Publications by authors named "Hao Li"

4,527 Publications

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Retraction notice to "Amelioration of imiquimod-induced psoriasis-like dermatitis in mice by DSW therapy inspired hydrogel" [BIOMAT 6 (2021) 299-311].

Bioact Mater 2022 Jan 20;7. Epub 2021 Jun 20.

State Key Laboratory of Powder Metallurgy, Central South University, Changsha, 410083, China.

[This retracts the article DOI: 10.1016/j.bioactmat.2020.08.007.].
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http://dx.doi.org/10.1016/j.bioactmat.2021.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9359889PMC
January 2022

Control the Nature of Photoluminescence of Emissive Metal Nanoclusters.

Chemphyschem 2022 Aug 10. Epub 2022 Aug 10.

Anhui University, Department of Chemistry and Chemical Engineering, 111 Jiulong Rd, 230601, Hefei, CHINA.

Photoluminescence (PL) serves as one of the most attractive chemical-physical properties of metal nanoclusters. However, the control over the PL nature of metal nanocluster as fluorescence or phosphorescence remains challenging. Basically, the PL nature control concerns the transition regulation of excited electrons in nanoclusters from their excited state to the ground state. Up to the present, some cases have been reported on adjusting the PL nature of emissive nanoclusters via different means, including the composition regulation, the isomerization, the aggregation, and the temperature variation. At the same time, theoretical calculations have been performed to thoroughly understand the PL nature transformation of these emissive nanoclusters in terms of their electronic structures and transition pathways. This Concept highlights the recent progress in controlling the PL nature of emissive nanoclusters as fluorescence or phosphorescence, which hopefully paves the way for fabricating novel nanoclusters or cluster-based nanomaterials with customized PL properties.
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http://dx.doi.org/10.1002/cphc.202200484DOI Listing
August 2022

Spatiotemporal evolution of pyroptosis and canonical inflammasome pathway in hSOD1 ALS mouse model.

BMC Neurosci 2022 Aug 9;23(1):50. Epub 2022 Aug 9.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Ave, Boston, MA, 02115, USA.

Background: Evidences indicate that inflammasome compounds participate in amyotrophic lateral sclerosis (ALS), a fatal progressive motoneuron degenerative disease. Researchers have observed the expressions of nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) related inflammasome components in specific regions of the central nervous system in different ALS models, but the cellular spatiotemporal evolution of this canonical inflammasome pathway and pyroptosis during ALS progression are unclear.

Methods: The spinal cords of hSOD1 mice (ALS mice) and age-matched littermates (CON mice) were dissected at pre-symptomatic stage (60 d), early- symptomatic stage (95 d), symptomatic stage (108 d) and late-symptomatic stage (122 d) of the disease. By using Nissl staining, double immunofluorescence labelling, qRT-PCR or western blot, we detected morphology change and the expression, cellular location of GSDMD, NLRP3, caspase-1 and IL-1β in the ventral horn of lumbar spinal cords over the course of disease.

Results: Neural morphology changes and GSDMD/NeuN double positive cells were observed in ventral horn from ALS mice even at 60 d of age, even though there were no changes of GSDMD mRNA and protein expressions at this stage compared with CON mice. With disease progression, compared with age-matched CON mice, increased expressions of GSDMD, NLRP3, activated caspase-1 and IL-1β were detected. Double immunofluorescence labeling revealed that NLRP3, caspase-1, IL-1β positive signals mainly localized in ventral horn neurons at pre- and early-symptomatic stages. From symptomatic stage to late-symptomatic stage, robust positive signals were co-expressed in reactive astrocytes and microglia.

Conclusions: Early activation of the canonical NLRP3 inflammasome induced pyroptosis in ventral horn neurons, which may participate in motor neuron degeneration and initiate neuroinflammatory processes during ALS progression.
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http://dx.doi.org/10.1186/s12868-022-00733-9DOI Listing
August 2022

Dynamic Memory Management in Massively Parallel Systems: A Case on GPUs.

ICS 2022 Jun 28;2022. Epub 2022 Jun 28.

University of South Florida, Tampa, FL, USA.

Due to the high level of parallelism, there are unique challenges in developing system software on massively parallel hardware such as GPUs. One such challenge is designing a dynamic memory allocator whose task is to allocate memory chunks to requesting threads at runtime. State-of-the-art GPU memory allocators maintain a global data structure holding metadata to facilitate allocation/deallocation. However, the centralized data structure can easily become a bottleneck in a massively parallel system. In this paper, we present a novel approach for designing dynamic memory allocation without a centralized data structure. The core idea is to let threads follow a random search procedure to locate free pages. Then we further extend to more advanced designs and algorithms that can achieve an order of magnitude improvement over the basic idea. We present mathematical proofs to demonstrate that (1) the basic random search design achieves asymptotically lower latency than the traditional queue-based design and (2) the advanced designs achieve significant improvement over the basic idea. Extensive experiments show consistency to our mathematical models and demonstrate that our solutions can achieve up to two orders of magnitude improvement in latency over the best-known existing solutions.
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http://dx.doi.org/10.1145/3524059.3532387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357265PMC
June 2022

Association between diabetes duration and 1-year prognosis of stroke: A national registry study.

Brain Behav 2022 Aug 8:e2725. Epub 2022 Aug 8.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background And Purpose: Diabetes mellitus is a strong independent risk factor for stroke recurrence. However, the association between diabetes duration and the prognosis of stroke remains uncertain. We aimed to characterize whether an association exists between diabetes duration and stroke outcomes in patients with ischemic stroke or transient ischemic attack (TIA).

