Publications by authors named "Chao Yan"

689 Publications

Analysis of Risk Factors for Coronary Artery Lesion in Children with Kawasaki Disease.

J Coll Physicians Surg Pak 2022 Aug;32(8):1037-1041

Department of Pediatrics, People's Hospital of Linquan County, Anhui Province, China.

Objective: To determine the frequency of coronary artery lesion (CAL) in children with Kawasaki disease (KD) and to analyse the related risk factors of CAL and the predictive value of risk factors for CAL.

Study Design: A descriptive study.

Place And Duration Of Study: Department of Pediatrics, People's Hospital of Linquan County, Anhui Province, China, from January 2019 to January 2022.

Methodology: Clinical data of 71 children with KD were retrospectively analysed, including 31 in the CAL group and 40 in the non-CAL group. The age, gender, days of fever, blood routine, plasma N-terminal B-type natriuretic peptide (NT-proBNP), and Kobayashi score were registered as independent variables of all the children, and the presence or absence of CAL was used as the dependent variable. All the independent variables were subjected to univariate analysis between the groups, and those with significance in univariate analysis were further subjected to unconditional binary logistic regression analysis. A receiver operating curve (ROC) was drawn to analyse the predictive power and optimal cut-off value of related risk factors for CAL.

Results: On univariate analysis, age, NT-proBNP and Kobayashi's score were closely related to CAL (all p<0.05). Multivariate analysis showed that NT-proBNP and Kobayashi scores were independent risk factors for CAL in children with KD. ROC curve analysis showed that the area under the curve (AUC) of NT-proBNP and Kobayashi scores were 0.771 and 0.732, respectively, at optimal critical values of 543.12 ng/L and 7.50 points, respectively.

Conclusion: The frequency of CAL in children with KD is high. NT-proBNP and Kobayashi scores are independent risk factors for the occurrence of CAL in children with KD, and they have good predictive performance for the diagnosis of CAL.

Key Words: Kawasaki disease, Children, Coronary artery lesion, Risk factors, Kobayashi score, NT-pro BNP.
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http://dx.doi.org/10.29271/jcpsp.2022.08.1037DOI Listing
August 2022

Maps of cropping patterns in China during 2015-2021.

Sci Data 2022 08 5;9(1):479. Epub 2022 Aug 5.

Key Laboratory of Spatial Data Mining &Information Sharing of Ministry of Education, Academy of Digital China (Fujian), Fuzhou University, Fuzhou, 350116, Fujian, China.

Multiple cropping is a widespread approach for intensifying crop production through rotations of diverse crops. Maps of cropping intensity with crop descriptions are important for supporting sustainable agricultural management. As the most populated country, China ranked first in global cereal production and the percentages of multiple-cropped land are twice of the global average. However, there are no reliable updated national-scale maps of cropping patterns in China. Here we present the first recent annual 500-m MODIS-based national maps of multiple cropping systems in China using phenology-based mapping algorithms with pixel purity-based thresholds, which provide information on cropping intensity with descriptions of three staple crops (maize, paddy rice, and wheat). The produced cropping patterns maps achieved an overall accuracy of 89% based on ground truth data, and a good agreement with the statistical data (R ≥ 0.89). The China Cropping Pattern maps (ChinaCP) are available for public download online. Cropping patterns maps in China and other countries with finer resolutions can be produced based on Sentinel-2 Multispectral Instrument (MSI) images using the shared code.
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http://dx.doi.org/10.1038/s41597-022-01589-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356131PMC
August 2022

FXR deficiency in hepatocytes disrupts the bile acid homeostasis and inhibits autophagy to promote liver injury in Schistosoma japonicum-infected mice.

PLoS Negl Trop Dis 2022 Aug 5;16(8):e0010651. Epub 2022 Aug 5.

Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical University, Xuzhou, People's Republic of China.

Background: Schistosomiasis, with 250 million people affected, is characterized by its serious hepatic inflammatory response and fibrosis formation, which could lead to dangerous complications, such as portal hypertension, splenomegaly and even ascites. But until now, the pathogenesis of schistosomiasis remains largely unknown. Farnesoid X Receptor (FXR), a bile acid-activated nuclear transcription factor mainly expresses in hepatocytes in the liver, can regulate liver diseases by controlling bile acid metabolism.

Methodology/principal Findings: In this study, we found that the expression of FXR was decreased in the liver of infected mice as shown by western blot and RT-qPCR assays. Furthermore, hepatocyte-specific FXR-deficient mice (FXRflox/floxAlbCre, FXR-HKO) were generated and infected with ~16 cercariae of S. japonicum for five weeks. We found that FXR deficiency in hepatocytes promoted the progression of liver injury, aggravated weight loss and death caused by infection, and promoted inflammatory cytokines production, such as IL-6, IL-1β, TNF-α, IL-4, IL-10, and IL-13. Surprisingly, hepatic granulomas and fibrosis were not affected. In addition, using UPLC-MS/MS spectrometry, it was found that S. japonicum infection resulted in elevated bile acids in the liver of mice, which was more obvious in FXR-deficient mice. Meanwhile, autophagy was induced in littermate control mice due to the infection, but it was significantly decreased in FXR-HKO mice.

Conclusions/significance: All these findings suggest that FXR deficiency in hepatocytes disrupts bile acid homeostasis and inhibits autophagy, which may aggravate the damages of hepatocytes caused by S. japonicum infection. It highlights that FXR in hepatocytes plays a regulatory role in the progression of schistosomiasis.
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http://dx.doi.org/10.1371/journal.pntd.0010651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355238PMC
August 2022

Keeping synthetic patients on track: feedback mechanisms to mitigate performance drift in longitudinal health data simulation.

