Selenium (Se) deficiency causes impaired growth of fish skeletal muscle due to the retarded hypertrophy of muscle fibers. However, the inner mechanisms remain unclear. According to our previous researches, we infer this phenomenon is associated with Se deficiency-induced high concentration of reactive oxygen species (ROS), which could suppress the target of rapamycin complex 1 (TORC1) pathway-mediated protein synthesis by inhibiting protein kinase B (Akt), an upstream protein of TORC1. To test this hypothesis, juvenile zebrafish (45 days post fertilization) were fed a basal Se-adequate diet or a basal Se-deficient diet, or them supplemented with an antioxidant (DL-α-tocopherol acetate, designed as VE) or a TOR activator (MHY1485) for 30 days. Zebrafish fed Se-deficient diets exhibited a clear Se-deficient status in skeletal muscle, which was not influenced by dietary VE and MHY1485. Se deficiency significantly elevated ROS concentrations, inhibited Akt activity and TORC1 pathway, suppressed protein synthesis in skeletal muscle, and impaired hypertrophy of skeletal muscle fibers. However, these negative effects of Se deficiency were partly (except that on ROS concentration) alleviated by dietary MHY1485 and completely alleviated by dietary VE. These data strongly support our speculation that Se deficiency-induced high concentration of ROS exerts a clear inhibiting effect on TORC1 pathway-mediated protein synthesis by regulating Akt activity, thereby restricting the hypertrophy of skeletal muscle fibers in fish. Our findings provide a mechanistic explanation for Se deficiency-caused retardation of fish skeletal muscle growth, contributing to a better understanding of the nutritional necessity and regulatory mechanisms of Se in fish muscle physiology.

OBJECTIVES/GOALS: The aims of this study were to: 1) determine the involvement of each Fc gamma receptor isoform in antibody-mediated crosslinking and internalization of LILRB4 in acute monocytic leukemia and 2) elucidate the role of this crosslinking and internalization in antibody-mediated immune regulation of these malignant cells. METHODS/STUDY POPULATION: To determine the involvement of Fc gamma receptors in antibody-mediated complex internalization, we generated acute monocytic leukemia cell lines with CRISPR-Cas9 knockout of each Fc gamma receptor isoform. We tested the effects of each knockout on anti-LILRB4 antibody-mediated internalization by flow cytometry and confirmed our findings with confocal microscopy. To elucidate the role of this crosslinking and internalization in immune regulation of acute monocytic leukemia, we conducted preliminary ELISA-based studies of the inflammatory signaling and cytokine release profiles of wild-type and Fc gamma receptor knockout cells treated with the LILRB4-targeting antibody. RESULTS/ANTICIPATED RESULTS: We have concluded that Fc gamma receptor I (CD64) plays a role in LILRB4 crosslinking and internalization by our anti-LILRB4 antibody and there are also contributions from Fc gamma receptor IIA (CD32A) observed in the absence of CD64 on the cell surface. Preliminary signaling studies have demonstrated that Fc gamma receptor-mediated antibody crosslinking and internalization of LILRB4 decreases anti-inflammatory signaling downstream of LILRB4 as well as pro-inflammatory signaling downstream of Fc gamma receptors, particularly in the absence of CD64 on the cell surface. The immunomodulatory effect of antibody-mediated LILRB4 crosslinking and internalization is being confirmed in follow-up signaling, cytokine release and lymphocyte activation studies. DISCUSSION/SIGNIFICANCE: This study will improve the efficacy of LILRB4-targeting antibody therapeutics for patients suffering from acute monocytic leukemia and help characterize CD64 and CD32A as potential clinical biomarkers for patients undergoing LILRB4-targeting antibody immunotherapeutic treatment, currently in first-in-human clinical trials.

The current study aims to confirm the positive effects of dietary nano-Se on nutrients deposition and muscle fibre formation in grass carp fed with high-fat diet (HFD) before overwintering and to reveal its possible molecular mechanism. The lipid deposition, protein synthesis and muscle fibre formation in grass carp fed with regular diet (RD), HFD or HFD supplemented with nano-Se (0·3 or 0·6 mg/kg) for 60 d were tested. Results show that nano-Se significantly reduced lipid content, dripping loss and fibre diameter (P < 0·05), but increased protein content, post-mortem pH24 h and muscle fibre density (P < 0·05) in muscle of grass carp fed with HFD. Notably, dietary nano-Se decreased lipid deposition in the muscle by regulating amp-activated protein kinase activity and increased protein synthesis and fibre formation in muscle by activating target of rapamycin and myogenic determining factors pathways. In summary, dietary nano-Se can regulate the nutrients deposition and muscle fibre formation in grass carp fed with HFD, which exhibit potential benefit for improving flesh quality of grass carp fed with HFD.

