Fisetin alleviates cerebral ischemia/reperfusion injury by regulating Sirt1/Foxc1/Ubqln1 pathway-mediated proteostasis.

BACKGROUND: Cerebral ischemia/reperfusion injury (IRI) is pathologically associated with protein damage. The flavonoid fisetin has good therapeutic effects on cerebral IRI. However, the role of fisetin in regulating protein damage during cerebral IRI development remains unclear. This study investigated the pharmacological effects of fisetin on protein damage during cerebral IRI progression and defined the underlying mechanism of action. METHODS: In vivo and in vitro models of cerebral IRI were established by middle cerebral artery occlusion/reperfusion (MACO/R) and oxygen-glucose deprivation/reperfusion (OGD/R) treatment, respectively. Triphenyl tetrazolium chloride staining was performed to detect cerebral infarct size, and the modified neurologic severity score was used to examine neurological deficits. LDH activity and protein damage were assessed using kits. HT22 cell vitality and apoptosis were examined using CCK-8 assay and TUNEL staining, respectively. Interactions between Foxc1, Ubqln1, Sirt1, and Ezh2 were analyzed using CoIP, ChIP and/or dual-luciferase reporter gene assays. RESULTS: Fisetin alleviated protein damage and ubiquitinated protein aggregation and neuronal death caused by MCAO/R and OGD/R. Ubqln1 knockdown abrogated the inhibitory effect of fisetin on OGD/R-induced protein damage, ubiquitinated protein aggregation, and neuronal death in HT22 cells. Further experiments demonstrated that Foxc1 functions as a transcriptional activator of Ubqln1 and that Sirt1 promotes Foxc1 expression by deacetylating Ezh2 and inhibiting its activity. Furthermore, Sirt1 knockdown abrogated fisetin-mediated biological effects on OGD/R-treated HT22 cells. CONCLUSION: Fisetin improved proteostasis during cerebral IRI by regulating the Sirt1/Foxc1/Ubqln1 signaling axis. Our findings strongly suggest that fisetin-mediated inhibition of protein damage after ischemic stroke is a part of the mechanism through which fisetin is neuroprotective in cerebral IRI.

A chromosome-level genome assembly for the Silkie chicken resolves complete sequences for key chicken metabolic, reproductive, and immunity genes.

A set of high-quality pan-genomes would help identify important genes that are still hidden/incomplete in bird reference genomes. In an attempt to address these issues, we have assembled a de novo chromosome-level reference genome of the Silkie (Gallus gallus domesticus), which is an important avian model for unique traits, like fibromelanosis, with unclear genetic foundation. This Silkie genome includes the complete genomic sequences of well-known, but unresolved, evolutionarily, endocrinologically, and immunologically important genes, including leptin, ovocleidin-17, and tumor-necrosis factor-α. The gap-less and manually annotated MHC (major histocompatibility complex) region possesses 38 recently identified genes, with differentially regulated genes recovered in response to pathogen challenges. We also provide whole-genome methylation and genetic variation maps, and resolve a complex genetic region that may contribute to fibromelanosis in these animals. Finally, we experimentally show leptin binding to the identified leptin receptor in chicken, confirming an active leptin ligand-receptor system. The Silkie genome assembly not only provides a rich data resource for avian genome studies, but also lays a foundation for further functional validation of resolved genes.

Selection on the promoter regions plays an important role in complex traits during duck domestication.

BACKGROUND: Identifying the key factors that underlie complex traits during domestication is a great challenge for evolutionary and biological studies. In addition to the protein-coding region differences caused by variants, a large number of variants are located in the noncoding regions containing multiple types of regulatory elements. However, the roles of accumulated variants in gene regulatory elements during duck domestication and economic trait improvement are poorly understood. RESULTS: We constructed a genomics, transcriptomics, and epigenomics map of the duck genome and assessed the evolutionary forces that have been in play across the whole genome during domestication. In total, 304 (42.94%) gene promoters have been specifically selected in Pekin duck among all selected genes. Joint multi-omics analysis reveals that 218 genes (72.01%) with selected promoters are located in open and active chromatin, and 267 genes (87.83%) with selected promoters were highly and differentially expressed in domestic trait-related tissues. One important candidate gene ELOVL3, with a strong signature of differentiation on the core promoter region, is known to regulate fatty acid elongation. Functional experiments showed that the nearly fixed variants in the top selected ELOVL3 promoter in Pekin duck decreased binding ability with HLF and increased gene expression, with the overexpression of ELOVL3 able to increase lipid deposition and unsaturated fatty acid enrichment. CONCLUSIONS: This study presents genome resequencing, RNA-Seq, Hi-C, and ATAC-Seq data of mallard and Pekin duck, showing that selection of the gene promoter region plays an important role in gene expression and phenotypic changes during domestication and highlights that the variants of the ELOVL3 promoter may have multiple effects on fat and long-chain fatty acid content in ducks.

