Publications by authors named "Jia Wu"

395 Publications

Increased CD4CD8 Double-Positive T Cell in Patients with Primary Sjögren's Syndrome Correlated with Disease Activity.

J Immunol Res 2021 14;2021:6658324. Epub 2021 May 14.

Department of Clinical Laboratory Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.

Primary Sjogren's syndrome (pSS) is an autoimmune disease that invades lacrimal glands, salivary glands, and other exocrine glands, but its pathogenic mechanism is still unclear. CD4CD8 double-positive T (DPT) cells have been discovered in recent years to play an important role in autoimmune diseases and viral infections, but the frequency and significance of DPT in primary Sjogren's syndrome are still unclear. This study detected the frequency of DPT in the peripheral blood of patients with pSS and detected the clinical indicators and cytokines in patients. We then analyzed the correlation between DPT and clinical indicators, cytokines, and disease activity scores. The results showed that the peripheral DPT frequency of pSS patients was significantly higher than that of healthy controls. The peripheral DPT frequency was negatively correlated with ESR, IgA, and IgG, and peripheral DPT frequency was positively correlated with anti-inflammatory cytokine IL-10. Analysis of DPT and pSS disease activity scores found that DPT frequency had a negative correlation with ESSDAI and SSDAI. This study suggests that peripheral DPT may play a protective role in pSS. The frequency of peripheral DPT cells can be used as an indicator for disease activity. Regulating the expression of peripheral DPT cells is expected to become a new strategy for treatment of pSS.
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http://dx.doi.org/10.1155/2021/6658324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140824PMC
May 2021

Children's shyness and neural responses to social exclusion: Patterns of midfrontal theta power usually not observed until adolescence.

Cogn Affect Behav Neurosci 2021 Jun 5. Epub 2021 Jun 5.

Department of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, Ontario, Canada.

Adverse peer experiences, such as social exclusion, are known risks for socioemotional problems among shy youth. Yet, little is known about how shy children and adolescents process social exclusion in the brain and whether these responses are amplified in adolescence. Using the Cyberball task, we examined mediofrontal theta (4-7 Hz) event-related EEG spectral power during conditions of fair play and social exclusion in 122 participants (58 children, ages 10-12 years, and 64 adolescents, ages 14-17 years). Age effects of the task showed that adolescents displayed heightened theta power to both outright rejection and baseline "not my turn" events, whereas children showed higher theta power to rejection compared with "not my turn" events. Further results on individual differences showed that children with relatively higher levels of shyness displayed enhanced theta power to both rejection and "not my turn" events-a pattern that also was observed in adolescents. These findings suggest that a pattern of heightened neural sensitivity to both outright social exclusion and threats of exclusion, which is the norm by adolescence, also is observed in children with higher levels of shyness. The similar neural response pattern might be driven by salient social motivations that similarly modify the social cognition and behaviors of these groups and might reflect neural antecedents of rejection sensitivity.
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http://dx.doi.org/10.3758/s13415-021-00916-7DOI Listing
June 2021

Daily cannabis use in adolescents who smoke tobacco is associated with altered late-stage feedback processing: A high-density electrical mapping study.

J Psychiatr Res 2021 Jul 23;139:82-90. Epub 2021 May 23.

Child Study Center, Yale University School of Medicine, New Haven, CT, 06510, USA.

Impairments in feedback processing, often associated with risk-taking behavior, may have implications for development of substance abuse in adolescents. The most commonly used substances by adolescents include tobacco and cannabis, with some individuals using both substances, potentially heightening risk. Our objective was to examine feedback processing and impulsivity in adolescents who smoke cigarettes and use cannabis daily (N = 21), comparing them with adolescents who smoke cigarettes daily and use cannabis occasionally (N = 18) and non-smoking (N = 27) adolescents. To do this, the Balloon Analog Risk Task (BART) with concurrent EEG was used to measure risk-related feedback processing, and impulsivity was measured using the Barratt's impulsiveness scale (BIS-11). It was found that adolescent daily tobacco/cannabis smoking was associated with higher BIS-11 scores, shortened feedback-related-negativity (FRN) latencies and reduced P300 amplitudes. In addition, FRN latencies during win conditions were inversely associated with tobacco-use severity, indicated by scores on the Fagerstrom Test for Nicotine Dependence (FTND), and with BIS-11 scores. Adolescents with concurrent tobacco and cannabis use show altered feedback processing and higher impulsivity. Future work should disentangle whether the effect reflects risk, consequences of use or both.
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http://dx.doi.org/10.1016/j.jpsychires.2021.05.022DOI Listing
July 2021

Predicting Progression of COVID-19 Infection to Prioritize Medical Resource Allocation: A Novel Triage Model Based on Patient Characteristics and Symptoms at Presentation.

Front Public Health 2021 11;9:610280. Epub 2021 May 11.

Zhejiang Provincial People's Hospital, Hangzhou, China.

The COVID-19 global pandemic has posed unprecedented challenges to health care systems all over the world. The speed of the viral spread results in a tsunami of patients, which begs for a reliable screening tool using readily available data to predict disease progression. Multicenter retrospective cohort study was performed to develop and validate a triage model. Patient demographic and non-laboratory clinical data were recorded. Using only the data from Zhongnan Hospital, step-wise multivariable logistic regression was performed, and a prognostic nomogram was constructed based on the independent variables identifies. The discrimination and calibration of the model were validated. External independent validation was performed to further address the utility of this model using data from Jinyintan Hospital. A total of 716 confirmed COVID-19 cases from Zhongnan Hospital were included for model construction. Men, increased age, fever, hypertension, cardio-cerebrovascular disease, dyspnea, cough, and myalgia are independent risk factors for disease progression. External independent validation was carried out in a cohort with 201 cases from Jinyintan Hospital. The area under the curve (AUC) was 0.787 (95% confidence interval [CI]: 0.747-0.827) in the training group and 0.704 (95% CI: 0.632-0.777) in the validation group. We developed a novel triage model based on basic and clinical data. Our model could be used as a pragmatic screening aid to allow for cost efficient screening to be carried out such as over the phone, which may reduce disease propagation through limiting unnecessary contact. This may help allocation of limited medical resources.
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http://dx.doi.org/10.3389/fpubh.2021.610280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144294PMC
June 2021

A nitrate transporter encoded by ZmNPF7.9 is essential for maize seed development.

