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1.
J Proteomics ; 250: 104385, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34606990

RESUMO

Candida albicans is the most common human fungal pathogen in immunocompromised individuals. With the emergence of clinical fungal resistance, there is an urgent need to develop novel antifungal agents. AMP-17, a novel antimicrobial peptide from Musca domestica, has an antifungal effect against C. albicans, but its mechanism of antifungal action remains unclear. In the current study, we performed a proteomics analysis in C. albicans using TMT technique under the treatment of AMP-17. A total of 3931 proteins were identified, of which 3600 included quantitative information. With a 1.5-fold change threshold and a t-test p-value < 0.05 as standard, 423 differentially expressed proteins (DEPs) were up-regulated and 180 DEPs were down-regulated in the AMP-17/control. Notably, GO enrichment revealed that DEPs associated with the cell wall, RNA and oxidative stress were significantly up-regulated, while DEPs involved in ergosterol metabolism and membrane were significantly down-regulated in the AMP-17/control. KEGG pathway enrichment revealed that DEPs involved seven significant metabolic pathways, mainly involved oxidative phosphorylation, RNA degradation, propanoate metabolism and fatty acid metabolism. These results show that AMP-17 induces a complex organism response in C. albicans, indicating that AMP-17 may inhibit growth by affecting multiple targets in C. albicans cells. SIGNIFICANCE: Antimicrobial peptides (AMPs) are an important part of the innate immune system of organisms and having broad range of activity against fungi, bacteria and viruses. These AMPs are considered as probable candidate for forthcoming drugs, due to their broad range of activity, lesser toxicity and decreased resistance development by target cells. AMP-17, a novel antimicrobial peptide from M. domestica, has significant antifungal activity against C. albicans. It has been confirmed that AMP-17 can play an antifungal effect by destroying the cell wall and cell membrane of C. albicans in previous studies, but its mechanism of action at the protein level is currently unclear. In the current study, using the TMT-based quantitative proteomics method, 603 differentially expressed proteins were identified in the cells of C. albicans treated with AMP-17 for 12 h, and these DEPs were closely related to cell wall, cell membrane, RNA degradation and oxidative stress. The results provide new insights into the potential mechanism of action of AMP- 17 against C. albicans. Meanwhile, it provides certain technical support and theoretical basis for the research and development of novel peptide drugs.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34599553

RESUMO

The safety of energy storage equipment has always been a stumbling block to the development of battery, and sodium ion battery is no exception. However, as an ultimate solution, the use of non-flammable electrolyte is susceptible to the side effects, and its poor compatibility with electrode, causing failure of batteries. Here, we report a non-flammable electrolyte design to achieve high-performance sodium ion battery, which resolves the dilemma via regulating the solvation structure of electrolyte by hydrogen bonds and optimizing the electrode-electrolyte interphase. The reported non-flammable electrolyte allows stable charge-discharge cycling of both sodium vanadium phosphate@hard carbon and Prussian blue@hard carbon full pouch cell for more than 120 cycles with a capacity retention of > 85% and high cycling Coulombic efficiency (99.7%).

3.
Nat Commun ; 12(1): 5743, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593817

RESUMO

Machine learning has been increasingly used for protein engineering. However, because the general sequence contexts they capture are not specific to the protein being engineered, the accuracy of existing machine learning algorithms is rather limited. Here, we report ECNet (evolutionary context-integrated neural network), a deep-learning algorithm that exploits evolutionary contexts to predict functional fitness for protein engineering. This algorithm integrates local evolutionary context from homologous sequences that explicitly model residue-residue epistasis for the protein of interest with the global evolutionary context that encodes rich semantic and structural features from the enormous protein sequence universe. As such, it enables accurate mapping from sequence to function and provides generalization from low-order mutants to higher-order mutants. We show that ECNet predicts the sequence-function relationship more accurately as compared to existing machine learning algorithms by using ~50 deep mutational scanning and random mutagenesis datasets. Moreover, we used ECNet to guide the engineering of TEM-1 ß-lactamase and identified variants with improved ampicillin resistance with high success rates.

