Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
49,829
result(s) for
"Xie, Li"
Sort by:
Observation of inhomogeneous plasmonic field distribution in a nanocavity
The progress of plasmon-based technologies relies on an understanding of the properties of the enhanced electromagnetic fields generated by the coupling nanostrucutres1–6. Plasmon-enhanced applications include advanced spectroscopies7–10, optomechanics11, optomagnetics12 and biosensing13–17. However, precise determination of plasmon field intensity distribution within a nanogap remains challenging. Here, we demonstrate a molecular ruler made from a set of viologen-based, self-assembly monolayers with which we precisely measures field distribution within a plasmon nanocavity with ~2-Å spatial resolution. We observed an unusually large plasmon field intensity inhomogeneity that we attribute to the formation of a plasmonic comb in the nanocavity. As a consequence, we posit that the generally adopted continuous media approximation for molecular monolayers should be used carefully.The strength of the plasmonic field between a plasmonic particle and a Au surface can be measured at ~2-Å resolution by following the Raman peaks of a suitably labelled self-assembly monolayer.
Journal Article
Epidemiologic Features of Kawasaki Disease in Shanghai From 2013 Through 2017
Background: We sought to investigate epidemiologic features of Kawasaki disease (KD) in Shanghai from 2013 through 2017 and identify risk factors for coronary artery lesions (CAL). Methods: As in our previous three surveys, a set of questionnaires and diagnostic guidelines for KD were sent to 50 hospitals providing pediatric medical care in Shanghai. Medical records of KD patients diagnosed from January 2013 through December 2017 were retrospectively analyzed. Multivariate logistic regression analysis was performed to identify risk factors for CAL. Results: A total of 4,452 cases were enrolled. Male-to-female ratio was 1.7:1. The incidence of KD was 68.8 to 107.3 per 100,000 children aged <5 years from 2013 to 2017. Age at onset ranged from 15 days to 14.0 years (median: 1.8 years). KD occurred more frequently in spring and summer. Of 4,325 patients (97.0%) receiving intravenous immunoglobulin (IVIG), 362 (8.4%) were resistant to initial IVIG. CAL occurred in 406 (9.1%) patients, including 118 (2.7%) with medium aneurysms and 31 (0.7%) with giant aneurysms. Recurrent cases were 60 (1.3%). No death was found in this survey. Higher platelet levels, lower albumin levels, male sex, incomplete KD, IVIG resistance, and receiving initial IVIG ≤4 days or >10 days, were independently associated with CAL. Conclusions: The incidence of KD in Shanghai had substantially increased while the proportion of CAL had substantially decreased as compared with our previous surveys. Higher platelet levels, lower albumin levels, male sex, incomplete KD, IVIG resistance, and receiving initial IVIG ≤4 days or >10 days, were risk factors for CAL.
Journal Article
Elucidation of genome-wide understudied proteins targeted by PROTAC-induced degradation using interpretable machine learning
Proteolysis-targeting chimeras (PROTACs) are hetero-bifunctional molecules that induce the degradation of target proteins by recruiting an E3 ligase. PROTACs have the potential to inactivate disease-related genes that are considered undruggable by small molecules, making them a promising therapy for the treatment of incurable diseases. However, only a few hundred proteins have been experimentally tested for their amenability to PROTACs, and it remains unclear which other proteins in the entire human genome can be targeted by PROTACs. In this study, we have developed PrePROTAC, an interpretable machine learning model based on a transformer-based protein sequence descriptor and random forest classification. PrePROTAC predicts genome-wide targets that can be degraded by CRBN, one of the E3 ligases. In the benchmark studies, PrePROTAC achieved a ROC-AUC of 0.81, an average precision of 0.84, and over 40% sensitivity at a false positive rate of 0.05. When evaluated by an external test set which comprised proteins from different structural folds than those in the training set, the performance of PrePROTAC did not drop significantly, indicating its generalizability. Furthermore, we developed an embedding SHapley Additive exPlanations (eSHAP) method, which extends conventional SHAP analysis for original features to an embedding space through in silico mutagenesis. This method allowed us to identify key residues in the protein structure that play critical roles in PROTAC activity. The identified key residues were consistent with existing knowledge. Using PrePROTAC, we identified over 600 novel understudied proteins that are potentially degradable by CRBN and proposed PROTAC compounds for three novel drug targets associated with Alzheimer’s disease.
Journal Article
Neuronal dynamics direct cerebrospinal fluid perfusion and brain clearance
The accumulation of metabolic waste is a leading cause of numerous neurological disorders, yet we still have only limited knowledge of how the brain performs self-cleansing. Here we demonstrate that neural networks synchronize individual action potentials to create large-amplitude, rhythmic and self-perpetuating ionic waves in the interstitial fluid of the brain. These waves are a plausible mechanism to explain the correlated potentiation of the glymphatic flow
1
,
2
through the brain parenchyma. Chemogenetic flattening of these high-energy ionic waves largely impeded cerebrospinal fluid infiltration into and clearance of molecules from the brain parenchyma. Notably, synthesized waves generated through transcranial optogenetic stimulation substantially potentiated cerebrospinal fluid-to-interstitial fluid perfusion. Our study demonstrates that neurons serve as master organizers for brain clearance. This fundamental principle introduces a new theoretical framework for the functioning of macroscopic brain waves.
Rhythmic neural activity drives cerebrospinal fluid perfusion through brain parenchyma to enhance brain cleansing.
