and the carbonate solvent will induce hydrofluoric acid (HF) formation and solid-electrolyte interphase (SEI) film regeneration, respectively. HF erosion will aggravate the dissolution of transition metal ions and structural degradation of cathode materials, while the destruction/regeneration of SEI films will consume active lithium and hinder Li diffusion at the anode side. Besides, the self-discharge behavior will also enlarge the graphite layer spacing, thus decreasing the graphitization degree of graphite anodes and causing anode failure. These findings will aid in the development of strategies for improving the safety of LIBs with high energy density.
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http://dx.doi.org/10.1021/acsami.0c20835DOI Listing
February 2021

Injectable Hyaluronic Acid Hydrogel for the Co-Delivery of Gemcitabine Nanoparticles and Cisplatin for Malignant Ascites Therapy.

J Biomed Nanotechnol 2020 Dec;16(12):1727-1739

Malignant ascites indicate the presence of malignant cells in the peritoneal cavity that lower patient survival and reduce quality of life. Current chemotherapy regimens suffer from the dilution of ascites and rapid metabolism limiting their therapeutic efficacy. The storage and sustained release of drugs at the tumor site represents a promising strategy to improve drug efficacy. The aim of this study was to develop injectable hyaluronic acid hydrogel containing polymeric gemcitabine nanoparticles and cisplatin for the local treatment of malignant ascites through a dual sustained drug release pattern. Cell uptake assays showed that the drug-loaded nanoparticles readily entered tumor cells. Apoptosis and cell cycle analysis showed that the hydrogel system could enhance tumor cell apoptosis and arrest more cells in the G1 phase. In vivo experiments indicated that mice treated with the drug-loaded hydrogels manifested the most significant efficacy in ascites volume, tumor nodules, body weight, abdominal circumference, and survival. The expression of Ki-67 and CD31 also significantly decreased compared with other groups, indicative of anti-tumor activity. In addition, intraperitoneal administration of the hydrogel system led to no significant damage to vital organs. These findings confirm the clinical potential of the drug-loaded hydrogel system for the treatment of malignant ascites.
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http://dx.doi.org/10.1166/jbn.2020.3002DOI Listing
December 2020

Stress-Induced Neural Plasticity Mediated by Glial GPCR REMO-1 Promotes C. elegans Adaptive Behavior.

Cell Rep 2021 01;34(2):108607

Laboratory of Developmental Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address:

Animal nervous systems remodel following stress. Although global stress-dependent changes are well documented, contributions of individual neuron remodeling events to animal behavior modification are challenging to study. In response to environmental insults, C. elegans become stress-resistant dauers. Dauer entry induces amphid sensory organ remodeling in which bilateral AMsh glial cells expand and fuse, allowing embedded AWC chemosensory neurons to extend sensory receptive endings. We show that amphid remodeling correlates with accelerated dauer exit upon exposure to favorable conditions and identify a G protein-coupled receptor, REMO-1, driving AMsh glia fusion, AWC neuron remodeling, and dauer exit. REMO-1 is expressed in and localizes to AMsh glia tips, is dispensable for other remodeling events, and promotes stress-induced expression of the remodeling receptor tyrosine kinase VER-1. Our results demonstrate how single-neuron structural changes affect animal behavior, identify key glial roles in stress-induced nervous system plasticity, and demonstrate that remodeling primes animals to respond to favorable conditions.
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http://dx.doi.org/10.1016/j.celrep.2020.108607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845533PMC
January 2021