Methods: Between 2015 and 2018, 14,674 patients with ischemic stroke or TIA within 7 days and older than 18 years from the Third China National Stroke Registry (CNSR-III) were included in this analysis. Diabetes duration at baseline was collected by face-to-face interviews and further categorized into groups of without diabetes, diabetes < 4, 4 to <8 and ≥8 years. The association between diabetes duration and clinical outcomes, including stroke recurrence, poor function outcome (modified Rankin Scale score of 3-6), and all-cause mortality at the 1-year follow-up after stroke onset, was evaluated by a multivariable Cox proportional hazard regression model, competing risk model and logistic regression model with adjustment for demographic and clinical features.

Results: Among the 14,674 patients included, the average age was 62.0 years, and 68.5% were male. There were 1419 (9.7%) patients who had stroke recurrence, 1912 (13.0%) who had poor function outcome, and 478 (3.3%) who had all-cause mortality at the 1-year follow-up. After adjusting for potential covariates, a diabetes duration ≥8 years was associated with an increased risk of 1-year stroke recurrence (adjusted hazards ratio [HR], 1.31; 95% CI, 1.05-1.64; p = .02) in comparison to those without Diabetes mellitus. Using a competing risk regression model, a diabetes duration ≥8 years was a significant risk factor for stroke recurrence (HR, 1.31; 95% CI, 1.12-1.53). In contrast, there was no significant association between diabetes duration < 4, 4 to <8 years and clinical outcomes.

Conclusions: Long-term diabetes duration (≥8 years), but not short-term diabetes duration, was associated with an increased risk of 1-year stroke recurrence in patients with ischemic stroke or TIA.
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http://dx.doi.org/10.1002/brb3.2725DOI Listing
August 2022

Development and Validation of a Deep Learning Model for Brain Tumor Diagnosis and Classification Using Magnetic Resonance Imaging.

JAMA Netw Open 2022 Aug 1;5(8):e2225608. Epub 2022 Aug 1.

National Center for Clinical Medicine of Neurological Diseases, Beijing, People's Republic of China.

Importance: Deep learning may be able to use patient magnetic resonance imaging (MRI) data to aid in brain tumor classification and diagnosis.

Objective: To develop and clinically validate a deep learning system for automated identification and classification of 18 types of brain tumors from patient MRI data.

Design, Setting, And Participants: This diagnostic study was conducted using MRI data collected between 2000 and 2019 from 37 871 patients. A deep learning system for segmentation and classification of 18 types of intracranial tumors based on T1- and T2-weighted images and T2 contrast MRI sequences was developed and tested. The diagnostic accuracy of the system was tested using 1 internal and 3 external independent data sets. The clinical value of the system was assessed by comparing the tumor diagnostic accuracy of neuroradiologists with vs without assistance of the proposed system using a separate internal test data set. Data were analyzed from March 2019 through February 2020.

Main Outcomes And Measures: Changes in neuroradiologist clinical diagnostic accuracy in brain MRI scans with vs without the deep learning system were evaluated.

Results: A deep learning system was trained among 37 871 patients (mean [SD] age, 41.6 [11.4] years; 18 519 women [48.9%]). It achieved a mean area under the receiver operating characteristic curve of 0.92 (95% CI, 0.84-0.99) on 1339 patients from 4 centers' data sets in diagnosis and classification of 18 types of tumors. Higher outcomes were found compared with neuroradiologists for accuracy and sensitivity and similar outcomes for specificity (for 300 patients in the Tiantan Hospital test data set: accuracy, 73.3% [95% CI, 67.7%-77.7%] vs 60.9% [95% CI, 46.8%-75.1%]; sensitivity, 88.9% [95% CI, 85.3%-92.4%] vs 53.4% [95% CI, 41.8%-64.9%]; and specificity, 96.3% [95% CI, 94.2%-98.4%] vs 97.9%; [95% CI, 97.3%-98.5%]). With the assistance of the deep learning system, the mean accuracy of neuroradiologists among 1166 patients increased by 12.0 percentage points, from 63.5% (95% CI, 60.7%-66.2%) without assistance to 75.5% (95% CI, 73.0%-77.9%) with assistance.

Conclusions And Relevance: These findings suggest that deep learning system-based automated diagnosis may be associated with improved classification and diagnosis of intracranial tumors from MRI data among neuroradiologists.
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http://dx.doi.org/10.1001/jamanetworkopen.2022.25608DOI Listing
August 2022

Corrigendum: Biomarking and induction of apoptosis in ovarian cancer using bifunctional polyethyleneimine-caged platinum nanoclusters.

Front Oncol 2022 20;12:983959. Epub 2022 Jul 20.

Department of Light Chemical Engineering, School of Textiles, Zhengzhou, China.

[This corrects the article DOI: 10.3389/fonc.2022.898917.].
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http://dx.doi.org/10.3389/fonc.2022.983959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346211PMC
July 2022

Machine learning models based on immunological genes to predict the response to neoadjuvant therapy in breast cancer patients.

Front Immunol 2022 22;13:948601. Epub 2022 Jul 22.

Department of Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Breast cancer (BC) is the most common malignancy worldwide and neoadjuvant therapy (NAT) plays an important role in the treatment of patients with early BC. However, only a subset of BC patients can achieve pathological complete response (pCR) and benefit from NAT. It is therefore necessary to predict the responses to NAT. Although many models to predict the response to NAT based on gene expression determined by the microarray platform have been proposed, their applications in clinical practice are limited due to the data normalization methods during model building and the disadvantages of the microarray platform compared with the RNA-seq platform. In this study, we first reconfirmed the correlation between immune profiles and pCR in an RNA-seq dataset. Then, we employed multiple machine learning algorithms and a model stacking strategy to build an immunological gene based model (Ipredictor model) and an immunological gene and receptor status based model ICpredictor model) in the RNA-seq dataset. The areas under the receiver operator characteristic curves for the Ipredictor model and ICpredictor models were 0.745 and 0.769 in an independent external test set based on the RNA-seq platform, and were 0.716 and 0.752 in another independent external test set based on the microarray platform. Furthermore, we found that the predictive score of the Ipredictor model was correlated with immune microenvironment and genomic aberration markers. These results demonstrated that the models can accurately predict the response to NAT for BC patients and will contribute to individualized therapy.
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http://dx.doi.org/10.3389/fimmu.2022.948601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352856PMC
August 2022

Ionizing radiation damage and repair from 3D-genomic perspective.

