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Skeletal muscle is heterogeneous tissue, composed of fast-twitch fibers primarily relying on glycolysis and slow-twitch fibers primarily relying on oxidative phosphorylation. The relative expression and balance of glycolysis and oxidative phosphorylation in skeletal muscle are crucial for muscle growth and skeletal muscle metabolism. Here, we employed multi-omics approaches including transcriptomics, proteomics, phosphoproteomics, and metabolomics to unravel the role of circMYLK4, a differentially expressed circRNA in fast and slow-twitch muscle fibers, in muscle fiber metabolism. We discovered that circMYLK4 inhibits glycolysis and promotes mitochondrial oxidative phosphorylation. Mechanistically, circMYLK4 interacts with the voltage-gated calcium channel auxiliary subunit CACNA2D2, leading to the inhibition of Ca2+ release from the sarcoplasmic reticulum. The decrease in cytoplasmic Ca2+ concentration inhibits the expression of key enzymes, PHKB and PHKG1, involved in glycogen breakdown, thereby suppressing glycolysis. On the other hand, the increased fatty acid ß-oxidation enhances the tricarboxylic acid cycle and mitochondrial oxidative phosphorylation. In general, circMYLK4 plays an indispensable role in maintaining the metabolic homeostasis of skeletal muscle.
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Glicólise , Fosforilação Oxidativa , Animais , Camundongos , Metabolismo Energético , Canais de Cálcio/metabolismo , Canais de Cálcio/genética , Músculo Esquelético/metabolismo , Humanos , Cálcio/metabolismo , MasculinoRESUMO
The SPRY domain-containing SOCS box proteins SPSB1, SPSB2, and SPSB4 utilize their SPRY/B30.2 domain to interact with a short region in the N-terminus of inducible nitric oxide synthase (iNOS), and recruit an E3 ubiquitin ligase complex to polyubiquitinate iNOS, resulting in the proteasomal degradation of iNOS. Inhibitors that can disrupt the endogenous SPSB-iNOS interactions could be used to augment cellular NO production, and may have antimicrobial and anticancer activities. We previously reported the rational design of a cyclic peptide inhibitor, cR8, cyclo(RGDINNNV), which bound to SPSB2 with moderate affinity. We, therefore, sought to develop SPSB inhibitors with higher affinity. Here, we show that cyclic peptides cR7, cyclo(RGDINNN), and cR9, cyclo(RGDINNNVE), have ~6.5-fold and ~2-fold, respectively, higher SPSB2-bindng affinities than cR8. We determined high-resolution crystal structures of the SPSB2-cR7 and SPSB2-cR9 complexes, which enabled a good understanding of the structure-activity relationships for these cyclic peptide inhibitors. Moreover, we show that these cyclic peptides displace full-length iNOS from SPSB2, SPSB1, and SPSB4, and that their inhibitory potencies correlate well with their SPSB2-binding affinities. The strongest inhibition was observed for cR7 against all three iNOS-binding SPSB proteins.
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Peptídeos Cíclicos , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Humanos , Proteínas Supressoras da Sinalização de Citocina/química , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo II/química , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Ligação Proteica , Relação Estrutura-AtividadeRESUMO
Purpose: To investigate and quantify the effect of continuous esketamine infusion at different doses on the bispectral index (BIS) during sevoflurane anesthesia. Methods: A total of 120 patients scheduled for elective laparoscopic renal surgery were randomly divided into three groups. Under steady anesthesia and surgical situations, the patient was started on continuous infusion of the study drug: 0.125 mg/kg/h esketamine (group E1), 0.25 mg/kg/h esketamine (group E2), and the same volume of saline (group C). The primary outcome was changes in BIS value after 15 min (T15), 30 min (T30), 45 min (T45), and 60 min (T60) of drug infusion. The secondary outcomes were 95% spectral edge frequency (SEF95), electromyogram (EMG), heart rate (HR), and mean arterial pressure (MAP) from T0 to T60. Furthermore, postoperative pain, postoperative recovery, and perioperative adverse events were evaluated. Results: Compared with group C, group E1 exhibited significant BIS elevation at T30-T60 and group E2 at T15-T60 (P < 0.001). Compared with group E1, group E2 showed a more significant BIS elevation at T15-T60 (P < 0.001). The area under the curve (AUC) of BIS and SEF95 were significantly higher in group E2 than in groups C and E1 (P < 0.05). BIS value for any of the three groups was significantly correlated with SEF95 (P < 0.001). No significant differences were observed in the AUC of EMG, HR, and MAP among the three groups. Intraoperative remifentanil consumption and postoperative NRS of pain on movement were significantly reduced in group E2 compared with groups C and E1 (P < 0.05). Conclusion: Continuous infusion of both 0.125 and 0.25 mg/kg/h of esketamine increased the BIS value during sevoflurane anesthesia, and the BIS value gradually stabilized with the prolongation of the infusion time.