J Am Med Inform Assoc 2022 Aug 4. Epub 2022 Aug 4.

Department of Computer Science, Vanderbilt University, Nashville, Tennessee, USA.

Objective: Synthetic data are increasingly relied upon to share electronic health record (EHR) data while maintaining patient privacy. Current simulation methods can generate longitudinal data, but the results are unreliable for several reasons. First, the synthetic data drifts from the real data distribution over time. Second, the typical approach to quality assessment, which is based on the extent to which real records can be distinguished from synthetic records using a critic model, often fails to recognize poor simulation results. In this article, we introduce a longitudinal simulation framework, called LS-EHR, which addresses these issues.

Materials And Methods: LS-EHR enhances simulation through conditional fuzzing and regularization, rejection sampling, and prior knowledge embedding. We compare LS-EHR to the state-of-the-art using data from 60 000 EHRs from Vanderbilt University Medical Center (VUMC) and the All of Us Research Program. We assess discrimination between real and synthetic data over time. We evaluate the generation process and critic model using the area under the receiver operating characteristic curve (AUROC). For the critic, a higher value indicates a more robust model for quality assessment. For the generation process, a lower value indicates better synthetic data quality.

Results: The LS-EHR critic improves discrimination AUROC from 0.655 to 0.909 and 0.692 to 0.918 for VUMC and All of Us data, respectively. By using the new critic, the LS-EHR generation model reduces the AUROC from 0.909 to 0.758 and 0.918 to 0.806.

Conclusion: LS-EHR can substantially improve the usability of simulated longitudinal EHR data.
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http://dx.doi.org/10.1093/jamia/ocac131DOI Listing
August 2022

Chromosome-level assembly of Gymnocypris eckloni genome.

Sci Data 2022 08 2;9(1):464. Epub 2022 Aug 2.

State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, 810016, China.

Gymnocypris eckloni is widely distributed in isolated lakes and the upper reaches of the Yellow River and play significant roles in the trophic web of freshwater communities. In this study, we generated a chromosome-level genome of G. eckloni using PacBio, Illumina and Hi-C sequencing data. The genome consists of 23 pseudo-chromosomes that contain 918.68 Mb of sequence, with a scaffold N50 length of 43.54 Mb. In total, 23,157 genes were annotated, representing 94.80% of the total predicted protein-coding genes. The phylogenetic analysis showed that G. eckloni was most closely related to C. carpio with an estimated divergence time of ~34.8 million years ago. For G. eckloni, we identified a high-quality genome at the chromosome level. This genome will serve as a valuable genomic resource for future research on the evolution and ecology of the schizothoracine fish in the Qinghai-Tibetan Plateau.
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http://dx.doi.org/10.1038/s41597-022-01595-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346132PMC
August 2022

Lysosomal protein transmembrane 5 promotes lung-specific metastasis by regulating BMPR1A lysosomal degradation.

Nat Commun 2022 Jul 16;13(1):4141. Epub 2022 Jul 16.

Department of Urology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Institute of Urology, Nanjing University, Nanjing, Jiangsu, 210008, China.

Organotropism during cancer metastasis occurs frequently but the underlying mechanism remains poorly understood. Here, we show that lysosomal protein transmembrane 5 (LAPTM5) promotes lung-specific metastasis in renal cancer. LAPTM5 sustains self-renewal and cancer stem cell-like traits of renal cancer cells by blocking the function of lung-derived bone morphogenetic proteins (BMPs). Mechanistic investigations showed that LAPTM5 recruits WWP2, which binds to the BMP receptor BMPR1A and mediates its lysosomal sorting, ubiquitination and ultimate degradation. BMPR1A expression was restored by the lysosomal inhibitor chloroquine. LAPTM5 expression could also serve as an independent predictor of lung metastasis in renal cancer. Lastly, elevation of LAPTM5 expression in lung metastases is a common phenomenon in multiple cancer types. Our results reveal a molecular mechanism underlying lung-specific metastasis and identify LAPTM5 as a potential therapeutic target for cancers with lung metastasis.
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http://dx.doi.org/10.1038/s41467-022-31783-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288479PMC
July 2022

Efficacy and Safety of Conversion Therapy by Intraperitoneal and Intravenous Paclitaxel Plus Oral S-1 in Gastric Cancer Patients With Peritoneal Metastasis: A Prospective Phase II Study.

Front Oncol 2022 20;12:905922. Epub 2022 Jun 20.

Department of General Surgery, Gastrointestinal Surgery, Shanghai Key laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) has shown promising results in gastric cancer (GC) with peritoneal metastasis. However, clinical practice experience of NIPS is still lacking in China. In this study, we investigate the efficacy and safety of NIPS in Chinese patients.

Methods: Eligible patients received NIPS every 3 weeks. Gastrectomy was performed for patients who met the criteria of conversion surgery. The primary end point was 1-year overall survival (OS) rate. Secondary end points were the response rate, toxic effects, conversion surgery outcomes and median survival time (MST).

Results: Sixty-seven patients were enrolled. The primary endpoint was achieved with 1-year OS rate reached 67.2% (95% CI, 56.8%-79.4%). Conversion surgery was performed in 42 patients (62.9%), and R0 resection was achieved in 23 patients (54.8%) with the MST of 31.3 months (95% CI, 24.3-38.3). And the MST was 19.3 months (95% CI, 16.4-22.2) for all patients. Toxicity and surgical complications were well-tolerated. Moreover, sex, R0 resection, pathological nodal stage and tumor regression grade (TRG) were independent prognostic factors for patients who underwent conversion surgery.

