To investigate the effects of co-infection with Clonorchis sinensis (C. sinensis) on T cell exhaustion levels in patients with chronic hepatitis B, we enrolled clinical cases in this study, including the patients with concomitant C. sinensis and HBV infection. In this study, we detected inhibitory receptors and cytokine expression in circulating CD4+ and CD8+ T cells by flow cytometry. PD-1 and TIM-3 expression levels were significantly higher on CD4+ T and CD8+ T cells from co-infected patients than on those from the HBV patients. In addition, CD4+ T cells and CD8+ T cells function were significantly inhibited by C. sinensis and HBV co-infection compared with HBV single infection, secreting lower levels of Interferon gamma (IFN-γ), Interleukin-2 (IL-2), and TNF-α. Our current results suggested that C. sinensis co-infection could exacerbate T cell exhaustion in patients with chronic hepatitis B. PD-1 and TIM-3 could be novel biomarkers for T cell exhaustion in patients with Clonorchis sinensis and chronic hepatitis B co-infection. Furthermore, it may be one possible reason for the weaker response to antiviral therapies and the chronicity of HBV infection in co-infected patients. We must realize the importance of C. sinensis treatment for HBV-infected patients. It might provide useful information for clinical doctors to choose the right treatment plans.

This paper discusses a general class of replicator–mutator equations on a multidimensional fitness space. We establish a novel probabilistic representation of weak solutions of the equation by using the theory of Fokker–Planck–Kolmogorov (FPK) equations and a martingale extraction approach. We provide examples with closed-form probabilistic solutions for different fitness functions considered in the existing literature. We also construct a particle system and prove a general convergence result to the unique solution of the FPK equation associated with the extended replicator–mutator equation with respect to a Wasserstein-like metric adapted to our probabilistic framework.

Nutritional Risk Screening index is a standard tool to assess nutritional risk, but epidemiological data are scarce on controlling nutritional status (CONUT) as a prognostic marker in acute haemorrhagic stroke (AHS). We aimed to explore whether the CONUT may predict a 3-month functional outcome in AHS. In total, 349 Chinese patients with incident AHS were consecutively recruited, and their malnutrition risks were determined using a high CONUT score of ≥ 2. The cohort patients were divided into high-CONUT (≥ 2) and low-CONUT (< 2) groups, and primary outcomes were a poor functional prognosis defined as the modified Rankin Scale (mRS) score of ≥ 3 at post-discharge for 3 months. Odds ratios (OR) with 95 % confidence intervals (CI) for the poor functional prognosis at post-discharge were estimated by using a logistic analysis with additional adjustments for unbalanced variables between the high-CONUT and low-CONUT groups. A total of 328 patients (60·38 ± 12·83 years; 66·77 % male) completed the mRS assessment at post-discharge for 3 months, with 172 patients at malnutrition risk at admission and 104 patients with a poor prognosis. The levels of total cholesterol and total lymphocyte counts were significantly lower in high-CONUT patients than low-CONUT patients (P = 0·012 and < 0·001, respectively). At 3-month post discharge, there was a greater risk for the poor outcome in the high-CONUT compared with the low-CONUT patients at admission (OR: 2·32, 95 % CI: 1·28, 4·17). High-CONUT scores independently predict a 3-month poor prognosis in AHS, which helps to identify those who need additional nutritional managements.

The oriental armyworm Mythimna separata (Walker) (Lepidoptera: Noctuidae) is a major migratory pest of cereal crops in East Asia, South Asia and Australia. To comprehensively understand the ecological tolerance of M. separata, we collected life table data of individuals from four consecutive generations reared under outdoor natural fluctuating temperatures from 15 April to 17 October 2018 in Yangling, Shaanxi, China. The results showed that the immature stage in early summer and summer were shorter than in spring and autumn. High mortality in late larval instar and pupal stages was observed in the summer generation. The adult pre-oviposition period in autumn was longer than the other seasons. The population in the earlier two seasons had heavier pupae and higher fecundity than the population in the latter two seasons. The intrinsic rate of increase and the finite rate of increase was the highest in early summer (r = 0.1292 day−1, λ = 1.1391 day−1), followed by spring (r = 0.1102 day−1, λ = 1.1165 day−1), and was the lowest in summer (r = 0.0281 day−1, λ = 1.0293 day−1). The results of this study would be useful to predict the population dynamics of M. separata and deepen our standing of the adaptiveness of this migratory pest in natural fluctuating ambient environments.

