Publications by authors named "Qian Xu"

1,495 Publications

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Decoding the dopamine transporter imaging for the differential diagnosis of parkinsonism using deep learning.

Eur J Nucl Med Mol Imaging 2022 May 19. Epub 2022 May 19.

Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern , Bern, Switzerland.

Purpose: This work attempts to decode the discriminative information in dopamine transporter (DAT) imaging using deep learning for the differential diagnosis of parkinsonism.

Methods: This study involved 1017 subjects who underwent DAT PET imaging ([C]CFT) including 43 healthy subjects and 974 parkinsonian patients with idiopathic Parkinson's disease (IPD), multiple system atrophy (MSA) or progressive supranuclear palsy (PSP). We developed a 3D deep convolutional neural network to learn distinguishable DAT features for the differential diagnosis of parkinsonism. A full-gradient saliency map approach was employed to investigate the functional basis related to the decision mechanism of the network. Furthermore, deep-learning-guided radiomics features and quantitative analysis were compared with their conventional counterparts to further interpret the performance of deep learning.

Results: The proposed network achieved area under the curve of 0.953 (sensitivity 87.7%, specificity 93.2%), 0.948 (sensitivity 93.7%, specificity 97.5%), and 0.900 (sensitivity 81.5%, specificity 93.7%) in the cross-validation, together with sensitivity of 90.7%, 84.1%, 78.6% and specificity of 88.4%, 97.5% 93.3% in the blind test for the differential diagnosis of IPD, MSA and PSP, respectively. The saliency map demonstrated the most contributed areas determining the diagnosis located at parkinsonism-related regions, e.g., putamen, caudate and midbrain. The deep-learning-guided binding ratios showed significant differences among IPD, MSA and PSP groups (P < 0.001), while the conventional putamen and caudate binding ratios had no significant difference between IPD and MSA (P = 0.24 and P = 0.30). Furthermore, compared to conventional radiomics features, there existed average above 78.1% more deep-learning-guided radiomics features that had significant differences among IPD, MSA and PSP.

Conclusion: This study suggested the developed deep neural network can decode in-depth information from DAT and showed potential to assist the differential diagnosis of parkinsonism. The functional regions supporting the diagnosis decision were generally consistent with known parkinsonian pathology but provided more specific guidance for feature selection and quantitative analysis.
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http://dx.doi.org/10.1007/s00259-022-05804-xDOI Listing
May 2022

Clinical Characteristics and Outcome Between Gallbladder Squamous Cell Carcinoma and Adenocarcinoma: A Propensity Matched Analysis Based on the Surveillance, Epidemiology, and End Results Database.

Front Oncol 2022 2;12:833447. Epub 2022 May 2.

Department of Abdominal Cancer, Cancer Center, West China Hospital of Sichuan University, Chengdu, China.

Background: Gallbladder squamous cell carcinoma (GSCC) is a rare carcinoma with limited evidence in literature, making it particularly difficult to study. Surveillance, Epidemiology, and End Results Database (SEER) were used to stress the clinicopathological features and outcomes associated with this tumor.

Methods: SEER registries were used to identify GSCC and gallbladder adenocarcinoma (GAC) cases from 2004 to 2015. The Propensity matching (PSM) method was used for minimized potential difference between the two types and the utmost. Patients with GSCC versus GAC were compared using the clinicopathological features and outcomes.

Results: There were 121 patients with GSCC and 6 580 patients had GAC. Compared with the GAC cohort, the GSCC cohort had a lower proportion of well-differentiated histology (3.3% vs. 12.1%, < 0.001) and was diagnosed at a later T-stage ( < 0.001). Regarding treatment, patients treated with surgery, chemotherapy or radiation were associated with significantly better outcome than patients without undergoing these treatment modalities. In both univariate and multivariate analyses, GSCC histology was associated with worse prognosis than GAC histology.

Conclusions: Patients with GSCC were associated with a worse outcome than the GAC cohort. The independent risk factors for patients with GSCC are surgery and chemotherapy.
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http://dx.doi.org/10.3389/fonc.2022.833447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108327PMC
May 2022

Fighting misinformation on social media: effects of evidence type and presentation mode.

Health Educ Res 2022 May 18. Epub 2022 May 18.

Department of Strategic Communications, School of Communications, School of Communications, Elon University, 2850 Campus Box, Elon, NC 27244, USA.

Designing corrective messages to debunk misinformation online is an important practice toward ending the coronavirus disease (COVID-19) pandemic as health-related misinformation has proliferated on social media misguiding disease prevention measures. Despite research on the use of statistical evidence and message modality in persuasion, the effects of evidence type (assertions with versus without statistical evidence) and presentation mode (text-only versus image-only versus text-plus-image) have been understudied. This study examined the impact of evidence type and presentation mode on individuals' responses to corrective messages about COVID-19 on social media. The results showed that the presence of statistical evidence in assertions reduced message elaboration, which in turn reduced the effects of the message in correcting misperceptions, decreased perceived message believability and lowered social media users' intentions to further engage with and disseminate the corrective message. Compared to the text-only modality and the text-plus-image modality, the image-only modality triggered significantly lower levels of message elaboration, which subsequently heightened message believability and increased user engagement intentions. The theoretical and practical implications are discussed.
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http://dx.doi.org/10.1093/her/cyac011DOI Listing
May 2022

Electrospun chitosan/polyethylene oxide nanofibers mat loaded with copper (II) as a new sensor for colorimetric detection of tetracycline.

Int J Biol Macromol 2022 May 14. Epub 2022 May 14.