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Ketamina , Sevoflurano , Humanos , Sevoflurano/administração & dosagem , Sevoflurano/farmacologia , Ketamina/administração & dosagem , Ketamina/farmacologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Relação Dose-Resposta a Droga , Infusões Intravenosas , Anestésicos Inalatórios/administração & dosagem , Método Duplo-Cego , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controleRESUMO
BACKGROUND: Skeletal muscle is composed of muscle fibers with different physiological characteristics, which plays an important role in regulating skeletal muscle metabolism, movement and body homeostasis. The type of skeletal muscle fiber directly affects meat quality. However, the transcriptome and gene interactions between different types of muscle fibers are not well understood. RESULTS: In this paper, we selected 180-days-old Large White pigs and found that longissimus dorsi (LD) muscle was dominated by fast-fermenting myofibrils and soleus (SOL) muscle was dominated by slow-oxidizing myofibrils by frozen sections and related mRNA and protein assays. Here, we selected LD muscle and SOL muscle for transcriptomic sequencing, and identified 312 differentially expressed mRNA (DEmRs), 30 differentially expressed miRNA (DEmiRs), 183 differentially expressed lncRNA (DElRs), and 3417 differentially expressed circRNA (DEcRs). The ceRNA network included ssc-miR-378, ssc-miR-378b-3p, ssc-miR-24-3p, XR_308817, XR_308823, SMIM8, MAVS and FOS as multiple core nodes that play important roles in muscle development. Moreover, we found that different members of the miR-10 family expressed differently in oxidized and glycolytic muscle fibers, among which miR-10a-5p was highly expressed in glycolytic muscle fibers (LD) and could target MYBPH gene mRNA. Therefore, we speculate that miR-10a-5p may be involved in the transformation of muscle fiber types by targeting the MYHBP gene. In addition, PPI analysis of differentially expressed mRNA genes showed that ACTC1, ACTG2 and ACTN2 gene had the highest node degree, suggesting that this gene may play a key role in the regulatory network of muscle fiber type determination. CONCLUSIONS: We can conclude that these genes play a key role in regulating muscle fiber type transformation. Our study provides transcriptomic profiles and ceRNA interaction networks for different muscle fiber types in pigs, providing reference for the transformation of pig muscle fiber types and the improvement of meat quality.
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Redes Reguladoras de Genes , Animais , Suínos , MicroRNAs/genética , MicroRNAs/metabolismo , Perfilação da Expressão Gênica , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Transcriptoma , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Lysine acetyltransferase 7 (KAT7), a histone acetyltransferase, has recently been identified as an oncoprotein and has been implicated in the development of various malignancies. However, its specific role in head and neck squamous carcinoma (HNSCC) has not been fully elucidated. Our study revealed that high expression of KAT7 in HNSCC patients is associated with poor survival prognosis and silencing KAT7 inhibits the Warburg effect, leading to reduced proliferation, invasion, and metastatic potential of HNSCC. Further investigation uncovered a link between the high expression of KAT7 in HNSCC and tumor-specific glycolytic metabolism. Notably, KAT7 positively regulates Lactate dehydrogenase A (LDHA), a key enzyme in metabolism, to promote lactate production and create a conducive environment for tumor proliferation and metastasis. Additionally, KAT7 enhances LDHA activity and upregulates LDHA protein expression by acetylating the lysine 118 site of LDHA. Treatment with WM3835, a KAT7 inhibitor, effectively suppressed the growth of subcutaneously implanted HNSCC cells in mice. In conclusion, our findings suggest that KAT7 exerts pro-cancer effects in HNSCC by acetylating LDHA and may serve as a potential therapeutic target. Inhibiting KAT7 or LDHA expression holds promise as a therapeutic strategy to suppress the growth and progression of HNSCC.
