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"Wang Ye, Wang Ye"
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Parallel population and parallel human : a cyber-physical social approach
\"This book is a result of an ambitious research agenda I made for myself almost 30 years ago after reading Karl Popper's The Open Society and its Enemies. To me, the open society should have no enemies, we must find a way to build the bridge between Popper's utopian social engineering and piecemeal social engineering, perhaps through the Cyber-enabled Social Movement Organizations and Operations (CeSMO), and that would be my research for the rest of my professional career. I had promised myself to write a book entitled The Open Society and its Friends, and even created a new name for my ambition, Bemonad, for Becoming and Being Gottfried Leibniz's Monad, which was redefined as the atom of intelligence for Popper's Artificial World in the sense of ancient Greek philosopher Democritus' atom for matters in the Physical World. Of course, I realized very soon that it is simply a dream and a mission impossible. However, this had dramatically changed my career path from intelligent control for robotic systems to a mixture of science, technology, engineering, and social studies for complex intelligent systems, or an interdisciplinary approach by today's term, starting from my technical report at NASA/UA Space Engineering Research Center (SERC) on Shadow Systems in 1994 and ending up with the creation of the Program for Advanced Research in Complex Systems (PARCS) at the University of Arizona, Tucson, Arizona in 1999.\"-- Provided by publisher.
Book
Population Pharmacokinetics of Colistin Sulfate in Critically Ill Patients: Exposure and Clinical Efficacy
Background: Presently, colistin is commercially available in two different forms, namely, colistin sulfate and its sulphomethylated derivative, colistimethate sodium (CMS). However, in the currently reported studies, most of the clinical studies on colistin for parenteral use are referred to as CMS. Data on the pharmacokinetics (PK), clinical efficacy, and side effects of colistin sulfate in clinical use have not been reported. Methods: This retrospective study was performed on carbapenem-resistant organism (CRO)-infected patients treated with colistin sulfate for more than 72 h. The population pharmacokinetic model was developed using the NONMEM program. The clinical outcomes including clinical treatment efficacy, microbiological eradication, and nephrotoxicity were assessed. Monte Carlo simulation was utilized to calculate the probability of target attainment (PTA) in patients with normal or decreased renal function. Results: A total of 42 patients were enrolled, of which 25 (59.52%) patients were considered clinical treatment success and 29 (69.06%) patients had successful bacteria elimination at the end of treatment. Remarkably, no patient developed colistin sulfate-related nephrotoxicity. A total of 112 colistin concentrations with a range of 0.28–6.20 mg/L were included for PK modeling. The PK characteristic of colistin was well illustrated by a one-compartment model with linear elimination, and creatinine clearance (CrCL) was identified as a covariate on the clearance of colistin sulfate that significantly explained inter-individual variability. Monte Carlo simulations showed that the recommended dose regimen of colistin sulfate, according to the label sheet, of a daily dose of 1–1.5 million IU/day, given in 2–3 doses, could attain PTA > 90% for MICs ≤ 0.5 μg/mL, and that a daily dose of 1 million IU/day could pose a risk of subtherapeutic exposure for MIC ≥1 μg/ml in renal healthy patients. Conclusion: Renal function significantly affects the clearance of colistin sulfate. A dose of 750,000 U every 12 h was recommended for pathogens with MIC ≤1 μg/ml. The dosage recommended by the label inserts had a risk of subtherapeutic exposure for pathogens with MIC ≥2 μg/ml. Despite higher exposure to colistin in patients with acute renal insufficiency, dose reduction was not recommended.
Journal Article
Post-infection cognitive impairments in a cohort of elderly patients with COVID-19
Background
Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for monitoring the cognitive decline in the elderly population. This study aims to assess the current cognitive status and the longitudinal cognitive decline in elderly patients recovered from COVID-19.
Methods
This cross-sectional study recruited 1539 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to April 10, 2020. In total, 466 uninfected spouses of COVID-19 patients were selected as controls. The current cognitive status was assessed using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and the longitudinal cognitive decline was assessed using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge.