Trends Genet 2022 Aug 4. Epub 2022 Aug 4.

Institute of Health Service and Transfusion Medicine, Beijing 100850, China. Electronic address:

Ionizing radiation (IR)-induced DNA damage and repair are complex and occur at hierarchical chromatin structures; radiobiology needs to be studied from a 3D-genomic perspective. Differences in IR damage and repair throughout the 3D genome may help to explain differences in radiosensitivity.
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http://dx.doi.org/10.1016/j.tig.2022.07.004DOI Listing
August 2022

Clinical Outcomes of Doxycycline, Azithromycin, and Chloramphenicol for the Treatment of Severe Patients with Scrub Typhus.

Int J Antimicrob Agents 2022 Aug 4:106647. Epub 2022 Aug 4.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, P. R. China; School of Public Health, Anhui Medical University, Hefei, China. Electronic address:

Background: Previous studies have evaluated the treatment efficacy of patients with mild to moderate scrub typhus (ST), however, the efficacy of treating severe ST with different antibiotics remained obscure.

Methods: A retrospective study was performed to include severe ST patients in China. The treatment efficacy of doxycycline, azithromycin, or chloramphenicol were compared by using treatment failure and the time to defervescence as primary outcomes.

Results: In total, 876 severe ST patients who initially received doxycycline, azithromycin, or chloramphenicol treatment were recruited. Treatment failure rate was not significantly different between those receiving doxycycline and azithromycin therapy (6.0% vs 11.4%, p=0.109). However, a higher rate of treatment failure was observed for chloramphenicol than doxycycline therapy (14.6% vs 6.0%, p=0.004). No significant difference was observed for the time to defervescence in those receiving doxycycline, azithromycin, and chloramphenicol treatment respectively. Further subgroup analysis revealed a higher risk of treatment failure related to chloramphenicol than doxycycline in patients with acute kidney injury (AKI), pneumonia, and shock; a higher risk of treatment failure related to azithromycin than doxycycline in patients with meningitis. Significant correlation between azithromycin resistance and meningitis (p=0.009), between chloramphenicol resistance and acute respiratory distress syndrome (ARDS) (p<0.001) were obsevered by cramer's V correlation coefficients. Multivariate Cox regression analysis revealed significant association between time to defervescence and presence of ARDS, shock, myocarditis, meningitis, and AKI.

Conclusion: Significant therapy effect of azithromycin and doxycycline was observed for severe patients, by contrast, a lower therapy effect was observed for chloramphenicol in treating severe patients.
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http://dx.doi.org/10.1016/j.ijantimicag.2022.106647DOI Listing
August 2022

Hernandezine, a natural herbal alkaloid, ameliorates type 2 diabetes by activating AMPK in two mouse models.

Phytomedicine 2022 Jul 28;105:154366. Epub 2022 Jul 28.

State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address:

Background: AMP-activated protein kinase (AMPK) is an effective target for treating diabetes. However, successful drug development is delayed due to issues including toxicity. Plant-derived natural product AMPK activators have emerged as a new way to treat diabetes due to its potential low safety risks. Here, we studied the effect of hernandezine (HER), a natural product derived from Thalictrum, in activating AMPK and treating T2D in mouse models.

Method: We tested HER in various cells and tissues, including primary hepatocytes, skeletal myotubes cell lines, as well as major metabolic tissues from diabetic (db/db) and diet-induced obesity (DIO) model mice. The effect of HER on glucose uptake via AMPK in vitro and in vivo was confirmed utilizing cell transfection and adenovirus interference analysis. Tissue staining assessed the effect of HER on adipogenesis. Real-time quantitative polymerase chain reaction (real-time PCR) was applied to verify the effect of HER on transcription factors. Western blot analysis was used to determine the activation of phosphorylated AMPK and ACC pathways.

Results: Biochemically, we found that HER prevented pAMPK from dephosphorylation to prolong its activity, disproving previous direct activation model and providing a new model to explain HER-mediated AMPK activation. HER could be orally delivered to animals and has a 3-fold long half-life in vivo as compared to metformin. Importantly, long-term oral HER treatment potently reduced body weight and blood glucose in both type 2 diabetes mullitus (T2DM) mouse models by increasing glucose disposal and reducing lipogenesis, and appeared not to induce cardiac hypertrophy.

Conclusion: Natural product HER indirectly activates AMPK by suppressing its dephosphorylation. Oral HER effectively alleviated hyperglycemia and reduced body weight in T2D mouse models, appeared to have a low risk of causing cardiac hypertrophy, and might be a potential therapeutic option for T2DM.
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http://dx.doi.org/10.1016/j.phymed.2022.154366DOI Listing
July 2022

Stochastic exciton-scattering theory of optical line shapes: Renormalized many-body contributions.

J Chem Phys 2022 Aug;157(5):054103

School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, Georgia 30332, USA.

Spectral line shapes provide a window into the local environment coupled to a quantum transition in the condensed phase. In this paper, we build upon a stochastic model to account for non-stationary background processes produced by broad-band pulsed laser stimulation, as distinguished from those for stationary phonon bath. In particular, we consider the contribution of pair-fluctuations arising from the full bosonic many-body Hamiltonian within a mean-field approximation, treating the coupling to the system as a stochastic noise term. Using the Itô transformation, we consider two limiting cases for our model, which lead to a connection between the observed spectral fluctuations and the spectral density of the environment. In the first case, we consider a Brownian environment and show that this produces spectral dynamics that relax to form dressed excitonic states and recover an Anderson-Kubo-like form for the spectral correlations. In the second case, we assume that the spectrum is Anderson-Kubo like and invert to determine the corresponding background. Using the Jensen inequality, we obtain an upper limit for the spectral density for the background. The results presented here provide the technical tools for applying the stochastic model to a broad range of problems.
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http://dx.doi.org/10.1063/5.0095575DOI Listing
August 2022

A tree-structure-guided graph convolutional network with contrastive learning for the assessment of parkinsonian hand movements.