Conclusion: The NIPS is effective and safe in treating GC patients with peritoneal metastasis. Male patients, patients who underwent R0 resection, patients with ypN0-1 or TRG 1 after conversion surgery are more likely to benefit from the NIPS.

Clinical Trial Registration: http://www.chictr.org.cn/, identifier https://clinicaltrials.gov/ ().
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http://dx.doi.org/10.3389/fonc.2022.905922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251062PMC
June 2022

3D tracking of ferrous iron in the epileptic mouse brain and screening of iron homeostasis regulators with a two-photon fluorescent probe.

STAR Protoc 2022 Jul 1;3(3):101522. Epub 2022 Jul 1.

Jiangsu Collaborative Innovation Centre of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Wenyuan Road 1, Nanjing 210023, China. Electronic address:

The development of techniques for tracking active ferrous iron (Fe) distribution has greatly promoted the biological studies of iron. Here, we present an innovative application of a 3D two-photon fluorescent probe for Fe tracking in the epileptic mouse brain, which has expanded the toolbox of screening for iron homeostasis regulators and contributed to the discovery of new chemical entities for the treatment of epilepsy. For complete details on the use and execution of this protocol, please refer to Shao et al. (2022).
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http://dx.doi.org/10.1016/j.xpro.2022.101522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9256948PMC
July 2022

Emotion Context Insensitivity is generalized in individuals with major depressive disorder but not in those with subclinical depression.

J Affect Disord 2022 09 28;313:204-213. Epub 2022 Jun 28.

Key Laboratory of Brain Functional Genomics (MOE&STCSM), Affiliated Mental Health Center (ECNU), School of Psychology and Cognitive Science, East China Normal University, Shanghai, China. Electronic address:

Background: Depressed individuals experience deficits in emotional reactivity. One well-established theory is the Emotion Context Insensitivity (ECI) theory. To better understand impairments in emotional reactivity, we investigated whether the ECI theory is applicable to anticipatory, consummatory, and remembered affect, in both clinical and subclinical depression.

Methods: Participants were divided into four groups: Major Depressive Disorder Group (MDD, N = 60), Control Group for MDD (Control, N = 50), Subclinical Depression Group (SD, N = 56), and Control Group for SD (Control, N = 56). The Hamilton Depression Rating Scale and the Beck Depression Inventory were used to assess the severity of depression and anhedonia symptoms. The Monetary Incentive Delay Task evaluated participants' affective responses towards monetary stimuli.

Results: The MDD group was more insensitive to both monetary reward and loss across most types of affect than was the control group. Compared with the controls, the SD group exhibited lower reactivity in anticipatory positive affect but enhanced reactivity in consummatory positive, anticipatory, and remembered negative affect.

Limitations: Emotional affect was evaluated by subjective ratings, which may lack objectivity. Additionally, laboratory settings and monetary rewards used in this study may cause the results less generalized to daily life and to other types of rewards.

Conclusion: The pattern of emotional reactivity in the MDD group was partly consistent with the ECI theory, whereas the SD group showed greater arousal and instability of emotional reactions. These different patterns could facilitate the understanding of emotional reactivity and develop further treatments across the course of depression.
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http://dx.doi.org/10.1016/j.jad.2022.06.069DOI Listing
September 2022

Do Local Religious Beliefs Affect Firms' Earnings Management Practice? Evidence From the United States.

Front Psychol 2022 13;13:883596. Epub 2022 Jun 13.

Center for Quantitative Economics, Jilin University, Changchun, China.

This paper investigates whether local religious beliefs have a significant impact on the practice of earnings management. We extend the existing literature on the role of firm characteristics in mitigating earnings management by showing that local religious beliefs significantly impact the practice of earnings management. Specifically, exploring firms located in the U.S. counties that vary from 2000 through 2010, we document the negative relationship between religiosity and earnings management using multivariate regression analysis. Our results show that firms in counties with strong religious social norms are less likely to engage in earnings management. Furthermore, we attempt to mitigate endogeneity concerns by employing a modified Difference-Differences model and Propensity score matching methods. We find that the negative effects of religion on earnings management still hold. Overall, these findings emphasize the empirical relevance of the association between the local social norms and earnings manipulations.
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http://dx.doi.org/10.3389/fpsyg.2022.883596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234393PMC
June 2022

Insufficient Condensable Organic Vapors Lead to Slow Growth of New Particles in an Urban Environment.

Environ Sci Technol 2022 07 24;56(14):9936-9946. Epub 2022 Jun 24.