Results
Compared with controls, COVID-19 patients had lower TICS-40 scores and higher IQCODE scores [TICS-40 median (IQR): 29 (25 to 32) vs. 30 (26 to 33),
p
< 0.001; IQCODE median (IQR): 3.19 (3.00 to 3.63) vs. 3.06 (3.00 to 3.38),
p
< 0.001]. Severe COVID-19 patients had lower TICS-40 scores and higher IQCODE scores than non-severe COVID-19 patients [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33),
p
< 0.001; IQCODE median (IQR): 3.63 (3.13 to 4.31) vs. 3.13 (3.00 to 3.56),
p
< 0.001] and controls [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33),
p
< 0.001; IQCODE median (IQR) 3.63 (3.13 to 4.31) vs. 3.06 (3.00 to 3.38),
p
< 0.001]. Severe COVID-19 patients had a higher proportion of cases with current cognitive impairment and longitudinal cognitive decline than non-severe COVID-19 patients [dementia: 25 (10.50 %) vs. 9 (0.69 %),
p
< 0.001; Mild cognitive impairment (MCI): 60 (25.21 %) vs. 63 (4.84 %),
p
< 0.001] and controls [dementia: 25 (10.50 %) vs. 0 (0 %),
p
< 0.001; MCI: 60 (25.21 %) vs. 20 (4.29 %),
p
< 0.001)]. COVID-19 severity, delirium and COPD were risk factors of current cognitive impairment. Low education level, severe COVID-19, delirium, hypertension and COPD were risk factors of longitudinal cognitive decline.
Conclusions
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with an increased risk of long-term cognitive decline in elderly population. COVID-19 patients, especially severe patients, should be intensively monitored for post-infection cognitive decline.
Journal Article
UDP-glucosyltransferase regulates grain size and abiotic stress tolerance associated with metabolic flux redirection in rice
Grain size is an important component trait of grain yield, which is frequently threatened by abiotic stress. However, little is known about how grain yield and abiotic stress tolerance are regulated. Here, we characterize
GSA1
, a quantitative trait locus (QTL) regulating grain size and abiotic stress tolerance associated with metabolic flux redirection.
GSA1
encodes a UDP-glucosyltransferase, which exhibits glucosyltransferase activity toward flavonoids and monolignols.
GSA1
regulates grain size by modulating cell proliferation and expansion, which are regulated by flavonoid-mediated auxin levels and related gene expression. GSA1 is required for the redirection of metabolic flux from lignin biosynthesis to flavonoid biosynthesis under abiotic stress and the accumulation of flavonoid glycosides, which protect rice against abiotic stress.
GSA1
overexpression results in larger grains and enhanced abiotic stress tolerance. Our findings provide insights into the regulation of grain size and abiotic stress tolerance associated with metabolic flux redirection and a potential means to improve crops.
Increasing grain yield needs to be put in the context of environmental stress. Here, the authors reveal that a UDP-glucosyltransferase is associated with regulation of rice grain size, abiotic stress tolerance, flavonoid-mediated auxin signaling, and redirection of carbon flux to flavonoid glycosides synthesis.
Journal Article
cMolGPT: A Conditional Generative Pre-Trained Transformer for Target-Specific De Novo Molecular Generation
Deep generative models applied to the generation of novel compounds in small-molecule drug design have attracted a lot of attention in recent years. To design compounds that interact with specific target proteins, we propose a Generative Pre-Trained Transformer (GPT)-inspired model for de novo target-specific molecular design. By implementing different keys and values for the multi-head attention conditional on a specified target, the proposed method can generate drug-like compounds both with and without a specific target. The results show that our approach (cMolGPT) is capable of generating SMILES strings that correspond to both drug-like and active compounds. Moreover, the compounds generated from the conditional model closely match the chemical space of real target-specific molecules and cover a significant portion of novel compounds. Thus, the proposed Conditional Generative Pre-Trained Transformer (cMolGPT) is a valuable tool for de novo molecule design and has the potential to accelerate the molecular optimization cycle time.
Journal Article
Strain Effects in Twisted Spiral Antimonene
Van der Waals (vdW) layered materials exhibit fruitful novel physical properties. The energy band of such materials depends strongly on their structures, and a tremendous variation in their physical properties can be deduced from a tiny change in inter‐layer spacing, twist angle, or in‐plane strain. In this work, a kind of vdW layered material of spiral antimonene is constructed, and the strain effects in the material are studied. The spiral antimonene is grown on a germanium (Ge) substrate and is induced by a helical dislocation penetrating through few atomic‐layers of antimonene (β‐phase). The as‐grown spiral is intrinsically strained, and the lattice distortion is found to be pinned around the dislocation. Both spontaneous inter‐layer twist and in‐plane anisotropic strain are observed in scanning tunneling microscope (STM) measurements. The strain in the spiral antimonene can be significantly modified by STM tip interaction, leading to a variation in the surface electronic density of states (DOS) and a large modification in the work function of up to a few hundreds of millielectron‐volts (meV). Those strain effects are expected to have potential applications in building up novel piezoelectric devices. Antimonene spirals are epitaxially grown on a germanium substrate. Owing to the presence of a helical dislocation, the as‐grown spiral is anisotropically strained. The strain in the spiral can be changed by scanning tunneling microscopy tip manipulation, resulting in modulations of the electronic density of states and the work function.