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Proliferação de Células , Neoplasias de Cabeça e Pescoço , Histona Acetiltransferases , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Animais , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Acetilação , Linhagem Celular Tumoral , Histona Acetiltransferases/metabolismo , Histona Acetiltransferases/genética , Camundongos , L-Lactato Desidrogenase/metabolismo , L-Lactato Desidrogenase/genética , Lisina Acetiltransferases/metabolismo , Lisina Acetiltransferases/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Efeito Warburg em Oncologia , Masculino , Feminino , Movimento Celular , Ensaios Antitumorais Modelo de Xenoenxerto , Invasividade Neoplásica , Isoenzimas/metabolismo , Isoenzimas/genéticaRESUMO
The intricate correlation between lattice geometry, topological behavior and charge degrees of freedom plays a key role in determining the physical and chemical properties of a quantum-magnetic system. Herein, we investigate the introduction of the unusual oxidation state as an alternative pathway to modulate the magnetic ground state in the well-known S = 1 Haldane system nickelate Y2BaNiO5 (YBNO). YBNO is topologically reduced to incorporate d9-Ni+ (S = 1/2) in the one-dimensional Haldane chain system. The random distribution of Ni+ for the first time results in the emergence of a one-dimensional ferromagnetic phase with a transition temperature far above room temperature. Theoretical calculations reveal that the antiferromagnetic interplay can evolve into ferromagnetic interactions with the presence of oxygen vacancies, which promotes the formation of ferromagnetic order within one-dimensional nickel chains. The unusual electronic instabilities in the nickel-based Haldane system may offer new possibilities towards unconventional physical and chemical properties from quantum interactions.
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African swine fever (ASF), caused by the ASF virus (ASFV), is a hemorrhagic and fatal viral disease that affects Eurasian wild boars and domestic pigs, posing a substantial threat to the global pig breeding industry. ASFV, a double-stranded DNA virus, possesses a large genome containing up to 160 open reading frames, most of which exhibit unknown functions. The B125R gene of ASFV, located at the 105595-105972 bp site in the ASFV-SY18 genome, remains unexplored. In this study, we discovered that B125R deletion did not affect recombinant virus rescue, nor did it hinder viral replication during the intermediate growth phase. Although the virulence of the recombinant strain harboring this deletion was attenuated, intramuscular inoculation of the recombinant virus in pigs at doses of 102 or 104 TCID50 resulted in mortality. Moreover, sequencing analysis of six recombinant strains obtained from three independent experiments consistently revealed an adenine insertion at the 47367-47375 bp site in the A104R gene due to the B125R deletion, leading to premature termination of this gene. Intriguingly, this insertion did not influence the transcription of the A104R gene between the recombinant and parental strains. Consequently, we postulate that the deletion of the B125R gene in ASFV-SY18 or other genotype II strains may marginally attenuate virulence in domestic pigs.
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Vírus da Febre Suína Africana , Febre Suína Africana , Suínos , Animais , Vírus da Febre Suína Africana/genética , Sus scrofa , Virulência , Mutação da Fase de Leitura , Deleção de GenesRESUMO
Vaccination is the most cost-effective method for preventing various infectious diseases. Compared with conventional vaccines, new-generation vaccines, especially recombinant protein or synthetic peptide vaccines, are safer but less immunogenic than crude inactivated microbial vaccines. The immunogenicity of these vaccines can be enhanced using suitable adjuvants. This is the main reason why adjuvants are of great importance in vaccine development. Several novel human emulsion-based vaccine adjuvants (MF59, AS03) have been approved for clinical use. This paper reviews the research progress on emulsion-based adjuvants and focuses on their mechanism of action. An outlook can be provided for the development of emulsion-based vaccine adjuvants.
