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1.
Neural Regen Res ; 17(4): 905-910, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34472492

RESUMO

Tobacco smoking is considered to be one of the main risk factors in the development of chronic pain. Long-term chronic exposure to nicotine and other forms of tobacco have been shown to be associated with an increased incidence of pain. Studies have shown that acupuncture can help smokers to reduce their desire to smoke, reduce their withdrawal symptoms, and avoid a relapse after treatment. However, little has been reported about the effects of acupuncture on pain sensitivity caused by long-term smoking. Models of hyperalgesia were established in rats exposed to nicotine for 6 weeks. After 6 weeks of continuous nicotine exposure, electroacupuncture at bilateral acupoints Zusanli (ST36) and Taichong (LR3) was performed 20 minutes per day for 6 days at a continuous wave with a frequency of 2 Hz and a stimulus intensity of 1 mA. The results revealed that electroacupuncture treatment increased the mechanical response threshold of hind paw of nicotine-dependent rats with hyperalgesia and up-regulated the protein expression of pain-related factors µ-opioid receptor, ß-endorphin and glutamic acid decarboxylase 65 in the spinal cord and midbrain periaqueductal gray and the protein expression of glutamic acid decarboxylase 67 in the spinal cord. These findings suggest that electroacupuncture treatment has positive analgesic effects on pain sensitivity caused by long-term chronic nicotine exposure. One possible mechanism for the improved analgesia is that electroacupuncture increases the expression of pain-related factors in the spinal cord and midbrain periaqueductal gray. This study was approved by Institutional Animal Care and Use Committee (IACUC) of the University of Miami (#18-167) on December 12, 2018.

2.
China CDC Wkly ; 3(42): 883-888, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34733576

RESUMO

What is already known about this topic?: Rabies is fatal while preventable. More than 99% of human rabies cases were caused by dog bites worldwide. Mass dog vaccination could interrupt dog-mediated rabies if achieving and maintaining a minimum coverage rate of 70%. What does this report contribute?: The results of this study show that roughly 23.7% of households owned dogs in Guangxi Zhuang Autonomous Region, China but only about 19.1% of these households reported having their dogs vaccinated. Possible positive factors were injury history of dog bites, awareness of the necessity, and policy help for the costs of dog vaccination, but negative factors were negative attitude and inaccessibility. What are the implications for public health practices?: Much more effort should be made to improve dog vaccination coverage in rural areas in Guangxi Zhuang Autonomous Region, China. Well-designed free mass vaccination campaigns with more accessibility and awareness campaigns are important to improve coverage.

3.
J Genet Genomics ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34757038

RESUMO

Melastomataceae have abundant morphological diversity with high economic and ornamental merit in Myrtales. The phylogenetic position of Myrtales is still contested. Here, we report the first chromosome-level genome assembly of Melastoma dodecandrum in Melastomataceae. The assembled genome size was 299.81 Mb with a contig N50 value of 3.00 Mb. Genome evolution analysis indicated that M. dodecandrum, Eucalyptus grandis and Punica granatum were clustered into a clade of Myrtales and formed a sister group with the ancestor of fabids and malvids. We found that M. dodecandrum experienced four whole-genome polyploidization events: the ancient event was shared with most eudicots, one event was shared with Myrtales, and the other two events were unique to M. dodecandrum. Moreover, we identified MADS-box genes and found that the AP1-like genes expanded, and AP3-like genes might have undergone subfunctionalization. We found that the SUAR63-like genes and AG-like genes showed different expression patterns in stamens, which may be associated with heteranthery. In addition, we found that LAZY1-like genes were involved in the negative regulation of stem branching development, which may be related to its creeping features. Our study sheds new light on the evolution of Melastomataceae and Myrtales, which provides a comprehensive genetic resource for future research.

