Geese evolved from migratory birds, and when they consume excessive high-energy feed, glucose is converted into triglycerides. A large amount of triglyceride deposition can induce incomplete ...oxidation of fatty acids, leading to lipid accumulation in the liver and the subsequent formation of fatty liver. In the Chaoshan region of Guangdong, China, Shitou geese develop a unique form of fatty liver through 24 h overfeeding of brown rice. To investigate the mechanisms underlying the formation of fatty liver in Shitou geese, we collected liver samples from normally fed and overfed geese. The results showed that the liver size in the treatment group was significantly larger, weighing 3.5 times more than that in the control group. Extensive infiltration of lipid droplets was observed in the liver upon staining of tissue sections. Biochemical analysis revealed that compared to the control group, the treatment group showed significantly elevated levels of total cholesterol (T-CHO), triglycerides (TG), and glycogen in the liver. However, no significant differences were observed in the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which are common indicators of liver damage. Furthermore, we performed a combined transcriptomic and lipidomic analysis of the liver samples and identified 1,510 differentially expressed genes (DEGs) and 1,559 significantly differentially abundant metabolites (SDMs). The enrichment analysis of the DEGs revealed their enrichment in metabolic pathways, cellular process-related signaling pathways, and specific lipid metabolism pathways. We also conducted KEGG enrichment analysis of the SDMs and compared them with the enriched signaling pathways obtained from the DEGs. In this study, we identified 3 key signaling pathways involved in the formation of fatty liver in Shitou geese, namely, the biosynthesis of unsaturated fatty acids, glycerol lipid metabolism, and glycerophospholipid metabolism. In these pathways, genes such as glycerol-3-phosphate acyltransferase, mitochondrial (GPAM), 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2), diacylglycerol O-acyltransferase 2 (DGAT2), lipase, endothelial (LIPG), lipoprotein lipase (LPL), phospholipase D family member 4 (PLD4), and phospholipase A2 group IVF (PLA2G4F) may regulate the synthesis of metabolites, including triacylglycerol (TG), phosphatidate (PA), 1,2-diglyceride (DG), phosphatidylethanolamine (PE), and phosphatidylcholine (PC). These genes and metabolites may play a predominant role in the development of fatty liver, ultimately promoting the accumulation of TG in the liver and leading to the progression of fatty liver.
Occluded person re-identification is a challenging task since the available data often suffers from information incompleteness and spatial misalignment. Most state-of-the-art occluded models rely on ...the external model to provide additional semantic information. However, for the time being, external models, such as the human parsing model and the pose estimation model cannot provide accurate semantic information under a complex occlusion environment and may introduce errors to the Re-ID model instead. In this paper, we propose an occluded person Re-ID model that mines the latent recognizable information of the person image itself, without the help of external models. Feature/Data uncertainty can reduce the influence of noisy samples in datasets and has been discussed in person Re-ID and face recognition, we extend the uncertainty to the micro feature level, and propose the spatial-wise and channel-wise feature uncertainty to constantly refine the features in the spatial domain and the channel domain respectively during feature construction by weakening the influence of noise features. Extensive experiments on the occluded datasets and holistic datasets have proved the effectiveness of our proposed methods.
Abstract Delivery of imaging agents to brain glioma is challenging because the blood–brain barrier(BBB) functions as a physiological checkpoint guarding the central nervous system from circulating ...large molecules. Moreover, the ability of existing probes to target glioma has been insufficient and needs to be improved. In present study, PEG-based long circulation, CdSe/ZnS quantum dots(QDs)-based nanoscale and fluorescence, asparagines-glycine-arginine peptides(NGR)-based specific CD13 recognition were integrated to design and synthesize a novel nanoprobe by conjugating biotinylated NGR peptides to avidin-PEG-coated QDs. Our data showed that the NGR-PEG-QDs were nanoscale with less than 100 nm and were stable in various pH(4.0 ~ 8.0). These nanomaterials with non-toxic concentrations could cross the BBB and target CD13-overexpressing glioma and tumor vasculature in vitro and in vivo , contributing to fluorescence imaging of this brain malignancy. These achievements allowed groundbreaking technological advances in targeted fluorescence imaging for the diagnosis and surgical removal of glioma, facilitating potential transformation toward clinical nanomedicine.