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(1) Background: African swine fever (ASF) is a highly contagious disease that causes high pig mortality. Due to the absence of vaccines, prevention and control are relatively challenging. The pathogenic African swine fever virus (ASFV) has a complex structure and encodes over 160 proteins, many of which still need to be studied and verified for their functions. In this study, we identified one of the unknown functional genes, C84L. (2) Methods: A gene deficient strain was obtained through homologous recombination and several rounds of purification, and its replication characteristics and virulence were studied through in vitro and in vivo experiments, respectively. (3) Results: Deleting this gene from the wild-type virulent strain SY18 did not affect its replication in porcine primary macrophages but reduced its virulence in pigs. In animal experiments, we injected pigs with a 102 TCID50, 105 TCID50 deletion virus, and a 102 TCID50 wild-type strain SY18 intramuscularly. The control group pigs reached the humane endpoint on the ninth day (0/5) and were euthanized. Two pigs in the 102 TCID50(2/5) deletion virus group survived on the twenty-first day, and one in the 105 TCID50(1/5) deletion virus group survived. On the twenty-first day, the surviving pigs were euthanized, which was the end of the experiment. The necropsies of the survival group and control groups' necropsies showed that the surviving pigs' liver, spleen, lungs, kidneys, and submaxillary lymph nodes did not show significant lesions associated with the ASFV. ASFV-specific antibodies were first detected on the seventh day after immunization; (4) Conclusions: This is the first study to complete the replication and virulence functional exploration of the C84L gene of SY18. In this study, C84L gene was preliminarily found not a necessary gene for replication, gene deletion strain SY18ΔC84L has similar growth characteristics to SY18 in porcine primary alveolar macrophages. The C84L gene affects the virulence of the SY18 strain.
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The slow formation of anammox biofilms presents a bottleneck for resolving anammox bacterial loss and achieving stable performance in biofilm-based partial denitrification-anammox (PD-A) processes. This study utilized iron-modified (K1/Fe3O4 NPs) carriers, which were prepared and used for the first time in PD-A processes. Parallel moving bed biofilm reactors (MBBRs) indicated that iron-modified carriers facilitated the formation of biofilms at a faster rate than K1 carriers, consequently improving the nitrogen removal performance of the process by over 40 %. 16S rDNA analysis showed that anammox bacteria were approximately four times more abundant in the iron-modified carrier biofilm than in the K1 carrier biofilm. XPS and zeta potential analysis suggested that the improved microbial affinity of the iron-modified carrier surface caused this. As a result, the iron-modified carriers facilitated the formation of anammox biofilms and enhanced PD-A performance.
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Oxidação Anaeróbia da Amônia , Desnitrificação , Oxirredução , Reatores Biológicos/microbiologia , Bactérias/genética , Biofilmes , Nitrogênio , Esgotos/microbiologiaRESUMO
To improve the pasting and gel properties of waxy corn starch (WCS), the native starch was modified by critical melting (CM) at the onset temperature (TO), peak temperature (TP), and conclusion temperature (TC) (labeled CMO, CMP, and CMC respectively). CM treatments significantly enhanced the thermal stability of the WCS, as indicated by the increase in the peak gelatinization temperature, pasting temperature, and peak time. In addition, after CMP treatment, the storage modulus, hardness, gumminess, springiness, and chewiness of starch gels significantly increased by 43.29 %, 31.14 %, 23.36 %, 8.26 %, and 61.43 %, respectively, and the syneresis rate significantly decreased by 19.69 % (p < 0.05). These results indicated that CMP treatments significantly improved the gelling ability and freeze-thaw stability of the WCS. These results are ascribed to the partial disruption and enhanced rearrangement of the starch crystalline structure. CMP treatment induced the crystalline structure of starch to be partially disrupted and a hard structure was formed on the surface of starch granules. The hard structure in CMP-treated starch supplied more attachment points for crystalline structure rearrangement during gelatinization. Therefore, the above results indicated that CMP treatments can be used to modify starch to improve the pasting and gel properties of starch-based food products.