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

Atmospheric new particle formation significantly affects global climate and air quality after newly formed particles grow above ∼50 nm. In polluted urban atmospheres with 1-3 orders of magnitude higher new particle formation rates than those in clean atmospheres, particle growth rates are comparable or even lower for reasons that were previously unclear. Here, we address the slow growth in urban Beijing with advanced measurements of the size-resolved molecular composition of nanoparticles using the thermal desorption chemical ionization mass spectrometer and the gas precursors using the nitrate CI-APi-ToF. A particle growth model combining condensational growth and particle-phase acid-base chemistry was developed to explore the growth mechanisms. The composition of 8-40 nm particles during new particle formation events in urban Beijing is dominated by organics (∼80%) and sulfate (∼13%), and the remainder is from base compounds, nitrate, and chloride. With the increase in particle sizes, the fraction of sulfate decreases, while that of the slow-desorbed organics, organic acids, and nitrate increases. The simulated size-resolved composition and growth rates are consistent with the measured results in most cases, and they both indicate that the condensational growth of organic vapors and HSO is the major growth pathway and the particle-phase acid-base reactions play a minor role. In comparison to the high concentrations of gaseous sulfuric acid and amines that cause high formation rates, the concentration of condensable organic vapors is comparably lower under the high NO levels, while those of the relatively high-volatility nitrogen-containing oxidation products are higher. The insufficient condensable organic vapors lead to slow growth, which further causes low survival of the newly formed particles in urban environments. Thus, the low growth rates, to some extent, counteract the impact of the high formation rates on air quality and global climate in urban environments.
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http://dx.doi.org/10.1021/acs.est.2c01566DOI Listing
July 2022

In Reply to the Letter to the Editor Regarding "A Reliable Nomogram Model to Predict the Recurrence of Chronic Subdural Hematoma After Burr Hole Surgery".

World Neurosurg 2022 Jul;163:145

Department of Neurosurgery, Qinghai Provincial People's Hospital, Xining, Qinghai, China. Electronic address:

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http://dx.doi.org/10.1016/j.wneu.2022.04.018DOI Listing
July 2022

Mannose-targeting Concanavalin A-Epirubicin Conjugate for Targeted Intravesical Chemotherapy of Bladder Cancer.

Chem Asian J 2022 Jun 17:e202200342. Epub 2022 Jun 17.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, 210023, P. R. China.

Intravesical instillation of chemotherapeutic drugs such as epirubicin (EPI) is routinely used to prevent tumor recurrence and progression after transurethral resection of bladder tumor. However, the lack of tumor selectivity often causes severe damage to normal bladder urothelium leading to intolerable side effects. Here, we analyzed abnormal changes in glycosylation in bladder cancer and identified mannose as the most aberrantly expressed glycan on the surface of bladder cancer cell lines and human bladder tumor tissues. We then constructed a lectin-drug conjugate by linking concanavalin A (ConA) - a lectin that specifically binds to mannose, with EPI through a pH-sensitive linker. This ConA-EPI conjugate conferred EPI with mannose-targeting ability and selectively internalized cancer cells in vitro. This conjugate showed selective cytotoxicity to cancer cells in vitro and better antitumor activity in an orthotopic mouse model of bladder cancer. Our lectin-drug conjugation strategy makes targeted intravesical chemotherapy of bladder cancer possible.
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http://dx.doi.org/10.1002/asia.202200342DOI Listing
June 2022

Electron coupled FeS/MoS heterostructure for efficient electrocatalytic ammonia synthesis under ambient conditions.

Dalton Trans 2022 Jun 27;51(25):9720-9727. Epub 2022 Jun 27.

School of Materials Science and Engineering, Hefei University of Technology, Hefei, 230009, PR China.

Developing efficient ammonia synthesis technology under ambient conditions is of vital importance. In this work, an FeS coupled MoS heterostructure with ultrathin features was designed by a one-step hydrothermal process for the electrochemical nitrogen reduction reaction. Density functional theory calculations reveal that the electronic structure of MoS greatly changes with the introduction of FeS. The modulated electronic structure of MoS not only exhibits enhanced conductivity but also facilitates the activation of N molecules due to its abundant electronic region. The optimized FeS/MoS nanosheet heterostructure achieves a high NH yield rate of 2.59 μmol h mg and a FE of 4.63% at -0.3 V RHE. Besides, the well-designed nanocomposite also shows excellent selectivity without NH by-products and exhibits good stability after electrocatalysis for 48 hours.
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http://dx.doi.org/10.1039/d2dt01467jDOI Listing
June 2022

The contribution of new particle formation and subsequent growth to haze formation.

Environ Sci Atmos 2022 May 22;2(3):352-361. Epub 2022 Mar 22.

Institute for Atmospheric and Earth System Research (INAR)/Physics, Faculty of Science, University of Helsinki Finland

We investigated the contribution of atmospheric new particle formation (NPF) and subsequent growth of the newly formed particles, characterized by high concentrations of fine particulate matter (PM). In addition to having adverse effects on visibility and human health, these haze particles may act as cloud condensation nuclei, having potentially large influences on clouds and precipitation. Using atmospheric observations performed in 2019 in Beijing, a polluted megacity in China, we showed that the variability of growth rates (GR) of particles originating from NPF depend only weakly on low-volatile vapor - highly oxidated organic molecules (HOMs) and sulphuric acid - concentrations and have no apparent connection with the strength of NPF or the level of background pollution. We then constrained aerosol dynamic model simulations with these observations. We showed that under conditions typical for the Beijing atmosphere, NPF is capable of contributing with more than 100 μg m to the PM mass concentration and simultaneously >10 cm to the haze particle (diameter > 100 nm) number concentration. Our simulations reveal that the PM mass concentration originating from NPF, strength of NPF, particle growth rate and pre-existing background particle population are all connected with each other. Concerning the PM pollution control, our results indicate that reducing primary particle emissions might not result in an effective enough decrease in total PM mass concentrations until a reduction in emissions of precursor compounds for NPF and subsequent particle growth is imposed.
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http://dx.doi.org/10.1039/d1ea00096aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119031PMC
May 2022

What controls the observed size-dependency of the growth rates of sub-10 nm atmospheric particles?