Journal Article
Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study
Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans.
We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed.
Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor.
A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
Journal Article
GRAIN SIZE AND NUMBER1 Negatively Regulates the OsMKKK10-OsMKK4-OsMPK6 Cascade to Coordinate the Trade-off between Grain Number per Panicle and Grain Size in Rice
Grain number and size are interactive agronomic traits that determine grain yield. However, the molecular mechanisms responsible for coordinating the trade-off between these traits remain elusive. Here, we characterized the rice (Oryza sativa) grain size and number1 (gsn1) mutant, which has larger grains but sparser panicles than the wild type due to disordered localized cell differentiation and proliferation. GSN1 encodes the mitogen-activated protein kinase phosphatase OsMKP1, a dual-specificity phosphatase of unknown function. Reduced expression of GSN1 resulted in larger and fewer grains, whereas increased expression resulted in more grains but reduced grain size. GSN1 directly interacts with and inactivates the mitogen-activated protein kinase OsMPK6 via dephosphorylation. Consistent with this finding, the suppression of mitogen-activated protein kinase genes OsMPK6, OsMKK4, and OsMKKK10 separately resulted in denser panicles and smaller grains, which rescued the mutant gsn1 phenotypes. Therefore, OsMKKK10-OsMKK4-OsMPK6 participates in panicle morphogenesis and acts on a common pathway in rice. We confirmed that GSN1 is a negative regulator of the OsMKKK10-OsMKK4-OsMPK6 cascade that determines panicle architecture. The GSN1-MAPK module coordinates the trade-off between grain number and grain size by integrating localized cell differentiation and proliferation. These findings provide important insights into the developmental plasticity of the panicle and a potential means to improve crop yields.
Journal Article
Spatiotemporal Dynamics of the Eco-Innovation Level of China’s Marine Economy
This paper aims to provide a reliable basis for formulating, revising, and selecting sustainable marine economic development plans through a scientific and comprehensive evaluation of the eco-innovation level of China’s marine economy. Based on the analysis of the three-stage theoretical model of marine economic eco-innovation, an index system for evaluating the eco-innovation level of China’s marine economy is first constructed. Also, an integration EWM-HDEMATEL method that balances objective and subjective weighting is introduced to determine the index weights. The proposed methods are applied to analyze the temporal and spatial variations in the eco-innovation level of China’s marine economy in 2006–2021, and the following conclusions are drawn. First, between 2006 and 2021, the average level of marine economic ecological innovation across all regions exhibited a steady upward trajectory. Second, regional imbalances in ecological innovation intensified over the study period, with the maximum disparity widening from a 1.6-fold difference in 2006 to a 2.5-fold difference in 2021. Third, although differences among the three principal marine economic zones were not pronounced, significant heterogeneity persisted within each zone, underscoring the need for targeted policies and interventions to achieve coordinated development. Fourth, regions performed better on the support environment and performance dimensions of marine economic ecological innovation than on the capacity and activity dimensions. These findings identify critical leverage points for policy action and carry important implications for promoting the balanced and sustainable development of marine economic ecological innovation efficiency.
Journal Article
Physiological clearance of amyloid-beta by the kidney and its therapeutic potential for Alzheimer’s disease
Amyloid-β (Aβ) accumulation in the brain is a pivotal event in the pathogenesis of Alzheimer’s disease (AD), and its clearance from the brain is impaired in sporadic AD. Previous studies suggest that approximately half of the Aβ produced in the brain is cleared by transport into the periphery. However, the mechanism and pathophysiological significance of peripheral Aβ clearance remain largely unknown. The kidney is thought to be responsible for Aβ clearance, but direct evidence is lacking. In this study, we investigated the impact of unilateral nephrectomy on the dynamic changes in Aβ in the blood and brain in both humans and animals and on behavioural deficits and AD pathologies in animals. Furthermore, the therapeutic effects of the diuretic furosemide on Aβ clearance via the kidney were assessed. We detected Aβ in the kidneys and urine of both humans and animals and found that the Aβ level in the blood of the renal artery was higher than that in the blood of the renal vein. Unilateral nephrectomy increased brain Aβ deposition; aggravated AD pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, and neuronal loss; and aggravated cognitive deficits in APP/PS1 mice. In addition, chronic furosemide treatment reduced blood and brain Aβ levels and attenuated AD pathologies and cognitive deficits in APP/PS1 mice. Our findings demonstrate that the kidney physiologically clears Aβ from the blood, suggesting that facilitation of Aβ clearance via the kidney represents a novel potential therapeutic approach for AD.
Journal Article