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China. Electronic address:

Using electrospun chitosan/polyethylene oxide nanofibers mat (CS/PEO NFM) as carrier, [email protected]/PEO NFM, a new tetracycline (TC) solid-state colorimetric sensor, were simply prepared by directly immobilizing Cu on surface of CS/PEO NFM. After immersing in TC solutions, [email protected]/PEO NFM can display visible color changes to the naked eye within 5.0 min, and the TC concentration-dependent color changes can also be quantitatively analyzed with a smartphone. Because Cu can enhance the adsorption of CS/PEO NFM for TC, [email protected]/PEO NFM possess a more sensitive response ability to TC, ensuring that the colorimetric sensing detection will not be interfered by other coexisting drugs. Due to the reversible combination of chitosan and Cu, the colorimetric sensing ability of [email protected]/PEO NFM can be regenerated even after being reused at least 4 times. In addition, the naked eye detection limit of [email protected]/PEO NFM-based colorimetric sensing is 65 μg kg, which does not exceed the maximum residue limit in milk samples set by China (100 μg kg). The obtained results fully indicated the practical application value of this method in preventing the hazard of TC residues.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.05.100DOI Listing
May 2022

The bacterial effector AvrRxo1 inhibits vitamin B6 biosynthesis to promote infection in rice.

Plant Commun 2022 May 14;3(3):100324. Epub 2022 Apr 14.

State Key Laboratory of Crop Biology, Shandong Provincial Key Laboratory for Biology of Vegetable Diseases and Insect Pests, College of Plant Protection, Shandong Agricultural University, Tai an, 271018 Shandong, PR China. Electronic address:

Xanthomonas oryzae pv. oryzicola (Xoc), which causes rice bacterial leaf streak, invades leaves mainly through stomata, which are often closed as a plant immune response against pathogen invasion. How Xoc overcomes stomatal immunity is unclear. Here, we show that the effector protein AvrRxo1, an ATP-dependent protease, enhances Xoc virulence and inhibits stomatal immunity by targeting and degrading rice OsPDX1 (pyridoxal phosphate synthase), thereby reducing vitamin B6 (VB6) levels in rice. VB6 is required for the activity of aldehyde oxidase, which catalyzes the last step of abscisic acid (ABA) biosynthesis, and ABA positively regulates rice stomatal immunity against Xoc. Thus, we provide evidence supporting a model in which a major bacterial pathogen inhibits plant stomatal immunity by directly targeting VB6 biosynthesis and consequently inhibiting the biosynthesis of ABA in guard cells to open stomata. Moreover, AvrRxo1-mediated VB6 targeting also explains the poor nutritional quality, including low VB6 levels, of Xoc-infected rice grains.
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http://dx.doi.org/10.1016/j.xplc.2022.100324DOI Listing
May 2022

Nano-Graphene Layer from Facile, Scalable and Eco-Friendly Liquid Phase Exfoliation Strategy as Effective Barrier Layer for High-Performance and Durable Direct Liquid Alcohol Fuel Cells.

Molecules 2022 May 9;27(9). Epub 2022 May 9.

Institute for Energy Research, Jiangsu University, Zhenjiang 212013, China.

Graphene, in spite of exceptional physio-chemical properties, still faces great limitations in its use and industrial scale-up as highly selective membranes (enhanced ratio of proton conductivity to fuel cross-over) in liquid alcohol fuel cells (LAFCs), due to complexity and high cost of prevailing production methods. To resolve these issues, a facile, low-cost and eco-friendly approach of liquid phase exfoliation (bath sonication) of graphite to obtain graphene and spray depositing the prepared graphene flakes, above anode catalyst layer (near the membrane in the membrane electrode assembly (MEA)) as barrier layer at different weight percentages relative to the base membrane Nafion 115 was utilized in this work. The 5 wt.% nano-graphene layer raises 1 M methanol/oxygen fuel cell power density by 38% to 91 mW·cm, compared to standard membrane electrode assembly (MEA) performance of 63 mW·cm, owing to less methanol crossover with mild decrease in proton conductivity, showing negligible voltage decays over 20 h of operation at 50 mA·cm. Overall, this work opens three prominent favorable prospects: exploring the usage of nano-materials prepared by liquid phase exfoliation approach, their effective usage in ion-transport membrane region of MEA and enhancing fuel cell power performance.
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http://dx.doi.org/10.3390/molecules27093044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100842PMC
May 2022

Case Report: Passive Handstand Promotes Cerebrovascular Elasticity Training and Helps Delay the Signs of Aging: A 40-Year Follow-Up Investigation.

Front Med (Lausanne) 2022 26;9:752076. Epub 2022 Apr 26.

Department of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.

Background: There are no long-term (>10 years) follow-up evaluations of the effects of handstand exercise or studies on the use of equipment for passive handstand exercise.

Objective: To report a 40-year follow-up investigation of a Chinese man who has been practicing passive handstand for 40 years.

Design: This observational investigation was conducted in Guizhou Province, China.

Participant: A (currently) 66-year-old Chinese man who had been practicing passive handstand exercise for 40 years was followed up.

Interventions: Physical and auxiliary examinations were carried out to determine the effects of long-term passive handstand exercise on the human body.

Main Measures: The participant's cerebrovascular, spinal health, mental health, and visual acuity as well as the presence of facial aging were examined.

Key Results: His cerebral vessels were healthy, he appeared younger than his peers, his cervical spondylosis improved, and his mental state and cognitive function were good.

Conclusion: Long-term passive handstand exercise can promote cerebrovascular elasticity training and delay signs of aging. We recommend promoting this passive handstand exercise to the public.
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http://dx.doi.org/10.3389/fmed.2022.752076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086612PMC
April 2022

Editorial: Genetic Pleiotropy in Complex Traits and Diseases.

Front Genet 2022 25;13:897383. Epub 2022 Apr 25.

Department of Epidemiology and Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, China.