Emerging evidence has implicated an important role of synapse-associated protein-97 (SAP97)-regulated GluA1-containing AMPARs membrane trafficking in cocaine restate and in contextual episodic memory ...of schizophrenia. Herein, we investigated the role of SAP97 in neuropathic pain following lumbar 5 spinal nerve transection (SNT) in rats. Our results showed that SNT led to upregulation of SAP97, enhanced the interaction between SAP97 and GluA1, and increased GluA1-containing AMPARs membrane trafficking in the dorsal horn. Microinjection of AAV-EGFP-SAP97 shRNA in lumbar 5 spinal dorsal horn inhibited SAP97 production, decreased SAP97-GluA1 interaction, reduced the membrane trafficking of GluA1-containing AMPARs, and partially attenuated neuropathic pain following SNT. Intrathecal injections of SAP97 siRNA or NASPM, an antagonist of GluA1-containing AMPARs, also partially reversed neuropathic pain on day 7, but not on day 14, after SNT. Spinal overexpression of SAP97 by AAV-EGFP-SAP97 enhanced SAP97-GluA1 interaction, increased the membrane insertion of GluA1-containing AMPARs, and induced abnormal pain in naïve rats. In addition, treatment with SAP97 siRNA or NASPM i.t. injection alleviated SNT-induced allodynia and hyperalgesia and exhibited a longer effect in female rats. Together, our results indicate that the SNT-induced upregulation of SAP97 via promoting GluA1-containing AMPARs membrane trafficking in the dorsal horn contributes to the pathogenesis of neuropathic pain. Targeting spinal SAP97 might be a promising therapeutic strategy to treatment of chronic pain.
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•SNT induced upregulation of SAP97 and increased membrane trafficking of GluA1-containing AMPARs.•Spinal knockdown SAP97 reduced membrane insertion of GluA1-AMPARs.•Spinal knockdown SAP97 or blockade of GluA1-AMPARs alleviated neuropathic pain.
Salmonella enterica
serovar Indiana (
S
. Indiana) has aroused widespread concern as an important zoonotic pathogen. The molecular mechanism of multidrug resistance (MDR) in
S
. Indiana is not known ...and should be assessed. We aim to investigate the molecular mechanism of MDR and the importance of large plasmids carried class 1 integrons in the MDR of foodborne
S
. Indiana. Class 1 integrons in 48
S
. Indiana isolates and 200 isolates of 7 other
Salmonella
serotypes were detected by polymerase chain reaction (PCR). To analyze the antimicrobial resistance genes (ARGs) of two
S
. Indiana isolates, designated
S
. Indiana 15 and
S
. Indiana 222, next-generation sequencing (NGS) was performed, and the resulting sequences were compared with the complete nucleotide sequences of
S
. Indiana D90 and
S
. Indiana C629. Comparative functional analysis was conducted between the
intI1
(1,014 bp) of
S
. Indiana 222 and the
intI1
(699 bp) of
S
. Indiana 15. Plasmid conjugation transfer analysis was performed to analyze the horizontal gene transfer of the integrons-related resistance genes with integron-positive and integron-negative
Salmonella
isolates. 64.58% of
S
. Indiana isolates carried class 1 integrons, which was significantly higher than that of other
Salmonella
serotypes (
p
< 0.001). The NGS results showed that the
S
. Indiana 15 and
S
. Indiana 222 isolates carried a large plasmid with a class 1 integron and multiple ARGs, similar to
S
. Indiana D90 and
S
. Indiana C629. Two integrases found in
S
. Indiana isolates belong to class 1 integrases and could integrate resistance genes into specific integration sites of the integrons. The conjugation frequency of
intI1
(1,014 bp) was 6.08 × 10
−5
, which was significantly higher than that of
intI1
(699 bp) (
p
< 0.01). The large plasmids carrying a class 1 integron and the number of ARGs were strongly correlated (
p
< 0.001). The conjugation frequency of integron-positive
S
. Indiana recipient isolates was significantly higher than that of integron-negative recipient isolates (
p
< 0.05).