Med Image Anal 2022 Jul 28;81:102560. Epub 2022 Jul 28.

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China. Electronic address:

Bradykinesia is one of the core motor symptoms of Parkinson's disease (PD). Neurologists typically perform face-to-face bradykinesia assessment in PD patients according to the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). As this human-expert assessment lacks objectivity and consistency, an automated and objective assessment scheme for bradykinesia is critically needed. In this paper, we propose a tree-structure-guided graph convolutional network with contrastive learning scheme to solve the challenge of difficulty in fine-grained feature extraction and insufficient model stability, finally achieving the video-based automated assessment of Parkinsonian hand movements, which represent a vital MDS-UPDRS component for examining upper-limb bradykinesia. Specifically, a tri-directional skeleton tree scheme is proposed to achieve effective fine-grained modeling of spatial hand dependencies. In this scheme, hand skeletons are extracted from videos, and then the spatial structures of these skeletons are constructed through depth-first tree traversal. Afterwards, a tree max-pooling module is employed to establish remote exchange between outer and inner nodes, hierarchically gather the most salient motion features, and hence achieve fine-grained mining. Finally, a group-sparsity-induced momentum contrast is also developed to learn similar motion patterns under different interference through contrastive learning. This can promote stable learning of discriminative spatial-temporal features with invariant motion semantics. Comprehensive experiments on a large clinical video dataset reveal that our method achieves competitive results, and outperforms other sensor-based and RGB-depth methods. The proposed method leads to accurate assessment of PD bradykinesia through videos collected by low-cost consumer cameras of limited capabilities. Hence, our work provides a convenient tool for PD telemedicine applications with modest hardware requirements.
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http://dx.doi.org/10.1016/j.media.2022.102560DOI Listing
July 2022

Development and Validation of a Machine Learning-Based Nomogram for Prediction of Ankylosing Spondylitis.

Rheumatol Ther 2022 Aug 6. Epub 2022 Aug 6.

The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China.

Introduction: Ankylosing spondylitis (AS) is a chronic progressive inflammatory disease of the spine and its affiliated tissues. AS mainly affects the axial bone, sacroiliac joint, hip joint, spinal facet, and adjacent ligaments. We used machine learning (ML) methods to construct diagnostic models based on blood routine examination, liver function test, and kidney function test of patients with AS. This method will help clinicians enhance diagnostic efficiency and allow patients to receive systematic treatment as soon as possible.

Methods: We consecutively screened 348 patients with AS through complete blood routine examination, liver function test, and kidney function test at the First Affiliated Hospital of Guangxi Medical University according to the modified New York criteria (diagnostic criteria for AS). By using random sampling, the patients were randomly divided into training and validation cohorts. The training cohort included 258 patients with AS and 247 patients without AS, and the validation cohort included 90 patients with AS and 113 patients without AS. We used three ML methods (LASSO, random forest, and support vector machine recursive feature elimination) to screen feature variables and then took the intersection to obtain the prediction model. In addition, we used the prediction model on the validation cohort.

Results: Seven factors-erythrocyte sedimentation rate (ESR), red blood cell count (RBC), mean platelet volume (MPV), albumin (ALB), aspartate aminotransferase (AST), and creatinine (Cr)-were selected to construct a nomogram diagnostic model through ML. In the training cohort, the C value and area under the curve (AUC) value of this nomogram was 0.878 and 0.8779462, respectively. The C value and AUC value of the nomogram in the validation cohort was 0.823 and 0.8232055, respectively. Calibration curves in the training and validation cohorts showed satisfactory agreement between nomogram predictions and actual probabilities. The decision curve analysis showed that the nonadherence nomogram was clinically useful when intervention was decided at the nonadherence possibility threshold of 1%.

Conclusion: Our ML model can satisfactorily predict patients with AS. This nomogram can help orthopedic surgeons devise more personalized and rational clinical strategies.
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http://dx.doi.org/10.1007/s40744-022-00481-6DOI Listing
August 2022

Identification of COVID-19-Specific Immune Markers Using a Machine Learning Method.

Front Mol Biosci 2022 19;9:952626. Epub 2022 Jul 19.

School of Life Sciences, Shanghai University, Shanghai, China.

Notably, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a tight relationship with the immune system. Human resistance to COVID-19 infection comprises two stages. The first stage is immune defense, while the second stage is extensive inflammation. This process is further divided into innate and adaptive immunity during the immune defense phase. These two stages involve various immune cells, including CD4 T cells, CD8 T cells, monocytes, dendritic cells, B cells, and natural killer cells. Various immune cells are involved and make up the complex and unique immune system response to COVID-19, providing characteristics that set it apart from other respiratory infectious diseases. In the present study, we identified cell markers for differentiating COVID-19 from common inflammatory responses, non-COVID-19 severe respiratory diseases, and healthy populations based on single-cell profiling of the gene expression of six immune cell types by using Boruta and mRMR feature selection methods. Some features such as IFI44L in B cells, S100A8 in monocytes, and NCR2 in natural killer cells are involved in the innate immune response of COVID-19. Other features such as ZFP36L2 in CD4 T cells can regulate the inflammatory process of COVID-19. Subsequently, the IFS method was used to determine the best feature subsets and classifiers in the six immune cell types for two classification algorithms. Furthermore, we established the quantitative rules used to distinguish the disease status. The results of this study can provide theoretical support for a more in-depth investigation of COVID-19 pathogenesis and intervention strategies.
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http://dx.doi.org/10.3389/fmolb.2022.952626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344575PMC
July 2022

Pentagalloylglucose disrupts the PALB2-BRCA2 interaction and potentiates tumor sensitivity to PARP inhibitor and radiotherapy.