Severe cracking and unsatisfied mechanical performance are the major challenges of manufacturing titanium aluminide (TiAl) components by selective laser melting (SLM). In this work, graphene oxide (GO) sheets were introduced onto the metal powder surface to improve the manufacturability of SLM of a Ti–48Al–2Cr–2Nb (at.%) alloy and enhance the mechanical strength of the laser-fabricated parts. The effect of laser power and GO content on the macromorphology of single-track processing was investigated, showing that the crack-free track could be obtained with the addition of 0.1–0.5 wt.% GO under a laser power of 110 W. In addition, the characterization of multilayer buildups via electron backscatter diffraction and backscatter electron imaging reveals the grain refinement during SLM of GO/TiAl nanocomposites. Finally, the strength of the as-built samples was examined using micro-hardness test, showing a maximal increase of 21.9% by adding 0.3 wt.% GO into the TiAl powders from laser-fabricated samples without GO.

Taurine (TAU) plays important roles in the metabolism of bile acids, cholesterol and lipids. However, little relevant information has been available in fish where TAU has been identified as a conditionally essential nutrient. The present study aimed to investigate the effects of dietary TAU on the metabolism of bile acids, cholesterol and lipids in tiger puffer, which is both an important aquaculture species and a good research model, having a unique lipid storage pattern. An 8-week feeding trial was conducted in a flow-through seawater system. Three experimental diets differed only in TAU level, that is, 1·7, 8·2 and 14·0 mg/kg. TAU supplementation increased the total bile acid content in liver but decreased the content in serum. TAU supplementation also increased the contents of total cholesterol and HDL-cholesterol in both liver and serum. The hepatic bile acid profile mainly includes taurocholic acid (94·48 %), taurochenodeoxycholic acid (4·17 %) and taurodeoxycholic acid (1·35 %), and the contents of all these conjugated bile acids were increased by dietary TAU. The hepatic lipidomics analysis showed that TAU tended to decrease the abundance of individual phospholipids and increase those of some individual TAG and ceramides. The hepatic mRNA expression study showed that TAU stimulated the biosynthesis of both bile acids and cholesterol, possibly via regulation of farnesoid X receptor and HDL metabolism. TAU also stimulated the hepatic expression of lipogenic genes. In conclusion, dietary TAU stimulated the hepatic biosynthesis of both bile acids and cholesterol and tended to regulate lipid metabolism in multiple ways.

Echinococcus granulosus sensu stricto (s.s.), Echinococcus multilocularis and Echinococcus canadensis are the common causes of human echinococcosis in China. An accurate species identification tool for human echinococcosis is needed as the treatments and prognosis are different among species. The present work demonstrates a method for the simultaneous detection of these three Echinococcus species based on multiplex polymerase chain reaction (mPCR). Specific primers of this mPCR were designed based on the mitochondrial genes and determined by extensive tests. The method can successfully detect either separated or mixed target species, and generate expected amplicons of distinct size for each species. Sensitivity of the method was tested by serially diluted DNA, showing a detection threshold as less as 0.32 pg for both E. granulosus s.s. and E. canadensis, and 1.6 pg for E. multilocularis. Specificity assessed against 18 other parasites was found to be 100% except weakly cross-react with E. shiquicus. The assay was additionally applied to 69 echinococcosis patients and 38 healthy persons, confirming the high reliability of the method. Thus, the mPCR described here has high application potential for clinical identification purposes, and can further provide a useful tool for evaluation of serology and imaging method.

