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"Lu, Lin"
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Bottom-up synthetic ecology study of microbial consortia to enhance lignocellulose bioconversion
Lignocellulose is the most abundant organic carbon polymer on the earth. Its decomposition and conversion greatly impact the global carbon cycle. Furthermore, it provides feedstock for sustainable fuel and other value-added products. However, it continues to be underutilized, due to its highly recalcitrant and heterogeneric structure. Microorganisms, which have evolved versatile pathways to convert lignocellulose, undoubtedly are at the heart of lignocellulose conversion. Numerous studies that have reported successful metabolic engineering of individual strains to improve biological lignin valorization. Meanwhile, the bottleneck of single strain modification is becoming increasingly urgent in the conversion of complex substrates. Alternatively, increased attention has been paid to microbial consortia, as they show advantages over pure cultures, e.g., high efficiency and robustness. Here, we first review recent developments in microbial communities for lignocellulose bioconversion. Furthermore, the emerging area of synthetic ecology, which is an integration of synthetic biology, ecology, and computational biology, provides an opportunity for the bottom-up construction of microbial consortia. Then, we review different modes of microbial interaction and their molecular mechanisms, and discuss considerations of how to employ these interactions to construct synthetic consortia via synthetic ecology, as well as highlight emerging trends in engineering microbial communities for lignocellulose bioconversion.
Journal Article
A high capacity small molecule quinone cathode for rechargeable aqueous zinc-organic batteries
Rechargeable aqueous zinc-organic batteries are promising energy storage systems with low-cost aqueous electrolyte and zinc metal anode. The electrochemical properties can be systematically adjusted with molecular design on organic cathode materials. Herein, we use a symmetric small molecule quinone cathode, tetraamino-p-benzoquinone (TABQ), with desirable functional groups to protonate and accomplish dominated proton insertion from weakly acidic zinc electrolyte. The hydrogen bonding network formed with carbonyl and amino groups on the TABQ molecules allows facile proton conduction through the Grotthuss-type mechanism. It guarantees activation energies below 300 meV for charge transfer and proton diffusion. The TABQ cathode delivers a high capacity of 303 mAh g
−1
at 0.1 A g
−1
in a zinc-organic battery. With the increase of current density to 5 A g
−1
, 213 mAh g
−1
capacity is still preserved with stable cycling for 1000 times. Our work proposes an effective approach towards high performance organic electrode materials.
The flexible structural design of organic materials make them promising candidates for cathode in rechargeable batteries. Here, the authors report a tetraamino-p-benzoquinone cathode which realizes facile proton conduction by the Grotthuss-type mechanism and shows excellent electrochemical performance.
Journal Article
Mechanisms of Acupuncture in the Regulation of Oxidative Stress in Treating Ischemic Stroke
Ischemic stroke is the major type of cerebrovascular disease usually resulting in death or disability among the aging population globally. Oxidative stress has been closely linked with ischemic stroke. Disequilibrium between excessive production of reactive oxygen species (ROS) and inherent antioxidant capacity leads to subsequent oxidative damage in the pathological progression of ischemic brain injury. Acupuncture has been applied widely in treating cerebrovascular diseases from time immemorial in China. This review mainly lays stress on the evidence to illuminate the possible mechanisms of acupuncture therapy in treating ischemic stroke through regulating oxidative stress. We found that by regulating a battery of molecular signaling pathways involved in redox modulation, acupuncture not only activates the inherent antioxidant enzyme system but also inhibits the excessive generation of ROS. Acupuncture therapy possesses the potential in alleviating oxidative stress caused by cerebral ischemia, which may be linked with the neuroprotective effect of acupuncture.
Journal Article
Liquid biopsy in lung cancer: significance in diagnostics, prediction, and treatment monitoring
Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so it is necessary to find new tumor markers for early diagnosis and individualized treatment. Tumor markers contribute to the early diagnosis of lung cancer and play important roles in early detection and treatment, as well as in precision medicine, efficacy monitoring, and prognosis prediction. The pathological diagnosis of lung cancer in small biopsy specimens determines whether there are tumor cells in the biopsy and tumor type. Because biopsy is traumatic and the compliance of patients with multiple biopsies is poor, liquid biopsy has become a hot research direction. Liquid biopsies are advantageous because they are nontraumatic, easy to obtain, reflect the overall state of the tumor, and allow for real-time monitoring. At present, liquid biopsies mainly include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. This review introduces the research progress and clinical application prospect of liquid biopsy technology for lung cancer.