Environ Sci Atmos 2022 May 23;2(3):449-468. Epub 2022 Mar 23.

Department of Environmental Science (ACES), Bolin Centre for Climate Research, Stockholm University Stockholm Sweden.

The formation and growth of atmospheric particles involving sulfuric acid and organic vapors is estimated to have significant climate effects. To accurately represent this process in large-scale models, the correct interpretation of the observations on particle growth, especially below 10 nm, is essential. Here, we disentangle the factors governing the growth of sub-10 nm particles in the presence of sulfuric acid and organic vapors, using molecular-resolution cluster population simulations and chamber experiments. We find that observed particle growth rates are determined by the combined effects of (1) the concentrations and evaporation rates of the condensing vapors, (2) particle population dynamics, and (3) stochastic fluctuations, characteristic to initial nucleation. This leads to a different size-dependency of growth rate in the presence of sulfuric acid and/or organic vapors at different concentrations. Specifically, the activation type behavior, resulting in growth rate increasing with the particle size, is observed only at certain vapor concentrations. In our model simulations, cluster-cluster collisions enhance growth rate at high vapor concentrations and their importance is dictated by the cluster evaporation rates, which demonstrates the need for accurate evaporation rate data. Finally, we show that at sizes below ∼2.5-3.5 nm, stochastic effects can importantly contribute to particle population growth. Overall, our results suggest that interpreting particle growth observations with approaches neglecting population dynamics and stochastics, such as with single particle growth models, can lead to the wrong conclusions on the properties of condensing vapors and particle growth mechanisms.
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http://dx.doi.org/10.1039/d1ea00103eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119032PMC
May 2022

Interface and electronic structure engineering induced Prussian blue analogues with ultra-stable capability for aqueous NH storage.

Nanoscale 2022 Jun 16;14(23):8501-8509. Epub 2022 Jun 16.

School of Material Science & Engineering, Jiangsu University of Science and Technology, Zhenjiang, 212003, Jiangsu, China.

Aqueous ammonium ion batteries (AAIBs) are considered potential energy storage solutions due to their faster kinetics, eco-friendliness, and high safety. Yet, appropriate electrode material for AAIBs is in continual investigation. Here, Prussian blue analogues (PBAs), NaNi[Fe(CN)], are applied by a covalent bond assisted engineering with polyaniline (PANI) polymerization. The synthesized PANI/NaNi[Fe(CN)] hybrid (PNFF) inherited the advantages of the high conductivity of PANI and the stability of PBAs. The content of PANI had an effect on the electrochemical performance of PNFF. When served as cathode for AAIBs, the as-prepared PNFF-60 (PNFF with adjusted PANI content) delivers an enhanced reversible capacity of 92.5 mA h g at 100 mA g after 200 cycles. Even at a high current density of 2000 mA g, 95.2% capacity retention (1000 cycles) can be achieved by PNFF-60. The ammonium storage mechanism of PNFF-60 is fully investigated by Raman and XPS/FTIR analysis. Moreover, an aqueous NH full cell is assembled by coupling the [email protected] ([email protected]) anode, exhibiting durable cycling stability. This work adds to the understanding of constructing PBAs-based hybrid electrodes for ammonium ion storage devices.
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http://dx.doi.org/10.1039/d2nr01735kDOI Listing
June 2022

Forecasting the future clinical events of a patient through contrastive learning.

J Am Med Inform Assoc 2022 May 31. Epub 2022 May 31.

Department of Computer Science, Vanderbilt University, Nashville, Tennessee, USA.

Objective: Deep learning models for clinical event forecasting (CEF) based on a patient's medical history have improved significantly over the past decade. However, their transition into practice has been limited, particularly for diseases with very low prevalence. In this paper, we introduce CEF-CL, a novel method based on contrastive learning to forecast in the face of a limited number of positive training instances.

Materials And Methods: CEF-CL consists of two primary components: (1) unsupervised contrastive learning for patient representation and (2) supervised transfer learning over the derived representation. We evaluate the new method along with state-of-the-art model architectures trained in a supervised manner with electronic health records data from Vanderbilt University Medical Center and the All of Us Research Program, covering 48 000 and 16 000 patients, respectively. We assess forecasting for over 100 diagnosis codes with respect to their area under the receiver operator characteristic curve (AUROC) and area under the precision-recall curve (AUPRC). We investigate the correlation between forecasting performance improvement and code prevalence via a Wald Test.

Results: CEF-CL achieved an average AUROC and AUPRC performance improvement over the state-of-the-art of 8.0%-9.3% and 11.7%-32.0%, respectively. The improvement in AUROC was negatively correlated with the number of positive training instances (P < .001).

Conclusion: This investigation indicates that clinical event forecasting can be improved significantly through contrastive representation learning, especially when the number of positive training instances is small.
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http://dx.doi.org/10.1093/jamia/ocac086DOI Listing
May 2022

Field Detection of Highly Oxygenated Organic Molecules in Shanghai by Chemical Ionization-Orbitrap.

Environ Sci Technol 2022 May 20. Epub 2022 May 20.

Univ. Lyon, Université Claude Bernard Lyon 1, CNRS, IRCELYON, 69626 Villeurbanne, France.