4.
Int J Mol Sci ; 22(19)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34638684

RESUMO

Maternal obesity disrupts both placental angiogenesis and fetus development. However, the links between adipocytes and endothelial cells in maternal obesity are not fully understood. The aim of this study was to characterize exosome-enriched miRNA from obese sow's adipose tissue and evaluate the effect on angiogenesis of endothelial cells. Plasma exosomes were isolated and analyzed by nanoparticle tracking analysis (NTA), electron morphological analysis, and protein marker expression. The number of exosomes was increased as the gestation of the sows progressed. In addition, we found that exosomes derived from obese sows inhibited endothelial cell migration and angiogenesis. miRNA detection showed that miR-221, one of the miRNAs, was significantly enriched in exosomes from obese sows. Further study demonstrated that exosomal miR-221 inhibited the proliferation and angiogenesis of endothelial cells through repressing the expression of Angptl2 by targeting its 3' untranslated region. In summary, miR-221 was a key component of the adipocyte-secreted exosomal vesicles that mediate angiogenesis. Our study may be a novel mechanism showing the secretion of "harmful" exosomes from obesity adipose tissues causes placental dysplasia during gestation.

5.
Sci Total Environ ; : 150723, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34610410

RESUMO

Exploring the cost-effective pathways for restoring ecosystems is a fundamental aspect for scientific communities and policy-makers aiming for a sustainable future. The South China karst region has experienced severe environmental degradation because of unsustainable management practices in this vulnerable social-ecological context. However, it has also become one of the most stunning areas following its remarkable forest recovery over recent decades as a result of large-scale ecological restoration programs. There is an extensive body of literature focusing on how ecological restoration programs have altered the degraded environment in this region. By searching and comparing the published peer-reviewed articles, we reviewed the studies related to the effects of ecological restoration programs from the point of view of ecological, socio-economic, and integrated social-ecological impacts, as well as influencing factors and restoration approaches. We found independent evidence to support that large-scale ecological restoration programs increased biomass and carbon sequestration since 2000 across this region. The farmers' livelihoods have spontaneously transited from agriculture into forestry or non-farming sectors without financial compensation or incentive schemes, which coincided with a positive correlation between the implementation of ecological restoration programs and poverty alleviation. However, due to a lack of clear "before and after" comparisons, many studies have indirectly determined the impacts of ecological restoration with non-negligible uncertainties. In addition, considering the critical interactions between belowground and aboveground processes in karst regions, special attention should be given to the selection of tree species and restoration measures according to different bedrock types. In the future, to better understand the impact of ecological restoration on social-ecological systems, research could be advanced by considering data access, context-based analysis, measurement-targeted assessment, and cross-scale integration.

6.
Biomolecules ; 11(9)2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34572527

RESUMO

Amino acids are critical for mammalian target of rapamycin complex 1 (mTORC1) activation on the lysosomal surface. Amino acid transporters SLC38A9 and SLC36A1 are the members of the lysosomal amino acid sensing machinery that activates mTORC1. The current study aims to clarify the interaction of SLC38A9 and SLC36A1. Here, we discovered that leucine increased expressions of SLC38A9 and SLC36A1, leading to mTORC1 activation. SLC38A9 interacted with SLC36A1 and they enhanced each other's expression levels and locations on the lysosomal surface. Additionally, the interacting proteins of SLC38A9 in C2C12 cells were identified to participate in amino acid sensing mechanism, mTORC1 signaling pathway, and protein synthesis, which provided a resource for future investigations of skeletal muscle mass.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34563627

RESUMO

CONTEXT: Patients with gastric cancer experience health-related quality of life (HRQOL) decline during adjuvant chemotherapy following gastrectomy. OBJECTIVES: This pilot study aimed to evaluate the preliminary effect and feasibility of electro-acupuncture (EA) for HRQOL and symptom burden in these patients. METHODS: In this open-label, multi-center, parallel controlled trial, gastric cancer patients who planned to receive adjuvant chemotherapy were randomly assigned to receive high-dose EA (seven times each chemotherapy cycle for three cycles), low-dose EA (three times each chemotherapy cycle), or usual care only. The acupoints prescription consisted of bilateral ST36, PC6, SP4, and DU20, EX-HN3, and selected Back-shu points. Patients completed the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) weekly, and the Edmonton Symptom Assessment System (ESAS). The primary outcome was the difference among the groups on the gastric cancer subscale (GaCS) of the FACT-Ga. RESULTS: Of the 66 randomized patients, 58 were analyzed according to intention-to-treat principle, and 45 were in the per-protocol set (PPS). The average scores in PPS of GaCS were 52.12±9.71, 51.85±12.36, and 45.37±8.61 in high-dose EA, low-dose EA, and control groups, respectively. EA was significantly associated with improved average GaCS scores when compared with control group (51.98±10.91 versus 45.37±8.61, p=0.039). EA treatment also produced ESAS relief at the end of intervention (14.36±12.28 versus 23.91±15.52, p=0.027). Participants in EA groups had fewer grade ≥3 leukopenia (0% versus 15.79%, p=0.031) and neutropenia (2.56% versus 26.31%, p=0.012). CONCLUSIONS: EA showed promising effects in improving HRQOL, controlling symptom burden, and reducing toxicity during adjuvant chemotherapy in gastric cancer patients. Future adequately powered trials are feasible and needed to confirm the specific effect of EA.

