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Whereas genetic susceptibility increases the risk for major depressive disorder (MDD), non-genetic protective factors may mitigate this risk. In a large-scale prospective study of US Army soldiers, we examined whether trait resilience and/or unit cohesion could protect against the onset of MDD following combat deployment, even in soldiers at high polygenic risk.
Data were analyzed from 3079 soldiers of European ancestry assessed before and after their deployment to Afghanistan. Incident MDD was defined as no MDD episode at pre-deployment, followed by a MDD episode following deployment. Polygenic risk scores were constructed from a large-scale genome-wide association study of major depression. We first examined the main effects of the MDD PRS and each protective factor on incident MDD. We then tested the effects of each protective factor on incident MDD across strata of polygenic risk.
Polygenic risk showed a dose–response relationship to depression, such that soldiers at high polygenic risk had greatest odds for incident MDD. Both unit cohesion and trait resilience were prospectively associated with reduced risk for incident MDD. Notably, the protective effect of unit cohesion persisted even in soldiers at highest polygenic risk.
Polygenic risk was associated with new-onset MDD in deployed soldiers. However, unit cohesion – an index of perceived support and morale – was protective against incident MDD even among those at highest genetic risk, and may represent a potent target for promoting resilience in vulnerable soldiers. Findings illustrate the value of combining genomic and environmental data in a prospective design to identify robust protective factors for mental health.
Heading date (HD) and flowering date (FD) are critical for yield potential and stability, so understanding their genetic foundation is of great significance in wheat breeding. Three related recombinant inbred line populations with a common female parent were developed to identify quantitative trait loci (QTL) for HD and FD in four environments. In total, 25 putative additive QTL and 20 pairwise epistatic effect QTL were detected in four environments. The additive QTL were distributed across 17 wheat chromosomes. Of these, QHd-1A, QHd-1D, QHd-2B, QHd-3B, QHd-4A, QHd-4B and QHd-6D were major and stable QTL for HD. QFd-1A, QFd-2B, QFd-4A and QFd-4B were major and stable QTL for FD. In addition, an epistatic interaction test showed that epistasis played important roles in controlling wheat HD and FD. Genetic relationships between HD/FD and five yield-related traits (YRTs) were characterized and ten QTL clusters (C1–C10) simultaneously controlling YRTs and HD/FD were identified. The present work laid a genetic foundation for improving yield potential in wheat molecular breeding programmes.
Abnormal thyroid function is prevalent among women and has been linked to increased risk of chronic disease. Posttraumatic stress disorder (PTSD) has been linked to thyroid dysfunction in some studies; however, the results have been inconsistent. Thus, we evaluated trauma exposure and PTSD symptoms in relation to incident thyroid dysfunction in a large longitudinal cohort of civilian women.
We used data from 45 992 women from the ongoing Nurses’ Health Study II, a longitudinal US cohort study that began in 1989. In 2008, history of trauma and PTSD were assessed with the Short Screening Scale for Diagnostic and Statistical Manual of Mental Disorders, fourth edition, PTSD, and incident thyroid dysfunction was determined by participants’ self-report in biennial questionnaires of physician-diagnosed hypothyroidism and Graves’ hyperthyroidism. The study period was from 1989 to 2013. Proportional hazard models were used to estimate multivariable-adjusted hazard ratios and 95% confidence intervals (CIs) for incident hypothyroidism and Graves’ hyperthyroidism.
In multivariable-adjusted models, we found significant associations for PTSD only with hypothyroidism [p-trend <0.001; trauma with no PTSD symptoms, 1.08 (95% CI 1.02–1.15); 1–3 PTSD symptoms, 1.12 (95% CI 1.04–1.21); 4–5 PTSD symptoms, 1.23 (95% CI 1.13–1.34); and 6–7 PTSD symptoms, 1.26 (95% CI 1.14–1.40)]. PTSD was not associated with risk of Graves’ hyperthyroidism (p-trend = 0.34). Associations were similar in sensitivity analyses restricted to outcomes with onset after 2008, when PTSD was assessed.