Secondary organic aerosol, formed through atmospheric oxidation processes, plays an important role in affecting climate and human health. In this study, we conducted a comprehensive campaign in the megacity of Shanghai during the 2019 International Import Expo (EXPO), with the first deployment of a chemical ionization─Orbitrap mass spectrometer for ambient measurements. With the ultrahigh mass resolving power of the Orbitrap mass analyzer (up to 140,000 Th/Th) and capability in dealing with massive spectral data sets by positive matrix factorization, we were able to identify the major gas-phase oxidation processes leading to the formation of oxygenated organic molecules (OOM) in Shanghai. Nine main factors from three independent sub-range analysis were identified. More than 90% of OOM are of anthropogenic origin and >60% are nitrogen-containing molecules, mainly dominated by the RO + NO and/or NO chemistry. The emission control during the EXPO showed that even though the restriction was effectual in significantly lowering the primary pollutants (20-70% decrease), the secondary oxidation products responded less effectively (14% decrease), or even increased (50 to >200%) due to the enhancement of ozone and the lowered condensation sink, indicating the importance of a stricter multi-pollutant coordinated strategy in primary and secondary pollution mitigation.
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http://dx.doi.org/10.1021/acs.est.1c08346DOI Listing
May 2022

Influence of Aerosol Chemical Composition on Condensation Sink Efficiency and New Particle Formation in Beijing.

Environ Sci Technol Lett 2022 May 12;9(5):375-382. Epub 2022 Apr 12.

Aerosol and Haze Laboratory, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100089, China.

Relatively high concentrations of preexisting particles, acting as a condensation sink (CS) of gaseous precursors, have been thought to suppress the occurrence of new particle formation (NPF) in urban environments, yet NPF still occurs frequently. Here, we aim to understand the factors promoting and inhibiting NPF events in urban Beijing by combining one-year-long measurements of particle number size distributions and PM chemical composition. Our results show that indeed the CS is an important factor controlling the occurrence of NPF events, with its chemical composition affecting the efficiency of the background particles in removing gaseous HSO (effectiveness of the CS) driving NPF. During our observation period, the CS was found to be more effective for ammonium nitrate-rich (NHNO-rich) fine particles. On non-NPF event days, particles acting as CS contained a larger fraction of NHNO compared to NPF event days under comparable CS levels. In particular, in the CS range from 0.02 to 0.03 s, the nitrate fraction was 17% on NPF event days and 26% on non-NPF event days. Overall, our results highlight the importance of considering the chemical composition of preexisting particles when estimating the CS and their role in inhibiting NPF events, especially in urban environments.
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http://dx.doi.org/10.1021/acs.estlett.2c00159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097482PMC
May 2022

Hesperadin suppresses pancreatic cancer through ATF4/GADD45A axis at nanomolar concentrations.

Oncogene 2022 06 12;41(25):3394-3408. Epub 2022 May 12.

Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China.

Pancreatic cancer (PC) is a fatal disease with poor survival and limited therapeutic strategies. In this study, we identified Hesperadin as a potent anti-cancer compound against PC, from a high-throughput screening of a commercial chemical library associated with cell death. Hesperadin induced potent growth inhibition in PC cell lines and patient-derived tumor organoids in a dose- and time-dependent manner, with IC values in the nanomolar range. Cellular studies showed that Hesperadin caused mitochondria damage in PC cells, resulting in reactive oxygen species production, ER stress and apoptotic cell death. Transcriptomic analysis using RNA-sequencing data identified GADD45A as a potential target of Hesperadin. Mechanistic studies showed that Hesperadin could increase GADD45A expression in PC cells via ATF4, leading to apoptosis. Moreover, immunohistochemical staining of 92 PC patient samples demonstrated the correlation between ATF4 and GADD45A expression. PC xenograft studies demonstrated that Hesperadin could effectively inhibit the growth of PC cells in vivo. Together, these findings suggest that Hesperadin is a novel drug candidate for PC.
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http://dx.doi.org/10.1038/s41388-022-02328-4DOI Listing
June 2022

Polyimidazolyl acetate ionic liquid grafted on cellulose filter paper as thin-film extraction phase for extraction of non-steroidal anti-inflammatory drugs from water.

J Sep Sci 2022 Jul 18;45(14):2621-2631. Epub 2022 May 18.

Guangzhou Institute of Chemistry, Chinese Academy of Sciences, Guangzhou, P. R. China.

Recently, pharmaceuticals and personal care products in the water environment exhibited potential risks to both human and aquatic organisms. In order to improve the sensitivity and accuracy of pharmaceutical detection, the polyimidazolyl acetate ionic liquid was synthesized by Radziszewski reaction and coated on cellulose filter papers as a thin-film extraction phase for extraction of non-steroidal anti-inflammatory drugs from water. The attenuated total reflection-infrared spectrometry, thermogravimetric analysis, and scanning electron microscope analyses demonstrated that the polyimidazolyl acetate ionic liquid was successfully prepared and attached to the surface of the cellulose filter paper through chemical bonding. The adsorption capacity of the homemade thin-film extraction material for the four non-steroidal anti-inflammatory drugs was greater than 8898 ng/cm under the optimum conditions, and the desorption rate was over 90%. Then, a paper-based thin-film extraction phase-high-performance liquid chromatography-tandem mass spectrometry method was established for the extraction of non-steroidal anti-inflammatory drugs in water. This method provided limits of detection and limits of quantification were in the range of 0.02-0.15 and 0.17-0.50 μg/L, respectively. Hence, the obtained thin-film extraction phase showed excellent recovery and reproducibility for the target non-steroidal anti-inflammatory drugs with carboxyl groups from water.
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http://dx.doi.org/10.1002/jssc.202200042DOI Listing
July 2022

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

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

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

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

Metal oxide nanoparticle-modified ITO electrode for high-performance solution-processed perovskite photodetectors.