Plant Sci 2021 Jul 30;308:110901. Epub 2021 Mar 30.

State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Taian, Shandong, 271018, China; College of Life Sciences, Capital Normal University, Beijing, 100048, China. Electronic address:

Nitrogen is an essential macronutrient for plants and regulates many aspects of plant growth and development. Nitrate is one of the major forms of nitrogen in plants. However, the role of nitrate uptake and allocation in seed development is not fully understood. Here, we identified the maize (Zea mays) small-kernel mutant zmnpf7.9 and characterized the candidate gene, ZmNPF7.9, which was the same gene as nitrate transport 1.5 (NRT1.5) in maize. This gene is specifically expressed in the basal endosperm transfer layer cells of maize endosperm. Dysfunction of ZmNPF7.9 resulted in delayed endosperm development, abnormal starch deposition and decreased hundred-grain weight. Functional analysis of cRNA-injected Xenopus oocytes showed that ZmNPF7.9 is a low-affinity, pH-dependent bidirectional nitrate transporter. Moreover, the amount of nitrate in mature seeds of the zmnpf7.9 mutant was reduced. These suggest that ZmNPF7.9 is involved in delivering nitrate from maternal tissues to the developing endosperm. Moreover, most of the key genes associated with glycolysis/gluconeogenesis, carbon fixation, carbon metabolism and biosynthesis of amino acids pathways in the zmnpf7.9 mutant were significantly down-regulated. Thus, our results demonstrate that ZmNPF7.9 plays a specific role in seed development and grain weight by regulating nutrition transport and metabolism, which might provide useful information for maize genetic improvement.
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http://dx.doi.org/10.1016/j.plantsci.2021.110901DOI Listing
July 2021

Increased alpha-band connectivity during tic suppression in children with Tourette syndrome revealed by source EEG analyses.

Biol Psychiatry Cogn Neurosci Neuroimaging 2021 May 12. Epub 2021 May 12.

Child Study Center, Yale University School of Medicine. Electronic address:

Background: Tourette syndrome (TS) is a neurodevelopmental disorder involving chronic motor and phonic tics. Most individuals with Tourette syndrome can suppress their tics for at least a short period of time. Yet, the brain correlates of tic suppression are still poorly understood.

Methods: In the current study, high-density electroencephalography (EEG) was recorded during a resting-state and a tic suppression session in 72 children with TS. Functional connectivity between cortical regions was assessed in the alpha band (8-13 Hz) using an EEG source connectivity method. Graph theory and network-based statistics were used to assess the global network topology and to identify brain regions showing increased connectivity during tic suppression.

Results: Graph theoretical analyses revealed distinctive global network topology during tic suppression, relative to rest. Using network-based statistics, we found a subnetwork of increased connectivity during tic suppression (p < .001). That subnetwork encompassed many cortical areas, including the right superior frontal gyrus and the left precuneus, which are involved in the default mode network. We also found a condition by age interaction, suggesting age-mediated increases in connectivity during tic suppression.

Conclusions: These results suggest that children with TS suppress their tics through a brain circuit involving distributed cortical regions, many of which are part of the default mode network. Brain connectivity during tic suppression also increases as youths with TS mature. These results highlight a mechanism by which children with TS may control their tics, which could be relevant for future treatment studies.
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http://dx.doi.org/10.1016/j.bpsc.2021.05.001DOI Listing
May 2021

Antibiotic stewardship algorithm to rationalise antibiotic use among hospitalised COVID-19 patients.

Ann Acad Med Singap 2021 Apr;50(4):366-368

Division of Infectious Diseases, Department of Medicine, National University Hospital, Singapore.

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April 2021

A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes.

Nat Commun 2021 05 11;12(1):2623. Epub 2021 May 11.

Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, People's Republic of China.

COVID-19 pandemic caused by SARS-CoV-2 constitutes a global public health crisis with enormous economic consequences. Monoclonal antibodies against SARS-CoV-2 can provide an important treatment option to fight COVID-19, especially for the most vulnerable populations. In this work, potent antibodies binding to SARS-CoV-2 Spike protein were identified from COVID-19 convalescent patients. Among them, P4A1 interacts directly with and covers majority of the Receptor Binding Motif of the Spike Receptor-Binding Domain, shown by high-resolution complex structure analysis. We further demonstrate the binding and neutralizing activities of P4A1 against wild type and mutant Spike proteins or pseudoviruses. P4A1 was subsequently engineered to reduce the potential risk for Antibody-Dependent Enhancement of infection and to extend its half-life. The engineered antibody exhibits an optimized pharmacokinetic and safety profile, and it results in complete viral clearance in a rhesus monkey model of COVID-19 following a single injection. These data suggest its potential against SARS-CoV-2 related diseases.
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http://dx.doi.org/10.1038/s41467-021-22926-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113581PMC
May 2021

Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features.

Nat Commun 2021 05 11;12(1):2722. Epub 2021 May 11.

