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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1561-1565, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627440

RESUMO

OBJECTIVE: To perform dried blood spots thalassemia gene detection in patients with positive blood phenotypes by microarray technology, and evaluate its value in clinical detection. METHODS: DNA samples were extracted from dried blood spots of 410 patients. Microarray technology was used to detect 3 deletion and 3 non-deletion types of α-thalassemia and 19 ß-thalassemia point mutations which were common gene mutions in China. RESULTS: There were 357 positive cases in all the 410 tested samples with the positive rate 87.07%, among which 299 cases (72.93%) carried deletion or point mutations of α-thalassemia, 29 cases (7.07%) carried point mutations of ß-thalassemia and 29 cases (7.07%) carried gene mutations of complex αß-thalassemia syndrome. The mutations of α-thalassemia were involved with --SEA heterozygous deletion (177 cases, 59.2%), αCS heterozygote (60 cases, 20.07%) and several other genotypes. The common mutations of ß- thalassemia were involved with ßCD41-42 heterozygote (10 cases, 34.48%) and ßCD17 heterozygote (9 cases, 31.03%). The mutations of complex αß-thalassemia syndrome were mainly involved with --SEA/αα+ßCD17/ßN (7 cases, 24.14%), αCSα/αα + ßCD41-42/ßN (3 cases, 10.34%) and -α4.2/αα + ßCD17/ßN (3 cases, 10.34%). CONCLUSION: The most common genetic mutations are --SEA for α-thalassemia and CD41-42 for ß-thalassemia in Liuzhou, Guangxi Zhuang Autonomous Region. A and ß-thalassemia can be detected at the same time by microarray chip technology in a high throughput manner.


Assuntos
Talassemia alfa , Talassemia beta , China , Humanos , Mutação , Análise de Sequência com Séries de Oligonucleotídeos , Talassemia alfa/genética , Talassemia beta/genética
2.
Parasit Vectors ; 14(1): 521, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34625097

RESUMO

BACKGROUND: Neospora caninum is an obligate intracellular parasite that invades host cells and replicates within the parasitophorous vacuole (PV), which resists fusion with host cell lysosomal compartments. To modify the PV, the parasite secretes an array of proteins, including dense granule proteins (GRAs). The vital role of GRAs in the Neospora life cycle cannot be overestimated. Despite this important role, only a subset of these proteins have been identified, and most of their functions have not been elucidated. Our previous study demonstrated that NcGRA17 is specifically targeted to the delimiting membrane of the parasitophorous vacuole membrane (PVM). In this study, we utilize proximity-dependent biotin identification (BioID) to identify novel components of the dense granules. METHODS: NcGRA17 was BirA* epitope-tagged in the Nc1 strain utilizing the CRISPR/Cas9 system to create a fusion of NcGRA17 with the biotin ligase BirA*. The biotinylated proteins were affinity-purified for mass spectrometric analysis, and the candidate GRA proteins from BioID data set were identified by gene tagging. To verify the biological role of novel identified GRA proteins, we constructed the NcGRA23 and NcGRA11 (a-e) knockout strains using the CRISPR/Cas9 system and analyzed the phenotypes of these mutants. RESULTS: Using NcGRA17-BirA* fusion protein as bait, we have identified some known GRAs and verified localization of 11 novel GRA proteins by gene endogenous tagging or overexpression in the Nc1 strain. We proceeded to functionally characterize NcGRA23 and NcGRA11 (a-e) by gene knockout. The lack of NcGRA23 or NcGRA11 (a-e) did not affect the parasite propagation in vitro and virulence in vivo. CONCLUSIONS: In summary, our findings reveal that BioID is effective in discovering novel constituents of N. caninum dense granules. The exact biological functions of the novel GRA proteins are yet unknown, but this could be explored in future studies.