Journal Article
The Lancet Commission on prostate cancer: planning for the surge in cases
For the Commission, we established four working groups, each of which examined a different aspect of prostate cancer: epidemiology and future projected trends in cases, the diagnostic pathway, treatment, and management of advanced disease, the main problem for most men diagnosed with prostate cancer worldwide. [...]novel methods of empowering patients, such as cloud-based medical record systems, should be exploited to enable doctors and patients to make informed, personalised case-management plans. Linking cloud-based records to artificial intelligence systems could allow access to context-sensitive, up-to-date advice for both patients and health professionals, and could be used to drive evidence-based change in all settings. [...]resource-sensitive guidelines should be implemented to maximise the effect of available therapies, especially surgery and radiotherapy, use of which is often limited in LMICs.
Journal Article
New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death
Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals and metabolites in the circulatory system. The senescence and death of ECs are not only adverse outcomes, but also causal contributors to endothelial dysfunction, an early risk marker of atherosclerosis. The pathophysiological process of EC senescence involves both structural and functional changes and has been linked to various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, and aberrant metabolite sensing and signaling. Multiple forms of EC death have been documented in atherosclerosis, including autophagic cell death, apoptosis, pyroptosis, NETosis, necroptosis, and ferroptosis. Despite this, the molecular mechanisms underlying EC senescence or death in atherogenesis are not fully understood. To provide a comprehensive update on the subject, this review examines the historic and latest findings on the molecular mechanisms and functional alterations associated with EC senescence and death in different stages of atherosclerosis.
Journal Article
Steering ecological-evolutionary dynamics to improve artificial selection of microbial communities
Microbial communities often perform important functions that depend on inter-species interactions. To improve community function via artificial selection, one can repeatedly grow many communities to allow mutations to arise, and “reproduce” the highest-functioning communities by partitioning each into multiple offspring communities for the next cycle. Since improvement is often unimpressive in experiments, we study how to design effective selection strategies in silico. Specifically, we simulate community selection to improve a function that requires two species. With a “community function landscape”, we visualize how community function depends on species and genotype compositions. Due to ecological interactions that promote species coexistence, the evolutionary trajectory of communities is restricted to a path on the landscape. This restriction can generate counter-intuitive evolutionary dynamics, prevent the attainment of maximal function, and importantly, hinder selection by trapping communities in locations of low community function heritability. We devise experimentally-implementable manipulations to shift the path to higher heritability, which speeds up community function improvement even when landscapes are high dimensional or unknown. Video walkthroughs:
https://go.nature.com/3GWwS6j
;
https://online.kitp.ucsb.edu/online/ecoevo21/shou2/
.
Effective artificial selection of microbial communities has proven challenging. In this simulation study, the authors investigate how to improve selection efficacy by increasing community function heritability through experimentally implementable perturbation strategies.
Journal Article
The certification effect of government R&D subsidies on innovative entrepreneurial firms’ access to bank finance
In this paper, we argue that obtaining government R&D subsidies has a certification effect and is used by innovative entrepreneurial firms as a legitimation strategy to access bank finance. We extend the extant literature on the certification effect by combining legitimacy theory with information asymmetry to build our theoretical framework. We test our theoretical model under China’s unique institutional setting, in particular, the weak intellectual property rights (IPR) protection. Using 549 listed and 192 unlisted Chinese innovative entrepreneurial firms from 2009 to 2013, we find a positive certification effect on the acquisition of bank loans for all those sample firms. This positive effect is more profound in unlisted firms in our sample than the listed ones. We further find that regional variation of IPR protection has a moderating effect on the effectiveness of the certification. The certification effect is more significant in those regions where IPR protection is weaker.
Journal Article
Diagnostic value of Lipoarabinomannan antigen for detecting Mycobacterium tuberculosis in adults and children with or without HIV infection
Objectives Even today, tuberculosis (TB) remains a leading public health problem; yet, the current diagnostic methods still have a few shortcomings. Lipoarabinomannan (LAM) provides an opportunity for TB diagnosis, and urine LAM detection seems to have a promising and widely applicable prospect. Design or methods Four databases were systematically searched for eligible studies, and the quality of the studies was evaluated using the quality assessment of diagnostic accuracy studies‐2 (QUADAS‐2). Graphs and tables were created to show sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR), the area under the curve (AUC), and so on. Results Based on the included 67 studies, the pooled sensitivity of urine LAM was 48% and specificity was 89%. In the subgroup analyses, the FujiLAM test had higher sensitivity (69%) and specificity (92%). Furthermore, among patients infected with human immunodeficiency virus (HIV), 50% of TB patients were diagnosed using a urine LAM test. Besides, the CD4+ cell count was inversely proportional to the sensitivity. Conclusions Urine LAM is a promising diagnostic test for TB, particularly using the FujiLAM in HIV‐infected adults whose CD4+ cell count is ≤100 per μl. Besides, the urine LAM test shows various sensitivities and specificities in different subgroups in terms of age, HIV infection status, CD4+ cell count, and testing method. Urine antigen is used as a promising biomarker associated with TB. Urine LAM test is a simple point‐of‐care test and easy to use and fast, achieving high diagnostic accuracy. Moreover, Urine LAM test shows various sensitivities and specificities in different subgroups including age, HIV infection, CD4+ cell count, and examination methods. Thus, Urine LAM test, a simple point‐of‐care test, has been easy to use and fast, achieving high diagnostic accuracy.
Journal Article