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Amilopectina , Zea mays , Zea mays/química , Amido/química , Temperatura , Géis/química , ViscosidadeRESUMO
Goose astroviruses (GoAstVs) are causative agents that account for fatal infection of goslings characterized by visceral urate deposition, resulting in severe economic losses in major goose-producing regions in China since 2017. In this study, we sought to unravel the intrinsic properties associated with adaptation and evolution in the host environment of GoAstVs. Consistent results from phylogenetic analysis and correspondence analysis performed on the codon usage patterns (CUPs) reveal 2 clusters of GoAstVs, namely, GoAstV-1 and GoAstV-2. However, multiple similar compositional characteristics were found, despite the high divergence between GoAstV-1 and GoAstV-2. Studies on the base composition of GoAstVs reveal an A/U bias, indicating a compositional constraint, while natural selection prevailed in determining the CUPs in the virus genome based on our neutrality plot analysis, reflecting high adaptive pressure to fit the host environment. Codon adaptation index (CAI) analysis revealed a higher degree of fitness to the CUPs of the corresponding host for GoAstVs than avian influenza virus and betacoronaviruses, which may be a favorable factor contributing to the high pathogenicity and wide distribution of GoAstVs in goslings. In addition, GoAstVs were less adapted to ducks and chickens, with significantly lower CAI values than to geese, which may be a reason for the different prevalence of GoAstVs among these species. Extensive investigations on dinucleotide distribution revealed a significant suppression of the CpG and UpA motifs in the virus genome, which may facilitate adaptation to the host's innate immune system by evading surveillance. In addition, our study reported the trends of increasing fitness to the host's microenvironment for GoAstVs through increasing adaptation to host CUPs and ongoing reduction of CpG motifs in the virus genome. The present analysis deepens our understanding of the basic biology, pathogenesis, adaptation and evolutionary pattern of GoAstVs, and contributes to the development of novel antiviral strategies.
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Avastrovirus , Gansos , Animais , Gansos/genética , Composição de Bases , Filogenia , Galinhas/genética , Códon , Avastrovirus/genéticaRESUMO
In this study, cinnamon essential oil and tea polyphenols were added to chitosan/ polyvinyl alcohol/ hydroxypropyl methylcellulose/ alizarin composite films to enhance their mechanical and functional properties. Their addition to the composite films enhanced their antibacterial and antioxidant properties and significantly improved its elongation at break (p < 0.05). Cinnamon essential oil reduced the water vapor permeability, water content, and water solubility of composite films and improved their transparency. The composite films with additive exhibited excellent UV-barrier ability and pH responsivity. Fourier Transform infrared spectroscopy and X-Ray Diffraction analyses confirmed hydrogen bond formation between the polymer molecules and additives. The results of Scanning Electron Microscope-Focused Ion Beam revealed improved surface and cross-section morphology of the films, leading to the generation of a cross-linked structure. Thermogravimetric and differential scanning calorimetry analysis indicated enhanced thermal stability of the composite films upon cinnamon essential oil addition. Analysis of storage quality indicators (TBARS value, TVC, and TVB-N) revealed that the composite films could prolong the freshness of surimi. The incorporation of cinnamon essential oil and tea polyphenols into the composite films has demonstrated significant potential as an effective and natural alternative for active food packaging.
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Quitosana , Óleos Voláteis , Polifenóis , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Quitosana/química , Álcool de Polivinil , Cinnamomum zeylanicum/química , Derivados da Hipromelose , Embalagem de Alimentos/métodos , CháRESUMO
Introduction: African swine fever (ASF) is an acute and highly contagious disease and its pathogen, the African swine fever virus (ASFV), threatens the global pig industry. At present, management of ASF epidemic mainly relies on biological prevention and control methods. Moreover, due to the large genome of ASFV, only half of its genes have been characterized in terms of function. Methods: Here, we evaluated a previously uncharacterized viral gene, L60L. To assess the function of this gene, we constructed a deletion strain (SY18ΔL60L) by knocking out the L60L gene of the SY18 strain. To evaluate the growth characteristics and safety of the SY18ΔL60L, experiments were conducted on primary macrophages and pigs, respectively. Results: The results revealed that the growth trend of the recombinant strain was slower than that of the parent strain in vitro. Additionally, 3/5 (60%) pigs intramuscularly immunized with a 105 50% tissue culture infectious dose (TCID50) of SY18ΔL60L survived the 21-day observation period. The surviving pigs were able to protect against the homologous lethal strain SY18 and survive. Importantly, there were no obvious clinical symptoms or viremia. Discussion: These results suggest that L60L could serve as a virulence- and replication-related gene. Moreover, the SY18ΔL60L strain represents a new recombinant live-attenuated ASFV that can be employed in the development of additional candidate vaccine strains and in the elucidation of the mechanisms associated with ASF infection.