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http://dx.doi.org/10.3389/fgene.2022.897383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081568PMC
April 2022

Engineering Aptamers with Selectively Enhanced Biostability in the Tumor Microenvironment.

Angew Chem Int Ed Engl 2022 May 10. Epub 2022 May 10.

Hunan University, College of Chemistry and Chemical Engineering, Department of Chemistry, 208 Yifu building, 410082, Changsha, CHINA.

Aptamers are emerging as promising molecular tools in cancer-targeted theranostics. Improving their in vivo stability has been a critical issue in promoting the clinical translation, but such efforts could lead to more serious side effects resulting from prolonged retention in normal organs. To address this problem, we developed an environment-responsive stabilization strategy for selective enhancement of aptamer biostability in the tumor microenvironment (TME). Briefly, with the end extension of an ATP Responsive Protection (ARP) module, the designed aptamer could be protected from nuclease degradation through the specific incorporation of ATP. Based on our in vivo results, this ARP-aptamer probe could be effectively accumulated in tumor via aptamer-based molecular recognition. It showed selectively prolonged tumor retention time, but rapid digestion in normal organs. Our strategy was expected to provide a new paradigm for the development of organ-specific nucleic acid-based imaging and therapeutic agents.
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http://dx.doi.org/10.1002/anie.202201220DOI Listing
May 2022

Eye gaze direction modulates nonconscious affective contextual effect.

Conscious Cogn 2022 May 5;102:103336. Epub 2022 May 5.

State Key Laboratory of Brain and Cognitive Sciences, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China; Chinese Institute for Brain Research, Beijing 102206, China.

Facial emotion recognition is inherently contextualized and may automatically incorporate affective information from the context. Here we investigate whether this affective contextual effect is modulated by a prominent social cue, namely, the gaze direction of the contextualized emotional face. We demonstrate that the perceived emotional expression of a visible target face is biased toward the emotion of an invisible contextual face, with this nonconscious affective contextual modulation dependent on the gaze direction of the target face. In particular, a target face gazing toward a contextual face induced a larger affective contextual effect than a face gazing away. Furthermore, this gaze modulation effect specifically occurred for invisible fearful contexts and hinged on individual trait anxiety levels. These findings show that social information delivered by gaze cues can modulate the fear-specific affective contextual effect without awareness, shedding new light on how compound socio-affective signals are automatically integrated into our perception of others' emotions.
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http://dx.doi.org/10.1016/j.concog.2022.103336DOI Listing
May 2022

Carcinoma-associated fibroblasts release microRNA-331-3p containing extracellular vesicles to exacerbate the development of pancreatic cancer the SCARA5-FAK axis.

Cancer Biol Ther 2022 Dec;23(1):378-392

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.

microRNA-331-3p (miR-331-3p) has been displayed as an oncogene in pancreatic cancer (PC). The current research set out to elucidate how miR-331-3p in carcinoma-associated fibroblasts (CAFs)-derived extracellular vesicles (EVs) facilitated the tumorigenesis in PC. First, a dual-luciferase reporter assay was adopted to investigate the relationship between miR-331-3p and SCARA5. In addition, EVs were isolated normal fibroblasts and CAFs, and these isolated EVs were co-cultured with PC cells. Cell proliferative and migrating/invasive potentials were further evaluated with the help of a CCK-8 and Transwell assays, respectively. Gain- and loss-of-function assays were also implemented to assess the role of miR-331-3p, SCARA5, and FAK pathway in PC cells. Lastly, xenograft nude mice were established to investigate the role of miR-331-3p . miR-331-3p negatively targeted SCARA5 and was highly expressed in CAFs-derived EVs, which accelerated the proliferative, migrating, and invasive potentials of PC cells. Meanwhile, over-expression of miR-331-3p enhanced the proliferative, migrating, and invasive properties of PC cells and promoted tumor growth by manipulating SCARA5/FAK axis, whereas SCARA5 countered the oncogenic effects of miR-331-3p. Overall, miR-331-3p in CAFs-derived EVs inhibits SCARA5 expression and activates the FAK pathway, thereby augmenting the progression of PC. Our study provides a potential therapeutic target for the treatment of PC.
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http://dx.doi.org/10.1080/15384047.2022.2041961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9090287PMC
December 2022

scTenifoldKnk: An efficient virtual knockout tool for gene function predictions via single-cell gene regulatory network perturbation.

Patterns (N Y) 2022 Mar 1;3(3):100434. Epub 2022 Feb 1.

Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA.

Gene knockout (KO) experiments are a proven, powerful approach for studying gene function. However, systematic KO experiments targeting a large number of genes are usually prohibitive due to the limit of experimental and animal resources. Here, we present scTenifoldKnk, an efficient virtual KO tool that enables systematic KO investigation of gene function using data from single-cell RNA sequencing (scRNA-seq). In scTenifoldKnk analysis, a gene regulatory network (GRN) is first constructed from scRNA-seq data of wild-type samples, and a target gene is then virtually deleted from the constructed GRN. Manifold alignment is used to align the resulting reduced GRN to the original GRN to identify differentially regulated genes, which are used to infer target gene functions in analyzed cells. We demonstrate that the scTenifoldKnk-based virtual KO analysis recapitulates the main findings of real-animal KO experiments and recovers the expected functions of genes in relevant cell types.
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http://dx.doi.org/10.1016/j.patter.2022.100434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9058914PMC
March 2022

The Chinese Parkinson's Disease Registry (CPDR): Study Design and Baseline Patient Characteristics.

Mov Disord 2022 May 3. Epub 2022 May 3.

Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.

Background: There is a lack of large multicenter Parkinson's disease (PD) cohort studies and limited data on the natural history of PD in China.