Department of Thoracic/Head and Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.

The mechanism by which anti-cancer immunity shapes early carcinogenesis of lung adenocarcinoma (ADC) is unknown. In this study, we characterize the immune contexture of invasive lung ADC and its precursors by transcriptomic immune profiling, T cell receptor (TCR) sequencing and multiplex immunofluorescence (mIF). Our results demonstrate that anti-tumor immunity evolved as a continuum from lung preneoplasia, to preinvasive ADC, minimally-invasive ADC and frankly invasive lung ADC with a gradually less effective and more intensively regulated immune response including down-regulation of immune-activation pathways, up-regulation of immunosuppressive pathways, lower infiltration of cytotoxic T cells (CTLs) and anti-tumor helper T cells (Th), higher infiltration of regulatory T cells (Tregs), decreased T cell clonality, and lower frequencies of top T cell clones in later-stages. Driver mutations, chromosomal copy number aberrations (CNAs) and aberrant DNA methylation may collectively impinge host immune responses and facilitate immune evasion, promoting the outgrowth of fit subclones in preneoplasia into dominant clones in invasive ADC.
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http://dx.doi.org/10.1038/s41467-021-22890-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113327PMC
May 2021

Enhancing Graph Neural Networks by a High-quality Aggregation of Beneficial Information.

Neural Netw 2021 Apr 24;142:20-33. Epub 2021 Apr 24.

School of Computer Science, National Engineering Research Center for Multimedia Software and Institute of Artificial Intelligence, Wuhan University, PR China; Shenzhen Research Institute, Wuhan University, PR China. Electronic address:

Graph Neural Networks (GNNs), such as GCN, GraphSAGE, GAT, and SGC, have achieved state-of-the-art performance on a wide range of graph-based tasks. These models all use a technique called neighborhood aggregation, in which the embedding of each node is updated by aggregating the embeddings of its neighbors. However, not all information aggregated from neighbors is beneficial. In some cases, a portion of the neighbor information may be harmful to the downstream tasks. For the high-quality aggregation of beneficial information, we propose a flexible method EGAI (Enhancing Graph neural networks by a high-quality Aggregation of beneficial Information). The core concept of this method is to filter out the redundant and harmful information by removing specific edges during each training epoch. The practical and theoretical motivations, considerations, and strategies related to this method are discussed in detail. EGAI is a general method that can be combined with many backbone models (e.g., GCN, GraphSAGE, GAT, and SGC) to enhance their performance in the node classification task. In addition, EGAI reduces the convergence speed of over-smoothing that occurs when models are deepened. Extensive experiments on three real-world networks demonstrate that EGAI indeed improves the performance for both shallow and deep GNN models, and to some extent, mitigates over-smoothing. The code is available at https://github.com/liucoo/egai.
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http://dx.doi.org/10.1016/j.neunet.2021.04.025DOI Listing
April 2021

PRAK Promotes the Pathogen Clearance by Macrophage Through Regulating Autophagy and Inflammasome Activation.

Front Immunol 2021 16;12:618561. Epub 2021 Apr 16.

Department of Immunology, School of Basic Medical Sciences, National Health Commission (NHC) Key Laboratory of Medical Immunology, Peking University, Beijing, China.

The p38 regulated/activated protein kinase (PRAK) is a protein kinase downstream of p38MAPK. The present study investigated its function in the macrophage. Myeloid-specific deletion of resulted in a significant reduction in F4/80CD11b peritoneal macrophages with decreased expression of MHC-II and CD80. Upon infection with , -deficient mice demonstrated an increased mortality, which was accompanied by a higher bacterial load in multiple tissues and elevated levels of proinflammatory cytokines in the serum. While the -deficient macrophage showed similar potency in phagocytosis assays, its bactericidal activity was severely impaired. Moreover, deficiency was associated with defects in ROS production, inflammasome activation as well as autophagy induction. Therefore, PRAK critically contributes to the clearance of intracellular pathogens by affecting multiple aspects of the macrophage function.
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http://dx.doi.org/10.3389/fimmu.2021.618561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085562PMC
April 2021

Protective Efficacy of Inactivated Vaccine against SARS-CoV-2 Infection in Mice and Non-Human Primates.

Virol Sin 2021 Apr 9. Epub 2021 Apr 9.

Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused more than 96 million infections and over 2 million deaths worldwide so far. However, there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the disease causative agent. Vaccine is the most effective approach to eradicate a pathogen. The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations. Here we evaluated the safety, immunogenicity, and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates. Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates, and subsequently provided partial (in low dose) or full (in high dose) protection of challenge in the tested animals. In addition, passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice. These results warranted positive outcomes in future clinical trials in humans.
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http://dx.doi.org/10.1007/s12250-021-00376-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034048PMC
April 2021

The N170 event-related potential reflects delayed neural response to faces when visual attention is directed to the eyes in youths with ASD.

Autism Res 2021 Mar 22. Epub 2021 Mar 22.

Child Study Center, Yale School of Medicine, New Haven, Connecticut, USA.