Sputtered binder-free Cu3N electrode materials for high-performance quasi-solid-state asymmetric supercapacitors.

Developing high-efficiency electrode materials is of great importance in manufacturing supercapacitor devices with superior electrochemical performance. Herein, we for the first time report a binder-free method for controllable growth of Cu3N electrode materials via magnetron sputtering for supercapacitor applications. Benefiting from their unique polyhedral structure and good electrical conductivity, Cu3N electrodes can achieve an areal capacity of 90.7 mC cm-2 at 1 mA cm-2 and outstanding cycling stability with a capacity retention of 97.4% after 20 000 cycles. In particular, the assembled Cu3N//active carbon quasi-solid-state asymmetric supercapacitor can exhibit a maximum energy density of 13.2 µW h cm-2 and a power density of 4.8 mW cm-2 with an operating voltage of 1.6 V. These remarkable performances demonstrate the great potential of sputtered Cu3N electrode materials for future energy storage applications.

Identification of p72 epitopes of African swine fever virus and preliminary application.

African swine fever virus (ASFV) causes a highly lethal hemorrhagic viral disease (ASF) of pigs that results in serious losses in China and elsewhere. The development of a vaccine and diagnosis technology for ASFV is essential to prevent and control the spread of ASF. The p72 protein of ASFV is highly immunogenic and reactive, and is a dominant antigen in ASF vaccine and diagnostic research. In this study, 17 p72 monoclonal antibodies (mAbs) were generated. Epitope mapping by a series of overlapping peptides expressed in Escherichia coli showed that these mAbs recognized a total of seven (1-7) linear B cell epitopes. These mAbs did not show significant neutralizing activity. Epitopes 1 (249HKPHQSKPIL258), 2 (69PVGFEYENKV77), 5 (195VNGNSLDEYSS205), and 7 (223GYKHLVGQEV233) are novel. Sequence alignment analysis revealed that the identified epitopes were highly conserved among 27 ASFV strains from nine genotypes. Preliminary screening using known positive and negative sera indicated the diagnostic potential of mAb-2B8D7. The results provide new insights into the antigenic regions of ASFV p72 and will inform the diagnosis of ASFV.

Exploring the effect of the microbiota on the production of duck striped eggs.

The microbiota has received plenty of attention in recent years due to its influence on host health and productivity. The striped eggs have reduced hatching performance and resulted in economic loss. The reasons are still unknown. Microbiota is one of the potentially important factors contributing to striped egg formation. This study investigates the relationship between the microbiota and striped eggs. The litter samples, feed samples, and cloacal swab samples of female ducks that produce striped eggs and normal eggs were performed for microbial diversity and composition using 16S rRNA sequencing. The results showed that there was no significant difference between feed microbiota and cloacal swab microbiota by alpha diversity, whereas, the number of microorganisms in the litter samples of female ducks that produced striped eggs was less than those of female ducks with normal eggs. There were compositional differences in litter microbiota of female ducks between the striped egg and the normal eggs. Among them, the abundance of Staphylococcus, Corynebacterium, and Brevibacterium in the litter of female ducks that produced striped eggs was significantly higher than that produced normal eggs. And these differential bacteria maybe affect the health of female ducks and cause abnormalities in the formation process of duck eggs. Therefore, the reduction of harmful bacteria may protect the reproductive health of female ducks and decrease the proportion of striped eggs. It provides an important reference to explore why female ducks produce striped eggs.

Genome-wide association study identified the candidate genes associated with angel wing trait in Pekin duck.