Cancer Lett 2022 Aug 1;546:215851. Epub 2022 Aug 1.

Department of Neurosurgery, Children's Hospital of Fudan University, Shanghai, 201102, China. Electronic address:

DNA damage repair plays a vital role in maintaining the genomic integrity of cells and has been exploited therapeutically in the treatment of cancer. We have previously demonstrated that the upregulation of CXorf67 in posterior fossa type A ependymoma sensitizes tumor cells to PARP inhibitors by suppressing the PALB2-BRCA2 protein-protein interaction (PPI). Here, we performed structure-based virtual screening of ∼2 million small molecular entities followed by NanoBiT-based screening, and determined that pentagalloylglucose (PGG) disrupts the PALB2-BRCA2 PPI. Structure-based molecular docking and in vitro binding affinity assays revealed that PGG occupies a well-defined binding groove in the tips of the fourth and fifth blades of the PALB2 WD40 domain. PGG reduces BRCA2 recruitment to DNA damage sites and inhibits the formation of RAD51 foci, suppressing homologous recombination repair. PGG also inhibits proliferation and survival in several cancer cell lines, including breast cancer and medulloblastoma cells, and suppresses the in vivo growth of tumor xenografts. Thus, PGG is a specific inhibitor of the PALB2-BRCA2 PPI, which has potential value in cancer treatment to sensitize tumors to PARP inhibitors and radiotherapy.
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http://dx.doi.org/10.1016/j.canlet.2022.215851DOI Listing
August 2022

A score to predict the stroke recurrence of patients with embolic stroke of undetermined source.

J Neurol 2022 Aug 4. Epub 2022 Aug 4.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Aim: We aimed to develop a score and validate it in a prospective cohort to identify the patients with ESUS at high risk for stroke recurrence.

Methods: We assessed the stroke recurrence in ESUS patients of the Third China National Stroke Registry. We performed multivariable logistic regression analysis to identify predictors of stroke recurrence in the derivation cohort. Based on the coefficient of each covariate of the fitted multivariable model, we generated an integer-based point scoring system. We validated the score in the validation cohort assessing its discrimination and calibration.

Results: 2415 patients were included: 1611 in the derivation and 804 in the validation sample. We developed a scoring system (0-15 points) by assigning 2 points for hypertension, 3 points for diabetes mellitus, 4 points for multiple stage infarction, 2 points for watershed involved infarction, 1 points for left atrial diameter index (per increasing 2.5 mm/m2) and 3 points for without statin at discharge. The rate of stroke recurrence was 5.9% per year (95% CI 4.2-7.6%) in patients with low risk(a score of 0-5), 9.4% (7.3-11.5%) in patients with intermediate risk (6-10), and 26.8% (16.5-37.1%) in patients with high risk (11-15). The AUC (area under curve of receiver operator characteristic curve) of the score in the derivation cohort and validation cohort was, respectively, 0.60 (0.55-0.65) and 0.63 (0.56-0.70). The score was well calibrated both in the derivation cohort (p = 0.36) and validation cohort (p = 0.26) with the Hosmer-Lemeshow test.

Conclusion: The developed score can improve risk stratification after ESUS in secondary care settings.
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http://dx.doi.org/10.1007/s00415-022-11277-7DOI Listing
August 2022

Interstitial pneumonitis associated with EGFR/ ALK tyrosine kinase inhibitors used in non-small cell lung cancer: an observational, retrospective, pharmacovigilance study.

Expert Opin Drug Saf 2022 Aug 5:1-6. Epub 2022 Aug 5.

Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Background: Epidermal Growth Factor Receptor/ Anaplastic Lymphoma Kinase Tyrosine kinase inhibitors (EGFR/ALK TKIs) may provoke fatal interstitial pneumonitis (IP). The study was conducted to characterize the main characteristics of EGFR/ALK TKI-induced IP and identify factors associated with death.

Research Design And Methods: A disproportionality analysis was conducted using Vigibase, the World Health Organization pharmacovigilance database. Clinical features of patients with EGFR/ALK-TKI-related IP were compared between the fatal and non-fatal groups.

Results: A total of 3355 EGFR/ALK-TKI-IP events were identified, over half of them from Asia (57.47%) and mostly the aged (63.21%). Osimertinib appeared the strongest IP association. The median time to onset (TTO) was 40 (interquartile range [IQR] 16-84) days. There were significant differences between the fatal and non-fatal groups in terms of reporting year and TKI regimens (P < 0.05). The fatality rate of erlotinib-induced IP was the highest (35.54%).

Conclusion: Our study showed that EGFR/ALK TKIs were associated with IP that had a high fatality rate and tended to occur earlier in fatal cases. It is necessary to raise awareness of IP surveillance when EGFR/ALK TKIs were administered.
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http://dx.doi.org/10.1080/14740338.2022.2110235DOI Listing
August 2022

SOX15 transcriptionally increases the function of AOC1 to modulate ferroptosis and progression in prostate cancer.

Cell Death Dis 2022 Aug 3;13(8):673. Epub 2022 Aug 3.

Department of Urology, the First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China.

