In this paper, Ba(Mg
1/3
Nb
2/3
)O
3
(BMN) ceramics with
x
(
x
= 0–9) wt% BaWO
4
were synthesized using the conventional solid-state sintering technique. Effects of BaWO
4
addition on the ...microstructure and microwave dielectric properties of BMN ceramics were evaluated. X-ray diffraction (XRD) analysis showed that there were three phases: main crystalline phase Ba(Mg
1/3
Nb
2/3
)O
3
and secondary phases BaWO
4
and Ba
5
Nb
4
O
15
. Meanwhile, the (100) super-lattice reflection peaks shifted to a higher 2θ angle with increasing BaWO
4
content. SEM photographs suggested that BaWO
4
working as a sintering additive promoted the densification and grain growth. The dielectric properties were examined by Vector network analyzer. The dielectric constant (ε
r
) was largely determined by the relative density and phase composition. Meanwhile, the addition of BaWO
4
had a positive effect on the
Q
×
f
value, for example the specimen with
x
= 5 possessed the highest
Q
×
f
value of 111,300 GHz. Optimum microwave dielectric properties (ε
r
= 31.7,
Q
×
f
= 111,300 GHz (
f
= 8 GHz) and τ
f
= 0.16 ppm/°C) were obtained for the specimen with
x
= 5 sintered at 1350 °C for 6 h.
A feeding trial was conducted to investigate the effects of dietary protein hydrolysate on the growth, digestive enzyme activity, and expression of genes related to amino acid transport and ...metabolism in larval snakehead. Five isonitrogenous (crude protein, 59%) and isolipidic (crude lipid, 13%) diets were formulated using pre-mixed protein hydrolysates to replace approximately 0% (control, PH0), 25% (PH25), 50% (PH50), 75% (PH75) and 100% (PH100) un-hydrolyzed pre-mixed protein. Triplicate groups of snakehead larvae (17 days post-hatching, initial body weight 122 ± 0.10 mg) were randomly assigned to 15 fiberglass fish tanks with a density of 750 larvae per tank, and fed four times daily for 20 days. At the end of the feeding trial, the growth metric was monitored, and tissues, including intestine and muscle, were separated for physiology and molecular biology analysis. The results showed that dietary protein hydrolysate quadratically increased final body weight (FBW, 2.57–3.73 g) and survival rate (SR, 53.33–60.14%), with the maximum value being observed in the PH75 group (FBW, 3.73 g; SR, 60.14%). Meanwhile, the optimal level of dietary protein hydrolysate elevated the activity of digestive enzymes including trypsin (1558.24–2520.37 U/gpro), lipase (22.37–36.26 U/gpro) and alkaline phosphatase (3.05–3.98 U/mgpro). Gene expression results revealed that protein hydrolysate inclusion quadratically elevated the expression of intestinal amino acid transporter y+LAT2 (0.96–1.51) and peptide transporter PepT1 (0.68–1.22), with the maximum value observed in the PH75 (1.51) and PH50 (1.22) groups, respectively. Meanwhile, the expression of muscle PepT1 (0.97–1.73) was up-regulated linearly, and y+LAT2 expression (0.54–1.01) quadratically decreased with the inclusion of protein hydrolysate. Dietary protein hydrolysate appeared activate the target of rapamycin (TOR) pathway in the muscle through the up-regulation of TOR expression (1.00–1.20) and down-regulation of 4EBP1 expression (0.56–1.01). Additionally, the expression of genes involved in the amino acids response (AAR) pathway in muscle, eIF2α (0.50–1.03), CHOP (0.36–1.09) and REDD1 (0.27–0.98), were linearly inhibited with the inclusion of protein hydrolysate. In above, the optimal level of dietary protein hydrolysate (75%) elevated the growth performance and improved the digestive tract of snakehead larvae. The beneficial role of protein hydrolysates in growth and development is partly attributed to the regulation of genes related to amino acid transport and metabolism.
•Physiological and metabolic changes associated with dietary protein hydrolysate inclusion were investigated in the study.•Optimal dietary protein hydrolysate level improved growth performance and digestive tract development of larval snakehead.•An appropriate level of protein hydrolysate activated the TOR pathway and inhibited the AAR pathway.•Appropriate dietary protein hydrolysate is essential to ensure the overall performance of larval snakehead.