Atypical neural response to faces is thought to contribute to social deficits in autism spectrum disorder (ASD). Compared to typically developing (TD) controls, individuals with ASD exhibit delayed brain responses to upright faces at a face-sensitive event-related potential (ERP), the N170. Given observed differences in patterns of visual attention to faces, it is not known whether slowed neural processing may simply reflect atypical looking to faces. The present study manipulated visual attention to facial features to examine whether directed attention to the eyes normalizes N170 latency in ASD. ERPs were recorded in 30 children and adolescents with ASD as well as 26 TD children and adolescents. Results replicated prior findings of shorter N170 latency to the eye region of the face in TD individuals. In contrast, those with ASD did not demonstrate modulation of N170 latency by point of regard to the face. Group differences in latency were most pronounced when attention was directed to the eyes. Results suggest that well-replicated findings of N170 delays in ASD do not simply reflect atypical patterns of visual engagement with experimental stimuli. These findings add to a body of evidence indicating that N170 delays are a promising marker of atypical neural response to social information in ASD. LAY SUMMARY: This study looks at how children's and adolescents' brains respond when looking at different parts of a face. Typically developing children and adolescents processed eyes faster than other parts of the face, whereas this pattern was not seen in ASD. Children and adolescents with ASD processed eyes more slowly than typically developing children. These findings suggest that observed inefficiencies in face processing in ASD are not simply reflective of failure to attend to the eyes.
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http://dx.doi.org/10.1002/aur.2505DOI Listing
March 2021

TigeCMN: On exploration of temporal interaction graph embedding via Coupled Memory Neural Networks.

Neural Netw 2021 Aug 4;140:13-26. Epub 2021 Mar 4.

Macquarie University, Australia. Electronic address:

With the increasing demand of mining rich knowledge in graph structured data, graph embedding has become one of the most popular research topics in both academic and industrial communities due to its powerful capability in learning effective representations. The majority of existing work overwhelmingly learn node embeddings in the context of static, plain or attributed, homogeneous graphs. However, many real-world applications frequently involve bipartite graphs with temporal and attributed interaction edges, named temporal interaction graphs. The temporal interactions usually imply different facets of interest and might even evolve over the time, thus putting forward huge challenges in learning effective node representations. Furthermore, most existing graph embedding models try to embed all the information of each node into a single vector representation, which is insufficient to characterize the node's multifaceted properties. In this paper, we propose a novel framework named TigeCMN to learn node representations from a sequence of temporal interactions. Specifically, we devise two coupled memory networks to store and update node embeddings in the external matrices explicitly and dynamically, which forms deep matrix representations and thus could enhance the expressiveness of the node embeddings. Then, we generate node embedding from two parts: a static embedding that encodes its stationary properties and a dynamic embedding induced from memory matrix that models its temporal interaction patterns. We conduct extensive experiments on various real-world datasets covering the tasks of node classification, recommendation and visualization. The experimental results empirically demonstrate that TigeCMN can achieve significant gains compared with recent state-of-the-art baselines.
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http://dx.doi.org/10.1016/j.neunet.2021.02.016DOI Listing
August 2021

The essential role of PRAK in tumor metastasis and its therapeutic potential.

Nat Commun 2021 03 19;12(1):1736. Epub 2021 Mar 19.

Department of Immunology, School of Basic Medical Sciences, Peking University. NHC Key Laboratory of Medical Immunology (Peking University), Beijing, China.

Metastasis is the leading cause of cancer-related death. Despite the recent advancements in cancer treatment, there is currently no approved therapy for metastasis. The present study reveals a potent and selective activity of PRAK in the regulation of tumor metastasis. While showing no apparent effect on the growth of primary breast cancers or subcutaneously inoculated tumor lines, Prak deficiency abrogates lung metastases in PyMT mice or mice receiving intravenous injection of tumor cells. Consistently, PRAK expression is closely associated with metastatic risk in human cancers. Further analysis indicates that loss of function of PRAK leads to a pronounced inhibition of HIF-1α protein synthesis, possibly due to reduced mTORC1 activities. Notably, pharmacological inactivation of PRAK with a clinically relevant inhibitor recapitulates the anti-metastatic effect of Prak depletion, highlighting the therapeutic potential of targeting PRAK in the control of metastasis.
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http://dx.doi.org/10.1038/s41467-021-21993-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979731PMC
March 2021

Prevalence and Characteristics of Hypoxic Hepatitis in COVID-19 Patients in the Intensive Care Unit: A First Retrospective Study.

Front Med (Lausanne) 2020 11;7:607206. Epub 2021 Feb 11.

Department of Head, Neck and Thyroid Surgery, Zhejiang Provincial People's Hospital, People's Hospital affiliated of Hangzhou Medical College, Hangzhou, China.

Coronavirus disease 2019 (COVID-19) has been associated with acute liver injury in reports worldwide. But no studies to date have described hypoxic hepatitis (HH) in patients with COVID-19. We aim to identify the prevalence of and possible mechanisms of HH in COVID-19 patients in the Intensive Care Unit (ICU). This retrospective study was conducted on 51 patients with confirmed SARS-CoV-2 infection in the ICU at Zhongnan Hospital of Wuhan University from December 21, 2019, to March 11, 2020. Information on clinical features of enrolled patients was collected for analysis. HH was observed in 5.88% of the ICU patients with SARS-CoV-2 infection. All HH patients were progressing to respiratory failure and peak alanine aminotransferase (ALT) values were 1665, 1414, and 1140 U/L during hospitalization, respectively. All patients with HH died as a result of the deterioration of multiple organ failure (MOF). The dynamic changes of ALT, aspartate transaminase (AST), and total bilirubin (TBIL) levels were more dramatic in HH groups. Levels of TBIL, C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6(IL-6) showed statistically significant elevation in HH cases compared with that in non-HH cases ( < 0.001). Besides, the median survival time of the HH group was significantly shorter than the non-HH group ( < 0.05). In ICU, HH was not a rare condition in patients with severe COVID-19 and has a high mortality. The main causes of HH are respiratory and cardiac failure and may be associated with the immune-mediated inflammatory response. Clinicians should search for any underlying hemodynamic or respiratory instability even in patients with normal ALT levels on admission.
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http://dx.doi.org/10.3389/fmed.2020.607206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928422PMC
February 2021

Co-occurring tobacco and cannabis use in adolescents: Dissociable relationships with mediofrontal electrocortical activity during reward feedback processing.