4.
Vet Microbiol ; 264: 109285, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34808432

RESUMO

Hepatitis-hydropericardium syndrome (HHS) in birds is mainly caused by virulent fowl adenovirus 4 (FAdV-4). A novel genotype, hypervirulent FAdV-4, emerged in 2015 with a high mortality rate ranging from 30 % to 100 % in chickens. Vaccination is an economically feasible method to control HHS. Although there have been various reports of inactivated vaccines from virulent wild-type FAdV-4 against HHS, biosafety threats of inactivated vaccines from potential pathogenic components have been presented to the poultry industry, and safer vaccines are urgently needed. A non-pathogenic recombinant FAdV-4 strain, designated as rHN20, was generated based on the hypervirulent strain in our previous study. Here, we developed a novel inactivated oil-adjuvanted vaccine derived from rHN20 strain and evaluated its immunogenicity in specific-pathogen-free chickens. Chickens subcutaneously or intramuscularly immunized with the inactivated vaccine produced high titers of neutralizing antibodies and were protected from a lethal dose of virulent wild-type FAdV-4 challenge. Collectively, an inactivated vaccine was developed, which was capable of providing full protection for chickens against HHS, and significantly reduced the potential biosafety threats.

5.
Future Virol ; 16(9): 587-590, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34721652

RESUMO

As an RNA virus, the fast evolution of SARS-CoV-2 is driven by the extensive RNA deamination by the host cells.

6.
J Gene Med ; : e3398, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34786791

RESUMO

BACKGROUND: Hereditary Factor VII Deficiency (FVIID) is a rare congenital autosomal recessive bleeding disorder. In clinical manifestations, its onset is caused by variant of the F7 gene (NM_019616) with strong heterogeneity. We identified a family with hematuria caused by a novel F7 compound heterozygous variant and studied the FVIID-dependent mechanism impacted by these variants. METHODS: Coagulation factors in the proband were functionally verified. We located pathogenic variants in relevant genes using next-generation sequencing after target enrichment and verified them by Sanger sequencing. We examined the coagulation activity and secretion pattern of recombinant FVII variants expressed in cells and observed their location and stability by immunofluorescence. RESULTS: We found a missense variant c.1207G>A (p.Gly403Ser) and a frameshift variant c.154_155del (p.Arg53fs) in the F7 gene of the proband. FVII activity tests showed that the variants significantly decreased its presence in the cell culture supernatant. Moreover, the R53fs mutant lacked the FVII functional domain and had no detectable activity. Immunofluorescence indicated that the p.Gly403Ser variant was distributed to the cell membrane and cytoplasm, while the FVII R53fs variant was not detected. Deficient FVII protein function and severe coagulation disorder are the likely causes of hematuria and other bleeding symptoms in the proband. CONCLUSION: The newly discovered F7 gene variants enrich the spectrum of hereditary FVII deficiency and provide a new foundation for the diagnosis and treatment of this type of coagulation disorder.

7.
Neurol Sci ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34783933

RESUMO

BACKGROUND: The spectrum of neurological diseases related to ATP1A3 gene mutations is highly heterogeneous and exhibits different phenotypes. Phenotype overlaps, including alternating hemiplegia of childhood (AHC), early infantile epileptic encephalopathy, and rapid-onset dystonia-parkinsonism (RDP), can also occur at extremely low incidences. Currently, over 90 types of pathogenic mutations have been identified in ATP1A3. PATIENTS AND METHODS: The family of a 2-year-11-month-old proband with AHC was recruited for this clinical investigation. The proband was screened for candidate mutation gene sites using next-generation sequencing and target-region capture technology. Sanger sequencing was used to identify carriers among family members. RESULTS: The mother of the proband with AHC was diagnosed with dystonia (later diagnosed as RDP). The biochemical and immune indices of the proband and the mother were not abnormal. Moreover, brain imaging of the proband revealed no significant abnormalities. However, the electroencephalogram of the mother was mildly abnormal, with no spike wave discharge. Brain MRI revealed slight cerebellar atrophy. Electromyography revealed neurogenic damage, with a decrease in the conduction velocity of the left ulnar and radial nerves. Based on the sequencing data, both the proband and her mother carried c.823G > C p. (Ala275Pro) heterozygotes; other family members were not identified as carriers. With a PolyPhen-2 score of 0.997 and SIFT score of 0.001, this mutation can be considered damaging. CONCLUSION: Family genotype-phenotype correlation analysis revealed that the phenotype and gene mutation were co-segregated, suggesting that it may be a pathogenic mutation.

