Effects of age on differential resistance to duck hepatitis A virus genotype 3 in Pekin ducks by 16 S and transcriptomics.

Duck hepatitis A virus genotype 3 (DHAV-3) is the major cause of viral hepatitis in ducks in Asia. Previous studies have shown that ducklings younger than 21 days are more susceptible to DHAV-3. To elucidate the mechanism by which age affects the differential susceptibility of Pekin ducks to DHAV-3, intestinal (n = 520), liver (n = 40) and blood (n = 260) samples were collected from control and DHAV-3-infected ducks at 7, 10, 14, and 21 days of age. Comparisons of plasma markers, mortality rates, and intestinal histopathological data showed that the resistance of Pekin ducks to DHAV-3 varied with age. 16 S sequencing revealed that the ileal microbial composition was influenced by age, and this correlation was greater than that recorded for caecal microbes. Candidatus Arthromitus, Bacteroides, Corynebacterium, Enterococcus, Romboutsia, and Streptococcus were the differntially abundant microbes in the ileum at the genus level after DHAV-3 infection and were significantly correlated with 7 differentially expressed genes (DEGs) in 7- and 21-day-old ducklings. 3 immunity-related pathways were significantly different between 7- and 21-day-old ducklings, especially for IFIH1-mediated induction of the interferon-alpha/beta pathway, which induces differential production of CD8(+) T cells and was influenced by a combination of differentially abundant microbiota and DEGs. We found that microbes in the ileum changed regularly with age. The intestinal microbiota was associated with the expression of genes in the liver through IFIH1-mediated induction of the interferon-alpha/beta pathway, which may partially explain why younger ducklings were more susceptible to DHAV-3 infection.

Near-Infrared-Activatable PROTAC Nanocages for Controllable Target Protein Degradation and On-Demand Antitumor Therapy.

As a novel protein knockdown tool, proteolysis targeting chimeras (PROTACs) can induce potent degradation of target proteins by hijacking E3 ubiquitin ligases. However, the uncontrollable protein disruption of PROTACs is prone to cause "off-target" toxicity after systemic administration. Herein, we designed a photocaged-PROTAC (phoBET1) and loaded it in UCNPs-based mesoporous silica nanoparticles (UMSNs) to construct a NIR light-activatable PROTAC nanocage (UMSNs@phoBET1) for controllable target protein degradation. Upon NIR light (980 nm) irradiation, UMSNs@phoBET1 nanocages could be activated to release active PROTAC via a controlled pattern for degrading bromodomain-containing protein 4 (BRD4) and inducing MV-4-11 cancer cell apoptosis. In vivo experiments demonstrated that UMSNs@phoBET1 nanocages were capable of responding to NIR light in tumor tissues to achieve BRD4 degradation and effectively suppress tumor growth. This NIR light-activatable PROTAC nanoplatform compensates for the current shortcomings of short-wavelength light-controlled PROTACs and presents a paradigm for the precise regulation of PROTACs in living tissues.

Metabolome-Based Genome-Wide Association Study of Duck Meat Leads to Novel Genetic and Biochemical Insights.

Meat is among the most consumed foods worldwide and has a unique flavor and high nutrient density in the human diet. However, the genetic and biochemical bases of meat nutrition and flavor are poorly understood. Here, 3431 metabolites and 702 volatiles in 423 skeletal muscle samples are profiled from a gradient consanguinity segregating population generated by Pekin duck × Liancheng duck crosses using metabolomic approaches. The authors identified 2862 metabolome-based genome-wide association studies (mGWAS) signals and 48 candidate genes potentially modulating metabolite and volatile levels, 79.2% of which are regulated by cis-regulatory elements. The level of plasmalogen is significantly associated with TMEM189 encoding plasmanylethanolamine desaturase 1. The levels of 2-pyrrolidone and glycerophospholipids are regulated by the gene expression of AOX1 and ACBD5, which further affects the levels of volatiles, 2-pyrrolidone and decanal, respectively. Genetic variations in GADL1 and CARNMT2 determine the levels of 49 metabolites including L-carnosine and anserine. This study provides novel insights into the genetic and biochemical basis of skeletal muscle metabolism and constitutes a valuable resource for the precise improvement of meat nutrition and flavor.

Genome-wide association study reveals the genetic determinism of serum biochemical indicators in ducks.