Angel wing is a developmental wing deformity that can influence breeding and reproduction in the commercial duck industry. The nutrition foundation of angel wing trait was initially explored, but the genetic basic remains poorly understood. In this study, we identified candidate genes and single-nucleotide polymorphisms (SNPs) associated with angel wing trait in Pekin ducks using a genome-wide association study (GWAS) and selective sweep analysis. The GWAS results showed that nine SNPs across five chromosomes were significantly correlated with the angel wing trait. In total, 468 selection signals were shown between the angel wing ducks and normal ducks, and these signals harbored 154 genes, which were enriched in the nervous system and metabolism. This study provides the new insights into the genetic factors that may influence duck angel wing.

Transcranial Sonography as a Diagnostic Tool for Depressive Disorders.

BACKGROUND: Transcranial sonography (TCS) is an available and noninvasive neuroimaging method that has been found to reduce the echogenicity of the brainstem raphe (BR) in patients with depression. Applying the criteria of the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV), we performed a meta-analysis of the diagnostic accuracy of TCS. METHODS: A systematic search was conducted in PubMed, EMBASE, The Cochrane Library, and Web of Science. The databases were searched from inception to December 2021. The quality of the included literature was assessed using the QUADAS-2. Heterogeneity analysis was performed. A summary receiver operating characteristic (SROC) curve was generated to evaluate the diagnostic accuracy of TCS. RESULTS: We included 12 studies with 809 patients. The pooled sensitivity was 0.66 (95% confidence interval [CI]: 0.61-0.71), and the specificity was 0.84 (95% CI: 0.80-0.87). The combined positive likelihood ratio (LR) was 3.84 (95% CI: 2.68-5.51), the negative LR was 0.41 (95% CI: 0.29-0.57), and the diagnostic odds ratio (DOR) was 11.45 (95% CI: 5.57-23.02). The area under the curve (AUC) of the plotted SROC curve was 0.86 (95% CI: 0.83-0.89). The meta-regression and subgroup analyses found no source of heterogeneity. CONCLUSION: TCS has high potential and efficacy in diagnosing depression and may be a reasonable test to perform clinically for the assessment of depression.

A vesicular stomatitis virus-based African swine fever vaccine prototype effectively induced robust immune responses in mice following a single-dose immunization.

Introduction: African swine fever (ASF) is a highly contagious hemorrhagic fever disease in pigs caused by African swine fever virus (ASFV). It is very difficult to control and prevent ASF outbreaks due to the absence of safe and effective vaccines. Methods: In order to develop a safe and effective ASF vaccine for the control and prevention of ASF, two ASFV recombinant vesicular stomatitis virus (VSV) live vector vaccine prototypes, containing the gene of p72, and a chimera of p30 and p54, were developed based on the replication-competent VSV, and named VSV-p72 and VSV-p35. The immune potency of VSV-p72 or VSV-p35 alone and in combination was evaluated in BALB/c mice via intramuscular and intranasal vaccination. Results: The results indicated that whether administered alone or in combination, the two vaccine prototypes showed acceptable safety in mice and, more importantly, induced high-level specific antibodies against p72, p30, and p54 of ASFV and a strong cellular immune response 28 days after vaccination. The sera from mice vaccinated with the vaccine prototypes significantly inhibited ASFV from infecting porcine alveolar macrophages (PAMs) in vitro. Most notably, the immunized sera from a mixture of VSV-p35 and VSV-p72 inhibited ASFV from infecting PAMs, with an inhibition rate of up to 78.58%. Conclusion: Overall, our findings suggest that ASFV recombinant VSV live vector vaccine prototypes may become a promising candidate vaccine for the control and prevention of ASF.

Chromosome-level genome assembly of the Muscovy duck provides insight into fatty liver susceptibility.

The Muscovy duck (Cairina moschata) is an economically important poultry species, which is susceptible to fatty liver. Thus, the Muscovy duck may serve as an excellent candidate animal model of non-alcoholic fatty liver disease. However, the mechanisms underlying fatty liver development in this species are poorly understood. In this study, we report a chromosome-level genome assembly of the Muscovy duck, with a contig N50 of 11.8 Mb and scaffold N50 of 83.16 Mb. The susceptibility of Muscovy duck to fatty liver was mainly attributed to weak lipid catabolism capabilities (fatty acid ß-oxidation and lipolysis). Furthermore, conserved noncoding elements (CNEs) showing accelerated evolution contributed to fatty liver formation by down-regulating the expression of genes involved in hepatic lipid catabolism. We propose that the susceptibility of Muscovy duck to fatty liver is an evolutionary by-product. In conclusion, this study revealed the potential mechanisms underlying the susceptibility of Muscovy duck to fatty liver.