Amine oxidase copper-containing 1 (AOC1) is considered an oncogene in many types of tumors. Nevertheless, there have been no investigations of AOC1 and its regulatory mechanism in prostate cancer. Here, we reveal a novel action of AOC1 and a tumor suppressor mechanism in prostate cancer. AOC1 is downregulated in prostate cancer. Abatement of AOC1 in prostate cancer tissue is positively correlated with the tumor size, lymph node metastasis, and Gleason score for prostate cancer. Conversely, high expression of AOC1 is significantly associated with reduced proliferation and migration in prostate cancer both in vitro and in vivo. We show that the anticancer effect of AOC1 is mediated by its action on spermidine which leads to the activation of reactive oxygen species and ferroptosis. AOC1 expression in prostate cancer is positively regulated by the transcription factor SOX15. Therefore, SOX15 can transcriptionally promote AOC1 expression and strengthen this effect. Targeting AOC1 and SOX15 may be promising for the treatment of prostate cancer.
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http://dx.doi.org/10.1038/s41419-022-05108-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349193PMC
August 2022

PPAR-γ alleviates the inflammatory response in TNF-α-induced fibroblast-like synoviocytes by binding to p53 in rheumatoid arthritis.

Acta Pharmacol Sin 2022 Aug 2. Epub 2022 Aug 2.

Inflammation and Immune Mediated Disease Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.

Rheumatoid arthritis (RA) is characterized by synovial inflammation, synoviocyte expansion and damage to cartilage and bone. We recently reported that peroxisome proliferator-activated receptor (PPAR)-γ inhibited the proliferation and activation of fibroblast-like synoviocytes (FLS), and was downregulated in RA synovial. In this study we investigated the role of PPAR-γ in RA and the underlying mechanisms. Adjuvant-induced arthritis (AIA) was induced in rats; from D15, AIA rats were orally administered pioglitazone (30 mg·kg·d) or rosiglitazone (4 mg·kg·d) for 14 days. Collagen-induced arthritis (CIA) was induced in wild-type and Ppar-γ mice. We showed that the expression of PPAR-γ was significantly reduced, whereas that of TNF-α was markedly increased in human RA FLS. In CIA mice, knockdown of PPAR-γ expression (Ppar-γ) aggravated the ankle inflammation. Similarly, T0070907 (a PPAR-γ antagonist) or si-PPAR-γ promoted the activation and inflammation of TNF-α-induced FLS in vitro. On the contrary, administration of PPAR-γ agonist pioglitazone or rosiglitazone, or injection of ad-Ppar-γ into the ankle of AIA rat in vivo induced overexpression of PPAR-γ, reduced the paw swelling and inflammation, and downregulated activation and inflammation of FLS in RA. Interesting, injection of ad-Ppar-γ into the ankle also reversed the ankle inflammation in Ppar-γ CIA mice. We conducted RNA-sequencing and KEGG pathway analysis, and revealed that PPAR-γ overexpression was closely related to p53 signaling pathway in TNF-α-induced FLS. Co-IP study confirmed that p53 protein was bound to PPAR-γ in RA FLS. Taken together, PPAR-γ alleviates the inflammatory response of TNF-α-induced FLS by binding p53 in RA.
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http://dx.doi.org/10.1038/s41401-022-00957-9DOI Listing
August 2022

Adherence to Stroke Care Performance Measures in Different Regions in China, 2015-2019: Evidence From the Chinese Stroke Center Alliance.

Neurology 2022 Aug 2. Epub 2022 Aug 2.

China National Clinical Research Center for Neurological Diseases, Beijing, China.

Background And Objectives: To explore regional discrepancy of the adherence to guideline-recommended stroke interventions, with respect to the stroke belt division (north vs. south), the economic development division (east vs. middle vs. west), and potential interaction.

Methods: We conducted a retrospective observational study using data from the Chinese Stroke Center Alliance (CSCA) from August 2015 to August 2019. The primary outcome was hospital personnel adherence to eleven individual guideline-recommended treatments. The co-primary outcomes included two summary measures: a composite score (range, 0 [nonadherence] to 1[perfect adherence]), and an all-or-none binary outcome for adherence to evidence-based stroke. Regional disparities were assessed according to the stroke belt division and the economic development division respectively, as well as the interaction between these two divisions. Multivariate regression models with generalized estimating equations were used to analyze the outcomes.

Results: This study included 838,229 patients with acute ischemic stroke (AIS) from 1,473 hospitals. The overall quality of care in the non-belt regions (southern China) was higher than the stroke-belt regions (northern China), as reflected by a higher composite score (0.77vs 0.75; adjusted OR: 1.03 [95% CI, 1.02-1.04]; P < 0.001) and a higher all-or-none measure (25.5% vs 22.0%; 1.32 [1.17-1.49], P < 0.001). Patients in the East and the Central had higher odds of using intravenous tissue-type plasminogen activator (East: 1.81 [95% CI, 1.51-2.18], P < 0.001; Central: 1.57 [95% CI, 1.26-1.95], P < 0.001), early antithrombotics (East: 1.77 [1.49-2.11], P < 0.001; Central: 1.37 [1.12-1.66], P < 0.001), lipid-lowering medications (East: 1.29 [1.08-1.53], P < 0.001), and DVT prophylaxis (East: 1.28 [1.08-1.50], P = 0.003) compared to those in the West. Patients in the non-belt regions had higher odds of getting dysphagia screening (1.82 [1.55-2.13], P < 0.001) and rehabilitation assessment (which though varied among different economic development levels). Reflected by significant interaction effects, for patients in the East, those in the non-belt regions had greater odds of receiving anticoagulation (1.62 [1.34-1.96]; P < 0.001) but lower odds of receiving antihtrombotics (0.63 [0.52-0.77]; P < 0.001) and antidiabetic medication (0.87 [0.77-0.99]; P= 0.03); for patients in the West, those in the non-belt regions were less likely to receive antihypertensive (0.64 [0.46-0.88]; P = 0.004) and antidiabetic (0.66 [0.54-0.81]; P < 0.001) medications.