8.
Behav Brain Res ; 418: 113631, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34715146

RESUMO

The dorsolateral striatum (DLS) is involved in addiction, reward, and alcohol related behaviors. The DLS primarily receives excitatory inputs which are gated by post-synaptic AMPA receptors. We antagonized AMPA receptors in the DLS to investigate how such modulation affects binge-like alcohol drinking in male and female C57BL/6J mice and whether an associated alcohol drinking history alters dorsomedial striatum (DMS) and DLS AMPA receptor expression. We also investigated the effect of intra-DLS NBQX on locomotor activity and saccharin drinking in mice. Mice were allowed free access to 20% alcohol for two hours each day for a total of seven days. Mice received an intra-DLS infusion of one of four concentrations of NBQX (saline, 0.15, 0.5, or 1.5 µg/side), an AMPA receptor antagonist, immediately prior to alcohol access on day 7. Two-hour binge alcohol intakes, locomotor activity, and blood alcohol concentrations were determined. Intra-DLS NBQX reduced binge-like alcohol drinking in a U-shaped manner in male and female mice. Intake predicted blood alcohol concentration, and locomotor activity was not affected. In a follow up experiment, we assessed whether the most effective NBQX concentration for reducing alcohol consumption also reduced saccharin drinking, finding intra-DLS NBQX did not alter saccharin drinking in male and female mice. These data suggest that AMPA receptors in the DLS play a role in the modulation of binge-like alcohol drinking. These findings further validate the importance of the DLS for alcohol related behaviors and alcohol use disorder.

9.
Probiotics Antimicrob Proteins ; 13(6): 1833-1846, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34595668

RESUMO

In this study, we expressed rAvBD1-2-6-13 protein through Lactococcus lactis NZ3900, and the effects of the recombinant L. lactis NZ3900 as an immune enhancer and immune adjuvant were verified using in vivo and in vitro tests. In vitro tests revealed that recombinant L. lactis NZ3900 significantly activated the NF-κB signaling pathway and IRF signaling pathway in J774-Dual™ report cells and significantly increased the transcript levels of IL-10, IL-12p70, CD80, and CD86 in chicken PBMCs and chicken HD11 cells. In vivo experiments revealed that the immunized group supplemented with recombinant L. lactis NZ3900 as an adjuvant had significantly higher serum antibody titers and higher proliferative activity of PBMCs in the blood of the chickens immunized with NDV live and inactivated vaccines. Our study shows that the recombinant L. lactis NZ3900 has strong immunomodulatory activity both in vivo and in vitro and is a potential immune enhancer. Our work lays the foundation for the research and development of new animal immune enhancers for application in the poultry industry.