Online Monitoring Technology of Metal Powder Bed Fusion Processes: A Review.

Metal powder bed fusion (PBF) is an advanced metal additive manufacturing (AM) technology. Compared with traditional manufacturing techniques, PBF has a higher degree of design freedom. Currently, although PBF has received extensive attention in fields with high-quality standards such as aerospace and automotive, there are some disadvantages, namely poor process quality and insufficient stability, which make it difficult to apply the technology to the manufacture of critical components. In order to surmount these limitations, it is necessary to monitor the process. Online monitoring technology can detect defects in time and provide certain feedback control, so it can greatly enhance the stability of the process, thereby ensuring its quality of the process. This paper presents the current status of online monitoring technology of the metal PBF process from the aspects of powder recoating monitoring, powder bed inspection, building process monitoring, and melt layer detection. Some of the current limitations and future trends are then highlighted. The combination of these four-part monitoring methods can make the quality of PBF parts highly assured. We unanimously believe that this article can be helpful for future research on PBF process monitoring.

Modular-assembled laser system for a long-baseline atom interferometer.

The Zhaoshan long-baseline Atom Interferometer Gravitation Antenna (ZAIGA) is a new, to the best of our knowledge, type of large-scale atom interferometer facility under construction for the study of gravitation and related problems. To meet the different requirements of the laser system for the atom interferometer using various atoms (including 85Rb, 87Rb, 87Sr, and 88Sr), we design and implement a modular assembled laser system. By dividing the laser system into different basic units according to their functions and modularizing each unit, the laser system is made highly scalable while being compact and stable. Its intensity stability is better than 0.1% in 102s and 0.5% in 104s. We test the performance of the laser system with two experimental systems, i.e., an 85Rb-87Rb dual-species ultracold atom source and an 85Rb atom interferometer. The 85Rb-87Rb dual-species magneto-optical trap and the 85Rb atom interference fringes are realized by using this laser system, indicating that its technical performance can meet the major experimental requirements.

The Relationship Between Patent Foramen Ovale and Unexplained Dizziness: A Prospective Analysis in China.

Introduction: Patent foramen ovale (PFO) is potentially associated with abnormal embolisms, and it results in mixing of arteriovenous blood when its right-to-left shunt (RLS) emerges. Present studies have found that PFO is a risk factor that can lead to many diseases. However, few studies have examined the relationship between PFO and dizziness. Methods: This study was a large single-center, prospective, controlled study. From March 2019 to March 2021, we recruited patients with dizziness were divided into two groups: "explained" and "unexplained". All patients were submitted to contrast-enhanced transcranial Doppler ultrasound and screened for PFO. Transesophageal heart ultrasound or right heart catheterization was used to confirm PFO. Additionally, multiple factors were collected and statistical analysis was performed between the two groups. Results: Among the 244 patients included, 123 were in the "explained" group and 121 were in the "unexplained" group. The prevalence of PFO in the "explained" group was 34 (27.4%) compared to 79 (64.7%) in the "unexplained" group. In the "explained" group, 7 were RLS level IV, 6 were level III, 7 were level II, and 14 were level I. For the "unexplained" group, the numbers of patients with levels IV, III, II and I were 27, 26, 12 and 14, respectively. Univariate analysis revealed that PFO (χ2= 34.77, P < 0.001) and age (t = -3.49, P < 0.001) seemed to be potential risk factor candidates for "unexplained" dizziness. In multiple regression analysis, age (OR = 0.97; 95% CI 0.95-0.99) and the prevalence of PFO (OR = 4.37; 95% CI 2.50-7.63) were statistically significant. Massively shunted PFO showed more pronounced risk factors (OR = 8.76; 95% CI 4.04-19.03). Conclusion: There was a high prevalence of PFO and a greater RLS level in unexplained dizziness. PFO and age were independent risk factors for unexplained dizziness. When treating with unexplained dizziness, especially among young people, we must pay attention to the presence of PFO.