BACKGROUND: The serum is rich in nutrients and plays an essential role in electrolyte and acid-base balance, maintaining cellular homeostasis. In addition, serum parameters have been commonly used as essential biomarkers for clinical diagnosis. However, little is known about the genetic mechanism of the serum parameters in ducks. RESULTS: This study measured 18 serum parameters in 320 samples of the F2 segregating population generated by Mallard × Pekin duck. The phenotypic correlations showed a high correlation between LDH, HBDH, AST, and ALT (0.59-0.99), and higher coefficients were also observed among TP, ALB, HDL-C, and CHO (0.46-0.87). And then, we performed the GWAS to reveal the genetic basis of the 18 serum biochemical parameters in ducks. Fourteen candidate protein-coding genes were identified with enzyme traits (AST, ALP, LDH, HBDH), and 3 protein-coding genes were associated with metabolism and protein-related serum parameters (UA, TG). Moreover, the expression levels of the above candidate protein-coding genes in different stages of breast muscle and different tissues were analyzed. Furthermore, the genes located within the high-LD region (r2 > 0.4 and - log10(P) < 4) neighboring the significant locus also remained. Finally, 86 putative protein-coding genes were used for GO and KEGG enrichment analysis, the enzyme-linked receptor protein signaling pathway and ErbB signaling pathway deserve further focus. CONCLUSIONS: The obtained results can contribute to new insights into blood metabolism and provide new genetic biomarkers for application in duck breeding programs.

Increase Dietary Fiber Intake Ameliorates Cecal Morphology and Drives Cecal Species-Specific of Short-Chain Fatty Acids in White Pekin Ducks.

The current study was to investigate the modulatory effects of total dietary fiber (TDF) levels on cecal morphology and the response of microbiota to maintain gut health for duck growth. A total of 192 14-day-old male white Pekin ducks were randomly allocated to three dietary groups and fed diets, containing 12.4, 14.7, and 16.2% TDF, respectively, until 35 days under the quantitative feed intake. Each dietary group consisted of eight replicate cages of eight birds. The results revealed that 14.7 and 16.2% TDF groups significantly promoted growth performance and improved villus height, the ratio of villus to crypt, muscle layer thickness, and goblet cells per villus of cecum in ducks. qPCR results showed that the transcriptional expression of Claudin-1, Muc2, IGF-1, and SLC16A1 was significantly upregulated in cecum in 14.7 and 16.2% TDF groups. Meanwhile, the concentration of IGF-1 in circulating was significantly increased in 14.7 and 16.2% TDF groups while that of DAO was significantly decreased in 16.2% TDF group. Furthermore, the concentrations of butyrate, isobutyrate, valerate, and isovalerate in cecum were conspicuously improved in 14.7 and 16.2% TDF groups while that of propionate was significantly decreased. In addition, the concentrations of butyrate, isobutyrate, valerate, and isovalerate in cecum presented negative correlations with the concentration of DAO in circulating. 16S rRNA gene sequencing results showed that the 14.7% TDF group importantly elevated the microbial richness. Simultaneously, butyrate-producing bacteria like the family Lachnospiraceae, Oscillospiraceae, and Erysipelatoclostridiaceae were enriched as biomarkers in the 16.2% TDF group. Correlation network analysis revealed that the associations between specific bacteria and short-chain fatty acids (SCFAs) induced by different TDF levels, and the correlations among bacteria were also witnessed. For example, the genus Monoglobus and CHKCI002 showed a positive correlation with butyrate, and there was a positively coexistent association between Monoglobus and CHKCI002. In summary, these data revealed that increasing the TDF level could enhance the cecal morphology and drive cecal species-specific of SCFAs in ducks.

Research on Self-Noise Characteristics of Nine Types of Seismometers Obtained by PDF Representation Using Continuous Seismic Data from the Malingshan Seismic Station, China.

The self-noise level of a seismometer can determine the performance of the seismic instrument and limit the ability to use seismic data to solve geoscience problems. Accurately measuring and simultaneously comparing the self-noise models from different types of seismometers has long been a challenging task due to the constraints of observation conditions. In this paper, the self-noise power spectral density (PSD) values of nine types of seismometers are calculated using four months of continuous seismic waveforms from Malingshan seismic station, China, and nine self-noise models are obtained based on the probability density function (PDF) representation. For the seismometer STS-2.5, the self-noise levels on the horizontal channels (E−W and N−S) are significantly higher than that on the vertical channel (U−D) in the microseism band (0.1 Hz to 1 Hz), which is a computing bias caused by the misalignment between the sensors in the horizontal direction, while the remarkably elevated noise on the horizontal channels at the low frequencies (<0.6 Hz) may originate from the local variation of atmospheric pressure. As for the very broadband seismometers Trillium-Horizon-120 and Trillium-120PA, and the ultra-broadband seismometers Trillium-Horizon-360 and CMG-3T-360, there is a trade-off between the microseism band range and low-frequency range in the PSD curves of the vertical channel. When the level of self-noise in the microseism band is high, the self-noise at low frequencies is relatively low. Although compared with the other very broadband seismometers, the self-noise level of the vertical component of the STS-2.5 is 3 dB to 4 dB lower at frequencies less than 1 Hz, the self-noise level of the STS-2.5 at high frequencies (>2 Hz) is slightly higher than others. From our observations, we conclude that the nine seismometers cannot reach the lowest noise level in all frequency bands within the working range.