S
. Indiana containing large plasmids carrying a class 1 integron more easily captured resistance genes from other bacteria (
S
. Enteritidis and
S
. Derby), which could be an important cause of the emerging pandemic of MDR clones.
Graphical abstract
S
. Indiana containing large plasmids carrying a class 1 integron more easily captured resistance genes from other bacteria (
S
. Enteritidis and
S
. Derby), which could be an important cause of the emerging pandemic of MDR clones.
Uncovering genetic variation through resequencing is limited by the fact that only sequences with similarity to the reference genome are examined. Reference genomes are often incomplete and cannot ...represent the full range of genetic diversity as a result of geographical divergence and independent demographic events. To more comprehensively characterize genetic variation of pigs (
), we generated de novo assemblies of nine geographically and phenotypically representative pigs from Eurasia. By comparing them to the reference pig assembly, we uncovered a substantial number of novel SNPs and structural variants, as well as 137.02-Mb sequences harboring 1737 protein-coding genes that were absent in the reference assembly, revealing variants left by selection. Our results illustrate the power of whole-genome de novo sequencing relative to resequencing and provide valuable genetic resources that enable effective use of pigs in both agricultural production and biomedical research.
Lysine-specific demethylase 6B (KDM6B) serves as a key mediator of gene transcription. It regulates expression of proinflammatory cytokines and chemokines in variety of diseases. Herein, the role and ...the underlying mechanisms of KDM6B in inflammatory pain were studied.
The inflammatory pain was conducted by intraplantar injection of complete Freund's adjuvant (CFA) in rats. Immunofluorescence, Western blotting, qRT-PCR, and chromatin immunoprecipitation (ChIP)-PCR were performed to investigate the underlying mechanisms.
CFA injection led to upregulation of KDM6B and decrease in the level of H3K27me3 in the dorsal root ganglia (DRG) and spinal dorsal horn. The mechanical allodynia and thermal hyperalgesia following CFA were alleviated by the treatment of intrathecal injection of GSK-J4, and by microinjection of AAV-EGFP-KDM6B shRNA in the sciatic nerve or in lumbar 5 dorsal horn. The increased production of tumor necrosis factor-α (TNF-α) following CFA in the DRGs and dorsal horn was inhibited by these treatments. ChIP-PCR showed that CFA-induced increased binding of nuclear factor κB with TNF-α promoter was repressed by the treatment of microinjection of AAV-EGFP-KDM6B shRNA.
These results suggest that upregulated KDM6B via facilitating TNF-α expression in the DRG and spinal dorsal horn aggravates inflammatory pain.
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•Preparing three PANI nanostructures in HCl, H2SO4, and HNO3 reaction media during a slow interfacial polymerization.•Obtaining nanofibrous, nanogranular and hollow ball–like ...morphologies in the order of oxidizability of acids.•Demonstrating high specific capacitance, good rate performance and long cycle life of PANI nanofibers.
Three nanostructured polyanilines (PANIs) were prepared by interfacial polymerization using different inorganic acids including HCl, H2SO4, and HNO3 as reaction media, respectively. The morphology-dependent structure and properties of as-prepared PANIs were characterized by means of scanning electron microscope, ultraviolet-visible spectra, Fourier transform infrared spectroscopy and X-ray diffraction patterns. Meanwhile, the electrochemical performance of the fabricated electrodes was evaluated by cyclic voltammetry, galvanostatic charge/discharge measurement, and electrochemical impedance spectroscopy. It is found that the reaction medium plays a vital role in deciding the final morphology and structure of product when a slow reaction rate occurred in interfacial polymerization. The as-prepared PANIs exhibited nanofibrous, nanogranular and hollow ball-like morphologies according to the order of the relative oxidizing ability of HCl<H2SO4<HNO3, respectively. Furthermore, the capacitive properties of these composites as electrode materials highly depended not only on their morphologies but also on the conductivity, crystalline property and the inhibitory role of the lattice during the redox process, as well as the interparticle contact resistance. It is demonstrated that PANI nanofibers prepared in HCl medium exhibited high specific capacitance, good rate performance and long cycle life for the supercapacitor application.