Factors associated with symptomatic intracranial haemorrhage after intravenous thrombolysis in severe white matter lesions: a retrospective analysis.

BACKGROUND AND PURPOSE: White matter lesions (WMLs) are thought to cause damage to the blood-brain barrier, thereby aggravating bleeding after intravenous thrombolysis. However, the risk factors for symptomatic cerebral haemorrhage after thrombolysis are still unclear. This study explored the risk factors for bleeding in patients with severe WMLs after intravenous thrombolysis to prevent bleeding as soon as possible. METHODS: A large single-centre observational study conducted a retrospective analysis of intravenous thrombolysis in patients with severe WMLs from January 2018 to March 2021. According to whether symptomatic cerebral haemorrhage occurred, the patients were divided into two groups, and then statistical analysis was performed. RESULTS: After a retrospective analysis of the data of nearly 1000 patients with intravenous thrombolysis and excluding invalid information, 146 patients were included, of which 23 (15.8%) patients had symptomatic cerebral haemorrhage. Univariate analysis showed that a history of hypertension (20% vs 4.9%, p=0.024), hyperlipidaemia (38.7% vs 9.6%, p<0.001), the National Institutes of Health Stroke Scale (NIHSS) score before thrombolysis (median 17 vs 6, p<0.001), low-density lipoprotein levels (median 2.98 vs 2.44, p=0.011), cholesterol levels (mean 4.74 vs 4.22, p=0.033), platelet count (median 161 vs 191, p=0.031), platelet distribution width (median 15.2 vs 12.1, p=0.001) and sodium ion levels (median 139.81 vs 138.67, p=0.043) were significantly associated with symptomatic cerebral haemorrhage. Further multivariate logistic regression analysis showed that hyperlipidaemia (OR=9.069; 95% CI 2.57 to 32.07; p=0.001) and the NIHSS score before thrombolysis (OR=1.33; 95% CI 1.16 to 1.52; p<0.001) were comprehensive risk factors for symptomatic cerebral haemorrhage. CONCLUSION: Hyperlipidaemia and the NIHSS score before thrombolysis are independent risk factors for bleeding after intravenous thrombolysis in patients with severe WMLs. Delaying the onset of white matter and preventing risk factors for bleeding will help improve the prognosis of cerebral infarction and reduce mortality. These risk factors need to be further evaluated in future studies.

Three chromosome-level duck genome assemblies provide insights into genomic variation during domestication.

Domestic ducks are raised for meat, eggs and feather down, and almost all varieties are descended from the Mallard (Anas platyrhynchos). Here, we report chromosome-level high-quality genome assemblies for meat and laying duck breeds, and the Mallard. Our new genomic databases contain annotations for thousands of new protein-coding genes and recover a major percentage of the presumed "missing genes" in birds. We obtain the entire genomic sequences for the C-type lectin (CTL) family members that regulate eggshell biomineralization. Our population and comparative genomics analyses provide more than 36 million sequence variants between duck populations. Furthermore, a mutant cell line allows confirmation of the predicted anti-adipogenic function of NR2F2 in the duck, and uncovered mutations specific to Pekin duck that potentially affect adipose deposition. Our study provides insights into avian evolution and the genetics of oviparity, and will be a rich resource for the future genetic improvement of commercial traits in the duck.

Treatment Strategies for Cryptogenic Stroke Patients with Patent Foramen Ovale: What Do We Choose?