Neuroimage Clin 2021 Feb 20;30:102592. Epub 2021 Feb 20.

Child Study Center, Yale University School of Medicine, New Haven, CT, United States; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States.

Differences in corticostriatal neural activity during feedback processing of rewards and losses have been separately related to cannabis and tobacco use but remain understudied relative to co-use in adolescents. Using high-density EEG (128 electrode system, 1000 Hz sampling), we examined event-related potentials (ERPs) elicited by monetary reward, neutral, and loss feedback during performance on a non-learning four-choice guessing task in a sample of non-deprived daily-cigarette-smoking adolescents (n = 36) who used tobacco and cannabis regularly (TC adolescents), and non-smoking healthy control adolescents (HCs) (n = 29). Peak amplitudes and latencies of mediofrontal ERPs indexing feedback-related negativities (FRNs) were used as outcomes in repeated-measures ANOVAs. No differences in FRNs were observed between TC and HC adolescents. Within TC adolescents, cannabis-use and tobacco-use variables had distinct relationships with the FRN, with cannabis-related problem severity being positively correlated with FRN amplitude during reward feedback and tobacco-related problem severity being negatively correlated with FRN latency during non-loss feedback (i.e., reward and neutral). These findings suggest that co-occurring cannabis and tobacco use may have dissociable relationships with feedback processing relating to each drug and support an incentive salience model of addiction severity related to cannabis use in adolescents.
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http://dx.doi.org/10.1016/j.nicl.2021.102592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932890PMC
February 2021

A Staging Auxiliary Diagnosis Model for Nonsmall Cell Lung Cancer Based on the Intelligent Medical System.

Comput Math Methods Med 2021 8;2021:6654946. Epub 2021 Feb 8.

PET-CT Center, The Second Xiangya Hospital of Central South University, Changsha 410083, China.

At present, human health is threatened by many diseases, and lung cancer is one of the most dangerous tumors that threaten human life. In most developing countries, due to the large population and lack of medical resources, it is difficult for doctors to meet patients' needs for medical treatment only by relying on the manual diagnosis. Based on massive medical information, the intelligent decision-making system has played a great role in assisting doctors in analyzing patients' conditions, improving the accuracy of clinical diagnosis, and reducing the workload of medical staff. This article is based on the data of 8,920 nonsmall cell lung cancer patients collected by different medical systems in three hospitals in China. Based on the intelligent medical system, on the basis of the intelligent medical system, this paper constructs a nonsmall cell lung cancer staging auxiliary diagnosis model based on convolutional neural network (CNNSAD). CNNSAD converts patient medical records into word sequences, uses convolutional neural networks to extract semantic features from patient medical records, and combines dynamic sampling and transfer learning technology to construct a balanced data set. The experimental results show that the model is superior to other methods in terms of accuracy, recall, and precision. When the number of samples reaches 3000, the accuracy of the system will reach over 80%, which can effectively realize the auxiliary diagnosis of nonsmall cell lung cancer and combine dynamic sampling and migration learning techniques to train nonsmall cell lung cancer staging auxiliary diagnosis models, which can effectively achieve the auxiliary diagnosis of nonsmall cell lung cancer. The simulation results show that the model is better than the other methods in the experiment in terms of accuracy, recall, and precision.
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http://dx.doi.org/10.1155/2021/6654946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886591PMC
February 2021

High expression of heme oxygenase-1 in tumor-associated macrophages characterizes a poor-prognosis subtype in nasopharyngeal carcinoma.

Aging (Albany NY) 2021 02 11;13(4):5674-5685. Epub 2021 Feb 11.

Department of Radiation Oncology, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu Province, China.

Tumor-associated macrophages (TAMs) are important components of the tumor microenvironment, which are characterized by pro-tumor M2 phenotype and correlate with poor survival of nasopharyngeal carcinoma (NPC). Heme oxygenase-1 (HO-1) plays a crucial role in macrophage polarization toward M2 phenotype, but its prognosis significance in NPC has been rarely determined. To gain insights into the HO-1 expression profile and to determine the clinical significance of HO-1 in NPC, we performed immunohistochemistry analyses in 126 NPC specimens. CD163, a highly specific marker of M2 macrophages, was used as a surrogate for the polarization state of TAMs. Our results showed that high expression of HO-1 and CD163 were detected in TAMs for 57.9% (73/126) and 61.9% (78/126) of the studied patients, and both of them were significantly associated with worse survival. Additionally, a significant correlation between the intensities of HO-1 and CD163 was identified, and HO-1 exhibited a superior ability in predicting survival compared with CD163. Our study revealed for the first time that overexpression of HO-1 characterized a poor-prognosis subtype in NPC. Individualized therapy targeting HO-1 might serve as a promising treatment modality for NPC.
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http://dx.doi.org/10.18632/aging.202492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7950251PMC
February 2021

Systematic analysis of purified astrocytes after SCI unveils Zeb2os function during astrogliosis.