3.
Zhongguo Zhen Jiu ; 41(9): 1029-35, 2021 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-34491654

RESUMO

OBJECTIVE: To investigate the mechanism of electroacupuncture (EA) with the involvement of sarcoplasmic reticulum Ca2+-ATPase2a (SERCA2a)/phospholamban (PLB) on the synergistic and attenuated effect of aconitine for heart failure. METHODS: Thirty SPF-ranked SD rats were randomly divided into a control group, a model group, an EA group, an aconitine group and an EA plus aconitine group, with 6 rats in each group. The rat model of acute heart failure was established by infusion of high-dose propranolol hydrochloride solution into the right femoral vein. After stabilized for 10 min in the modeled rats, EA was exerted at "Neiguan" (PC 6), with disperse-dense wave, 2 Hz/15 Hz in frequency, 3 mA in intensity, for 30 min in the EA group and the EA plus aconitine group; aconitine solution (10 µg/kg) was injected from the left femoral veins in the rats in the aconitine group and the EA plus aconitine group. Hemodynamic indexes such as the left ventricular systolic pressure (LVSP) and the maximum rate of increase/decrease of left ventricular pressure (±dp/dtmax) were detected and arrhythmia types were observed and scored. SERCA2a protein and PLB protein expressions in left ventricular myocardial tissue of rats were detected by multiplex fluorescence Western blot. RESULTS: Compared with the control group, LVSP and ±dp/dtmax all were decreased after modeling and at each time point after intervention in the model group (P<0.01). Compared with the model group, ±dp/dtmax was increased in the aconitine group and the EA group at 1 min after intervention (P<0.01, P<0.05), +dp/dtmax was increased at 10 to 60 min after intervention in the aconitine group and at 20 to 60 min after intervention in the EA group (P<0.01, P<0.05), LVSP was increased at 1 min after intervention in the EA group (P<0.01), while LVSP and ±dp/dtmax were all increased at 1 to 60 min after intervention in the EA plus aconitine group (P<0.01, P<0.05). Compared with the aconitine group, LVSP and +dp/dtmax were increased at 1 min after intervention in the EA group (P<0.01, P<0.05), LVSP and ±dp/dtmax at 1 min after intervention while +dp/dtmax at 20 to 60 min after intervention were all increased in the EA plus aconitine group (P<0.01, P<0.05). Compared with the EA group, +dp/dtmax was higher at 10 to 60 min after intervention in the EA plus aconitine group (P<0.01). Compared with the model group, arrhythmia score was higher in the aconitine group (P<0.01). Compared with the aconitine group, arrhythmia score was lower in the EA group and the EA plus aconitine group (P<0.01). As compared with the control group, the expression of SERCA2a protein in the left ventricular cardiomyocytes was decreased (P<0.01), while the expression of PLB protein was increased in the model group (P<0.01). Compared with the model group, the expression of SERCA2a protein was increased in both the EA group and the EA plus aconitine group (P<0.05, P<0.01), and PLB protein expression was decreased in each intervention group respectively (P<0.01, P<0.05). As compared with the EA group and the aconitine group, the expression of SERCA2a protein was increased and the expression of PLB protein was decreased in the EA plus aconitine group separately (P<0.05, P<0.01). CONCLUSION: The intervention with electroacupuncture achieves the synergism/ attenuation effect of aconitine for the improvements in heart failure probably by up-regulating the expression of SERCA2a and down-regulating the expression of PLB in myocardial tissue.


Assuntos
Eletroacupuntura , Insuficiência Cardíaca , Aconitina , Animais , Proteínas de Ligação ao Cálcio , Insuficiência Cardíaca/terapia , Ratos , Ratos Sprague-Dawley
4.
Cancer Biol Med ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34495597

RESUMO

OBJECTIVE: Multiple brain metastases are a severe condition for cancer patients. To date, no general consensus exists regarding the optimal treatment procedure for multiple brain metastases. Radiotherapy is the most commonly used treatment option. The role of surgical resection for multiple brain metastases is unclear. The aim of this study was to compare the outcomes of patients with multiple brain metastases treated with either surgery or stereotactic radiosurgery (SRS). METHODS: The medical records of 279 consecutive adult patients with multiple brain metastases treated with either surgery (26 patients) or SRS (253 patients) were retrospectively reviewed. Propensity score matching was conducted to correct for discrepancies in the baseline characteristics, and 78 patients (26 receiving surgery and 52 receiving SRS) were chosen for comparison of outcomes, such as overall survival, local tumor control rate, and symptom improvement. RESULTS: The tumor size in the surgery group was significantly greater than that in the SRS group after propensity score matching. However, the neurological recovery rate, incidence of leptomeningeal metastasis after surgery, 1-year local tumor control rate, and overall survival were not significantly different between groups. CONCLUSIONS: Our data demonstrate that surgery and radiosurgery have identical overall survival and local tumor control rates in patients with 2 to 4 brain metastases. Although SRS remains the primary and standard option for patients with brain metastasis, surgery offers several distinct advantages, such as establishing a diagnosis or relieving mass effects, and may additionally be beneficial in carefully selected patients with 2-4 brain metastases.