IMPORTANCE: The treatment of cryptogenic stroke patients with patent foramen ovale to prevent recurrence of stroke, especially when patients consider drug prevention alone, has caused serious treatment dilemmas in clinical practice. OBJECTIVE: To study the safety and efficacy of different treatment strategies using a network meta-analysis of randomized controlled trials in this population with cryptogenic stroke and patent foramen ovale. STUDY SELECTION: PUBMED, EMBASE, The Cochrane Library, WangFang, and China National Knowledge Infrastructure were searched to identify RCT comparing different treatment strategies. Eleven randomized studies were included (n = 5706). MAIN OUTCOMES: The primary efficacy outcome was recurrence of ischemic stroke, including fatal and non-fatal ischemic strokes. The primary safety outcome was major hemorrhage, but closure surgery includes systemic thrombotic events, persistent atrial fibrillation, surgical deaths and other major events. RESULTS: In terms of efficacy and safety events, compared with antiplatelet, the OR of vitamin K antagonists for stroke recurrence was 0.81 (95% CI, 0.41-1.6), the OR of surgical closure was 0.38 (95% CI, 0.16-0.63), and the OR of NOAC was 0.79 (95% CI, 0.27-2.3). Compared with antiplatelet, the safety event OR of vitamin K antagonists was 1.7 (95% CI, 0.65-4.8), the OR of surgical closure was 1.7 (95% CI, 0.68-3.8), and the OR of NOAC was 2.2 (95% CI, 0.67-7.6). CONCLUSION: In terms of effectiveness, surgical occlusion has the best performance, while anticoagulation is the second best. Vitamin K antagonists and non-vitamin K antagonists are difficult to distinguish between the best in effectiveness. Antiplatelet drugs are considered the worst option. Regarding the safety results, it is generally believed that there are no obvious beneficial interventions, but antiplatelet drugs are considered to be relatively best, followed by surgical intervention and vitamin K antagonists, and non-vitamin K antagonists are considered to be the least safe.

Prediction of Peking duck intramuscle fat content by near-infrared spectroscopy.

Peking duck is the most representative of the meat-type duck breed, and it is also one of the most popular meats in Asia. Few studies were reported on the fast assessment of duck meat quality. This study aimed to develop a fast measuring of duck fat content by using the near-infrared spectroscopy (NIRS) method. We measured 273 duck breast muscle intramuscle fat (IMF) content and spectra. Partial least-squares regression (PLSR) was used to model the fat content prediction by using the spectra in the wavelengths between 950 and 1650 nm. The best predictive abilities were obtained after the first derivative pretreatment, with coefficient of calibration (R2C) of 0.92, with coefficient of prediction (R2P) of 0.90, ratio performance to deviation (RPD) of 2.72, and ratio of error range (RER) of 15.45, for samples of 30 g duck. Results demonstrated that the near-infrared spectroscopy is a useful tool for fat content assessment of Peking duck meat.

All acousto-optic modulator laser system for a 12 m fountain-type dual-species atom interferometer.

We design and implement a laser system for 85Rb and 87Rb dual-species atom interferometers based on acousto-optic frequency shift and tapered amplifier laser technologies. We use eight-pass acousto-optic modulators to generate repumping lasers for 85Rb and 87Rb atoms. The maximum frequency shift of the laser is 2.8 GHz, and the diffraction efficiency is higher than 20%. We use high-frequency acousto-optic modulators to generate the Raman lasers. This laser system uses only two seed lasers to provide the various frequencies required by 85Rb and 87Rb dual-species atom interferometers, which greatly improves laser usage. The laser system is applied in the equivalence principle test experiment using an 85Rb and 87Rb dual-species atom interferometer. The signal of atoms launched to 12 meters is successfully observed, and the resolution of gravity differential measurement is improved from 8×10-9 g to 1×10-10g.

Genome-wide association study reveals novel loci associated with feeding behavior in Pekin ducks.

BACKGROUND: Feeding behavior traits are an essential part of livestock production. However, the genetic base of feeding behavior traits remains unclear in Pekin ducks. This study aimed to determine novel loci related to feeding behavior in Pekin ducks. RESULTS: In this study, the feeding information of 540 Pekin ducks was recorded, and individual genotype was evaluated using genotyping-by-sequencing methods. Genome-wide association analysis (GWAS) was conducted for feeding behavior traits. Overall, thirty significant (P-value < 4.74E-06) SNPs for feeding behavior traits were discovered, and four of them reached the genome-wide significance level (P-value < 2.37E-07). One genome-wide significance locus associated with daily meal times was located in a 122.25 Mb region on chromosome 2, which was within the intron of gene ubiquitin-conjugating enzyme E2 E2 (UBE2E2), and could explain 2.64% of the phenotypic variation. This locus was also significantly associated with meal feed intake, and explained 2.72% of this phenotypic variation. CONCLUSIONS: This study is the first GWAS for feeding behavior traits in ducks. Our results provide a list of candidate genes associated with feeding behavior, and also help to better understand the genetic mechanisms of feeding behavior patterns in ducks.