Cell Rep 2021 Feb;34(5):108721

The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Center for Stem Cell and Regenerative Medicine, UT Brown Foundation Institute of Molecular Medicine, Houston, TX 77030, USA; MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA. Electronic address:

Spinal cord injury (SCI) is one of the most devastating neural injuries without effective therapeutic solutions. Astrocytes are the predominant component of the scar. Understanding the complex contributions of reactive astrocytes to SCI pathophysiologies is fundamentally important for developing therapeutic strategies. We have studied the molecular changes in the injury environment and the astrocyte-specific responses by astrocyte purification from injured spinal cords from acute to chronic stages. In addition to protein-coding genes, we have systematically analyzed the expression profiles of long non-coding RNAs (lncRNAs) (>200 bp), which are regulatory RNAs that play important roles in the CNS. We have identified a highly conserved lncRNA, Zeb2os, and demonstrated using functional assays that it plays an important role in reactive astrogliosis through the Zeb2os/Zeb2/Stat3 axis. These studies provide valuable insights into the molecular basis of reactive astrogliosis and fill the knowledge gap regarding the function(s) of lncRNAs in astrogliosis and SCI.
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http://dx.doi.org/10.1016/j.celrep.2021.108721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920574PMC
February 2021

Inactivating SARS-CoV-2 by electrochemical oxidation.

Sci Bull (Beijing) 2021 Apr 30;66(7):720-726. Epub 2020 Dec 30.

State Key Laboratory of Catalysis, Collaborative Innovation Center of Chemistry for Energy Materials, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.

Fully inactivating SARS-CoV-2, the virus causing coronavirus disease 2019, is of key importance for interrupting virus transmission but is currently performed by using biologically or environmentally hazardous disinfectants. Herein, we report an eco-friendly and efficient electrochemical strategy for inactivating the SARS-CoV-2 using formed nickel oxide hydroxide as anode catalyst and sodium carbonate as electrolyte. At a voltage of 5 V, the SARS-CoV-2 viruses can be rapidly inactivated with disinfection efficiency reaching 95% in only 30 s and 99.99% in 5 min. Mass spectrometry analysis and theoretical calculations indicate that the reactive oxygen species generated on the anode can oxidize the peptide chains and induce cleavage of the peptide backbone of the receptor binding domain of the SARS-CoV-2 spike glycoprotein, and thereby disables the virus. This strategy provides a sustainable and highly efficient approach for the disinfection of the SARS-CoV-2 viruliferous aerosols and wastewater.
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http://dx.doi.org/10.1016/j.scib.2020.12.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832140PMC
April 2021

Systematic Review and Meta-Analysis of Effectiveness of Acceptance and Commitment Therapy in Patients with Breast Cancer.

Nurs Res 2021 Jan 21. Epub 2021 Jan 21.

Zhejiang Chinses Medical University, Hangzhou, China.

Background: The physical and psychological well-being of patients with breast cancer are an important global issue. Acceptance and commitment therapy (ACT) aims to equip patients with the skills to respond and adapt to difficult circumstances. However, the extent of the physical and psychological outcomes of this therapy in patients with breast cancer remains unclear.

Objectives: To summarize available evidence and assess the efficacy of ACT on physiological and psychological outcomes in patients with breast cancer.

Methods: Published randomized controlled studies were identified in MEDLINE, PsycInfo, Embase, Web of Science, CINAHL, and CNKI from inception to December 2019 and Cochrane Library, AMED, and Clinical trials.gov from inception to September 2020. Methodological rigor was assessed by two reviewers using the Cochrane Handbook for Systematic Review of Interventions. Sufficient data were statistically pooled with review manager; otherwise, a narrative summary was used.

Results: Thirteen trials were included in the review. Methodological quality varied across the studies. Meta-analyses demonstrated that ACT had moderate to large effects on reducing anxiety, depression, and stress and improving hope. Sensitivity analyses reached results similar to those of the meta-analyses. However, the effects of ACT on the physiological symptoms, fear of cancer recurrence, and psychological flexibility of patients with breast cancer remain inconclusive.

Discussion: ACT has beneficial effects on the anxiety, depression, stress, and hope of patients with breast cancer. The evidence of ACT on physiological symptoms, fear of cancer recurrence, and psychological flexibility needs to be treated with caution. Further studies are needed and should consider different delivery forms and also explore the mechanisms of each component of ACT under different cultural contexts.
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http://dx.doi.org/10.1097/NNR.0000000000000499DOI Listing
January 2021

Characterization of Novel Rhabdoviruses in Chinese Bats.

Viruses 2021 Jan 5;13(1). Epub 2021 Jan 5.

Institut Pasteur, Lyssavirus Epidemiology and Neuropathology Unit, 75724 Paris, France.

Bats, the second largest order of mammals worldwide, harbor specific characteristics such as sustaining flight, a special immune system, unique habits, and ecological niches. In addition, they are the natural reservoirs of a variety of emerging or re-emerging zoonotic pathogens. is one of the most diverse families of RNA viruses, which consists of 20 ecologically diverse genera, infecting plants, mammals, birds, reptiles, and fish. To date, three bat-related genera are described, named , , and . However, the prevalence and the distribution of these bat-related rhabdoviruses remain largely unknown, especially in China. To fill this gap, we performed a large molecular retrospective study based on the real-time reverse transcription polymerase chain reaction (RT-qPCR) detection of lyssavirus in bat samples (1044 brain and 3532 saliva samples, from 63 different bat species) originating from 21 provinces of China during 2006-2018. None of them were positive for lyssavirus, but six bat brains (0.6%) of bat species, originating from Hubei and Hainan provinces, were positive for vesiculoviruses or ledanteviruses. Based on complete genomes, these viruses were phylogenetically classified into three putative new species, tentatively named Yinshui bat virus (YSBV), Taiyi bat virus (TYBV), and Qiongzhong bat virus (QZBV). These results indicate the novel rhabdoviruses circulated in different Chinese bat populations.
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http://dx.doi.org/10.3390/v13010064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824899PMC
January 2021

The novel E-subgroup pentatricopeptide repeat protein DEK55 is responsible for RNA editing at multiple sites and for the splicing of nad1 and nad4 in maize.