PTSD was associated with higher risk of hypothyroidism in a dose-dependent fashion. Highlighted awareness for thyroid dysfunction may be especially important in women with PTSD.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
The response of soil microbial communities to soil quality changes is a sensitive indicator of soil ecosystem health. The current work investigated soil microbial communities under different fertilization treatments in a 31-year experiment using the phospholipid fatty acid (PLFA) profile method. The experiment consisted of five fertilization treatments: without fertilizer input (CK), chemical fertilizer alone (MF), rice (Oryza sativa L.) straw residue and chemical fertilizer (RF), low manure rate and chemical fertilizer (LOM), and high manure rate and chemical fertilizer (HOM). Soil samples were collected from the plough layer and results indicated that the content of PLFAs were increased in all fertilization treatments compared with the control. The iC15:0 fatty acids increased significantly in MF treatment but decreased in RF, LOM and HOM, while aC15:0 fatty acids increased in these three treatments. Principal component (PC) analysis was conducted to determine factors defining soil microbial community structure using the 21 PLFAs detected in all treatments: the first and second PCs explained 89.8% of the total variance. All unsaturated and cyclopropyl PLFAs except C12:0 and C15:0 were highly weighted on the first PC. The first and second PC also explained 87.1% of the total variance among all fertilization treatments. There was no difference in the first and second PC between RF and HOM treatments. The results indicated that long-term combined application of straw residue or organic manure with chemical fertilizer practices improved soil microbial community structure more than the mineral fertilizer treatment in double-cropped paddy fields in Southern China.
Pathogenesis of pregnancy toxemia (PT) is believed to be associated with the disruption of lipid metabolism. The present study aimed to explore the underlying mechanisms of lipid metabolism disorder in the livers of ewes with PT. In total, 10 pregnant ewes were fed normally (control group) whereas another 10 were subjected to 70% level feed restriction for 15 days to establish a pathological model of PT. Results showed that, as compared with the controls, the levels of blood β-hydroxybutyrate (BHBA), non-esterified fatty acids (NEFAs) and cholesterol were greater (P<0.05) and blood glucose level was lower (P<0.05) in PT ewes. The contents of NEFAs, BHBA, cholesterol and triglyceride were higher (P<0.05) and glycerol content was lower (P<0.05) in hepatic tissues of PT ewes than those of the controls. For ewes with PT, excessive fat vacuoles were observed in liver sections stained with hematoxylin–eosin; furthermore, inner structures of hepatocytes including nuclei, mitochondria and endoplasmic reticulum were damaged seriously according to the results of transmission electron microscope. Real-time PCR data showed that compared with the controls, the expression of hepatic genes involved in fatty acid oxidation (FAO) and triglyceride synthesis (TGS) was enhanced (P<0.05) whereas that related to acetyl-CoA metabolism (ACM) was repressed (P<0.05) in PT ewes. Generally, our results showed that negative energy balance altered the expression of genes involved in FAO, ACM and TGS, further caused lipid metabolism disorder in livers, resulting in PT of ewes. Our findings may provide the molecular basis for novel therapeutic strategies against this systemic metabolic disease in sheep.
Extensive insecticide use has led to the resistance of mosquitoes to these insecticides, posing a major barrier to mosquito control. Previous Solexa high-throughput sequencing of Culex pipiens pallens in the laboratory has revealed that the abundance of a novel microRNA (miRNA), miR-13664, was higher in a deltamethrin-sensitive (DS) strain than a deltamethrin-resistant (DR) strain. Real-time quantitative PCR revealed that the miR-13664 transcript level was lower in the DR strain than in the DS strain. MiR-13664 oversupply in the DR strain increased the susceptibility of these mosquitoes to deltamethrin, whereas inhibition of miR-13664 made the DS strain more resistant to deltamethrin. Results of bioinformatic analysis, quantitative reverse-transcriptase polymerase chain reaction, luciferase assay and miR mimic/inhibitor microinjection revealed CpCYP314A1 to be a target of miR-13664. In addition, downregulation of CpCYP314A1 expression in the DR strain reduced the resistance of mosquitoes to deltamethrin. Taken together, our results indicate that miR-13664 could regulate deltamethrin resistance by interacting with CpCYP314A1, providing new insights into mosquito resistance mechanisms.