Ca2+-sensing receptor (CaSR) represents a potential therapeutic target for inflammatory bowel diseases and strongly prefers aromatic amino acid ligands. We investigated the regulatory effects of dietary supplementation with aromatic amino acids – tryptophan, phenylalanine and tyrosine (TPT) – on the CaSR signalling pathway and intestinal inflammatory response. The in vivo study was conducted with weanling piglets using a 2 × 2 factorial arrangement in a randomised complete block design. Piglets were fed a basal diet or a basal diet supplemented with TPT and with or without inflammatory challenge. The in vitro study was performed in porcine intestinal epithelial cell line to investigate the effects of TPT on inflammatory response using NPS-2143 to inhibit CaSR. Dietary supplementation of TPT alleviated histopathological injury and decreased myeloperoxidase activity in intestine challenged with lipopolysaccharide. Dietary supplementation of TPT decreased serum concentration of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-12, granulocyte-macrophage colony-stimulating factor, TNF-α), as well as the mRNA abundances of pro-inflammatory cytokines in intestine but enhanced anti-inflammatory cytokines IL-4 and transforming growth factor-β mRNA levels compared with pigs fed control diet and infected by lipopolysaccharide. Supplementation of TPT increased CaSR and phospholipase Cβ2 protein levels, but decreased inhibitor of NF-κB kinase α/β and inhibitor of NF-κB (IκB) protein levels in the lipopolysaccharide-challenged piglets. When the CaSR signalling pathway was blocked by NPS-2143, supplementation of TPT decreased the CaSR protein level, but enhanced phosphorylated NF-κB and IκB levels in IPEC-J2 cells. To conclude, supplementation of aromatic amino acids alleviated intestinal inflammation as mediated through the CaSR signalling pathway.

Let $A$ be an expansive dilation on $\mathbb{R}^{n}$ and $\unicode[STIX]{x1D711}:\mathbb{R}^{n}\times [0,\infty )\rightarrow [0,\infty )$ an anisotropic growth function. In this article, the authors introduce the anisotropic weak Musielak–Orlicz Hardy space $\mathit{WH}_{A}^{\unicode[STIX]{x1D711}}(\mathbb{R}^{n})$ via the nontangential grand maximal function and then obtain its Littlewood–Paley characterizations in terms of the anisotropic Lusin-area function, $g$-function or $g_{\unicode[STIX]{x1D706}}^{\ast }$-function, respectively. All these characterizations for anisotropic weak Hardy spaces $\mathit{WH}_{A}^{p}(\mathbb{R}^{n})$ (namely, $\unicode[STIX]{x1D711}(x,t):=t^{p}$ for all $t\in [0,\infty )$ and $x\in \mathbb{R}^{n}$ with $p\in (0,1]$) are new. Moreover, the range of $\unicode[STIX]{x1D706}$ in the anisotropic $g_{\unicode[STIX]{x1D706}}^{\ast }$-function characterization of $\mathit{WH}_{A}^{\unicode[STIX]{x1D711}}(\mathbb{R}^{n})$ coincides with the best known range of the $g_{\unicode[STIX]{x1D706}}^{\ast }$-function characterization of classical Hardy space $H^{p}(\mathbb{R}^{n})$ or its weighted variants, where $p\in (0,1]$.

Image segmentation is a key process in analyzing biological images. However, it is difficult to detect the differences between foreground and background when the image is unevenly illuminated. The unambiguous segmenting of multi-well plate microscopy images with various uneven illuminations is a challenging problem. Currently, no publicly available method adequately solves these various problems in bright-field multi-well plate images. Here, we propose a new method based on contrast values which removes the need for illumination correction. The presented method is effective enough to distinguish foreground and therefore a model organism (Caenorhabditis elegans) from an unevenly illuminated microscope image. In addition, the method also can solve a variety of problems caused by different uneven illumination scenarios. By applying this methodology across a wide range of multi-well plate microscopy images, we show that our approach can consistently analyze images with uneven illuminations with unparalleled accuracy and successfully solve various problems associated with uneven illumination. It can be used to process the microscopy images captured from multi-well plates and detect experimental subjects from an unevenly illuminated background.

To evaluate the effects of different anthropogenic activities on zooplankton and the pelagic ecosystem, we conducted seasonal cruises in 2010 to assess spatial heterogeneity among the mesozooplankton communities of Xiangshan Bay, a subtropical semi-enclosed bay in China. The evaluation included five different areas: a kelp farm, an oyster farm, a fish farm, the thermal discharge area of a power plant, and an artificial reef, and we aimed to identify whether anthropogenic activities dominated spatial variation in the mesozooplankton communities. The results demonstrated clear spatial heterogeneity among the mesozooplankton communities of the studied areas, dominantly driven by natural hydrographic properties, except in the area near the thermal discharge outlet of the power station. In the outlet area, thermal shock caused by the discharge influenced the mesozooplankton community by decreasing abundance and biomass throughout the four seasons, even causing a shift in the dominant species near the outlet during summer from Acartia pacifica to eurythermal and warm water taxa. Unique features of the mesozooplankton community in the oyster farm may be due to the combined effects of oyster culture and the natural environment in the branch harbour. However, kelp and fish culture, and the construction of an artificial reef did not exert any obvious influence on the mesozooplankton communities up to 2010, probably because of the small scale of the aquaculture and a time lag in the rehabilitation effects of the artificial reef. Thus, our results suggested that the dominant factors influencing spatial variations of mesozooplankton communities in Xiangshan Bay were still the natural hydrographic properties, but the thermal discharge was an anthropogenic activity that changed the pelagic ecosystem, and should be supervised.