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The second step in the de novo sphingolipid biosynthesis is the reduction of 3-ketodihydrosphingosine by 3-ketodihydrosphingosine reductase (KDSR) to produce dihydrosphingosine (sphinganine). Fungal TSC10 and mammalian KDSR (also named FVT-1) proteins are the enzymes responsible for this process and they belong to the short-chain dehydrogenase/reductase (SDR) superfamily. Albeit that both fungal and mammalian 3-ketodihydrosphingosine reductases were identified more than a decade ago, no structure of these enzymes from any species has been experimentally determined. Here we report the crystal structure of the catalytic domain of TSC10 from Cryptococcus neoformans in complex with NADPH. cnTSC10 adopts a Rossmann fold with a central seven-stranded ß-sheet flanked by α-helices on both sides. Several regions are disordered that include the segment connecting the serine and tyrosine residues of the catalytic triad, the so-called 'substrate loop', and the C-terminal region that often participates in homo-tetramerization in other SDRs. In addition, the cofactor NADPH is not fully ordered. These structural features indicate that the catalytic site of cnTSC10 possesses significant flexibility. cnTSC10 is predominantly dimeric in solution while a minor portion of the protein forms homo-tetramer. The crystal structure reveals that the homo-dimer interface involves both hydrophobic and hydrophilic interactions mediated by helices α4 and α5, as well as the loop connecting strand ß4 and helix α4. Because residues forming hydrogen bonds and salt bridges in the dimer interface are not conserved between fungal TSC10 and mammalian KDSR proteins, it might be possible to develop inhibitors that selectively target fungal TSC10 dimerization.
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Cryptococcus neoformans , Sequência de Aminoácidos , Sítios de Ligação , Cryptococcus neoformans/metabolismo , Cristalografia por Raios X , Modelos Moleculares , NADP/metabolismo , Oxirredutases/metabolismoRESUMO
African swine fever (ASF) is a viral haemorrhagic disease found in domestic and wild boars caused by the African swine fever virus (ASFV). A highly virulent strain was used to evaluate the efficacy of newly developed vaccine candidates. The ASFV strain SY18 was isolated from the first ASF case in China and is virulent in pigs of all ages. To evaluate the pathogenesis of ASFV SY18 following intraoral (IO) and intranasal (IN) infections, a challenge trial was conducted in landrace pigs, with intramuscular (IM) injection as a control. The results showed that the incubation period of IN administration with 40-1000 50 % tissue culture infective dose (TCID50) was 5-8 days, which was not significantly different from that of IM inoculation with 200 TCID50. A significantly longer incubation period, 11-15 days, was observed in IO administration with 40-5000 TCID50. Clinical features were similar among all infected animals. Symptoms, including high fever (≥40.5 °C), anorexia, depression, and recumbency, were observed. No significant differences were detected in the duration of viral shedding during fever. There was no significant difference in disease outcome, and all animals succumbed to death. This trial showed that IN and IO infections could be used for the efficacy evaluation of an ASF vaccine. The IO infection model, similar to that of natural infection, is highly recommended, especially for the primary screening of candidate vaccine strains or vaccines with relatively weak immune efficacy, such as live vector vaccines and subunit vaccines.