Wave loading on marine structures is the major external force to be considered in the design of such structures. The accurate prediction of the nonlinear high-order components of the wave loading has been an unresolved challenging problem. In this paper, the nonlinear harmonic components of hydrodynamic forces on a bottom-mounted vertical cylinder are investigated experimentally. A large number of experiments were conducted in the Danish Hydraulic Institute shallow water wave basin on the cylinder, both on a flat bed and a sloping bed, as part of a European collaborative research project. High-quality data sets for focused wave groups have been collected for a wide range of wave conditions. The high-order harmonic force components are separated by applying the ‘phase-inversion’ method to the measured force time histories for a crest focused wave group and the same wave group inverted. This separation method is found to work well even for locally violent nearly-breaking waves formed from bidirectional wave pairs. It is also found that the
th-harmonic force scales with the
th power of the envelope of both the linear undisturbed free-surface elevation and the linear force component in both time variation and amplitude. This allows estimation of the higher-order harmonic shapes and time histories from knowledge of the linear component alone. The experiments also show that the harmonic structure of the wave loading on the cylinder is virtually unaltered by the introduction of a sloping bed, depending only on the local wave properties at the cylinder. Furthermore, our new experimental results reveal that for certain wave cases the linear loading is actually less than 40 % of the total wave loading and the high-order harmonics contribute more than 60 % of the loading. The significance of this striking new result is that it reveals the importance of high-order nonlinear wave loading on offshore structures and means that such loading should be considered in their design.
Group-3 medulloblastoma (MBL) is highly resistant to radiation (IR) and chemotherapy and has the worst prognosis. Hence, there is an urgent need to elucidate targets that sensitize these tumors to chemotherapy and IR. Employing standard assays for viability and sensitization to IR, we identified PRDX1 as a therapeutic target in Group-3 MBL. Specifically, targeting PRDX1 by RNAi or inhibition by Adenanthin led to specific killing and sensitization to IR of Group-3 MBL cells. We rescued sensitization of Daoy and UW228 cells by hypermorphic expression of PRDX1. PRDX1 knockdown caused oxidative DNA damage and induced apoptosis. We correlated PRDX1 expression to patient outcomes in a validated MBL tumor-microarray. Whole genome sequencing identified pathways/genes that were dysregulated with PRDX1 inhibition or silencing. Our in vivo studies in mice employing flank/orthotopic tumors from patient derived xenografts/Group-3 MBL cells confirmed in vitro observations. Animals with tumors in which PRDX1 was targeted by RNAi or Adenanthin (using mini osmotic pumps) showed decreased tumor burden and increased survival when compared to controls. Since, Adenanthin does not cross the blood brain barrier (BBB) we used HAV6 peptide to transiently disrupt the BBB and deliver Adenanthin to the tumor. Immunohistochemistry confirmed that targeting PRDX1 resulted in increased oxidative DNA damage, apoptosis and decreased proliferation. In summary, we have validated PRDX1 as a therapeutic target in group-3 MBL, identified Adenanthin as a potent chemical inhibitor of PRDX1 and confirmed the role of HAV peptide (in the transient modulation of BBB permeability) in an orthotopic model of group-3 MBL.