Mouse strain differences in immobility and in sensitivity to antidepressants have been observed in the forced swimming test (FST) and the tail suspension test (TST). However, the neurotransmitter systems and neural substrates that contribute to these differences remain unknown. To investigate the role of the hippocampal serotonin transporter (5-HTT), we measured baseline immobility and the immobility responses to fluoxetine (FLX) in the FST and the TST in male CD-1, C57BL/6, DBA and BALB/c mice. We observed strain differences in baseline immobility time, with CD-1 mice showing the longest and DBA mice showing the shortest. In contrast, DBA and BALB/c mice showed the highest sensitivity to FLX, whereas CD-1 and C57BL/6 mice showed the lowest sensitivity. Also we found strain differences in both the total 5-HTT protein level and the membrane-bound 5-HTT level (estimated by Vmax) as follows: DBA > BALB/c > CD-1 = C57BL/6. The uptake efficiency of the membrane-bound 5-HTT (estimated by 1/Km) was highest in DBA and BALB/c mice and lowest in CD-1 and C57BL/6 mice. A correlation analysis of subregions within the hippocampus revealed that immobility time was negatively correlated with Vmax and positively correlated with Km in the hippocampus. Therefore a higher uptake capacity of the membrane-bound 5-HTT in the hippocampus was associated with lower baseline immobility and greater sensitivity to FLX. These results suggest that alterations in hippocampal 5-HTT activity may contribute to mouse strain differences in the FST and the TST.

A real-time fluorescent polymerase chain reaction (PCR) assay was established to detect Streptococcus suis serotype 2. Primers and Taqman probe were designed according to cps2I (capsular polysaccharide 2I) gene using bio-software Primer Express2.0 and Oligo6.0. An 81 bp DNA fragment was amplified from S. suis serotype 2 genomic DNA, and the PCR product was cloned into pMD18-T vector and confirmed by DNA sequencing. The real-time fluorescent PCR amplification curve on a Lightcycler® showed that the method is accurate and specific for S. suis serotype 2 amplification, whereas reference bacteria S. suis, Escherichia coli, Salmonella sp., Staphylococcus aureus, Shigella sp., Listeria monocytogenes strains and a blank control were all negative. Tenfold serial dilutions of S. suis serotype 2 were used to measure the sensitivity of real-time fluorescent PCR: ten copies of bacteria could be detected in one PCR reaction and only 30 min were required for a single test. To examine the stability of the real-time fluorescent PCR, the positive control was detected at two different times. The threshold cycle (Ct) values showed no statistical differences (P>0.05). Thus, this method was stable and repeatable. These results indicate that this real-time fluorescent PCR technique could be applied for epidemic supervision in entry–exit inspection and quarantine.

The prototype of a field-emission pressure sensor with a novel structure based on the quantum tunnel effect is designed and manufactured. Moreover the nano crystalline silicon film technology is introduced into the fabrication of the device effectively, which performs the function mostly as the field-emission material, the device field-emission characteristic of the nano silicon film is investigated, the experimental results show that the measured current density emitted from the effective area of the sensor can reach 53.5A/m2, when the exterior electric field is 5.6×105V/m.

We have studied the influence of interface roughness scattering on the mobility of two-dimensional electron gas(2DEG) in GaAs-AlGaAs modulation-doped heterostructures(MDH) both experimentally and theoretically. When the background ionized impurity concentration in the GaAs layer is smaller than 2.5×1015cm-3, our investigation shows that interface roughness scattering is the dominant scattering mechanism in the high 2DEG density(Nş ≥5× 1011cm2) GaAs-AlGaAs MDH. We also demonstrate that interface roughness scattering is about an order of magnitude stronger than alloy disorder scattering in GaAs-AlGaAs MDH if the AlGaAs/GaAs interface fluctuation is only one monolayer of GaAs.