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Gao, P.

Publications and source records attributed to Gao, P..

4 recordsLinked to original sources

Microbial and Metabolic Succession on Common Building Materials Under High Humidity Conditions

Despite considerable efforts to characterize the ecology of bacteria and fungi in the built environment (BE), the metabolic mechanisms underpinning their colonization and successional dynamics remain unclear. Here, we applied bacterial/viral particle counting, qPCR, 16S and ITS rRNA amplicon sequencing, and metabolomics to longitudinally characterize the ecological dynamics of four commonly used building materials maintained at high humidity conditions (~94% RH). We varied the natural inoculum provided to each material by placing them in different occupied spaces, and we wet the surface of half of the samples of each material to simulate a flooding event. As expected, different materials showed different bacterial and viral particle abundance, with wet materials having higher growth rates and lower alpha diversity compared to non-wetted materials. Wetting described the majority of the variance in bacterial, fungal and metabolite structure, and material type only influenced bacterial and metabolic diversity, while location of inoculation was only weakly associated with bacterial and fungal beta diversity. Metabolites indicative of microbial activity were identified, as were those that were native to the surface material. Glucose-phosphate was abundant on all materials (except mold-free gypsum) and was correlated with Enterobacteriaceae, which could indicate a potential bacterial nutrient source. A compound consistent with scopoletin, a plant metabolite with antimicrobial activity, was significantly negatively correlated with Bacillus and positively correlated with Pseudomonas and enriched in medium density fiberboard (MDF) materials. In wet samples, the alkaloids nigragillin and fumigaclavine C, both with antimicrobial properties, were significantly positively correlated with the fungal phylum Ascomycota. Nigragillin, was also negatively correlated with Bacillus and Pseudomonas abundance. Thiabendazole and azoxystrobin (anti-fungal compounds) were highly abundant on mold-resistant gypsum wallboard and likely directly influenced the decreased fungal growth observed on this material. The mold-resistant gypsum material also showed a significant increase in bacterial alpha diversity, and bacterial and viral particle abundance, as well as a decrease in metabolite diversity, likely a result of reduced fungal growth. Penicillium taxa were positively correlated with thiabendazole, which suggested the persistence of resistant strains. Also, specific to the wet samples, Bacillus abundance was positively correlated with the azoxystrobin, suggesting bi-directional competitive adaptation, and positively correlated with metabolites known to interfere with Pseudomonas biofilm formation, which could explain the anti-correlation between these taxa. As expected, high moisture conditions enabled faster growth of inoculating microorganisms, whose composition, chemistry, and competition was shaped by surface material, suggesting that both fungal and bacterial growth need to be considered when determining the impact of dampness in built environments.

microbiology

5-Hydroxymethylcytosines from Circulating Cell-free DNA as Diagnostic and Prognostic Markers for Hepatocellular Carcinoma