Journal Article
Network pharmacology and molecular docking analyses on Lianhua Qingwen capsule indicate Akt1 is a potential target to treat and prevent COVID‐19
Objectives Coronavirus disease 2019 (COVID‐19) is rapidly spreading worldwide. Lianhua Qingwen capsule (LQC) has shown therapeutic effects in patients with COVID‐19. This study is aimed to discover its molecular mechanism and provide potential drug targets. Materials and Methods An LQC target and COVID‐19–related gene set was established using the Traditional Chinese Medicine Systems Pharmacology database and seven disease‐gene databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein‐protein interaction (PPI) network were performed to discover the potential mechanism. Molecular docking was performed to visualize the patterns of interactions between the effective molecule and targeted protein. Results A gene set of 65 genes was generated. We then constructed a compound‐target network that contained 234 nodes of active compounds and 916 edges of compound‐target pairs. The GO and KEGG indicated that LQC can act by regulating immune response, apoptosis and virus infection. PPI network and subnetworks identified nine hub genes. The molecular docking was conducted on the most significant gene Akt1, which is involved in lung injury, lung fibrogenesis and virus infection. Six active compounds of LQC can enter the active pocket of Akt1, namely beta‐carotene, kaempferol, luteolin, naringenin, quercetin and wogonin, thereby exerting potential therapeutic effects in COVID‐19. Conclusions The network pharmacological strategy integrates molecular docking to unravel the molecular mechanism of LQC. Akt1 is a promising drug target to reduce tissue damage and help eliminate virus infection. A Lianhua Qingwen capsule (LQC) target and COVID‐19 related gene set is established to construct compound‐target pharmacology network. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis indicate the regulating effect of LQC on apoptosis, antivirus, immune defense, and inflammatory response. Protein‐protein interaction network and critical subnetworks are constructed to identify hub gene target. The most significant gene, Akt 1, is selected to perform molecular docking with active compounds of LQC. Six compounds are finally recognized as potential anti‐COVID‐19 agents.
Journal Article
The impact of quarantine on mental health status among general population in China during the COVID-19 pandemic
Quarantine and isolation measures urgently adopted to control the COVID-19 pandemic might potentially have negative psychological and social effects. We conducted this cross-sectional, nationwide study to ascertain the psychological effect of quarantine and identify factors associated with mental health outcomes among population quarantined to further inform interventions of mitigating mental health risk especially for vulnerable groups under pandemic conditions. Sociodemographic data, attitudes toward the COVID-19, and mental health measurements of 56,679 participants from 34 provinces in China were collected by an online survey from February 28 to March 11, 2020. Of the 56,679 participants included in the study (mean [SD] age, 36.0 [8.2] years), 27,149 (47.9%) were male and 16,454 (29.0%) ever experienced home confinement or centralized quarantine during COVID-19 outbreak. Compared those without quarantine and adjusted for potential confounders, quarantine measures were associated with increased risk of total psychological outcomes (prevalence, 34.1% vs 27.3%; odds ratio [OR], 1.34; 95% CI, 1.28-1.39; P < 0.001). Multivariable logistic regression analyses showed that vulnerable groups of the quarantined population included those with pre-existing mental disorders or chronic physical diseases, frontline workers, those in the most severely affected areas during outbreak, infected or suspected patients, and those who are less financially well-off. Complying with quarantine, being able to take part in usual work, and having adequate understanding of information related to the outbreak were associated with less mental health issues. These results suggest that quarantine measures during COVID-19 pandemic are associated with increased risk of experiencing mental health burden, especially for vulnerable groups. Further study is needed to establish interventions to reduce mental health consequences of quarantine and empower wellbeing especially in vulnerable groups under pandemic conditions.
Journal Article
qPRF: A system to accelerate population receptive field modeling
BOLD response can be fitted using the population receptive field (PRF) model to reveal how visual input is represented on the cortex (Dumoulin and Wandell, 2008). Fitting the PRF model costs considerable time, often requiring days to analyze BOLD signals for a small cohort of subjects. We introduce the qPRF (“quick PRF”), a system for accelerated PRF modeling that reduced the computation time by a factor >1,000 without losing goodness-of-fit when compared to another widely available PRF modeling package (Kay et al., 2013) on a benchmark of data from the Human Connectome Project (HCP; Van Essen et al. (2013). The system achieves this level of acceleration by pre-computing a tree-like data structure, which it rapidly searches during the fitting step for an optimal parameter combination. We tested the method on a constrained four-parameter version of the PRF model (Strategy 1 herein) and an unconstrained five-parameter PRF model, which the qPRF fitted at comparable speed (Strategy 2). We show how an additional search step can guarantee optimality of qPRF solutions with little additional time cost (Strategy 3). To assess the quality of qPRF solutions, we compared our Strategy 1 solutions to those provided by Benson et al. (2018) who performed a similar four-parameter fit. Both hemispheres of the 181 subjects in the HCP dataset (a total of 10,753,572 vertices, each with a unique BOLD time series of 1800 frames) were analyzed by qPRF in 12.82 h on an ordinary CPU. The absolute difference in R2 achieved by the qPRF compared to Benson et al. (2018) was negligible, with a median of 0.025% (R2 units being between 0% and 100%). In general, the qPRF yielded a slightly better fitting solution, achieving a greater R2 on 70.2% of vertices. We also assess the qPRF method’s model-recovery ability using a simulated dataset. The qPRF may facilitate the development and use of more elaborate models based on the PRF framework and may pave the way for novel clinical applications.