9.
Fish Physiol Biochem ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581919

RESUMO

Memory drove a critical process of feeding habit transformation in Chinese perch when they re-trained to eat dead prey fish. To investigate the regulatory mechanism of cAMP-response element-binding protein (CREB) signaling pathway on the memory of Chinese perch during feeding habit transformation, the phosphorylation levels of upstream signal proteins of CREB between the control group (trained once) and the experimental group (trained twice) were measured. The results illustrated that the re-training was correlated to phosphorylation of extracellular regulated protein kinase (ERK1/2) and calcium/calmodulin-dependent protein kinase II (CaMKII), and dephosphorylation of protein kinase A (PKA) of Chinese perch. Inhibition of ERK1/2-CREB pathway decreased the mRNA levels of memory-related genes ((fos-related antigen 2 (fra2), CCAAT enhancer-binding protein delta (c/ebpb), immediate-early gene zif268 (zif268), proto-oncogenes c-fos (c-fox) and synaptotagmin-IV (sytIV)) and mRNA levels of appetite-related genes (agouti-related peptide (agrp) and ghrelin), and activation of PP1-CREB pathway increased the phosphorylated levels of CREB, the mRNA levels of memory-related genes (fra2, c/ebpb, zif268, and c-fox), and the mRNA levels of appetite-related genes (pro-opiomelanocortin (pomc) and leptin) in primary brain cells of Chinese perch. The memory in Chinese perch feeding habit transformation was associated with the ERK1/2-CREB and PP1-CREB pathways, which could regulate the transcription of memory-related genes and appetite-related genes.

11.
Cancer Lett ; 521: 130-141, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34461179

RESUMO

The maintenance and expansion of cancer stem-like cells (CSCs) is necessary for metastasis. Although protease-activated receptor 2 (PAR2) is strongly associated with colorectal cancer (CRC) progression, it is unclear how it regulates distal metastasis, and no studies have shown the involvement of CSCs. In this study, we demonstrated that high PAR2 protein expression was correlated with metastatic CRC and poor prognosis in patients with stage III-IV CRC. CSCs from cell lines and patients showed higher levels of PAR2 than that of corresponding non-CSCs, and PAR2 inhibition reduced the CSC properties of the cell lines. Mechanistically, PAR2 inhibition switched the division mode of CSCs from symmetrical to asymmetrical via the ERK/GSK-3ß/ß-catenin pathway. We also identified periostin as a direct transcriptional target of ß-catenin that mediates CSC self-renewal via PAR2 signaling. In a mouse xenograft model, PAR2 knockdown significantly attenuated liver metastasis. Finally, PAR2 expression was positively correlated with ß-catenin and periostin in the primary sites of CRC with distant metastasis. Overall, our results indicate that PAR2 activation enhances CSC self-renewal and promotes metastasis through ß-catenin and its target gene, periostin, in CRC.