BMC Plant Biol 2020 Dec 9;20(1):553. Epub 2020 Dec 9.

State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Taian, Shandong, 271018, PR China.

Background: Pentatricopeptide repeat (PPR) proteins compose a large protein family whose members are involved in both RNA processing in organelles and plant growth. Previous reports have shown that E-subgroup PPR proteins are involved in RNA editing. However, the additional functions and roles of the E-subgroup PPR proteins are unknown.

Results: In this study, we developed and identified a new maize kernel mutant with arrested embryo and endosperm development, i.e., defective kernel (dek) 55 (dek55). Genetic and molecular evidence suggested that the defective kernels resulted from a mononucleotide alteration (C to T) at + 449 bp within the open reading frame (ORF) of Zm00001d014471 (hereafter referred to as DEK55). DEK55 encodes an E-subgroup PPR protein within the mitochondria. Molecular analyses showed that the editing percentage of 24 RNA editing sites decreased and that of seven RNA editing sites increased in dek55 kernels, the sites of which were distributed across 14 mitochondrial gene transcripts. Moreover, the splicing efficiency of nad1 introns 1 and 4 and nad4 intron 1 significantly decreased in dek55 compared with the wild type (WT). These results indicate that DEK55 plays a crucial role in RNA editing at multiple sites as well as in the splicing of nad1 and nad4 introns. Mutation in the DEK55 gene led to the dysfunction of mitochondrial complex I. Moreover, yeast two-hybrid assays showed that DEK55 interacts with two multiple organellar RNA-editing factors (MORFs), i.e., ZmMORF1 (Zm00001d049043) and ZmMORF8 (Zm00001d048291).

Conclusions: Our results demonstrated that a mutation in the DEK55 gene affects the mitochondrial function essential for maize kernel development. Our results also provide novel insight into the molecular functions of E-subgroup PPR proteins involved in plant organellar RNA processing.
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http://dx.doi.org/10.1186/s12870-020-02765-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727260PMC
December 2020

Integrated imaging and molecular analysis to decipher tumor microenvironment in the era of immunotherapy.

Semin Cancer Biol 2020 Dec 5. Epub 2020 Dec 5.

Department of Radiation Oncology, Stanford University, Stanford, California, 94305, USA.

Radiological imaging is an integral component of cancer care, including diagnosis, staging, and treatment response monitoring. It contains rich information about tumor phenotypes that are governed not only by cancer cellintrinsic biological processes but also by the tumor microenvironment, such as the composition and function of tumor-infiltrating immune cells. By analyzing the radiological scans using a quantitative radiomics approach, robust relations between specific imaging and molecular phenotypes can be established. Indeed, a number of studies have demonstrated the feasibility of radiogenomics for predicting intrinsic molecular subtypes and gene expression signatures in breast cancer based on MRI. In parallel, promising results have been shown for inferring the amount of tumor-infiltrating lymphocytes, a key factor for the efficacy of cancer immunotherapy, from standard-of-care radiological images. Compared with the biopsy-based approach, radiogenomics offers a unique avenue to profile the molecular makeup of the tumor and immune microenvironment as well as its evolution in a noninvasive and holistic manner through longitudinal imaging scans. Here, we provide a systematic review of the state of the art radiogenomics studies in the era of immunotherapy and discuss emerging paradigms and opportunities in AI and deep learning approaches. These technical advances are expected to transform the radiogenomics field, leading to the discovery of reliable imaging biomarkers. This will pave the way for their clinical translation to guide precision cancer therapy.
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http://dx.doi.org/10.1016/j.semcancer.2020.12.005DOI Listing
December 2020

Redox-Responsive Oil-In-Dispersion Emulsions Stabilized by Similarly Charged Ferrocene Surfactants and Alumina Nanoparticles.

Langmuir 2020 Dec 23;36(48):14589-14596. Epub 2020 Nov 23.

State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, P.R. China.

A redox-responsive oil-in-dispersion emulsion was developed by using a cationic ferrocene surfactant (FcCOCN) and AlO nanoparticles, in which the required concentrations of FcCOCN and AlO nanoparticles are as low as 0.001 mM (≈0.005 cmc) and 0.006 wt %, respectively. Rapid demulsification can be successfully achieved through a redox trigger, resulting from the transition of FcCOCN from a normal cationic surfactant form into a strongly hydrophilic Bola type form (FcCOCN). Moreover, FcCOCN together with the particles almost resides in the aqueous phase and can be recovered after the reduction reaction. Not only the amount of surfactant and nanoparticles are significantly reduced but also the emulsifier (surfactant and alumina) can be recycled and reused from the aqueous phase, which is a sustainable and economical strategy for various applications.
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http://dx.doi.org/10.1021/acs.langmuir.0c02350DOI Listing
December 2020

Physiological Mechanisms of Improved Smut Resistance in Sugarcane Through Application of Silicon.

Front Plant Sci 2020 5;11:568130. Epub 2020 Nov 5.

College of Agriculture, South China Agricultural University, Guangzhou, China.