12.
Evol Bioinform Online ; 17: 11769343211052013, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646060

RESUMO

SARS-CoV-2 needs to efficiently make use of the resources from hosts in order to survive and propagate. Among the multiple layers of regulatory network, mRNA translation is the rate-limiting step in gene expression. Synonymous codon usage usually conforms with tRNA concentration to allow fast decoding during translation. It is acknowledged that SARS-CoV-2 has adapted to the codon usage of human lungs so that the virus could rapidly proliferate in the lung environment. While this notion seems to nicely explain the adaptation of SARS-CoV-2 to lungs, it is unable to tell why other viruses do not have this advantage. In this study, we retrieve the GTEx RNA-seq data for 30 tissues (belonging to over 17 000 individuals). We calculate the RSCU (relative synonymous codon usage) weighted by gene expression in each human sample, and investigate the correlation of RSCU between the human tissues and SARS-CoV-2 or RaTG13 (the closest coronavirus to SARS-CoV-2). Lung has the highest correlation of RSCU to SARS-CoV-2 among all tissues, suggesting that the lung environment is generally suitable for SARS-CoV-2. Interestingly, for most tissues, SARS-CoV-2 has higher correlations with the human samples compared with the RaTG13-human correlation. This difference is most significant for lungs. In conclusion, the codon usage of SARS-CoV-2 has adapted to human lungs to allow fast decoding and translation. This adaptation probably took place after SARS-CoV-2 split from RaTG13 because RaTG13 is less perfectly correlated with human. This finding depicts the trajectory of adaptive evolution from ancestral sequence to SARS-CoV-2, and also well explains why SARS-CoV-2 rather than other viruses could perfectly adapt to human lung environment.

13.
J Appl Genet ; 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34655422

RESUMO

During SARS-CoV-2 proliferation, the translation of viral RNAs is usually the rate-limiting step. Understanding the molecular details of this step is beneficial for uncovering the origin and evolution of SARS-CoV-2 and even for controlling the pandemic. To date, it is unclear how SARS-CoV-2 competes with host mRNAs for ribosome binding and efficient translation. We retrieved the coding sequences of all human genes and SARS-CoV-2 genes. We systematically profiled the GC content and folding energy of each CDS. Considering that some fixed or polymorphic mutations exist in SARS-CoV-2 and human genomes, all algorithms and analyses were applied to both pre-mutate and post-mutate versions. In SARS-CoV-2 but not human, the 5-prime end of CDS had lower GC content and less RNA structure than the 3-prime part, which was favorable for ribosome binding and efficient translation initiation. Globally, the fixed and polymorphic mutations in SARS-CoV-2 had created an even lower GC content at the 5-prime end of CDS. In contrast, no similar patterns were observed for the fixed and polymorphic mutations in human genome. Compared with human RNAs, the SARS-CoV-2 RNAs have less RNA structure in the 5-prime end and thus are more favorable of fast translation initiation. The fixed and polymorphic mutations in SARS-CoV-2 are further amplifying this advantage. This might serve as a strategy for SARS-CoV-2 to adapt to the human host.

14.
Int J Mol Sci ; 22(20)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34681668

RESUMO

Acute intermittent porphyria (AIP) is an autosomal dominant genetic disease caused by a lack or decrease in hydroxymethylbilane synthase (HMBS) activity. It is characterized by acute nerve and visceral attacks caused by factors in the process of heme synthesis. The penetrance rate of this disease is low, and the heterogeneity is strong. Here, we reported two novel HMBS mutations from two unrelated Chinese AIP patients and confirmed the pathogenicity of these two mutations. We found the HMBS c.760-771+2delCTGAGGCACCTGGTinsGCTGCATCGCTGAA and HMBS c.88-1G>C mutations by second-generation sequencing and Sanger sequencing. The in vitro expression analysis showed that these mutations caused abnormal HMBS mRNA splicing and premature termination or partial missing of HMBS protein. Homologous modeling analysis showed that the HMBS mutants lacked the amino acids which are crucial for the enzyme activity or the protein stability. Consistently, enzyme activity analysis confirmed that the HMBS mutants' overexpression cells exhibited the reduced enzyme activity compared with the HMBS wildtype overexpression cells. Our study identified and confirmed two novel pathogenic HMBS mutations which will expand the molecular heterogeneity of AIP and provide further scientific basis for the clinical diagnosis of AIP.