The mammalian target of rapamycin (mTOR) has been shown to be involved in lipopolysaccharide (LPS)-induced immune responses in many mammal cells. Here, we suggest that the mTOR pathway is involved in the intestinal inflammatory responses evoked by LPS treatment in chicken embryos. The intestinal tissue from Specific pathogen free chick embryos was cultured in the presence of LPS for 2 h. Secretory immunoglobulin A (sIgA) concentrations, messenger RNA (mRNA) expression of cytokines, and protein levels of nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), mTOR and p70 ribosomal S6 kinase (p70S6K) were determined. The results showed that LPS treatment increased sIgA concentrations in a dose-dependent manner. The mRNA levels of interleukine (IL)-6, IL-8, IL-10, tumor necrosis factor-α and Toll-like receptor (TLR) 4 were upregulated by LPS treatment (P<0.05). Lipopolysaccharide increased the phosphorylation of Jun N-terminal kinase (JNK), p38 MAPK and NF-κB (P<0.05) while decreasing the phosphorylation level of mTOR (P<0.05). Supplementation of leucine at doses of 10, 20 and 40 mM dose-dependently decreased sIgA production. Leucine supplementation at 40 mM restored the phosphorylation level of mTOR and p70S6K while suppressing the phosphorylation levels of NF-κB (P<0.05) and partially down-regulating the phosphorylation of p38 MAPK and JNK. The transcription of IL-6 was significantly decreased by leucine supplementation. These results suggested that leucine could alleviate LPS-induced inflammatory responses by down-regulating NF-κB signaling pathway and evoking mTOR/p70S6K signaling pathway, which may involve in the regulation of the intestinal immune system in chicken embryos.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
Fatigue cracking in polycrystalline NiTi was investigated using a multiscale experimental framework for average grain sizes (GS) from 10 to 1500 nm for the first time. Macroscopic fatigue crack growth rates, measured by optical digital image correlation, were connected to microscopic crack opening and closing displacements, measured by scanning electron microscope DIC (SEM-DIC) using a high-precision external SEM scan controller. Among all grain sizes, the 1500 nm GS sample exhibited the slowest crack growth rate at the macroscale, and the largest crack opening level (stress intensity at first crack opening) and minimum crack opening displacements at the microscale. Smaller GS samples (10, 18, 42, and 80 nm) exhibited nonmonotonic trends in their fatigue performance, yet the correlation was strong between macroscale and microscale behaviors for each GS. The samples that exhibited the fastest crack growth rates (42 and 80 nm GS) showed a small crack opening level and the largest crack opening displacements. The irregular trends in fatigue performance across the nanocrystalline GS samples were consistent with nonmonotonic values in the elastic modulus reported previously, both of which may be related to the presence of residual martensite only evident in the small GS samples (10 and 18 nm).
The effects of soluble fiber inclusion in gestation diets with varying fermentation characteristics (fermentation kinetics and short-chain fatty acids (SCFA)-profile) on lactational feed intake of sows and their piglet growth over two parities were investigated using an in vitro–in vivo methodology. After breeding, 90 multiparous Landrace sows were randomized to one of three experimental diets: the control (CON) diet, konjac flour (KF) diet or sugar beet pulp (SBP) diet. All diets had similar levels of net energy, CP, insoluble fiber and NDF, but KF and SBP diets had higher soluble fiber levels than the CON diet. During gestation, the sows were restrictively fed with three different diets, but during lactation, all the sows were similarly fed ad libitum. The three gestation diets were enzymatically hydrolyzed using pepsin and pancreatin, and enzymolyzed residues were used in in vitro fermentation. Gas and SCFA production were monitored during fermentation. After fermentation, enzymolyzed residues of KF or SBP diets resulted in higher final asymptotic gas volume than those of the CON diet. The enzymolyzed residues of KF diet were mainly part of rapidly fermented fractions, whereas those of SBP diet were mainly part of slowly fermented fractions. In addition, the acetic acid, butyric acid and total SCFA concentrations of enzymolyzed residues of KF diet were higher (P<0.01) than the control and SBP diets. In the in vivo studies, on day 90 of gestation, the KF diet sows had higher plasma SCFA concentration (P<0.05) at 4 h after feeding than the CON diet sows. Furthermore, the KF diet sows had lower plasma free fatty acid (FFA) concentration (P<0.01) at 4 h after feeding, and a lower value of homeostasis model assessment (HOMA)-insulin resistance (P<0.05), but a higher value of HOMA-insulin sensitivity (P<0.01). The KF diet sows also consumed more feed during lactation (P<0.01) and weaned significantly heavier pigs (P<0.01) than the CON diet sows. The overall results showed that the high fermentation capacity KF diet contributed to an increased lactational feed intake and improved performance of piglets in the second reproductive cycle.