A new isolated out-of-phase filtering power divider/combiner with high selectivity is presented. Based on a single-layer microstrip, required coupling strength and phase difference are achieved by two pairs of three-line coupled feeding structures. To realize desired bandpass responses, a specific resonator is located between the input and output coupled structures. By connecting a half-wavelength transmission line which is centrally loaded with a grounded resistor between two output ports, high port-to-port isolation is attained. Based on the impedance matrix of coupled three-line structure, theoretical filtering responses are predicted with the specified bandwidth and return loss. For demonstration, a prototype is designed, fabricated, and tested. Both simulated and measured results are displayed to verify the design mechanism.

Coastal eutrophication and hypoxia remain a persistent environmental crisis despite the great efforts to reduce nutrient loading and mitigate associated environmental damages. Symptoms of this crisis have appeared to spread rapidly, reaching developing countries in Asia with emergences in Southern America and Africa. The pace of changes and the underlying drivers remain not so clear. To address the gap, we review the up-to-date status and mechanisms of eutrophication and hypoxia in global coastal oceans, upon which we examine the trajectories of changes over the 40 years or longer in six model coastal systems with varying socio-economic development statuses and different levels and histories of eutrophication. Although these coastal systems share common features of eutrophication, site-specific characteristics are also substantial, depending on the regional environmental setting and level of social-economic development along with policy implementation and management. Nevertheless, ecosystem recovery generally needs greater reduction in pressures compared to that initiated degradation and becomes less feasible to achieve past norms with a longer time anthropogenic pressures on the ecosystems. While the qualitative causality between drivers and consequences is well established, quantitative attribution of these drivers to eutrophication and hypoxia remains difficult especially when we consider the social economic drivers because the changes in coastal ecosystems are subject to multiple influences and the cause–effect relationship is often non-linear. Such relationships are further complicated by climate changes that have been accelerating over the past few decades. The knowledge gaps that limit our quantitative and mechanistic understanding of the human-coastal ocean nexus are identified, which is essential for science-based policy making. Recognizing lessons from past management practices, we advocate for a better, more efficient indexing system of coastal eutrophication and an advanced regional earth system modeling framework with optimal modules of human dimensions to facilitate the development and evaluation of effective policy and restoration actions.

One challenge facing humans (and nonhuman animal) is that some options that appear attractive locally may not turn out best in the long run. To analyse this human learning problem, we explore human performance in a dynamic decision-making task that places local and global rewards in conflict. We found that experiences that included previous choices and rewards are not easily incorporated into people’s strategy to enhance their performance. Our results suggest that humans are easily driven by concerns about recent feedback, and that choice of a suboptimal behaviour option may be overcome by providing informative cues that indicate a clear immediate outcome for a better option.

Liriomyza trifolii is a significant pest of vegetable and ornamental crops across the globe. Microwave radiation has been used for controlling pests in stored products; however, there are few reports on the use of microwaves for eradicating agricultural pests such as L. trifolii, and its effects on pests at the molecular level is unclear. In this study, we show that microwave radiation inhibited the emergence of L. trifolii pupae. Transcriptomic studies of L. trifolii indicated significant enrichment of differentially expressed genes (DEGs) in ‘post-translational modification, protein turnover, chaperones’, ‘sensory perception of pain/transcription repressor complex/zinc ion binding’ and ‘insulin signaling pathway’ when analyzed with the Clusters of Orthologous Groups, Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes databases, respectively. The top DEGs were related to reproduction, immunity and development and were significantly expressed after microwave radiation. Interestingly, there was no significant difference in the expression of genes encoding heat shock proteins or antioxidant enzymes in L. trifolii treated with microwave radiation as compared to the untreated control. The expression of DEGs encoding cuticular protein and protein takeout were silenced by RNA interference, and the results showed that knockdown of these two DEGs reduced the survival of L. trifolii exposed to microwave radiation. The results of this study help elucidate the molecular response of L. trifolii exposed to microwave radiation and provide novel ideas for control.