Discussion: Stroke care performance measures differed across regions, along the stroke-belt division, and the economic development division. The overall quality of care in the non-stroke-belt regions was higher than the stroke-belt regions. The two divisions had interaction effects on several individual measures.
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http://dx.doi.org/10.1212/WNL.0000000000201024DOI Listing
August 2022

Sustainable Self-Cleaning Evaporators for Highly Efficient Solar Desalination Using a Highly Elastic Sponge-like Hydrogel.

ACS Appl Mater Interfaces 2022 Aug 1;14(31):36116-36131. Epub 2022 Aug 1.

National-Local Joint Engineering Laboratory for Energy Conservation in Chemical Process Integration and Resources Utilization, School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin 300401, China.

Interfacial evaporation using light-absorbing hydrogels offers efficient solar evaporation performance under natural sunlight, ensuring an affordable clean water supply. However, achieving light-absorbing hydrogels with durable and efficient utilization is still a challenge due to inevitable salt accumulation, a difficult-to-control surface morphology, and poor mechanical properties on the surfaces of hydrogel-based evaporators. In this work, a photothermal sponge-like hydrogel with a 3D interconnected porous structure was constructed using low-cost activated carbon as a photothermal material, as well as a double-network polymer chain as the basic skeleton using a simple foaming polymerization strategy. The sponge-like hydrogel evaporator showed tailored surface topography, adequate water transport, excellent elasticity and toughness, good salt rejection, and thermal localization properties. Under the irradiation of simulated sunlight (1.0 kW/m), a high evaporation rate of 2.33 kg·m·h was achieved. Furthermore, efficient salt self-cleaning behavior was achieved due to the fast ion diffusion within the 3D interconnected porous structures. Even in highly concentrated brine of 15 wt %, continuous and efficient water evaporation was still achieved. The excellent evaporation and salt rejection properties of this photothermal sponge-like hydrogel indicated its promising long-term sustainable utilization in seawater desalination.
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http://dx.doi.org/10.1021/acsami.2c08561DOI Listing
August 2022

On the shortest path problem of uncertain random digraphs.

Authors:
Hao Li Kun Zhang

Soft comput 2022 Jul 24:1-13. Epub 2022 Jul 24.

School of Mathematics, Renmin University of China, Beijing, 100872 China.

In the field of graph theory, the shortest path problem is one of the most significant problems. However, since varieties of indeterminated factors appear in complex networks, determining of the shortest path from one vertex to another in complex networks may be a lot more complicated than the cases in deterministic networks. To illustrate this problem, the model of uncertain random digraph will be proposed via chance theory, in which some arcs exist with degrees in probability measure and others exist with degrees in uncertain measure. The main focus of this paper is to investigate the main properties of the shortest path in uncertain random digraph. Methods and algorithms are designed to calculate the distribution of shortest path more efficiently. Besides, some numerical examples are presented to show the efficiency of these methods and algorithms.
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http://dx.doi.org/10.1007/s00500-022-07305-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308943PMC
July 2022

Soluble lectin-like oxidized low-density Lipoproteinreceptor-1 and recurrent stroke: A nested case-control study.

CNS Neurosci Ther 2022 Jul 31. Epub 2022 Jul 31.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Main Problem: The prognostic value of soluble lectin-like oxidized low-density lipoproteinreceptor-1 (sLOX-1) for stroke was unclearly. This study aimed to investigate the association between sLOX-1 and recurrent stroke in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA).

Methods: Data were obtained from the Third China National Stroke Registry. Eligible cases consisted of 400 patients who developed recurrent stroke within 1-year follow-up, 800 controls were selected using age- and sex-matched with a 1:2 case-control ratio. Conditional logistic regressions were used to evaluate the association between sLOX-1 and recurrent stroke.

Results: Among 1200 patients included in this study, the median (interquartile range) of sLOX-1 was 247.12 (132.81-413.58) ng/L. After adjustment for conventional confounding factors, the odds ratio with 95% confidence interval in the highest tertile versus the lowest tertile was 2.23 (1.61-3.08) for recurrent stroke, 2.31 (1.64-3.24) for ischemic stroke, 2.30 (1.66-3.19) for combined vascular events within 1-year follow-up. Furthermore, the addition of sLOX-1 to a conventional risk model had an incremental effect on predictive value for recurrent stroke (C-statistics 0.76, p < 0.0001; integrated discrimination improvement 13.38%, p < 0.0001; net reclassification improvement 55.39%, p < 0.0001). Similar results were observed when the timepoint was set up as 3 months. Subgroup analysis showed the association between higher sLOX-1 and recurrent stroke was more pronounced in patients with a history of stroke (p for interaction = 0.0062).

Conclusions: sLOX-1 was positively associated with the risk of recurrent stroke, which may be a candidate biomarker to improve risk stratification of recurrent stroke.
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http://dx.doi.org/10.1111/cns.13932DOI Listing
July 2022

Localization-adjusted diagnostic performance and assistance effect of a computer-aided detection system for pneumothorax and consolidation.

NPJ Digit Med 2022 Jul 30;5(1):107. Epub 2022 Jul 30.

Department of Medical Artificial Intelligence, Deepnoid, Inc., Seoul, Republic of Korea.