16.
Viruses ; 13(9)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34578267

RESUMO

Infectious bursal disease virus (IBDV) is a non-enveloped, bi-segmented double-stranded RNA virus and the causative agent of a poultry immunosuppressive disease known as infectious bursal disease (IBD). The novel variant IBDV (nVarIBDV) recently posed a great threat to the development of the poultry industry. In this study, we identified a novel segment-reassortant IBDV strain, IBDV-JS19-14701 (Genotype A2dB3). Phylogenic analysis showed that Segments A and B of IBDV-JS19-14701 were derived from emerging nVarIBDV (Genotype A2dB1) and long-prevalent HLJ0504-like strains (Genotype A3B3) in China, respectively. The pathogenicity of IBDV-JS19-14701 was further evaluated via animal experiments. IBDV-JS19-14701 exhibited a similar virulence to chickens with the nVarIBDV. The identification of this reassortment event is beneficial for understanding the epidemiology of nVarIBDV and will contribute to the efficient prevention and control of IBD.

17.
Thromb J ; 19(1): 64, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496879

RESUMO

BACKGROUND: Protein S deficiency (PSD) is an autosomal dominant hereditary disease. In 1984, familial PSD was reported to be prone to recurrent thrombosis. Follow-up studies have shown that heterozygous protein S (PROS1) mutations increase the risk of thrombosis. More than 300 PROS1 mutations have been identified; among them, only a small number of mutations have been reported its possible mechanism to reduce plasma protein S (PS) levels. However, whether PROS1 mutations affect protein structure and why it can induce PSD remains unknown. METHODS: The clinical phenotypes of the members of a family with thrombosis were collected. Their PS activity was measured using the coagulation method, whereas their protein C and antithrombin III activities were measured using methods such as the chromogenic substrate method. The proband and her parents were screened for the responsible mutation using second-generation whole exon sequencing, and the members of the family were verified for suspected mutations using Sanger sequencing. Mutant and wild type plasmids were constructed and transfected into HEK293T cells to detect the mRNA and protein expression of PROS1. RESULTS: In this family, the proband with venous thrombosis of both lower extremities, the proband's mother with pulmonary embolism and venous thrombosis of both lower extremities, and the proband's younger brother had significantly lower PS activity and carried a PROS1 c. 1820 T > C:p.Leu607Ser heterozygous mutation (NM_000313.3). However, no such mutations were found in family members with normal PS activity. The PS expression in the cell lysate and supernatant of the Leu607Ser mutant cells decreased, while mRNA expression increased. Immunofluorescence localization showed that there was no significant difference in protein localization before and after mutation. CONCLUSIONS: The analysis of family phenotype, gene association, and cell function tests suggest that the PROS1 Leu607Ser heterozygous mutation may be a pathogenic mutation. Serine substitution causes structural instability of the entire protein. These data indicate that impaired PS translation and synthesis or possible secretion impairment is the main pathogenesis of this family with hereditary PSD and thrombophilia.

18.
Sci Prog ; 104(3): 368504211039375, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490803

RESUMO

Porous media combustion has significant advantages of high thermal efficiency and low pollution emissions. However, the flow state in the porous media will affect the reaction rate. In order to increase the rate of chemical reactions, the fluid flow resistance in the porous media must be reduced. The pressure drop test of SiC foam ceramics was carried out. By changing the pore density of the experimental materials, the pressure drop characteristics of SiC foam ceramic are tested and analyzed. Based on the classical Ergun equation, a semi-empirical formula for calculating the pressure drop gradient of SiC foam ceramics with the airflow velocity is proposed. The two constants in the formula are calculated by measurement, and the applicability of the formula is verified. This formula can quickly analyze the pressure drop characteristics of SiC foam ceramic materials. The accurate measurement of pressure drop is helpful to determine the rated pressure of the head of foam ceramic burner and reduce the investment of front-end fans in industrial burners.