12.
Front Immunol ; 12: 702955, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394099

RESUMO

Type 1 diabetes is an autoimmune disease caused by T cell-mediated destruction of insulin-producing ß cells. BDC2.5 T cells in BDC2.5 CD4+ T cell receptor transgenic Non-Obese Diabetic (NOD) mice (BDC2.5 + NOD mice) can abruptly invade the pancreatic islets resulting in severe insulitis that progresses rapidly but rarely leads to spontaneous diabetes. This prevention of diabetes is mediated by T regulatory (Treg) cells in these mice. In this study, we investigated the role of interleukin 10 (IL-10) in the inhibition of diabetes in BDC2.5 + NOD mice by generating Il-10-deficient BDC2.5 + NOD mice (BDC2.5 + Il-10 -/- NOD mice). Our results showed that BDC2.5 + Il-10 -/- NOD mice displayed robust and accelerated diabetes development. Il-10 deficiency in BDC2.5 + NOD mice promoted the generation of neutrophils in the bone marrow and increased the proportions of neutrophils in the periphery (blood, spleen, and islets), accompanied by altered intestinal immunity and gut microbiota composition. In vitro studies showed that the gut microbiota from BDC2.5 + Il-10 -/- NOD mice can expand neutrophil populations. Moreover, in vivo studies demonstrated that the depletion of endogenous gut microbiota by antibiotic treatment decreased the proportion of neutrophils. Although Il-10 deficiency in BDC2.5 + NOD mice had no obvious effects on the proportion and function of Treg cells, it affected the immune response and activation of CD4+ T cells. Moreover, the pathogenicity of CD4+ T cells was much increased, and this significantly accelerated the development of diabetes when these CD4+ T cells were transferred into immune-deficient NOD mice. Our study provides novel insights into the role of IL-10 in the modulation of neutrophils and CD4+ T cells in BDC2.5 + NOD mice, and suggests important crosstalk between gut microbiota and neutrophils in type 1 diabetes development.

13.
Br J Pharmacol ; 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34378191

RESUMO

BACKGROUND AND PURPOSE: Aberrant lipid metabolism is recognized as a key feature of cancer cells. Our initial research on MS-based analysis of lipids in a multiple myeloma (MM) cell line showed a significant accumulation of lipids in multiple myeloma cells after proteasome inhibition. This finding prompted us to hypothesize that multiple myeloma cell survival depends on the maximal utilization of abnormally accumulated lipids. Therefore, we explored whether lipid metabolism-modulating agents would synergize with proteasome inhibitors. EXPERIMENTAL APPROACH: Lipid accumulation in multiple myeloma cells was measured by MS. Synergism between lipid regulators and proteasome inhibitors was assessed by cell viability and apoptosis. A novel stable derivative of fenofibrate (FCE) was synthesized and used to treat multiple myeloma cells in vitro and in vivo along with the proteasome inhibitor ixazomib. ChIP-seq, western blotting and RT-qPCR were performed to explore the potential mechanism(s) underlying the increase in lipid levels in multiple myeloma cells after proteasome inhibition. KEY RESULTS: Accumulation of lipids in multiple myeloma cells was induced by proteasome inhibition. Lipid-lowering drugs and MG-132 exerted a synergistic effect to kill multiple myeloma cells. FCE showed significant synergistic activity in vitro and in vivo with ixazomib. The abnormal lipid accumulation in multiple myeloma cells that was enhanced by proteasome inhibitors might be due to the elevated SREBP1/2 expression induced by ATF4. CONCLUSIONS AND IMPLICATIONS: Our results provide a proof of principle and support for the further clinical evaluation of the combination of lipid-modulating drugs with proteasome inhibitors in the treatment of multiple myeloma.

14.
ACS Nano ; 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34412474

RESUMO

Alloying-type anode materials are regarded as promising alternatives beyond intercalation-type carbonaceous materials for sodium storage owing to the high specific capacities. The rapid capacity decay arising from the huge volume change during Na+-ion insertion/extraction, however, impedes the practical application. Herein, we report an ultrafine antimony embedded in a porous carbon nanocomposite (Sb@PC) synthesized via facile in situ substitution of the Cu nanoparticles in a metal-organic framework (MOF)-derived octahedron carbon framework for sodium storage. The Sb@PC composite displays an appropriate redox potential (0.5-0.8 V vs Na/Na+) and excellent specific capacities of 634.6, 474.5, and 451.9 mAh g-1 at 0.1, 0.2, and 0.5 A g-1 after 200, 500, and 250 cycles, respectively. Such superior sodium storage performance is primarily ascribed to the MOF-derived three-dimensional porous carbon framework and ultrafine Sb nanoparticles, which not only provides a penetrating network for rapid transfer of charge carriers but also alleviates the agglomeration and volume expansion of Sb during cycling. Ex situ X-ray diffraction and in situ Raman analysis clearly reveal a five-stage reaction mechanism during sodiation and desodiation and demonstrate the excellent reversibility of Sb@PC for sodium storage. Furthermore, post-mortem analysis reveals that the robust structural integrity of Sb@PC can withstand continuous Na+-ion insertion/extraction. This work may provide insight into the effective design of high-capacity alloying-type anode materials for advanced secondary batteries.