Sugarcane smut caused by is a severe, global sugarcane disease with severe economic losses and is difficult to prevent. To explore more effective control techniques for smut, the effects and physiological mechanism of silicon (Si) on smut resistance in two smut-susceptible cultivars, ROC22 and Badila, were investigated. The results show that Si application significantly enhances smut resistance in ROC22 and Badila, and the incidence of sugarcane smut decreased by 11.57-22.58% (ROC22) and 27.75-46.67% (Badila). The incidence of smut is negatively correlated with the amount of Si applied and the Si content in sugarcane leaves, stems, and roots (highly significantly negatively correlated with stem Si content). Under stress, the activities of pathogenesis-related enzymes, chitinase and β-1,3-glucanase, secondary metabolism-related enzymes such as polyphenoloxidase (PPO) and phenylalanine-ammonia-lyase (PAL), and the contents of secondary metabolites, total soluble phenol, and lignin in sugarcane leaves treated with Si were significantly higher than those without Si (CK). The results also demonstrated that the content of malondialdehyde (MDA) and hydrogen peroxide (HO), the superoxide dismutase (SOD) activity of sugarcane leaves treated with Si increased in the seedling and tillering stages, and the peroxidase (POD) activity decreased in the seedling stage, which caused the accumulation of reactive oxygen species (ROS) that in turn triggered defense responses. Moreover, MDA and HO levels decreased, and the activities of SOD and POD increased at the jointing stage, which was beneficial to the removal of excessive ROS. Collectively, these results suggest that Si modulates pathogenesis-related protein activity, secondary metabolism, and active oxygen metabolism of sugarcane that positively regulate resistance to smut. This study is the first to reveal the physiological mechanism of Si in improving smut resistance in sugarcane, and the results provide a theoretical basis for the development of Si fertilizers to control sugarcane smut.
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http://dx.doi.org/10.3389/fpls.2020.568130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674639PMC
November 2020

The Case for Intermittent Carbapenem Dosing in Stable Haemodialysis Patients.

Antibiotics (Basel) 2020 Nov 16;9(11). Epub 2020 Nov 16.

Department of Medicine, National University Hospital, National University Health System, Singapore 119228, Singapore.

Purpose: Antimicrobial resistant infections are common in patients on haemodialysis, often needing long courses of carbapenems. This results in a longer hospital stay and risk of iatrogenic complications. However, carbapenems can be given intermittently to allow for earlier discharge. We aim to describe the clinical outcomes of intermittent versus daily meropenem in stable, intermittently haemodialysed patients.

Methods: In total, 103 records were examined retrospectively. Data collected include demographics, clinical interventions and outcomes such as hospital length of stay (LOS), 30-day readmission rates and adverse events.

Findings: Mean age 61.6 ± 14.2 years, 57.3% male. Most common bacteria cultured were Klebsiella pneumoniae (16.5%). The most common indication was pneumonia (27.2%). Mean duration of therapy on meropenem was 12.4 ± 14.4 days; eight patients needed more than 30 days of meropenem. In total, 55.3% did not have intervention for source control; 86.4% received daily dosing of meropenem; 7.8% patients received intermittent dosing of meropenem only, and 5.8 patients received both types of dosing regimens. LOS of the index admission was shorter for the intermittent arm (15.5 ± 7.6 days versus daily: 30.2 ± 24.5 days), though 30-day readmission was higher (50% versus daily: 38.2%).

Implications: We recommend further rigorous randomised controlled trials to investigate the clinical utility of intermittent meropenem dosing in patients on stable haemodialysis.
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http://dx.doi.org/10.3390/antibiotics9110815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696023PMC
November 2020

The Association of Sleep Hygiene and Drowsiness with Adverse Driving Events in Emergency Medicine Residents.

West J Emerg Med 2020 Oct 27;21(6):219-224. Epub 2020 Oct 27.

Yale Developmental Neurocognitive Driving Simulation Research Center (DrivSim Lab).

Introduction: Prior research shows that physicians in training are at risk for drowsy driving following their clinical duties, which may put them in danger of experiencing adverse driving events. This study explores the relationship between sleepiness, overall sleep hygiene, level of training, and adverse driving events following an overnight shift in emergency medicine (EM) residents.

Methods: Throughout the 2018-2019 academic year, 50 EM residents from postgraduate years 1-4 completed self-administered surveys regarding their sleepiness before and after their drive home following an overnight shift, any adverse driving events that occurred during their drive home, and their overall sleep hygiene.

Results: Fifty out of a possible 57 residents completed the survey for a response rate of 87.7%. Sleepiness was significantly associated with adverse driving events (beta = 0.31; P < .001). Residents with high sleepiness levels reported significantly more adverse driving events. Residents reported significantly higher sleepiness levels after completing their drive home (mean = 7.04, standard deviation [SD] = 1.41) compared to sleepiness levels before driving home (mean = 5.58, SD = 1.81). Residency training level was significantly associated with adverse driving events (beta = -0.59, P < .01). Senior residents reported significantly fewer adverse driving events compared to junior residents.

Conclusion: Emergency physicians in training are at risk for drowsy driving-related motor vehicle crashes following overnight work shifts. Trainees of all levels underestimated their true degree of sleepiness prior to initiating their drive home, while junior residents were at higher risk for adverse driving events.
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http://dx.doi.org/10.5811/westjem.2020.8.47357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673877PMC
October 2020

Review of conformal cooling system design and additive manufacturing for injection molds.

Math Biosci Eng 2020 08;17(5):5414-5431

Center for Advanced Jet Engineering Technologies (CaJET), School of Mechanical Engineering, Shandong University, Jinan 250061, China.

This paper points out the significance of cooling in injection molding and briefly reviews the development of cooling systems. The focus of this survey is on the physical model, development, and optimization of conformal cooling systems which have curved cooling circuits following the shape of mold cavity. Compared with traditional cooling systems, conformal cooling can greatly reduce the warpage defect and shorten the cooling cycle time. The computational design methods and additive manufacturing techniques that prompt the development of conformal cooling are deeply investigated. At the end of this survey, the future perspectives for conformal cooling design and manufacturing are discussed.
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http://dx.doi.org/10.3934/mbe.2020292DOI Listing
August 2020