RSC Adv 2022 Feb 16;12(9):5638-5647. Epub 2022 Feb 16.

Key Laboratory of Luminescence and Optical Information, Ministry of Education, Institute of Optoelectronic Technology, Beijing Jiaotong University Beijing 100044 P. R. China

Low dark current density plays a key role in determining the overall performance of perovskite photodetectors (PPDs). To achieve this goal, a hole transport layer (HTL) on the ITO side and a hole blocking layer (HBL) on the metal electrode side are commonly introduced in PPDs. Unlike traditional approaches, we realized a high-performance solution-processed broadband PPD using metal oxide (MO) nanoparticles (NPs) as the HBL on the ITO electrode and PCBM as another HBL on the metal electrode side to reduce the device dark current. The PPDs based on TiO and SnO NP-modified layers show similar device performances at -0.5 V: a greater than 10 on/off ratio; over 100 dB linear dynamic range (LDR) under different visible light illumination; around 0.2 A W responsivity (); greater than 10 jones detectivity (*); and ∼20 μs rise time of the device. The MO NP interfacial layer can significantly suppress charge injection in the dark, while the accumulated photogenerated charges at the interface between the MO layer and the perovskite layer introduce band bending, leading to dramatically increased current under illumination. Therefore, the dark current density of the devices is significantly reduced and the optical gain is drastically enhanced. However, after UV illumination, the dark current of the TiO device dramatically increases while the dark current of the SnO device can stay the same as before since the UV illumination-induced conductivity and barrier height changes in the TiO layer cannot recover after removing the UV irradiation. These results indicate that the TiO NP layer is suitable for making a vis-NIR photodetector, while the SnO NP layer is a good candidate for UV-vis-NIR photodetectors. The facile solution-processed high-performance perovskite photodetector using MO NP-modified ITO is highly compatible with low cost, flexible, and large-area electronics.
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http://dx.doi.org/10.1039/d1ra08764aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981377PMC
February 2022

The dynamic alteration of transcriptional regulation by crucial TFs during tumorigenesis of gastric cancer.

Mol Med 2022 04 14;28(1):41. Epub 2022 Apr 14.

Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Background: The mechanisms of Gastric cancer (GC) initiation and progression are complicated, at least partly owing to the dynamic changes of gene regulation during carcinogenesis. Thus, investigations on the changes in regulatory networks can improve the understanding of cancer development and provide novel insights into the molecular mechanisms of cancer.

Methods: Differential co-expression analysis (DCEA), differential gene regulation network (GRN) modeling and differential regulation analysis (DRA) were integrated to detect differential transcriptional regulation events between gastric normal mucosa and cancer samples based on GSE54129 dataset. Cytological experiments and IHC staining assays were used to validate the dynamic changes of CREB1 regulated targets in different stages.

Results: A total of 1955 differentially regulated genes (DRGs) were identified and prioritized in a quantitative way. Among the top 1% DRGs, 14 out of 19 genes have been reported to be GC relevant. The four transcription factors (TFs) among the top 1% DRGs, including CREB1, BPTF, GATA6 and CEBPA, were regarded as crucial TFs relevant to GC progression. The differentially regulated links (DRLs) around the four crucial TFs were then prioritized to generate testable hypotheses on the differential regulation mechanisms of gastric carcinogenesis. To validate the dynamic alterations of gene regulation patterns of crucial TFs during GC progression, we took CREB1 as an example to screen its differentially regulated targets by using cytological and IHC staining assays. Eventually, TCEAL2 and MBNL1 were proved to be differentially regulated by CREB1 during tumorigenesis of gastric cancer.

Conclusions: By combining differential networking information and molecular cell experiments verification, testable hypotheses on the regulation mechanisms of GC around the core TFs and their top ranked DRLs were generated. Since TCEAL2 and MBNL1 have been reported to be potential therapeutic targets in SCLC and breast cancer respectively, their translation values in GC are worthy of further investigation.
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http://dx.doi.org/10.1186/s10020-022-00468-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008954PMC
April 2022

Cannabis suppresses antitumor immunity by inhibiting JAK/STAT signaling in T cells through CNR2.

Signal Transduct Target Ther 2022 04 6;7(1):99. Epub 2022 Apr 6.

State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.

The combination of immune checkpoint blockade (ICB) with chemotherapy significantly improves clinical benefit of cancer treatment. Since chemotherapy is often associated with adverse events, concomitant treatment with drugs managing side effects of chemotherapy is frequently used in the combination therapy. However, whether these ancillary drugs could impede immunotherapy remains unknown. Here, we showed that 9-tetrahydrocannabinol (THC), the key ingredient of drugs approved for the treatment of chemotherapy-caused nausea, reduced the therapeutic effect of PD-1 blockade. The endogenous cannabinoid anandamide (AEA) also impeded antitumor immunity, indicating an immunosuppressive role of the endogenous cannabinoid system (ECS). Consistently, high levels of AEA in the sera were associated with poor overall survival in cancer patients. We further found that cannabinoids impaired the function of tumor-specific T cells through CNR2. Using a knock-in mouse model expressing a FLAG-tagged Cnr2 gene, we discovered that CNR2 binds to JAK1 and inhibits the downstream STAT signaling in T cells. Taken together, our results unveiled a novel mechanism of the ECS-mediated suppression on T-cell immunity against cancer, and suggest that cannabis and cannabinoid drugs should be avoided during immunotherapy.
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http://dx.doi.org/10.1038/s41392-022-00918-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983672PMC
April 2022

FimH confers mannose-targeting ability to Bacillus Calmette-Guerin for improved immunotherapy in bladder cancer.