The presence of Eschericia coli (E. coli) leads to potential outbreaks of disease, demonstrating the importance of understanding how such organisms survive in secondary environments such as soil. ...Biotic and abiotic soil characteristics play a role in E. coli survival, but it remains unclear how these two aspects interact with survival and whether it is linked to toxin genes. Here we evaluated the survival of three E. coli O157:H7strains: Shiga toxin-producing E. coli, its mutant without stx genes and strain without virulence genes in 4 distinct Chinese soils. To further disentangle the effects of microbial diversity, soils were manipulated to generate a gradient of microbial diversity (10−1, 10−6, and a sterile soil γ-irradiated control). Overall, our results showed the E. coli O157:H7 survival time decreased in all treatments, ranging from 8.23 ± 5.42 to 62.33 ± 35.80 days. The fastest decline was with the Shiga toxin-producing strain at 10−1 dilution, whereas the strain without virulence genes, persisted the longest 178 days in the γ sterilized control. These results confirmed the importance of biodiversity upon E. coli invasion and revealed virulence genes negatively influenced survival. The negative correlation between community niche or niche breadth of soil communities and survival, indicated that resource competition also was the major driver of E. coli O157:H7 survival. Moreover, path analyses revealed that soil pH exerted a critical role on the persistence of E. coli O157:H7, higher pH values produced longer survival time in each strain. These conclusions are of relevance for agricultural situations, where anthropogenic influences lead to decreased soil diversity, increased soil pH and resource input through manure application, which can potentially increase the survival time of E. coli O157:H7, the expanding the window of opportunity for food contamination.
•Non-virulent O157:H7 survived longer than those carrying virulent-genes.•Biotic resistance was more pronounced in soils with higher pH, indicating biotic and abiotic interactions.•Soil bacterial diversity drives O157:H7 survival through resource and niche competition.
The genetic changes and mechanisms underlying the progression of estrogen-dependent breast cancers to estrogen-independent, antiestrogen-resistant, and metastatic breast cancers are unclear despite ...being a major problem in endocrine therapy. To identify genes responsible for this progression, we carried out a genetic screening by an enhanced retroviral mutagen (ERM)-mediated random mutagenesis in the estrogen-dependent T47D breast cancer cells. We found that T47D cells contain only one p27kip1 (p27) allele coding for the p27 cyclin-dependent kinase (CDK) inhibitor. An ERM insertion into the p27 locus of T47D cells disrupted the p27 gene and created estrogen-independent and antiestrogen-resistant breast cancer cells that still maintained functional estrogen receptors. Disruption of p27 in T47D cells resulted in several changes, and most of these changes could be rescued by p27 restoration. First, CDK2 activity was increased in the absence of estrogen or in the presence of estrogen antagonists tamoxifen or ICI 182780; second, amplified in breast cancer 1 (AIB1), a cancer overexpressed transcriptional coactivator, was hyperphosphorylated, which made AIB1 a better coactivator for E2F1; and third, growth factor receptor binding protein 2-associated binder 2 (Gab2) and Akt activity were increased following E2F1 overactivation, leading to a significant enhancement of cell migration and invasion. Furthermore, the p27-deficient cells, but not T47D control cells, developed lung metastasis in an ovarian hormone-independent manner when they were i.v. injected into nude mice. In sum, loss of p27 activated AIB1, E2F1, Gab2, and Akt; increased cell migration and invasion; caused antiestrogen insensitivity; and promoted metastasis of breast cancer cells. These findings suggest that p27 plays an essential role in restriction of breast cancer progression.
Surufatinib showed superior efficacy in extrapancreatic neuroendocrine tumours (NETs) in the phase 3 SANET-ep study. In SANET-p, we aimed to assess the efficacy and safety of surufatinib in patients ...with advanced pancreatic NETs.
SANET-p was a multicentre, randomised, double-blind, placebo-controlled, phase 3 study, done in 21 hospitals across China. Eligible patients were adults (aged 18 years or older) with progressive, advanced, well differentiated pancreatic NETs, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and progression on up to two kinds of previous systemic regimens for advanced disease. Patients were randomly assigned (2:1) via an interactive web response system to receive 300 mg of surufatinib or placebo, taken orally once per day in consecutive 4-week treatment cycles until disease progression, intolerable toxicity, withdrawal of consent, poor compliance, use of other antitumour medication, pregnancy, loss to follow-up, or if the investigator deemed discontinuation in the patient's best interest. Randomisation was done centrally using stratified block randomisation (block size three), stratified by pathological grade, previous systemic antitumour treatment, and ECOG performance status score. Patients, investigators, research staff, and the sponsor study team were masked to treatment allocation. Crossover to surufatinib was permitted for patients in the placebo group with disease progression. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population, which included all patients in randomisation. A pre-planned interim analysis was done at 70% of the predicted progression-free survival events. This study is registered at ClinicalTrials.gov, NCT02589821.