•We describe a system to perform PRF modeling up to 1,500 times faster than others.•The system achieves equivalent goodness-of-fit as others.•A pre-computed tree and similarity-based search strategy underlie the acceleration.
Journal Article
Electroacupuncture ameliorates intestinal inflammation by activating α7nAChR-mediated JAK2/STAT3 signaling pathway in postoperative ileus
Inflammatory cytokines produced by muscularis macrophages largely contribute to the pathological signs of postoperative ileus (POI). Electroacupuncture (EA) can suppress inflammation, mainly or partly via activation of vagal efferent. The goal of this study was to investigate the mechanisms by which EA stimulation at an hindlimb region ameliorates inflammation in POI.
Intestinal motility and inflammation were examined after 24 h after intestinal manipulation (IM)-induced POI in mice. Local immune response in the intestinal muscularis, expression of macrophages, α7 nicotinic acetylcholine receptor (α7nAChR), Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) were determined by flow cytometry, Western Blot, qPCR and immunofluorescence. The effects of α7nAChR antagonists (methyllycaconitine and α-bungarotoxin) and JAK2/STAT3 inhibitors (AG490 and WP1066) were also administered in a subset of mice prior to EA. In the parasympathetic pathways, intestinal motility and inflammation were determined after cervical vagotomy and sub-diaphragmatic vagotomy. The expression of gamma absorptiometry aminobutyric acid (GABA
) receptor in dorsal motor nucleus of vagal (DMV) cholinergic neurons was assessed by immunofluorescence and the response to DMV microinjection of bicuculine (antagonist of GABA
receptor) or muscimol (agonist of GABA
receptor) were assessed.
EA suppressed intestinal inflammation and promoted gastrointestinal motility. Mechanistically, EA activated the α7nAChR-mediated JAK2/STAT3 signaling pathway in macrophages which reduced the production of inflammatory cytokines. Furthermore, we also demonstrated that hindlimb region stimulation drove vagal efferent output by inhibiting the expression of GABA
receptor in DMV to ameliorate inflammation.
The present study revealed that EA of hindlimb regions inhibited the expression of GABA
receptor in DMV neurons, whose excited vagal nerve, in turn suppressed IM-induced inflammation via activation of α7nAChR-mediated JAK2/STAT3 signaling pathway.
Journal Article
The Paradoxical Role of Uric Acid in Osteoporosis
Because of its high prevalence worldwide, osteoporosis is considered a serious public health concern. Many known risk factors for developing osteoporosis have been identified and are crucial if planning health care needs. Recently, an association between uric acid (UA) and bone fractures had been explored. Extracellular UA exhibits antioxidant properties by effectively scavenging free radicals in human plasma, but this benefit might be disturbed by the hydrophobic lipid layer of the cell membrane. In contrast, intracellular free oxygen radicals are produced during UA degradation, and superoxide is further enhanced by interacting with NADPH oxidase. This intracellular oxidative stress, together with inflammatory cytokines induced by UA, stimulates osteoclast bone resorption and inhibits osteoblast bone formation. UA also inhibits vitamin D production and thereby results in hyper-parathyroidism, which causes less UA excretion in the intestines and renal proximal tubules by inhibiting the urate transporter ATP-binding cassette subfamily G member 2 (ABCG2). At normal or high levels, UA is associated with a reduction in bone mineral density and protects against bone fracture. However, in hyperuricemia or gout arthritis, UA increases bone fracture risk because oxidative stress and inflammatory cytokines can increase bone resorption and decrease bone formation. Vitamin D deficiency, and consequent secondary hyperparathyroidism, can further increase bone resorption and aggravated bone loss in UA-induced osteoporosis.
Journal Article