Rationale
For disulfide‐containing peptides, mass spectrometric analyses are rarely comparably studied between their dithiol and disulfide forms. Persulfide ions afforded from peptides with a ...disulfide ring are from either an unusual N–Cα bond cleavage or a canonical peptide bond cleavage; their isomeric structures are, however, not identified just from peaks of mass spectra.
Methods
Isomeric structures of C3P4X5|C6M, C3MAP4X5|C6MB and P4X5C6|C3M were identified from a series of the X5 substituted dicysteine octapeptides using electrospray ionization tandem mass spectrometry for both their dithiol and disulfide forms. Formation mechanisms of different persulfide ions were investigated systematically by theoretical methods. Moreover, electrostatic potential‐mapped molecular van der Waals surfaces were used to determine the stabilities of the intermediates, which gave a further evaluation of favored bond cleavage.
Results
Mass spectral analyses indicated that the fragmented ions changed largely when an intramolecular disulfide bond was formed. New types of disulfide‐containing fragmented ions C3P4X5|C6M or C3MAP4X5|C6MB were thus proposed. Energy analysis showed that the N–Cα cleavage was not competitive energetically with that of the amide bond for Y5 and its phosphorylated analogue. However, the N–Cα cleavage products dominated for the S5‐ and T5‐containing peptides. Stabilities of the intermediates were found to be related with the electrostatic potential‐mapped molecular van der Waals surfaces.
Conclusions
Persulfide ions containing more residues than previously found were proposed not only from b7 ions but also from y6 ions. In addition, a new kind of phosphorylated analogue, C3P4pY5|C6M, is reported in this work. Our study provides convincing results for separating isomeric structures in the cases of N–Cα cleavages, which greatly assists in the structural identification of disulfide‐containing peptides.
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•The oxidation of TCEP by IrCl62− has been investigated kinetically over a wide pH range.•Observed second-order rate constant vs pH profile has been established.•Reaction mechanism ...involving phosphine radical cations is proposed and convincing.•The reactivity of the TCEP species towards an oxidant is deciphered for the first time.
Despite of wide applications of tris(2-carboxyethyl)phosphine (TCEP) as a reductant, the reductions of single electron oxidants by TCEP are poorly understood mechanistically. Herein the reduction of IrCl62− by TCEP was thus investigated kinetically over a wide pH range at 1.0 M ionic strength. Overall second-order kinetics was proved for the reduction, being first-order with respect to both Ir(IV) and TCEP, respectively. The redox stoichiometry was determined to be ΔIr(IV):ΔTCEP = 2:1 and the corresponding phosphine oxide (TCEPO) was identified as the oxidation product of TCEP by 1H NMR spectroscopy. A reaction mechanism was rationalized in term of parallel reactions of IrCl62− with all the TCEP protolysis species being as the rate-determining steps, in which phosphine radical cations were involved as the transient intermediates. Rate constants of the rate-determining steps were calculated, rendering a reactivity trend for the five TCEP species: P(CH2CH2CO2−)3 ≫ +HP(CH2CH2CO2−)3 ≈ +HP(CH2CH2CO2−)2(CH2CH2CO2H) ≫ +HP(CH2CH2CO2−)(CH2CH2CO2H)2 ≫ +HP(CH2CH2CO2H)3. This is the first time to decipher the reactivity of all the TCEP protolysis species in the redox reactions of TCEP. Additionally, activation parameters were also measured for the reaction of P(CH2CH2CO2−)3 with IrCl62− yielding ΔH5‡ = 26.3 ± 1.4 kJ∙mol−1 and ΔS5‡ = −48 ± 5 J∙K−1∙mol−1; a possible mode of electron transfer is discussed. No doubt, the mechanism and the reactivity derived from the present work can serve as a model for the oxidations of TCEP by other single electron oxidants that are involved in chemically- and biologically-important processes.
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