19.
BMC Mol Cell Biol ; 22(1): 46, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34551723

RESUMO

BACKGROUND: MDM2 is an E3 ubiquitin ligase that is able to ubiquitinate p53, targeting it for proteasomal degradation. Its homologue MDMX does not have innate E3 activity, but is able to dimerize with MDM2. Although mouse models have demonstrated both MDM2 and MDMX are individually essential for p53 regulation, the significance of MDM2-MDMX heterodimerization is only partially understood and sometimes controversial. MDM2C462A mice, where the C462A mutation abolishes MDM2 E3 ligase activity as well as its ability to dimerize with MDMX, die during embryogenesis. In contrast, the MDM2Y487A mice, where the Y487A mutation at MDM2 C-terminus significantly reduces its E3 ligase activity without disrupting MDM2-MDMX binding, survive normally even though p53 is expressed to high levels. This indicates that the MDM2-MDMX heterodimerization plays a critical role in the regulation of p53. However, it remains unclear whether MDMX is essential for the regulation of p53 protein levels in the context of an endogenous MDM2 C-terminal tail mutation. RESULTS: Here, we studied the significance of MDM2-MDMX binding in an MDM2 E3 ligase deficient context using the MDM2Y487A mouse embryonic fibroblast (MEF) cells. Surprisingly, down-regulation of MDMX in MDM2Y487A MEFs resulted in a significant increase of p53 protein levels. Conversely, ectopic overexpression of MDMX reduced p53 protein levels in MDM2Y487A MEFs. Mutations of the RING domain of MDMX prevented MDMX-MDM2 binding, and ablated MDMX-mediated suppression of p53 protein expression. Additionally, DNA damage treatment and nuclear sequestration of MDMX inhibited MDMX activity to suppress p53 protein expression. CONCLUSIONS: These results suggest that MDMX plays a key role in suppressing p53 protein expression in the absence of normal MDM2 E3 ligase activity. We found that the ability of MDMX to suppress p53 levels requires MDM2 binding and its cytoplasmic localization, and this ability is abrogated by DNA damage. Hence, MDMX is essential for the regulation of p53 protein levels in the context of an MDM2 C-terminal mutation that disrupts its E3 ligase activity but not MDMX binding. Our study is the first to examine the role of MDMX in the regulation of p53 in the context of endogenous MDM2 C-terminal mutant MEF cells.

20.
Cell Prolif ; 54(11): e13133, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34585448

RESUMO

OBJECTIVES: Maternal factors that are enriched in oocytes have attracted great interest as possible key factors in somatic cell reprogramming. We found that surfeit locus protein 4 (Surf4), a maternal factor, can facilitate the generation of induced pluripotent stem cells (iPSCs) previously, but the mechanism remains elusive. MATERIALS AND METHODS: In this study, we investigated the function and mechanism of Surf4 in somatic cell reprogramming using a secondary reprogramming system. Alkaline phosphatase (AP) staining, qPCR and immunofluorescence (IF) staining of expression of related markers were used to evaluate efficiency of iPSCs derived from mouse embryonic fibroblasts. Embryoid body and teratoma formation assays were performed to evaluate the differentiation ability of the iPSC lines. RNA-seq, qPCR and western blot analysis were applied to validate the downstream targets of Surf4. RESULTS: Surf4 can significantly facilitate the generation of iPSCs in a proliferation-independent manner. When co-expressed with Oct4, Sox2, Klf4 and c-Myc (OSKM), Surf4 can activate the response to endoplasmic reticulum (ER) stress at the early stage of reprogramming. We further demonstrated that Hspa5, a major ER chaperone, and the active spliced form of Xbp1 (sXbp1), a major mediator of ER stress, can mimic the effects of Surf4 on somatic cell reprogramming. Concordantly, blocking the unfolded protein response compromises the effect of Surf4 on reprogramming. CONCLUSIONS: Surf4 promotes somatic cell reprogramming by activating the response to ER stress.


Assuntos
Reprogramação Celular/fisiologia , Estresse do Retículo Endoplasmático/fisiologia , Fibroblastos/metabolismo , Proteínas de Membrana/metabolismo , Animais , Diferenciação Celular/fisiologia , Corpos Embrioides/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Camundongos , Fatores de Transcrição/metabolismo
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