Knowledge, attitudes and practices (KAP) of the population regarding severe fever with thrombocytopenia syndrome (SFTS) in endemic areas of Lu'an in China were assessed before and after an intervention programme. The pre-intervention phase was conducted using a sample of 425 participants from the 12 selected villages with the highest rates of endemic SFTS infection. A predesigned interview questionnaire was used to assess KAP. Subsequently, an intervention programme was designed and applied in the selected villages. KAP was re-assessed for each population in the selected villages using the same interview questionnaire. Following 2 months of the programme, 339 participants had completed the re-assessed survey. The impact of the intervention programme was evaluated using suitable statistical methods. A significant increase in the KAP and total KAP scores was noted following the intervention programme, whereas the proportion of correct knowledge, the positive attitudes and the effective practices toward SFTS of respondents increased significantly. The intervention programme was effective in improving KAP level of SFTS in populations that were resident in endemic areas.
We present techniques developed to calibrate and correct Murchison Widefield Array low-frequency (72–300 MHz) radio observations for polarimetry. The extremely wide field-of-view, excellent instantaneous (u, v)-coverage and sensitivity to degree-scale structure that the Murchison Widefield Array provides enable instrumental calibration, removal of instrumental artefacts, and correction for ionospheric Faraday rotation through imaging techniques. With the demonstrated polarimetric capabilities of the Murchison Widefield Array, we discuss future directions for polarimetric science at low frequencies to answer outstanding questions relating to polarised source counts, source depolarisation, pulsar science, low-mass stars, exoplanets, the nature of the interstellar and intergalactic media, and the solar environment.
Diarrhea is a common cause of morbidity and mortality and the incidence of diarrhea in the world has changed little over the past four decades. To assess the prevalence of and healthcare practices for diarrhea, a cross-sectional study was conducted in Pudong, Shanghai, China. In October 2014, a total of 5324 community residents were interviewed. Respondents were asked if they had experienced diarrhea (defined as ⩾3 passages of watery, loose, bloody, or mucoid stools within a 24-h period) in the previous month prior to the interview. The monthly prevalence of diarrhea was 4·1% (95% CI: 3·3–4·8), corresponding to an incidence rate of 0·54 episodes per person-year. The proportion of individuals with diarrhea who sought healthcare was 21·2% (95% CI: 13·4–29·0). Diarrhea continues to impose a considerable burden on the community and healthcare system in Pudong. Young age and travel were identified as predictors of increased diarrhea occurrence.
This study aimed to identify the effect of lateral neck dissection on voice change in thyroidectomised patients.
Medical records from 264 patients who underwent thyroidectomy with (n = 65) or without (n = 199) lateral neck dissection were reviewed. Clinical and voice evaluation data were compared between the two groups.
Patients who underwent surgery that included lateral neck dissection had lower fundamental frequencies and speaking fundamental frequencies. They also had a higher incidence of asymmetric mucosal wave and vocal fold oedema on videostroboscopy during the first month after surgery, with the incidence of vocal fold oedema remaining significantly higher at three months. Self-assessed voice quality scores were significantly higher in lateral neck dissection patients at both one and three months after surgery.
In thyroidectomised patients, lateral neck dissection lowers the vocal pitch in the initial period after surgery and induces vocal fold oedema that persists for several months. Although most objective parameters improved within a month, subjective symptoms lasted for longer.