J Immunother Cancer 2022 03;10(3)

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China

Background: Bladder cancer is a common disease worldwide with most patients presenting with the non-muscle-invasive form (NMIBC) at initial diagnosis. Postoperational intravesical instillation of BCG is carried out for patients with high-risk disease to reduce tumor recurrence and progression to muscle invasive disease. However, BCG can also have side effects or be ineffective in some patients because it cannot enter the cancer cells. Thus, to improve the efficacy of BCG immunotherapy is the long-term pursuit of the bladder cancer field.

Methods: To increase the adhesion of BCG to the urothelium we overexpressed FimH, a mannose binding protein naturally used by uropathogenic to adhere to human urothelium, onto the surface of BCG. The adhesion/internalization ability of rBCG-S.FimH was examined in mouse bladder by fluorescence microscopy. Preclinical evaluation of antitumor efficacy was carried out in orthotopic mouse models of bladder cancer and in human peripheral blood mononuclear cells. Mechanistic studies were carried out using toll-like receptor 4 (TLR4) knockout mice. Immune cells and cytokines in the serum, tumor and lymph nodes were analyzed by flow cytometry, PCR, ELISA and ELISPOT.

Results: rBCG-S.FimH exhibited markedly improved adhesion and more rapid internalization into urothelial cells than wild-type BCG, resulting in more potent antitumor activity in orthotopic murine models of bladder cancer. To our surprise, rBCG-S.FimH elicited a much more prominent Th1-biased immune response known to be positively correlated with BCG efficacy. Mechanistic studies using TLR4 knockout mouse showed that rBCG-S.FimH could induce enhanced dendritic cell activation and tumor antigen-specific immune response in a TLR4-dependent manner. Furthermore, human peripheral blood mononuclear cells stimulated by rBCG-S.FimH also showed better tumoricidal effects than those using wild-type BCG.

Conclusion: rBCG-S.FimH is a novel BCG strain with significantly improved efficacy against bladder cancer. Since intravesical BCG immunotherapy is the first-line treatment for NMIBC, which accounts for more than 70% of all bladder cancer cases, our results provide a compelling rationale for clinical development.
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http://dx.doi.org/10.1136/jitc-2021-003939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971803PMC
March 2022

Peptide ligand-SiO microspheres with specific affinity for phosphatidylserine as a new strategy to isolate exosomes and application in proteomics to differentiate hepatic cancer.

Bioact Mater 2022 Sep 21;15:343-354. Epub 2021 Dec 21.

School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China.

Exosomes are membrane bound extracellular vesicles that play an important role in many biological processes. While they have great application value, exosome isolation is still considered a major scientific challenge. In the present study, a novel separation strategy for exosomes is proposed based on the specific interaction between immobilized peptide ligands and phosphatidylserine moieties which are highly abundant on the surface of exosomes. With the new affinity method, intact model exosomes can be recovered with a high yield in a short processing time. The purity of exosome samples enriched from serum by the affinity method is far higher than that isolated by ultrafiltration, and similar to that obtained by density gradient centrifugation and ultracentrifugation. Moreover, the variety of contaminants co-isolated by the affinity method is relatively low due to its specific separation principle. Proteomics analysis of exosomes isolated by the affinity method from the serum of healthy, hepatocellular carcinoma patients, and intrahepatic cholangiocarcinoma patients was performed to prove the applicability of this method. In conclusion, our novel strategy shows characteristics of easy preparation, high specificity, and cost-effectiveness, and provides a promising approach for exosome isolation which should have wide applications.
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http://dx.doi.org/10.1016/j.bioactmat.2021.12.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8935132PMC
September 2022

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

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

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

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

Research Progress of Cell Membrane Biomimetic Nanoparticles for Tumor Therapy.

Nanoscale Res Lett 2022 Mar 22;17(1):36. Epub 2022 Mar 22.

The Affiliated Huai'an Hospital of Xuzhou Medical University and The Second People's Hospital of Huai'an, No. 62, Huaihai Road (S.), Huai'an, 223002, People's Republic of China.

Nanoparticles have unique properties and high design flexibility, which are thought to be safe, site-specific, and efficient drug delivery systems. However, nanoparticles as exogenous materials can provide recognition and be eliminated by the body's immune system, which considerably restricts their applications. To overcome these drawbacks, natural cell membrane coating method has attracted great attention in the field of drug delivery systems, which can prolong nanoparticles blood circulation time and avoiding the capture as well as elimination by the body immune system. Biomimetic nanoparticles via a top-down approach can avoid the laborious group modified engineering and keep the integrity of cell membrane structure and membrane antigens, which can be endowed with unique properties, such as immune escape, longer blood circulation time, targeting delivery and controlling drugs sustain-release. At the present research, erythrocyte membrane, cancer cell membrane, platelet membrane, lymphocyte membrane and hybrid membrane have been successfully coated into the surface of nanoparticles to achieve biological camouflage. Thus, integrating various kinds of cell membranes and nanoparticles into one system, the biomimetic nanoparticles can inherit unique biofunction and drug delivery properties to exhibit tumor targeting-delivery and antitumor outcomes. In this article, we will discuss the prospects and challenges of some basic cell membrane cloaking nanoparticles as a drug delivery system for cancer therapy.
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http://dx.doi.org/10.1186/s11671-022-03673-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8941025PMC
March 2022
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