15.
J Cardiol ; 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34454808

RESUMO

BACKGROUND: Patients with chronic kidney disease (CKD) and coronary instent restenosis (ISR) treated with drug-coated balloon (DCB) angioplasty have been excluded from randomized controlled trials. We aimed to investigate the clinical impact of CKD stratified by severity, on clinical outcomes for patients with ISR treated with DCB angioplasty. METHODS: This cohort study enrolled 1,376 patients treated with DCB angioplasty; 639 CKD patients defined as having an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and 737 patients with preserved renal function were identified. Risks of target vessel failure (TVF), all-cause mortality, and any repeated revascularization were analyzed. RESULTS: The CKD group had a significantly higher risk of TVF [adjusted hazard ratio (HR): 1.337; 95% confidence interval (CI): 1.125-1.590; p = 0.0010], all-cause mortality (adjusted HR: 2.553; 95% CI: 1.494-4.361; p = 0.0006), and any repeated revascularization (adjusted HR: 1.447; 95% CI: 1.087-1.927; p = 0.0114) compared with the non-CKD group. After multivariable adjustment, patients with severe CKD (eGFR = 15-29 mL/min/1.73 m2) and end-stage renal disease (ESRD) (eGFR <15 mL/min/1.73 m2) had a significantly higher risk of adverse events comparable to that in patients with preserved renal function. CONCLUSIONS: In this cohort study, patients with CKD and ISR undergoing DCB angioplasty had a significantly higher risk of adverse events compared with patients with preserved renal function, whereas subgroups with mild to moderate CKD did not display this difference. Different revascularization strategies may be considered for patients with severe CKD or ESRD with ISR.

16.
PLoS Comput Biol ; 17(8): e1009284, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34347784

RESUMO

Modeling the impact of amino acid mutations on protein-protein interaction plays a crucial role in protein engineering and drug design. In this study, we develop GeoPPI, a novel structure-based deep-learning framework to predict the change of binding affinity upon mutations. Based on the three-dimensional structure of a protein, GeoPPI first learns a geometric representation that encodes topology features of the protein structure via a self-supervised learning scheme. These representations are then used as features for training gradient-boosting trees to predict the changes of protein-protein binding affinity upon mutations. We find that GeoPPI is able to learn meaningful features that characterize interactions between atoms in protein structures. In addition, through extensive experiments, we show that GeoPPI achieves new state-of-the-art performance in predicting the binding affinity changes upon both single- and multi-point mutations on six benchmark datasets. Moreover, we show that GeoPPI can accurately estimate the difference of binding affinities between a few recently identified SARS-CoV-2 antibodies and the receptor-binding domain (RBD) of the S protein. These results demonstrate the potential of GeoPPI as a powerful and useful computational tool in protein design and engineering. Our code and datasets are available at: https://github.com/Liuxg16/GeoPPI.


Assuntos
Substituição de Aminoácidos , Modelos Químicos , Proteínas/metabolismo , Mutação Puntual , Ligação Proteica , Proteínas/química , Proteínas/genética
17.
Small ; : e2101650, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34453487

RESUMO

Taking into the consideration safety, environmental impact, and economic issue, the construction of aqueous batteries based on aqueous electrolyte has become an indispensable technical option for large-scale electrical energy storage. The narrow electrochemical window is the main problem of conventional aqueous electrolyte. Here, an economical room-temperature inorganic hydrated molten salt (RTMS) electrolyte with a large electrochemical stability window of 3.1 V is proposed. Compared with organic fluorinated molten salts, RTMS is composed of lithium nitrate hydrate and sodium nitrate with much lower cost. Based on the RTMS electrolyte, a hybrid Li/Na-ion full battery is fabricated from cobalt hexacyanoferrate cathode (NaCoHCF) and perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA) anode. The full cell with the RTMS electrolyte exhibits a fantastic performance with high capacity of 139 mAh g-1 at 1 C, 90 mAh g-1 at 20 C, and capacity retention of 94.7% over 500 cycles at 3 C. The excellent performances are contributed to the unique properties of RTMS with a large electrochemical window, solvated H2 O free and high mobility of Li+ , which exhibits excellent Li-ions insertion and extraction capacity of NaCoHCF. This RTMS cell provides a new economic choice for large-scale energy storage.