Objectives: The objective of this study was to launch the Chinese Parkinson's Disease Registry (CPDR) and to report its protocol, cross-sectional baseline data, and prospects for a comprehensive observational, longitudinal, multicenter study.

Methods: The CPDR recruited PD patients from 19 clinical sites across China between January 2018 and December 2020. Clinical data were collected prospectively using at least 17 core assessment scales. Patients were followed up for clinical outcomes through face-to-face interviews biennially.

Results: We launched the CPDR in China based on the Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network (PD-MDCNC). A total of 3148 PD patients were enrolled comprising 1623 men (51.6%) and 1525 women (48.4%). The proportions of early-onset PD (EOPD, age at onset ≤50 years) and late-onset PD (LOPD) were 897 (28.5%) and 2251 (71.5%), respectively. Stratification by age at onset showed that EOPD manifested milder motor and nonmotor phenotypes and was related to increased probability of dyskinesia. Comparison across genders suggested a slightly older average age at PD onset, milder motor symptoms, and a higher rate of developing levodopa-induced dyskinesias in women.

Conclusions: The CPDR is one of the largest multicenter, observational, longitudinal, and natural history studies of PD in China. It offers an opportunity to expand the understanding of clinical features, genetic, imaging, and biological markers of PD progression. © 2022 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.29037DOI Listing
May 2022

Attenuation of ROS/Chloride Efflux-Mediated NLRP3 Inflammasome Activation Contributes to Alleviation of Diabetic Cardiomyopathy in Rats after Sleeve Gastrectomy.

Oxid Med Cell Longev 2022 19;2022:4608914. Epub 2022 Apr 19.

Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250014, China.

Diabetic cardiomyopathy (DCM) can develop in diabetes mellitus and is a major cause of morbidity and mortality. Surgical bariatric surgery procedures, such as sleeve gastrectomy (SG), result in remission of type 2 diabetes and have benefits regarding systolic and diastolic myocardial function. The NLR family pyrin domain containing 3 (NLRP3) inflammasome appears to participate in the development of DCM. However, whether SG surgery affects myocardial NLRP3 inflammasome-related pyroptosis to improve cardiac function remains unclear. This study was aimed at investigating the effect of SG surgery on NLRP3-associated pyroptosis in rats with DCM. We also examined cellular phenotypes and molecular mechanisms in high glucose-stimulated myocytes. The rat model of DCM was established by high-fat diet feeding and low-dose streptozotocin injection. We observed a metabolic benefit of SG, including a reduced body weight, food intake, and blood glucose levels and restored glucose tolerance and insulin sensitivity postoperatively. We observed a marked decline in glucose uptake in rats with DCM, and this was restored after SG. Also, SG alleviated the dysfunction of myocardial contraction and diastole, delayed the progression of DCM, and reduced the NLRP3 inflammasome-mediated myocardial pyroptosis . H9c2 cardiomyocytes showed membrane disruption and DNA damage under a high glucose stimulus, which suggested myocardial pyroptosis. Using a ROS scavenger or chloride channel blocker restored myocardial NLRP3-mediated pyroptosis. Furthermore, we found that chloride efflux acted downstream of ROS generation. In conclusion, SG may ameliorate or even reverse the progression of DCM. Our study provides evidence that the SG operation alleviates NLRP3 inflammasome dysregulation in DCM. Clearance of ROS overburden and suppression of chloride efflux due to SG might act as the proximal event before inhibition of NLRP3 inflammasome in the myocardium, thus contributing to morphological and functional alleviation of DCM.
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http://dx.doi.org/10.1155/2022/4608914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9042617PMC
May 2022

Fabrication of polyoxometalate-modified palladium-nickel/reduced graphene oxide alloy catalysts for enhanced oxygen reduction reaction activity.

RSC Adv 2021 Dec 7;11(62):39118-39129. Epub 2021 Dec 7.

Institute for Energy Research, Jiangsu University Zhenjiang 212013 China

Designing advanced nanocatalysts for effectively catalyzing the oxygen reduction reaction (ORR) is of great importance for practical applications of direct methanol fuel cells (DMFCs). In this work, the reduced graphene oxide (rGO)-supported palladium-nickel (Pd-Ni/rGO) alloy modified by the novel polyoxometalate (POM) with Keggin structure (Pd-Ni/rGO-POM) is efficiently fabricated an impregnation technique. The physical characterizations such as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, inductively coupled plasma optical emission spectroscopy (ICP-OES), field emission scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (FESEM-EDX), and transmission electron microscopy (TEM) are utilized to confirm the structure, morphology, and chemical composition of the fabricated samples. The XRD results verify the formation of the POM-modified PdNi/rGO alloy electro-catalyst with the face-centered-cubic (fcc) structure and average crystallite size of 5.54 nm. The electro-catalytic activities of the nanocatalysts towards ORR in alkaline conditions are evaluated by cyclic voltammetry (CV), rotating disk electrode (RDE), and chronoamperometry (CA) analyses. The synthesized PdNi/rGO-POM nanomaterial shows remarkably greater ORR catalytic activity and better methanol resistance compared with the PdNi/rGO and Pd/rGO electro-catalysts. The promoted ORR activity of the PdNi/rGO-POM sample is attributed to the alloying of Pd and Ni components, the uniform scattering of Pd-Ni nanoparticles on rGO, and the alloyed catalyst being modified with POM. Moreover, these findings demonstrate that the resultant PdNi/rGO-POM material is attractive as a suitable and cost-effective cathodic catalyst for DMFCs, in which the decorated POMs play a vital role for the enhancement in the catalytic abilities of the nanocatalyst.
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http://dx.doi.org/10.1039/d1ra06936eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9044417PMC
December 2021

Development of novel androgen receptor antagonists based on the structure of darolutamide.

Bioorg Chem 2022 Apr 26;124:105829. Epub 2022 Apr 26.

Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Department of Chemistry, Zhejiang Normal University, 688 Yingbin Road, Jinhua 321004, China. Electronic address:

Androgen signaling pathway plays an important role in the occurrence and development of prostate cancer (PCa), and anti-androgen drugs are one of the most effective therapies for PCa. Darolutamide 4 (ODM-201) is a promising second- generation antiandrogen because of its unique chemical structure and good activity against androgen receptor (AR). Herein, the structure-activity relationship of ODM-201 was studied, and 37 analogues were synthesized. Half of them exhibited similar or better anti-AR transcriptional activity compared to ODM-201. In addition, the inhibitory activity of compound 28t against the two resistant mutants (AR-F876L and AR-T877A) was superior to that of ODM-201. This study provides a new clue for the further optimization of ODM-201 and the development of anti-CRPC drugs.
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http://dx.doi.org/10.1016/j.bioorg.2022.105829DOI Listing
April 2022

Effects of different light intensities on the transcriptome changes of duck retina and pineal gland.

Poult Sci 2022 Mar 12;101(6):101819. Epub 2022 Mar 12.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 613000, China. Electronic address:

The light intensity can affect the production performance of animals. The retina and pineal gland, closely linked, are directly photosensitive organs. This study evaluated the effect of light intensity on duck growth and investigated the effects of varying light intensities on retina and pineal gland transcriptome changes. The increase of light intensity will significantly decrease production performance, such as body weight, eviscerated weight, breast muscle weight, percentage of abdominal fat, etc. The RNA-seq revealed 967 and 201 differentially expressed genes (DEGs) in the retina and pineal gland under different light intensities, respectively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) in the retina showed the DEGs were enriched in ECM-receptor interaction, Focal adhesion, Cell adhesion molecules (CAMs), Cytokine-cytokine receptor interaction, Melanogenesis, etc. Meanwhile, the DEGs in the pineal gland were mainly enriched in pathways associated with the mTOR signaling pathway, melanin production pathway, etc. Our results indicated that different light intensities might affect the function of the retina and pineal gland, including the melanin production of the retina and the secretion of melatonin in the pineal gland. Our study can provide a theoretical basis for the molecular mechanism of the effects of different light intensities on the retina and pineal gland.
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http://dx.doi.org/10.1016/j.psj.2022.101819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065719PMC
March 2022

PSEN1 G417S mutation in a Chinese pedigree causing early-onset parkinsonism with cognitive impairment.

Neurobiol Aging 2022 Apr 11;115:70-76. Epub 2022 Apr 11.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address:

Presenilin 1 (PSEN1) mutations are a major cause of familial Alzheimer's disease. The pathogenic variant, PSEN1 p.G417S, has been reported to be associated with spastic paraparesis and cotton wool plaques in Japan. Here, we report a 3 generation Chinese pedigree that included 10 patients presenting with early-onset and rapid progression of parkinsonism with cognitive impairment in their third or fourth decade of life. Three additional living patients developed different degrees of cognitive impairment, without movement disorders. Magnetic resonance imaging of the brain showed white matter hyperintensities, multiple microbleeds, and enlarged perivascular spaces. Whole exome sequencing analysis of the proband detected the mutation, p.G417S, in PSEN1, which was completely co-segregated with the disease phenotype within the family by Sanger sequencing. 3D protein structures predicted that the mutation might influence contact with the lipid membrane and the interaction with beta-catenin. Our study provides insights into the heterogeneity in clinical presentation and imaging associated with mutations in PSEN1.
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http://dx.doi.org/10.1016/j.neurobiolaging.2022.03.016DOI Listing
April 2022

[Study on the central mechanism of acupuncture for post-stroke spasticity based on the Na/K-ATPase-EAATs-Glu pathway].

Zhen Ci Yan Jiu 2022 Apr;47(4):283-9

School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing 100029, China.

Objective: To observe the effect of acupuncture at "Yanglingquan" (GB34) and "Baihui" (GV20) on Na/K-ATPase, excitatory amino acid transporters (EAATs) and glutamate (Glu) in hippocampus of post-stroke spasticity rats, so as to explore the central mechanism in anti-spasticity.

Methods: In a total of 48 healthy SD rats, 12 rats were randomly selected to be included into sham operation group, and the remaining rats were used to make a middle cerebral artery occlusion (MCAO) model using a suture method. On the 3rd day after modeling, MCAO limb spasticity rats were screened by neurological deficit symptoms and muscle tension scores, and randomly divided into the model, GB34 (Hui-puncture at GB34) and GB34+GV20 (Hui-puncture at GB34 and horizontal insertion at GV20) groups (=12 rats in each group), and the treatment was lasted for 7 conse-cutive days. The neurological symptoms and muscle tension score were observed with the Zea Longa score and modified Ashworth scale (MAS). The levels of Glu, EAAT1 (GLAST) and EAAT2 (GLT-1) in the ischemic area of cerebral hippocampus were detected by ELISA, the expression of Na/K-ATPase α1 (ATP1α1) was detected by Western blot, the expression of ATP1α1 mRNA was detected by real-time PCR, and the expression of GLAST, GLT-1 and ATP1α1 was detected by immunofluorescence.

Results: After modeling, Zea Longa score and MAS score were increased (<0.01), the level of Glu in the ischemic area of cerebral hippocampus was increased (<0.01), while the expression levels of GLAST, GLT-1, ATP1α1 protein and mRNA were all decreased (<0.01) in the model group relevant to the sham operation group. After 7 days' treatment, all the increased and decreased levels of the indexes mentioned above were reversed in the two acupuncture groups relevant to the model group (<0.01, <0.05), and the effects of acupuncture at GB34+GV20 were obviously superior to that of acupuncture at GB34 (<0.05, <0.01).