While many deep-learning-based computer-aided detection systems (CAD) have been developed and commercialized for abnormality detection in chest radiographs (CXR), their ability to localize a target abnormality is rarely reported. Localization accuracy is important in terms of model interpretability, which is crucial in clinical settings. Moreover, diagnostic performances are likely to vary depending on thresholds which define an accurate localization. In a multi-center, stand-alone clinical trial using temporal and external validation datasets of 1,050 CXRs, we evaluated localization accuracy, localization-adjusted discrimination, and calibration of a commercially available deep-learning-based CAD for detecting consolidation and pneumothorax. The CAD achieved image-level AUROC (95% CI) of 0.960 (0.945, 0.975), sensitivity of 0.933 (0.899, 0.959), specificity of 0.948 (0.930, 0.963), dice of 0.691 (0.664, 0.718), moderate calibration for consolidation, and image-level AUROC of 0.978 (0.965, 0.991), sensitivity of 0.956 (0.923, 0.978), specificity of 0.996 (0.989, 0.999), dice of 0.798 (0.770, 0.826), moderate calibration for pneumothorax. Diagnostic performances varied substantially when localization accuracy was accounted for but remained high at the minimum threshold of clinical relevance. In a separate trial for diagnostic impact using 461 CXRs, the causal effect of the CAD assistance on clinicians' diagnostic performances was estimated. After adjusting for age, sex, dataset, and abnormality type, the CAD improved clinicians' diagnostic performances on average (OR [95% CI] = 1.73 [1.30, 2.32]; p < 0.001), although the effects varied substantially by clinical backgrounds. The CAD was found to have high stand-alone diagnostic performances and may beneficially impact clinicians' diagnostic performances when used in clinical settings.
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http://dx.doi.org/10.1038/s41746-022-00658-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339006PMC
July 2022

Association between serum lipid profile and liver fibrosis in patients infected with Schistosoma japonicum.

Parasit Vectors 2022 Jul 29;15(1):268. Epub 2022 Jul 29.

Transplantation Center, Third Xiangya Hospital, Central South University, Changsha, China.

Background: Liver fibrosis is thought to have a close relationship with lipid profile. The possible association between lipids and liver fibrosis of different etiologies has been widely explored. However, the association between lipids and liver fibrosis in patients infected with Schistosoma japonicum remains unclear. In the present study we undertook a preliminary exploration of the association between lipid profile and liver fibrosis, and developed a new predictive index for liver fibrosis in S. japonicum-infected patients.

Methods: A total of 1503 patients diagnosed with S. japonicum at Xiangyue Hospital, China were enrolled in this retrospective study. The patients were divided into two groups, i.e., those with and those without liver fibrosis, by two experienced schistosomiasis specialists, according to the results of liver ultrasound examination. Demographic, clinical, and laboratory data were collected. Multivariable logistic models were used to estimate the independent associations between lipid profile and liver fibrosis. Receiver operating characteristic (ROC) curves were used to assess the discriminative ability of the new index in predicting liver fibrosis in patients with schistosomiasis.

Results: Logistic regression analysis showed that high-density lipoprotein (HDL) [adjusted odds ratio (aOR), 95% confidence interval (CI) 7.334, 5.051-10.649; P < 0.001], low-density lipoprotein (LDL) (aOR, 95% CI 0.434, 0.370-0.509; P < 0.001), hemoglobin (HB) (aOR, 95% CI 0.979, 0.971-0.987; P < 0.001) and platelets (PLT) (aOR, 95% CI 0.996, 0.994-0.999; P < 0.001) were independently associated with liver fibrosis in patients with schistosomiasis. ROC analysis indicated that the combination of HDL, LDL and HB levels [(HDL × 100)/(LDL × HB)] had a higher area under the ROC curve (AUC = 0.773), and thus may better predict liver fibrosis than the aspartate transaminase-to-platelet ratio index (AUC = 0.608) and fibrosis index based on four factors (AUC = 0.624).

Conclusions: To the best of our knowledge, this is the first study to report that HDL, LDL, HB and PLT levels are independently associated with liver fibrosis in patients with schistosomiasis. (HDL × 100)/(LDL × HB) outperformed the aspartate transaminase-to-platelet ratio index and fibrosis index based on four factors in terms of ROC, and thus could be a new predictive index for liver fibrosis. These findings may help clinicians to more easily and effectively diagnose liver fibrosis in patients with schistosomiasis.
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http://dx.doi.org/10.1186/s13071-022-05359-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9336000PMC
July 2022

Transition Metal (Co, Ni, Fe, Cu) Single-Atom Catalysts Anchored on 3D Nitrogen-Doped Porous Carbon Nanosheets as Efficient Oxygen Reduction Electrocatalysts for Zn-Air Battery.

Small 2022 Jul 29:e2202476. Epub 2022 Jul 29.

Sauvage Laboratory for Smart Materials, School of Materials Science and Engineering, Harbin Institute of Technology (Shenzhen), Shenzhen, 518055, P. R. China.

Exploring highly active and cost-efficient single-atom catalysts (SACs) for oxygen reduction reaction (ORR) is critical for the large-scale application of Zn-air battery. Herein, density functional theory (DFT) calculations predict that the intrinsic ORR activity of the active metal of SACs follows the trend of Co > Fe > Ni ≈ Cu, in which Co SACs possess the best ORR activity due to its optimized spin density. Guided by DFT calculations, four kinds of transition metal single atoms embedded in 3D porous nitrogen-doped carbon nanosheets ([email protected], M = Co, Ni, Fe, Cu) are synthesized via a facile NaCl-template assisted strategy. The resulting [email protected] displays ORR activity trend in lines with the theoretical predictions, and the Co [email protected] exhibits the best ORR activity (E  = 0.851 V), being comparable to that of Pt/C under alkaline conditions. X-ray absorption fine structure (XAFS) spectra verify the atomically dispersed Co-N sites are the catalytically active sites. The highly active CoN sites and the unique 3D porous structure contribute to the outstanding ORR performance of Co [email protected] Furthermore, the Co [email protected] catalyst is employed as cathode in Zn-air battery, which can deliver a large power density of 220 mW cm and maintain robust cycling stability over 530 cycles.
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http://dx.doi.org/10.1002/smll.202202476DOI Listing
July 2022

Correction to: Enhanced tryptophan-kynurenine metabolism via indoleamine 2,3-dioxygenase 1 induction in dermatomyositis.

Clin Rheumatol 2022 Jul 28. Epub 2022 Jul 28.

Department of Dermatology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Rui Jin 2nd Road, Shanghai, 200025, China.

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http://dx.doi.org/10.1007/s10067-022-06317-6DOI Listing
July 2022
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