The lack of highly sensitive and specific diagnostic biomarkers is a major contributor to the poor outcomes of patients with hepatocellular carcinoma (HCC), the second-most common cause of cancer deaths worldwide. We sought to develop a clinically convenient and minimally-invasive approach that can be deployed at scale for the sensitive, specific, and highly reliable diagnosis of HCC, and to evaluate the potential prognostic value of this approach. The study cohort comprised of 2,728 subjects, including HCC patients (n = 1,208), controls (n = 965) (572 healthy individuals and 393 patients with benign lesions), as well as patients with chronic hepatitis B infection (CHB) (n =291), liver cirrhosis (LC) (n = 110), and cholangiocarcinoma (CCC) (n = 154), was recruited from three major liver cancer hospitals in Shanghai, China, from July 2016 to November 2017. Circulating cell-free DNA (cfDNA) were collected from plasma samples from these individuals before surgery or any radical treatment. Applying our 5hmC-Seal technique, the summarized 5-hydroxymethylcytosine (5hmC) profiles in cfDNA were obtained. Molecular annotation analysis suggested that the profiled 5hmC loci in cfDNA were enriched with liver tissue-derived regulatory markers (e.g., H3K4me1). We showed that a weighted diagnostic score (wd-score) based on 117 genes detected using the summarized 5hmC profiles in cfDNA accurately distinguished HCC patients from controls (AUC = 95.1%; 95% CI, 93.6-96.5%) in the validation set, markedly outperformed -fetoprotein (AFP) with superior sensitivity. The wd-scores, which not only detected early BCLC stages (e.g., Stage 0: AUC = 96.2%; 95% CI,94.1-98.4%) and small tumors (e.g., < 2 cm: AUC = 95.7%; 95% CI: 93.6-97.7%), also showed high capacity for distinguishing HCC from non-cancer patients with CHB/LC (AUC = 80.2%; 95% CI, 75.8-84.6%). Moreover, the prognostic value of 5hmC markers in cfDNA was evaluated for HCC recurrence, showing that a weighted prognostic score (wp-score) based on 16 marker genes predicted the recurrence risk (HR = 6.67; 95% CI, 2.81-15.82, p < 0.0001) in 555 patients who have been followed up after surgery. In conclusion, we have developed and validated a robust 5hmC-based diagnostic model that can be applied routinely with clinically feasible amount of cfDNA (e.g., from ~2-5 mL of plasma). Applying this new approach in the clinic could significantly improve the clinical outcomes of HCC patients, for example by early detection of those patients with surgically resectable tumors or as a convenient disease surveillance tool for recurrence.

cancer biology

Myricetin Attenuates LPS-induced Inflammation in RAW 264.7 Macrophages and Mouse Models

BackgroundMyricetin has been demonstrated to inhibit inflammation in a variety of diseases, but little is known about its characters in acute lung injury (ALI). In this study, we aimed to investigate the protective effects of myricetin on inflammation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and a LPS-induced lung injury model.\n\nMethodsSpecifically, we investigated its effects on lung edema and histological damage by lung W/D weight ratio, HE staining and Evans Blue dye. Then macrophage activation was detected by evaluating the TNF-, IL-6 and IL-1{beta} mRNA and protein iNOS and COX-2. Myricetin was used to detect the impact on the inflammatory responses in LPS-induced RAW264.7 cells with the same manners in mouse model. Finally, NF-{kappa}B and MAPK signaling pathways were investigated with Western blot assay in LPS-induced RAW264.7 cells.\n\nResultsMyricetin significantly inhibited the production of the pro-inflammatory cytokines in vitro and in vivo. The in vivo experiments showed that pretreatment with Myricetin markedly attenuated the development of pulmonary edema, histological severities and macrophage activation in mice with ALI. The underlying mechanisms were further demonstrated in vitro that myricetin exerted an anti-inflammatory effect through suppressing the NF-{kappa}B p65 and AKT activation in NF-{kappa}B pathway and JNK, p-ERK and p38 in mitogen-activated protein kinases signaling pathway.\n\nConclusionMyricetin alleviated ALI by inhibiting macrophage activation, and inhibited inflammation in vitro and in vivo. It may be a potential therapeutic candidate for the prevention of inflammatory diseases.

cell biology

A theory of multineuronal dimensionality, dynamics and measurement

In many experiments, neuroscientists tightly control behavior, record many trials, and obtain trial-averaged firing rates from hundreds of neurons in circuits containing billions of behaviorally relevant neurons. Di-mensionality reduction methods reveal a striking simplicity underlying such multi-neuronal data: they can be reduced to a low-dimensional space, and the resulting neural trajectories in this space yield a remarkably insightful dynamical portrait of circuit computation. This simplicity raises profound and timely conceptual questions. What are its origins and its implications for the complexity of neural dynamics? How would the situation change if we recorded more neurons? When, if at all, can we trust dynamical portraits obtained from measuring an infinitesimal fraction of task relevant neurons? We present a theory that answers these questions, and test it using physiological recordings from reaching monkeys. This theory reveals conceptual insights into how task complexity governs both neural dimensionality and accurate recovery of dynamic portraits, thereby providing quantitative guidelines for future large-scale experimental design.

neuroscience