18.
Proc Natl Acad Sci U S A ; 118(35)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34429358

RESUMO

Insect development is cooperatively orchestrated by the steroid hormone ecdysone and juvenile hormone (JH). The polycomb repressive complex 2 (PRC2)-mediated histone H3K27 trimethylation (H3K27me3) epigenetically silences gene transcription and is essential for a range of biological processes, but the functions of H3K27 methylation in insect hormone action are poorly understood. Here, we demonstrate that H3K27 methylation-mediated repression of Hairy transcription in the larval prothoracic gland (PG) is required for ecdysone biosynthesis in Bombyx and Drosophila H3K27me3 levels in the PG are dynamically increased during the last larval instar. H3K27me3 reduction induced by the down-regulation of PRC2 activity via inhibitor treatment in Bombyx or PG-specific knockdown of the PRC2 component Su(z)12 in Drosophila diminishes ecdysone biosynthesis and disturbs the larval-pupal transition. Mechanistically, H3K27 methylation targets the JH signal transducer Hairy to repress its transcription in the PG; PG-specific knockdown or overexpression of the Hairy gene disrupts ecdysone biosynthesis and developmental transition; and developmental defects caused by PG-specific Su(z)12 knockdown can be partially rescued by Hairy down-regulation. The application of JH mimic to the PG decreases both H3K27me3 levels and Su(z)12 expression. Altogether, our study reveals that PRC2-mediated H3K27 methylation at Hairy in the PG during the larval period is required for ecdysone biosynthesis and the larval-pupal transition and provides insights into epigenetic regulation of the crosstalk between JH and ecdysone during insect development.

19.
Bioinformatics ; 37(Suppl_1): i349-i357, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34252956

RESUMO

MOTIVATION: Recent advances in single-cell RNA-sequencing (scRNA-seq) technologies promise to enable the study of gene regulatory associations at unprecedented resolution in diverse cellular contexts. However, identifying unique regulatory associations observed only in specific cell types or conditions remains a key challenge; this is particularly so for rare transcriptional states whose sample sizes are too small for existing gene regulatory network inference methods to be effective. RESULTS: We present ShareNet, a Bayesian framework for boosting the accuracy of cell type-specific gene regulatory networks by propagating information across related cell types via an information sharing structure that is adaptively optimized for a given single-cell dataset. The techniques we introduce can be used with a range of general network inference algorithms to enhance the output for each cell type. We demonstrate the enhanced accuracy of our approach on three benchmark scRNA-seq datasets. We find that our inferred cell type-specific networks also uncover key changes in gene associations that underpin the complex rewiring of regulatory networks across cell types, tissues and dynamic biological processes. Our work presents a path toward extracting deeper insights about cell type-specific gene regulation in the rapidly growing compendium of scRNA-seq datasets. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. AVAILABILITY AND IMPLEMENTATION: The code for ShareNet is available at http://sharenet.csail.mit.edu and https://github.com/alexw16/sharenet.


Assuntos
Perfilação da Expressão Gênica , Análise de Célula Única , Teorema de Bayes , Disseminação de Informação , Análise de Sequência de RNA , Software
20.
Adv Mater ; 33(32): e2100921, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34218476

RESUMO

Sulfide solid electrolytes (SEs) are recognized as one of the most promising candidates for all-solid-state batteries (ASSBs), due to their superior ionic conductivity and remarkable ductility. However, poor air stability, complex synthesis process, low yield, and high production cost obstruct the large-scale application of sulfide SEs. Herein, a one-step gas-phase synthesis method for sulfide SEs with oxide raw materials in ambient air, completely getting rid of the glovebox and thus making large-scale production possible, is reported. By adjusting substituted elements and concentrations, the ionic conductivity of Li4- x Sn1- x Mx S4 can reach 2.45 mS cm-1 , which represents the highest value among all reported moist-air-stable and recoverable lithium-ion sulfide SEs reported. Furthermore, ASSBs with air/water-exposed and moderate-temperature-treated Li3.875 Sn0.875 As0.125 S4 even maintains superior performances with the highest reversible capacity (188.4 mAh g-1 ) and the longest cycle life (210 cycles), which also breaks the record. Therefore, it may become one of the most critical breakthroughs during the development of sulfide ASSBs toward its practical application and commercialization.

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