Between Feb 18, 2016, and Nov 11, 2019, of 264 patients who were screened, 172 (65%) patients were randomly assigned to receive surufatinib (n=113) or placebo (n=59). The median follow-up was 19·3 months (95% CI 9·3–19·4) in the surufatinib group and 11·1 months (5·7–35·9) in the placebo group. The median investigator-assessed progression-free survival was 10·9 months (7·5–13·8) for surufatinib versus 3·7 months (2·8–5·6) for placebo (hazard ratio 0·49, 95% CI 0·32–0·76; p=0·0011). The trial met the early stopping criteria at the interim analysis and was terminated on recommendation from the independent data monitoring committee. The most common grade 3 or worse treatment-related adverse events were hypertension (43 38% of 113 with surufatinib vs four 7% of 59 with placebo), proteinuria (11 10% vs one 2%), and hypertriglyceridaemia (eight 7% vs none). Treatment-related serious adverse events were reported in 25 (22%) patients in the surufatinib group and four (7%) patients in the placebo group. There were three on-treatment deaths in the surufatinib group, including two deaths due to adverse events (gastrointestinal haemorrhage possibly treatment-related and cerebral haemorrhage unlikely to be treatment-related), and one death attributed to disease progression. One on-treatment death in the placebo group was attributed to disease progression.
Surufatinib significantly improves progression-free survival and has an acceptable safety profile in patients with progressive, advanced pancreatic NETs, and could be a potential treatment option in this patient population.
Hutchison MediPharma.
A theory called the Regulatory Gate Hypothesis was previously proposed to considers that the rate limiting step in soil organic carbon (SOC) mineralization is independent of the size, community ...stricture or specific activity (mg CO2-C evolved g−1 biomass C) of the soil microbial biomass. Here we report new experiments to test this hypothesis. In the first experiment, six different soils were perfused with CHCl3-saturated water to model SOC release and to stop microbial activity. Apart from one highly organic soil, they all released SOC at low and roughly constant rates, over sixty three days. In the second experiment, when the freeze-dried perfusates were returned to the parent soils, their % mineralization ranged from 17 to 35% over ten days, in contrast to bulk SOC (range 0.46–0.77%). In the third experiment, two soils were given three consecutive fumigations, each followed by 10 days aerobic incubation. The microbial biomass was decreased by > 90%, yet SOC mineralization proceeded at the same rate as in nonfumigated soil. In the fourth experiment, the six soils were subjected to various perturbations, including non-perturbed controls, fumigation-incubation, air-drying rewetting, freeze-thaw (−20 °C and −80 °C) and sieving < 0.3 mm. After an initial flush due to the perturbations, the rates of mineralization became roughly equal in nearly all soil treatments and comparable to the control, despite significant declines in biomass. This shows that basal respiration was little affected by the perturbations. In Experiment five the effects of the perturbations on the microbial communities in the different soils and perturbations were determined. The bacterial community was significantly modified by both fumigation and air drying-rewetting, due mainly to increased Firmiculites and decreased Proteobacteria populations. Our findings suggest that mineralization of SOC is a two-stage process: firstly, non-bioavailable forms are converted abiologically to bioavailable forms (termed the Regulatory Gate), which, only then, undergo second process, biological mineralization. This finding has serious implications for theories of e.g. SOC dynamics, effects of global warming and soil nutrient cycling.
•CHCl3 fumigation killed >90% of microbial biomass. SOC mineralization unaffected.•CHCl3 greatly changed biomass, community structure and biomass specific activity.•Suggests SOC mineralization rate independent of biomass size and structure while accessibility of microorganisms is limited.•Suggests rate limiting step in SOC mineralization is abiotic.
Chronic obstructive pulmonary disease (COPD) deaths attributed to fine particulate matter (with an aerodynamic equivalent diameter <2.5 μm, PM2.5) exposure are a common global public health concern. ...Recent improvements in air quality and the corresponding health benefits have received much attention. Thus, we have explored the trends of PM2.5 pollution improvement on COPD deaths during an important period of air pollution control (2008-2017) in Pudong New Area, Shanghai, China. Data, including daily COPD death counts, meteorological variables, and ambient air pollutants, were collected from 2008 to 2017. Generalized additive models were fitted to evaluate the percent change (%) in pollution-related COPD deaths. The results showed that the number of days with daily PM2.5 concentrations <35 μg/m3 increased from 19 days (5.19%) in 2008 to 166 days (45.48%) in 2017, and PM2.5 concentrations >75 μg/m3 decreased from 222 days (60.66%) in 2008 to 33 days (9.04%) in 2017. The associations in the overall period between 2008 and 2017 was significant. In subperiod analysis, each 10 μg/m3 increment in PM2.5 was associated with a percent change (%) of 0.89 (95% confidence interval CI, 0.37, 1.42) at lag 5 and 0.78 (95% CI, 0.26, 1.30) at lag 6 during 2008-2013. Significant results were also found at lag 0-5 percent change (%), 1.12 (95% CI, 0.09, 2.17), lag 0-6 percent change (%), 1.52 (95% CI, 0.43, 2.62) and lag 0-7 percent change (%), 1.72 (95% CI, 0.57, 2.88) during 2008-2013. By contrast, no significant association was found between 2014 and 2017. In conclusion, the decreased COPD deaths associated with PM2.5 exposure were found, especially after the air quality improvement turning point in 2014.