Conclusion: Acupuncture can alleviate post-stroke spasticity effectively, which may be related to its effect in up-regulating the expressions of Na/K-ATPase and EAATs in hippocampus. The anti-spastic effect of acupuncture at GB34+GV20 is superior to GB34 alone.
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http://dx.doi.org/10.13702/j.1000-0607.20210922DOI Listing
April 2022

Nano-porous Al/Au skeleton to support MnO with enhanced performance and electrodeposition adhesion for flexible supercapacitors.

RSC Adv 2021 Jun 24;11(35):21405-21413. Epub 2021 Jun 24.

School of Materials Science and Engineering, South China University of Technology Guangzhou 510641 China

A nano-porous Al/Au skeleton is constructed to effectively improve the utilization rate of the active MnO and the overall adhesion between the current collector and MnO in an electrodeposition system. The Al/Au current collector is prepared by first forming a nano-porous structure on the surface of Al foil through etching modification, and subsequently coating an ultra-thin Au layer onto the Al foil. The active MnO is electrodeposited on the Al/Au current collector to fabricate a novel Al/Au/MnO electrode. The nano-porous skeleton supports MnO to grow autonomously inside-out. The ultra-thin Au layer acts as a transition layer to improve the overall conductivity of the current collector (0.35 Ω m) and to improve the adhesion with MnO as well. Owing to the highly porous structure, the electrochemical properties of the electrode are greatly improved, as evidenced by a remarkable specific capacitance of 222.13 mF cm at 0.2 mA cm and excellent rate capability of 63% capacitance retention at 6.0 mA cm. Furthermore, the assembled solid-state symmetric supercapacitor exhibits a high energy density of 0.68 mW h cm, excellent cyclic stability (86.3% capacitance retention after 2000 cycles), and prominent flexibility.
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http://dx.doi.org/10.1039/d1ra01923fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9034163PMC
June 2021

Mussel-inspired bioactive 3D-printable poly(styrene-butadiene-styrene) and the assessment of its potential as cranioplasty implants.

J Mater Chem B 2022 May 18;10(19):3747-3758. Epub 2022 May 18.

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, P. R. China.

Challenges in cranial defect reconstruction after craniotomy arise from insufficient osteogenesis and biofilm infection, which requires novel biomaterials. Herein, we propose a mussel-inspired bioactive poly(styrene-butadiene-styrene) (SBS) as a promising cranioplasty material. The catechol-modified quaternized chitosan (QCSC) was employed in the bio-inert surface of 3D-printed SBS to provide the contact-killing ability against bacterial biofilms. The polydopamine-decorated zeolitic imidazolate framework-8 (pZIF-8) and polydopamine hybrid hydroxyapatite (pHA) were further modified on the surface to further enhance the antibacterial property and osteogenesis activity, effectively killing bacteria by no less than two orders of magnitude and significantly facilitating osteogenic gene expression and mineralization. Due to the lack of research using SBS as a cranioplasty material, we believe that the modified SBS materials developed in this study and the assessment may be beneficial for developing novel cranioplasty implants.
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http://dx.doi.org/10.1039/d2tb00419dDOI Listing
May 2022

Association Study of Variants in Parkinson's Disease.

Front Neurosci 2022 8;16:846095. Epub 2022 Apr 8.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.

Increasing evidence reveals sex as an important factor in the development of Parkinson's disease (PD), but associations between genes on the sex chromosomes and PD remain unknown. is a gene located on the X chromosome which is known to cause X-linked syndromic mental retardation-33 (MRXS33) and X-linked Dystonia-Parkinsonism (XDP). In this study, we conducted whole-exome sequencing (WES) among 1,917 patients with early-onset or familial PD and 1,652 controls in a Chinese population. We detected a hemizygous frameshift variant c.29_53dupGGA(CAG)CTACCATCA(CTG)C (p.A19Dfs*50) in two unrelated male patients. Further segregation analysis showed an unaffected family member carried this variant, which suggested the penetrance of the variant may be age-related and incomplete. To verify the effects of on PD, genetic analyses were carried separately by gender. Analysis of rare variants by optimal sequence kernel association (SKAT-O) test showed a nominally significant difference in variant burden between the male PD patients and controls (2.01 vs. 1.38%, = 0.027). In the female group, none of the variant types showed significant association with PD in this study. In conclusion, we found rare variants in may be implicated in PD, but further genetic and functional analyses were needed.
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http://dx.doi.org/10.3389/fnins.2022.846095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024305PMC
April 2022

Establishment and Validation of a Non-invasive Diagnostic Nomogram to Identify Heart Failure in Patients With Coronary Heart Disease.

Front Cardiovasc Med 2022 7;9:875702. Epub 2022 Apr 7.

College of Medical Informatics, Chongqing Medical University, Chongqing, China.

Background: Heart failure (HF) is an end-stage manifestation of and cause of death in coronary heart disease (CHD). The objective of this study was to establish and validate a non-invasive diagnostic nomogram to identify HF in patients with CHD.

Methods: We retrospectively analyzed the clinical data of 44,772 CHD patients from five tertiary hospitals. Univariate logistic regression analyses and least absolute shrinkage and selection operator (LASSO) regression analyses were used to identify independent factors. A nomogram based on the multivariate logistic regression model was constructed using these independent factors. The concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC) were used to evaluate the predictive accuracy and clinical value of this nomogram.

Results: The predictive factors in the multivariate model included hypertension, age, and the total bilirubin, uric acid, urea nitrogen, triglyceride, and total cholesterol levels. The area under the curve (AUC) values of the nomogram in the training set, internal validation set, external validation set1, and external validation set2 were 0.720 (95% CI: 0.712-0.727), 0.723 (95% CI: 0.712-0.735), 0.692 (95% CI: 0.674-0.710), and 0.655 (95% CI: 0.634-0.677), respectively. The calibration curves indicated that the nomogram had strong calibration. DCA and CIC indicated that the nomogram can be used as an effective tool in clinical practice.