[Proximal femoral nail antirotation versus dynamic hip screw for intertrochanteric fracture in elders: a meta-analysis].

OBJECTIVE: To assess the efficacies of proximal femoral nail antirotation (PFNA) versus dynamic hip screw (DHS) for intertrochanteric fracture in elders. METHODS: The databases of PubMed, Embase, CENTRAL, CBM, CNKI and WANFANG were searched for the relevant randomized controlled trials (RCTs) up to May 18, 2013. After quality evaluation and data extraction by two authors independently, meta-analyses were performed with the RevMan5.1 software. And the levels of evidence were evaluated by the GRADEprofile 3.6 software. RESULTS: A total of 17 studies (n = 1 344) were included and there were 656 patients in PFNA group and 688 in DHS respectively. Meta-analyses showed that, as compared with DHS, PFNA could significantly decrease fixation failure rate (odds ratio (OR) = 0.26, 95% confidence interval (CI) = [0.12, 0.57], P = 0.0008), reduce average fracture healing time (weighted mean difference (WMD) = -15.11, 95%CI = [-24.36, -5.85], P = 0.001), improve excellent and good rate for Harris score (OR = 0.29, 95%CI = [0.15, 0.56], P = 0.0002), yield a higher Harris score (WMD = 6.88, 95%CI = [0.96, 12.80], P = 0.02) and reduce the rate of coxa vara (OR = 0.40, 95%CI = [0.18,0.92], P = 0.03). However, there was no statistical significance in 1-year mortality, postoperative nonunion and delayed union, postoperative femoral head necrosis, postoperative femoral fractures or femoral head necrosis. The importance of outcomes was "critical". And the level of evidences based on the GRADE approach was from "very low" to "low". CONCLUSION: PFNA is superior to DHS. Due to the limitations of the included studies, more large-sample and high-quality RCTs are required. And subgroup analysis based on fracture types should be performed.

[Locked plating with minimally invasive percutaneous plate osteosynthesis versus intramedullary nailing of distal extra-articular tibial fracture: a retrospective study].

OBJECTIVE: To compare the efficacies of minimally invasive plate osteosynthesis (MIPPO) and interlocking intramedullary nailing (IMN) in the treatment of extra-articular fractures of distal tibia. METHODS: Retrospective reviews were conducted for 126 patients with extra-articular distal tibia fractures. Treatment was either MIPPO (n = 61) or IMN (n = 65). The outcomes were assessed by comparing operating duration, time to union, the last follow-up American Orthopedic Foot and Ankle Society (AOFAS) score and complication rate. RESULTS: The average follow-up period was 23.7 (12-53) months. In the minimally invasive plate osteosynthesis group, there were deep infections (n = 2), superficial infections (n = 5), delayed union (n = 2), malunion (n = 2) and knee joint pain (n = 10) were observed. In addition, the average operating duration (85.9 ± 18.9 min), average time to union (17.3 ± 3.8 weeks) and average AOFAS (83.2 ± 11.9) were analyzed. In the interlocking intramedullary nailing group, there were delayed union (n = 3), malunion (n = 12) and knee joint pain (n = 22). And the average operating duration (83.3 ± 15.7 min), average time to union (16.5 ± 3.1 weeks) and average AOFAS (84.9 ± 12.0) were analyzed. No statistical significance existed in operating duration, time to union and the last follow-up AOFAS between two groups (P > 0.05). However, the rates of malformation and knee joint pain were higher in the intramedullary nail group than those in the plate group. And the difference was statistically significant (P = 0.015, P = 0.025). CONCLUSION: Both MIPPO and IMN are effective for extra-articular fractures of distal tibia. However, the former has the advantage of lowers rate of malformation and knee joint pain. Therefore a surgeon should consider the degree of injury while managing extra-articular fracture of distal tibia.