Hormone-sensitive lipase (HSL) is one of the rate-determining enzymes in the hydrolysis of TAG, playing a crucial role in lipid metabolism. However, the role of HSL-mediated lipolysis in systemic nutrient homoeostasis has not been intensively understood. Therefore, we used CRISPR/Cas9 technique and Hsl inhibitor (HSL-IN-1) to establish hsla-deficient (hsla -/-) and Hsl-inhibited zebrafish models, respectively. As a result, the hsla -/- zebrafish showed retarded growth and reduced oxygen consumption rate, accompanied with higher mRNA expression of the genes related to inflammation and apoptosis in liver and muscle. Furthermore, hsla -/- and HSL-IN-1-treated zebrafish both exhibited severe fat deposition, whereas their expressions of the genes related to lipolysis and fatty acid oxidation were markedly reduced. The TLC results also showed that the dysfunction of Hsl changed the whole-body lipid profile, including increasing the content of TG and decreasing the proportion of phospholipids. In addition, the systemic metabolic pattern was remodelled in hsla -/- and HSL-IN-1-treated zebrafish. The dysfunction of Hsl lowered the glycogen content in liver and muscle and enhanced the utilisation of glucose plus the expressions of glucose transporter and glycolysis genes. Besides, the whole-body protein content had significantly decreased in the hsla -/- and HSL-IN-1-treated zebrafish, accompanied with the lower activation of the mTOR pathway and enhanced protein and amino acid catabolism. Taken together, Hsl plays an essential role in energy homoeostasis, and its dysfunction would cause the disturbance of lipid catabolism but enhanced breakdown of glycogen and protein for energy compensation.

We report dispersion management based on a mismatched-grating compressor for a 100 PW level laser, which utilizes optical parametric chirped pulse amplification and also features large chirped pulse duration and an ultra-broadband spectrum. The numerical calculation indicates that amplified pulses with 4 ns chirped pulse duration and 210 nm spectral bandwidth can be directly compressed to sub-13 fs, which is close to the Fourier-transform limit (FTL). More importantly, the tolerances of the mismatched-grating compressor to the misalignment of the stretcher, the error of the desired grating groove density and the variation of material dispersion are comprehensively analyzed, which is crucially important for its practical application. The results demonstrate that good tolerances and near-FTL compressed pulses can be achieved simultaneously, just by keeping a balance between the residual second-, third- and fourth-order dispersions in the laser system. This work can offer a meaningful guideline for the design and construction of 100 PW level lasers.

A clear understanding of the solid-state reaction of kaolinite (Kln), quartz (Qtz), and sodium carbonate (Na2CO3) is of great significance for the process optimization of coal gangue calcined with Na2CO3. In this work, a comparative study of the isothermal solid-state reaction systems of Kln–Na2CO3 and Kln–Qtz–Na2CO3 was performed by means of X-ray diffraction (XRD), scanning electron microscope, and energy dispersion spectroscopy (SEM-EDS). The results showed that the calcined products both for these reaction systems mainly contain different kinds of sodium aluminum silicates (e.g., NaAlSiO4, Na1.55Al1.55Si0.45O4, and Na1.95Al1.95Si0.05O4) and various kinds of sodium silicates (e.g., Na2Si3O7, Na2SiO3, and Na6Si2O7). The mass percentage of Na2CO3 played a key role in the phase transformation, determining the Na/Al/Si molar ratio of the formed sodium aluminum silicates. Compared with the reaction system of Kln–Na2CO3, the existence of Qtz inhibited the formation of sodium aluminum silicates in the reaction system of Kln–Qtz–Na2CO3. It should be noted that the formed phases both for these reaction systems were slightly different from that of the thermodynamical calculated results of Na2O–SiO2–Al2O3 using FactSage™ software. According to both the experimental and calculated results, a reasonable batching area for coal gangue activation was proposed that the addition of Na2CO3 should be in the range of 20–50% of the total mass of Kln, Qtz, and Na2CO3.

During late Carboniferous time, the residual ocean basin gradually closed in West Junggar and only a small amount of seawater remained in the Hala’alat Mountain area, where discussions of provenance and tectonics are limited. In this study, LA-ICP-MS U–Pb dating and heavy mineral identification are conducted on the upper Carboniferous tuffaceous sandstones from the Hala’alat and Aladeyikesai formations in the Hala’alat Mountain area. The results reveal the low maturity of the clastic sediments, indicating proximal deposition. The Hala’alat Formation detrital zircons present a single peak (c. 330 Ma). Speculatively, the primary provenance is the Boshchekul–Chingiz Arc, and the secondary sources are the Darbut Tectono-Magmatic Belt and island arcs in the basin. The main peak and provenance of the Aladeyikesai Formation are similar to those of the Hala’alat Formation. Moreover, several age groups, namely, 370–344 Ma, 427–404 Ma and 478–476 Ma, potentially correspond to provenances of the Darbut Tectono-Magmatic Belt, the Boshchekul–Chingiz Arc and the Kujibai–Hongguleleng Ophiolitic Mélange Belt. In addition, the maximum depositional ages of the Hala’alat and Aladeyikesai formations calculated are 314.6 ± 1.54 Ma and 330.8 ± 0.61 Ma, respectively. Comprehensive analysis shows a relatively singular provenance of the Hala’alat Formation. While the provenance of the Aladeyikesai Formation shows inheritance, the provenance area extends northwards to the Kujibai–Hongguleleng Ophiolitic Mélange Belt. Furthermore, the closure of the Junggar Ocean during Carboniferous time caused the potential source region of the Hala’alat Mountain area to migrate northeastwards from Barleik Mountain to Xiemisitai Mountain. This study provides a basis for the analysis of regional geological evolution.