Conclusion: The developed predictive model combines the clinical and laboratory factors of patients with CHD and is useful in individualized prediction of HF probability for clinical decision-making during treatment and management.
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http://dx.doi.org/10.3389/fcvm.2022.875702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021443PMC
April 2022

Immune checkpoint inhibitor-associated ophthalmic adverse events: current understanding of its mechanisms, diagnosis, and management.

Int J Ophthalmol 2022 18;15(4):646-656. Epub 2022 Apr 18.

Department of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.

Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1 receptor/ligand have revolutionized cancer treatment, achieving unprecedented efficacy in numerous malignancies. Despite the excellent therapeutic effects of ICIs, medications, such as pembrolizumab, ipilimumab, nivolumab, atezolizumab, avelumab, and durvalumab, typically cause a broad spectrum of toxicity events termed as immune-related adverse events (irAEs). Out of all irAEs, ophthalmic adverse events occur infrequently and are not comprehensively recognized. The current understanding of ophthalmic irAEs is mainly derived from case reports and case series. In this review, based on relevant articles in the literature and current evidence, we summarize the incidences, manifestations, diagnoses, underlying mechanisms, treatments, and outcomes of ophthalmic irAEs and discuss possible management strategies. A better understanding of these features is critical for managing patients with ICI-associated ophthalmic adverse events.
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http://dx.doi.org/10.18240/ijo.2022.04.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8995716PMC
April 2022

What Is Long-Term Survival and Which First-Line Immunotherapy Brings Long-Term Survival for Advanced Wild-Type Non-Small Cell Lung Cancer: A Network Meta-Analysis Based on Integrated Analysis.

Front Immunol 2022 5;13:764643. Epub 2022 Apr 5.

Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Immune checkpoint inhibitors (ICIs) have significantly improved survival for advanced wild-type non-small cell lung cancer, but there is no direct comparison to confirm which first-line treatment may lead to the longest overall survival. What qualifies as long-term survival (LS) is even unclear.

Methods: By searching PubMed, Embase, and the Cochrane Central Register of Controlled Trials from January 2005 to December 2020, we included randomized controlled trials (RCTs) of first-line ICI-containing treatments to perform an integrated analysis (IA) to determine the criterion of LS and then screened regimens with LS for network meta-analysis (NMA). The main outcomes for NMA were median overall survival (mOS), 1-year survival rate (1ySR), and 2-year survival rate (2ySR); those for IA were the pooled mOS (POS), 1ySR (P1SR), and 2ySR (P2SR).

Results: By IA of 16 first-line ICIs from 20 RCTs, the POS was 16.20 (95% CI 14.79-17.60) months, with P1SR of 63% (95% CI 59-66%) and P2SR of 37% (33-41%). Thus, we defined LS as mOS ≥ POS (16.20 m) for regimens and screened for RCTs with outcomes meeting this criterion. Eleven ICI-based regimens can bring LS for the overall population, among which ICI with bevacizumab and chemotherapy achieved the longest POS of 19.50 m (16.90-22.10 m) and the highest P1SR (74%, 61%-87%) and P2SR (49%, 38%-61%). Pembrolizumab with chemotherapy ranked first in mOS and 1ySR, while atezolizumab plus bevacizumab and chemotherapy ranked first in 2ySR.

Conclusions: Through the IA of first-line treatment regimens, a POS of 16.20 m can be determined as the LS standard. Further considering 1ySR and 2ySR, atezolizumab combined with bevacizumab and chemotherapy or pembrolizumab plus chemotherapy are likely to bring the longest LS in the overall population, while single ICI may be adequate for patients with a high PD-L1 expression. ICIs with bevacizumab and chemotherapy may be the best combination for LS for its further advantage over time.
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http://dx.doi.org/10.3389/fimmu.2022.764643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016897PMC
April 2022

The association between LIN28A gene rare variants and Parkinson's disease in Chinese population.

Gene 2022 Jun 18;829:146515. Epub 2022 Apr 18.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China; Centre for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China; Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China. Electronic address:

Parkinson's disease (PD) is a neurodegenerative disease caused by aging, environmental and genetic factors, and many susceptibility genes have been found to increase the risk for PD. Lin28a, an RNA binding protein, is expressed prominently in neural progenitor cells. The expression of Lin28a is decreased gradually with neural differentiation and is implicated in oncogenesis, glucose metabolism, neurogenesis, and neurogliogenesis. However, few genetic studies have explored the association between rare variants of the LIN28A gene and PD yet. Our study recruited 3,879 PD patients and 2,931 controls, and they were divided into two cohorts, including the EOPD & FPD cohort and the LOPD cohort, separately sequenced by whole-exome sequencing and whole-genome sequencing. We found nine rare nonsynonymous variants in the coding region of the LIN28A gene, but the rare variants of this gene were not enriched in PD patients in both cohorts. Thence, our study did not support the association between the LIN28A gene and the PD risk in the Chinese mainland population.
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http://dx.doi.org/10.1016/j.gene.2022.146515DOI Listing
June 2022

The burden of aortic aneurysm in China from 1990 to 2019: findings from the Global Burden of Disease Study 2019.

BMC Public Health 2022 04 18;22(1):782. Epub 2022 Apr 18.

Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China, 410008.

Background: Aortic aneurysm (AA) is a global public health concern. However, little is known about the disease burden of AA in China.