Summary
Diverse host factors drive microbial variation in plant‐associated environments, whereas their genetic mechanisms remain largely unexplored. To address this, we coupled the analyses of plant ...genetics and microbiomes in this study. Using 100 tea plant (Camellia sinensis) cultivars, the microbiomes of rhizosphere, root endosphere and phyllosphere showed clear compartment‐specific assembly, whereas the subpopulation differentiation of tea cultivars exhibited small effects on microbial variation in each compartment. Through microbiome genome‐wide association studies, we examined the interactions between tea genetic loci and microbial variation. Notably, genes related to the cell wall and carbon catabolism were heavily linked to root endosphere microbial composition, whereas genes related to the metabolism of metal ions and small organic molecules were overrepresented in association with rhizosphere microbial composition. Moreover, a set of tea genetic variants, including the cytoskeleton‐related formin homology interacting protein 1 gene, were strongly associated with the β‐diversity of phyllosphere microbiomes, implying their interactions with the overall structure of microbial communities. Our results create a catalogue of tea genetic determinants interacting with microbiomes and reveal the compartment‐specific microbiome assembly driven by host genetics.
Rare studies investigated influence of neonicotinoid insecticides on the whole soil biota including non-target invertebrates and microorganisms. And less is known about the consequent intervention on ...soil C processes. This study aimed to decipher Collembola-fungi-bacteria interactive effects on pathways of maize C translocation, combining isotopic tracer analysis of relevant compartments with high-throughput sequencing for bacterial and fungal genetic profiles. Dinotefuran was applied at 0 or 100 μg kg−1 (a simulating residual dosage) to microcosms containing soils, Collembola and 13C labelled maize. Dinotefuran drastically reduced the density and maize-derived biomass C of Collembola, while intensifying antagonistic associations between soil organisms, with flourishing growth of Ascomycota and Actinobacteria, e.g., Streptomyces. This led to higher soil organic C (SOC) mineralization (elevated by 9.8–10.5%) across soils, attributing to the shift in microbial taxonomic and functional guild, e.g., with the increased abundance of genes aligned to cytochrome P450. Maize decomposition was controlled by Collembola that primarily fed on maize, via grazing behavior that facilitated labile maize C preferred decomposers, e.g., Xanthomonadaceae. These findings elucidate the influence of minute dinotefuran on intra-linkages between biomes (Collembola, fungi and bacteria), and highlight such legacy effects on maize and SOC mineralization.
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•Dinotefuran severely inhibited collembolan density and its C assimilation, shifting its diet from omnivorous to herbivorous.•Dinotefuran simplified microbial community structure and intensified the antagonistic connections between species.•Maize C decomposition was majorly driven by Collembolan density.•Dinotefuran promoted soil organic carbon mineralization, attributing to the shift in taxonomic and functional guild.
The distinctive symbiotic relationship between rhizobacteria and soybean (Glycine max) can enhance soil fertility and assist soybean defense heavy metal stress, such as cadmium (Cd), in soils. Soil ...viruses are critical for modulating microbial activities and enhancing host adaptability to soil contamination by encoding auxiliary metabolic genes (AMGs). However, the community structure, functional diversity and ecological roles of soil viruses and their dynamic interactions with soil-dwelling microbes under Cd stress remain unclear. Here, we characterized the bulk and rhizosphere bacterial community in a Cd-contaminated soybean field at five growth stages and investigated the rhizosphere microbial functional traits and the viral community after flowering using metagenomics. We showed that the rhizosphere bacterial community exhibited a stronger soybean development-dependent diversity pattern relative to bulk soil and had a more critical role in predicting Cd accumulation. The relative abundance of Actinobacteria in the rhizosphere increased with soybean development, particularly in the families Nocardioidaceae and Intrasporangiaceae, which were further identified as the main contributors of amino acid transport E and secondary metabolites Q genes. Viral analysis suggested an interactive and complementary assembly between viral and bacterial communities. Importantly, viruses exhibited a broader host range during the flowering period, and infected specific functional taxa such as Bradyrhizobium and Nocardioides, highlighting their potential impact on the rhizobia-soybean symbiosis and soybean growth and fitness. Furthermore, AMGs related to element cycling and microbial metabolism were identified and functionally and phylogenetically characterized, suggesting the contribution of these virus-encoded genes to biogeochemical cycles and soybean fitness under Cd stress. Together, our results expand our understanding of the ecological functions of rhizosphere viruses in Cd pollution-stressed soils, and provide insights in developing new strategies for bioremediation of contaminated soils.
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