The association between dietary Cu intake and mortality risk remains uncertain. We aimed to investigate the relationship of dietary Cu intake with all-cause mortality among Chinese adults. A total of 17 310 participants from the China Health and Nutrition Survey, a national ongoing open cohort of Chinese participants, were included in the analysis. Dietary intake was measured by three consecutive 24-h dietary recalls in combination with a weighing inventory over the same 3 d. The average intakes of the 3-d dietary macronutrients and micronutrients were calculated. The study outcome was all-cause mortality. During a median follow-up of 9·0 years, 1324 (7·6 %) participants died. After adjusting for sex, age, BMI, ever alcohol drinking, ever smoking, education levels, occupations, urban or rural residents, systolic blood pressure, diastolic blood pressure and the intakes of fat, protein and carbohydrate, the association between dietary Cu intake and all-cause mortality followed a J-shape (P for nonlinearity = 0·047). When dietary Cu intake was assessed as quartiles, compared with those in the first quartile (<1·60 mg/d), the adjusted hazard ratios for all-cause mortality were 0·87 (95 % CI (0·71, 1·07)), 0·98 (95 % CI (0·79, 1·21)) and 1·49 (95 % CI (1·19, 1·86)), respectively, in participants in the second (1·60–<1·83 mg/d), third (1·83–<2·09 mg/d) and fourth (≥2·09 mg/d) quartiles. A series of subgroup analyses and sensitivity analyses showed similar results. Overall, our findings emphasised the importance of maintaining optimal dietary Cu intake levels for prevention of premature death.

The great demographic pressure brings tremendous volume of beef demand. The key to solve this problem is the growth and development of Chinese cattle. In order to find molecular markers conducive to the growth and development of Chinese cattle, sequencing was used to determine the position of copy number variations (CNVs), bioinformatics analysis was used to predict the function of ZNF146 gene, real-time fluorescent quantitative polymerase chain reaction (qPCR) was used for CNV genotyping and one-way analysis of variance was used for association analysis. The results showed that there exists CNV in Chr 18: 47225201-47229600 (5.0.1 version) of ZNF146 gene through the early sequencing results in the laboratory and predicted ZNF146 gene was expressed in liver, skeletal muscle and breast cells, and was amplified or overexpressed in pancreatic cancer, which promoted the development of tumour through bioinformatics. Therefore, it is predicted that ZNF146 gene affects the proliferation of muscle cells, and then affects the growth and development of cattle. Furthermore, CNV genotyping of ZNF146 gene was three types (deletion type, normal type and duplication type) by Real-time fluorescent quantitative PCR (qPCR). The association analysis results showed that ZNF146-CNV was significantly correlated with rump length of Qinchuan cattle, hucklebone width of Jiaxian red cattle and heart girth of Yunling cattle. From the above results, ZNF146-CNV had a significant effect on growth traits, which provided an important candidate molecular marker for growth and development of Chinese cattle.

Hepatitis E is an increasingly serious worldwide public health problem that has attracted extensive attention. It is necessary to accurately predict the incidence of hepatitis E to better plan ahead for future medical care. In this study, we developed a Bi-LSTM model that incorporated meteorological factors to predict the prevalence of hepatitis E. The hepatitis E data used in this study are collected from January 2005 to March 2017 by Jiangsu Provincial Center for Disease Control and Prevention. ARIMA, GBDT, SVM, LSTM and Bi-LSTM models are adopted in this study. The data from January 2009 to September 2014 are used as the training set to fit models, and data from October 2014 to March 2017 are used as the testing set to evaluate the predicting accuracy of different models. Selecting models and evaluating the effectiveness of the models are based on mean absolute per cent error (MAPE), root mean square error (RMSE) and mean absolute error (MAE). A total of 44 923 cases of hepatitis E are detected in Jiangsu Province from January 2005 to March 2017. The average monthly incidence rate is 0.35 per 100 000 persons in Jiangsu Province. Incorporating meteorological factors of temperature, water vapour pressure, and rainfall as a combination into the Bi-LSTM Model achieved the state-of-the-art performance in predicting the monthly incidence of hepatitis E, in which RMSE is 0.044, MAPE is 11.88%, and MAE is 0.0377. The Bi-LSTM model with the meteorological factors of temperature, water vapour pressure, and rainfall can fully extract the linear and non-linear information in the hepatitis E incidence data, and has significantly improved the interpretability, learning ability, generalisability and prediction accuracy.