An outbreak of acute hepatitis recently occurred in a nursing home in Zhejiang Province, China. The objectives of this study were to confirm the outbreak and identify the aetiology, source and transmission patterns. All residents and staff in or near the nursing home during the period from 1 October 2014 to 21 May 2015 were investigated regarding hygiene and for epidemiological information including water and food (eating meat especially pork products). Serum and stool specimens were collected for detection of hepatitis E virus (HEV) antibodies using ELISA and RNA using RT–PCR. Samples that were RNA positive were genotyped. Of 185 senior residents and 24 staff in the nursing home, there were 37 laboratory-confirmed cases during the outbreak. Of these cases, 12 patients (three deaths) were symptomatic with jaundice, a common clinical symptom for hepatitis E infection. HEV strains were isolated from three cases and they formed a single cluster within genotype 4d. A case-control study was conducted to investigate potential risk factors for the outbreak and the results revealed that cases more often washed their dishes and rinsed their mouths using tap water than the controls (P < 0·05). Based on hygiene investigation and meteorological information, it is likely that HEV-infected sewage and faeces contaminated the water network on rainy days. Collectively, these results suggest that the outbreak of HEV genotype 4 infection was most likely caused by contaminated tap water rather than food.
There are six strains of the complete genomic sequences of black queen cell virus (BQCV) published in the GenBank, including South Africa (AF183905), South Korea (JX149531), Hungary 10 (EF517515), Poland 4 (EF517519), Poland 5 (EF517520) and Poland 6 (EF517521). Based on the six BQCV strains published in the GenBank, ten pairs of primers were designed in the present study using reverse transcription polymerase chain reaction to obtain the first complete genome sequence of a BQCV strain in China, called the BQCV China-JL1 strain (KP119603). A phylogenetic tree was then built to analyse their genetic relationships. The BQCV China-JL1 strain showed 86–93% similarity with the six strains published in the GenBank. The BQCV China-JL1 strain consisted of 8358 nucleotides (nt). The 5′-proximal open reading frame (ORF1) initiated at nt position 546 and terminated at nt position 4676, ORF3 initiated at nt position 4891 and terminated at nt position 5433, and the 3′-proximal ORF (ORF2) was located between nt positions 5750 and 8203.
The objective of this study was to determine if a moderate or high reduction of dietary CP, supplemented with indispensable amino acids (IAA), would affect growth, intestinal morphology and immunological parameters of pigs. A total of 40 barrows (initial BW=13.50±0.50 kg, 45±2 day of age) were used in a completely randomized block design, and allocated to four dietary treatments containing CP levels at 20.00%, 17.16%, 15.30% and 13.90%, respectively. Industrial AA were added to meet the IAA requirements of pigs. After 4-week feeding, blood and tissue samples were obtained from pigs. The results showed that reducing dietary CP level decreased average daily gain, plasma urea nitrogen concentration and relative organ weights of liver and pancreas (P<0.01), and increased feed conversion ratio (P<0.01). Pigs fed the 13.90% CP diet had significantly lower growth performance than that of pigs fed higher CP at 20.00%, 17.16% or 15.30%. Moreover, reducing dietary CP level decreased villous height in duodenum (P<0.01) and crypt depth in duodenum, jejunum and ileum (P<0.01). The reduction in the dietary CP level increased plasma concentrations of methionine, alanine (P<0.01) and lysine (P<0.05), and decreased arginine (P<0.05). Intriguingly, reducing dietary CP level from 20.00% to 13.90% resulted in a significant decrease in plasma concentration of IgG (P<0.05), percentage of CD3+T cells of the peripheral blood (P<0.01), also down-regulated the mRNA abundance of innate immunity-related genes on toll-like receptor 4, myeloid differentiation factor 88 (P<0.01) and nuclear factor kappa B (P<0.05) in the ileum. These results indicate that reducing dietary CP level from 20.00% to 15.30%, supplemented with IAA, had no significant effect on growth performance and had a limited effect on immunological parameters. However, a further reduction of dietary CP level up to 13.90% would lead to poor growth performance and organ development, associated with the modifications of intestinal morphology and immune function.