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Vírus da Febre Suína Africana , Febre Suína Africana , Vacinas Virais , Animais , Genótipo , Sus scrofa , Suínos , Vacinas AtenuadasRESUMO
African swine fever (ASF) is an acute infectious disease of domestic pigs and wild boars caused by the African swine fever virus (ASFV), with up to a 100% case fatality rate. The development of a vaccine for ASFV is hampered by the fact that the function of many genes in the ASFV genome still needs to be discovered. In this study, the previously unreported E111R gene was analyzed and identified as an early-expressed gene that is highly conserved across the different genotypes of ASFV. To further explore the function of the E111R gene, a recombinant strain, SY18ΔE111R, was constructed by deleting the E111R gene of the lethal ASFV SY18 strain. In vitro, the replication kinetics of SY18ΔE111R with deletion of the E111R gene were consistent with those of the parental strain. In vivo, high-dose SY18ΔE111R (105.0 TCID50), administered intramuscularly to pigs, caused the same clinical signs and viremia as the parental strain (102.0 TCID50), with all pigs dying on days 8-11. After being infected with a low dose of SY18ΔE111R (102.0 TCID50) intramuscularly, pigs showed a later onset of disease and 60% mortality, changing from acute to subacute infection. In summary, deletion of the E111R gene has a negligible effect on the lethality of ASFV and does not affect the viruses' ability to replicate, suggesting that E111R could not be the priority target of ASFV live-attenuated vaccine candidates.
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Vírus da Febre Suína Africana , Febre Suína Africana , Suínos , Animais , Virulência/genética , Deleção de Genes , Proteínas Virais/genética , Sus scrofa , Replicação ViralRESUMO
Emergence delirium (ED) is a common mental complication during recovery from anesthesia. However, studies on the effects of esketamine, an intravenous anesthetic for pediatrics, on ED are still lacking. This study aimed to investigate the effects of a single-dose of esketamine during anesthesia induction on ED after minor surgery in preschool children. A total of 230 children (aged 2-7 years) completed the study. The exposed group (0.46 mg kg-1: average dose of esketamine) was associated with an increased incidence of ED and a higher maximum Pediatric Anesthesia Emergence Delirium score than the non-exposed group. The length of post-anesthesia care unit stay was longer in the exposed group than the non-exposed group. In contrast, extubation time, face, legs, activity, cry, and consolability (FLACC) scores, and the proportions of rescue analgesics were comparable between the two groups. Furthermore, five factors, including preoperative anxiety scores, sevoflurane and propofol compared with sevoflurane alone for anesthesia maintenance, dezocine for postoperative analgesia, FLACC scores, and esketamine exposure, were associated with ED. In conclusion, a near-anesthetic single-dose of esketamine for anesthesia induction may increase the incidence of ED in preschool children after minor surgery. The use of esketamine in preschool children for minor surgery should be noticed during clinical practice.
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BACKGROUND: Postoperative delirium (POD) is a common surgical complication associated with increased morbidity and mortality in elderly. Although the underlying mechanisms remain elusive, perioperative risk factors were reported to be closely related to its development. This study was designed to investigate the association between the duration of intraoperative hypotension and POD incidence following thoracic and orthopedic surgery in elderly. METHOD: The perioperative data from 605 elderly undergoing thoracic and orthopedic surgery from January 2021 to July 2022 were analyzed. The primary exposure was a cumulative duration of mean arterial pressure (MAP) ≤ 65 mmHg. The primary end-point was the POD incidence assessed with confusion assessment method (CAM) or CAM-ICU for three days after surgery. Restricted cubic spline (RCS) was conducted to examine the continuous relationship between the duration of intraoperative hypotension and POD incidence adjusted with patients' demographics and surgery related factors. Then the duration of intraoperative hypotension was categorized into three groups: no hypotension, short (< 5 mins) or long duration (≥ 5 mins) of hypotension for further analysis. RESULT: The incidence of POD was 14.7% (89 cases out of 605) within three days after surgery. The duration of hypotension presented a non-linear and "inverted L-shaped" effect on POD development. Compared to no hypotension, long duration (adjusted OR 3.93; 95% CI: 2.07-7.45; P < 0.001) rather than short duration of MAP ≤65 mmHg (adjusted OR 1.18; 95% CI: 0.56-2.50; P = 0.671) was closely related to the POD incidence. CONCLUSION: Intraoperative hypotension (MAP ≤65 mmHg) for ≥5 mins was associated with an increased incidence of POD after thoracic and orthopedic surgery in elderly.