Methods: Following the general analytic strategy used in the Global Burden of Disease Study (GBD) 2019, we analyzed the mortality and years of life lost (YLLs) due to AA, stratified by sex, age, and province-level region in China from 1990 to 2019. The temporal trend of AA burden in China was analyzed and the main attributable risk factors for AA in China were also explored.

Results: In China, the total AA deaths were 17,038 (95% UI: 14,392-19,980) in 2019, an increase of 136.1% compared with that in 1990, with an age-standardized death rate (ASDR) of 0.93 (95% UI: 0.79-1.08) per 100,000 person-years in 2019, a decrease of 6.8%. Meanwhile AA caused 378,578 (95% UI: 315,980-450,479) YLLs in 2019, an increase of 102.6% compared with that in 1990, with a crude YLL rate of 26.6 (95% UI: 22.2-31.7) per 100,000 person-years, an increase of 68.6%. The AA mortality and YLLs were higher in males than in females. AA caused most YLLs in the 65- to 75-year-old age group. The AA mortality and YLLs varied significantly among provinces in China, and the change in ASDR showed a negative correlation with the sociodemographic index of different provinces, namely, more decline of ASDR in developed provinces. High systolic blood pressure was shown to be the most significant attributable risk factor for AA burden in both males and females, and smoking was another major attributable risk factor, especially in males.

Conclusions: The disease burden of AA increased significantly from 1990 to 2019 in China, with higher mortality and YLLs in males, senior populations, and among residents of most western provinces in China. High systolic blood pressure and smoking were two major attributable risk factors for AA mortality in China.
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http://dx.doi.org/10.1186/s12889-022-13221-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016999PMC
April 2022

APOLLO: An accurate and independently validated prediction model of lower-grade gliomas overall survival and a comparative study of model performance.

EBioMedicine 2022 May 15;79:104007. Epub 2022 Apr 15.

Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China, 211166; China International Cooperation Center for Environment and Human Health, Nanjing Medical University, Nanjing, China, 211166; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, China, 211166. Electronic address:

Background: Virtually few accurate and robust prediction models of lower-grade gliomas (LGG) survival exist that may aid physicians in making clinical decisions. We aimed to develop a prognostic prediction model of LGG by incorporating demographic, clinical and transcriptional biomarkers with either main effects or gene-gene interactions.

Methods: Based on gene expression profiles of 1,420 LGG patients from six independent cohorts comprising both European and Asian populations, we proposed a 3-D analysis strategy to develop and validate an Accurate Prediction mOdel of Lower-grade gLiomas Overall survival (APOLLO). We further conducted decision curve analysis to assess the net benefit (NB) of identifying true positives and the net reduction (NR) of unnecessary interventions. Finally, we compared the performance of APOLLO and the existing prediction models by the first systematic review.

Findings: APOLLO possessed an excellent discriminative ability to identify patients at high mortality risk. Compared to those with less than the 20 percentile of APOLLO risk score, patients with more than the 90 percentile of APOLLO risk score had significantly worse overall survival (HR=54·18, 95% CI: 34·73-84·52, P=2·66 × 10). Further, APOLLO can accurately predict both 36- and 60-month survival in six independent cohorts with a pooled AUC=0·901 (95% CI: 0·879-0·923), AUC=0·843 (95% CI: 0·815-0·871) and C-index=0·818 (95% CI: 0·800-0·835). Moreover, APOLLO offered an effective screening strategy for detecting LGG patients susceptible to death (NB=0·166, NR=40·1% and NB=0·258, NR=19·2%). The systematic comparisons revealed APOLLO outperformed the existing models in accuracy and robustness.

Interpretation: APOLLO has the demonstrated feasibility and utility of predicting LGG survival (http://bigdata.njmu.edu.cn/APOLLO).

Funding: National Key Research and Development Program of China (2016YFE0204900); Natural Science Foundation of Jiangsu Province (BK20191354); National Natural Science Foundation of China (81973142 and 82103946); China Postdoctoral Science Foundation (2020M681671); National Institutes of Health (CA209414, CA249096, CA092824 and ES000002).
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http://dx.doi.org/10.1016/j.ebiom.2022.104007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035655PMC
May 2022

Association of pyroptosis and severeness of COVID-19 as revealed by integrated single-cell transcriptome data analysis.

Immunoinformatics (Amst) 2022 Jun 10;6:100013. Epub 2022 Apr 10.

Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77845, USA.

Cytokine storm and inflammatory cytokine release syndrome are often found to be associated with severe instances of the 2019 coronavirus disease (COVID-19). However, factors that contribute to the development of the COVID-19-associated cytokine storm and intensify the hyperinflammatory response are not well known. Here, we integratively analyzed scRNAseq data of 37,607 immune cells of eight different cell types from four studies involving COVID-19 patients in either moderate or severe conditions. Our analysis showed that pyroptosis-a lytic, inflammatory type of programmed cell death-may play a critical role in the SARS-CoV-2-induced cytokine storm. The expression of the key markers of pyroptosis, such as pro-inflammatory cytokine genes and , is significantly higher in moderate and severe COVID-19 patients than in healthy controls. The pattern is more pronounced in macrophages and neutrophils than in adaptive immune cells such as T cells and B cells. Furthermore, the lack of interferon-gamma (IFN-γ) and overexpression of ninjurin 1 () in macrophages may exacerbate the systemic inflammation, as shown in severe COVID-19 patients. Finally, we developed a scoring metric to quantitatively assess single cell's pyroptotic state and demonstrated the use of this pyroptosis signature score to scRNAseq data. Taken together, our study underscores the importance of the pyroptosis pathway and highlights its clinical relevance, suggesting that pyroptosis is a cellular process that can be a potential target for the treatment of COVID-19 associated diseases.
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http://dx.doi.org/10.1016/j.immuno.2022.100013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8994680PMC
June 2022
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