5.
Invest Ophthalmol Vis Sci ; 62(12): 1, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473190

RESUMO

Purpose: HIV infection is associated with a variety of ocular surface diseases. Understanding the difference of the ocular microbiota between HIV-infected and healthy individuals as well as the influence of antiretroviral therapy will help to investigate the pathogenesis of these conditions. Methods: A cross-sectional study was conducted on subjects including HIV-negative individuals, untreated HIV-infected individuals, and HIV-infected individuals with antiretroviral therapy. Conjunctival microbiota was assessed by bacterial 16S rRNA sequencing of the samples obtained from the conjunctival swab. Results: The microbial richness in ocular surface was similar in HIV-negative, untreated HIV-positive, and highly active antiretroviral therapy (HAART) subjects. The bacterial compositions were similar in the two HIV infection groups but were significantly different from the HIV-negative group. HAART changed the beta diversity of bacterial community as determined by Shannon index. CD4+ T cell count had no significant influence on the diversity of ocular microbiota in HIV-infected individuals. Conclusions: The data revealed the compositional and structural difference in conjunctival microbial community in subjects with and without HIV infection, indicating that HIV infection or its treatment, may contribute to ocular surface dysbiosis.


Assuntos
Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Bactérias/genética , Túnica Conjuntiva/microbiologia , Microbioma Gastrointestinal/fisiologia , Infecções por HIV/tratamento farmacológico , RNA Ribossômico 16S/genética , Adulto , Bactérias/metabolismo , Túnica Conjuntiva/patologia , Estudos Transversais , DNA Viral/análise , Feminino , Seguimentos , HIV , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/metabolismo
6.
Int J Biol Macromol ; 190: 93-100, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34481851

RESUMO

pH-sensitive and amphiphilic chitosan derivatives can be used as hydrophobic drug carriers, and their rheological properties play a key role in their performance. In this paper, two pH-responsive and amphiphilic chitosan derivatives, N-(2-allyl-butyl glycidyl ether)-O-carboxymethyl chitosan (HBCC) and N-(2-ethylhexyl glycidyl ether)-O-carboxymethyl chitosan (H2ECC) were synthesized, and their rheological properties were studied. The influence of parameters including concentrations of HBCC and H2ECC, the degree of substitution, solution pH, and [Ca2+] on the rheological properties were investigated. The results showed that the overlap and entanglement concentration of HBCC and H2ECC was ca. 1.7 wt% and 5 wt%, respectively. The dilute and semidilute solutions showed Newtonian behavior. Above 5 wt%, strong networks formed, and shear-thinning behavior appeared at high shear rates (>10 s-1) for entangled solutions. A high degree of substitution and pH near the isoelectric points of HBCC and H2ECC corresponded to a low viscosity and viscoelasticity. In addition, Ca2+ played a shielding effect on the -COO- groups at low concentrations (<10 mmol/L), whereas it acted as a cross-linker when [Ca2+] ≥ 20 mmol/L. The intermolecular hydrogen bonds were examined by molecular dynamics simulations. The results provide new information related to the application of HBCC and H2ECC for hydrophobic drug packaging and transportation.

7.
ACS Chem Neurosci ; 12(17): 3250-3265, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34415727

RESUMO

Aluminum is an environmental neurotoxin that comes extensively in contact with human beings. Animal and human studies demonstrated that aluminum exposure increases the deposition of beta amyloid proteins in the brain as it was observed in Alzheimer's disease. The purpose of this study was to investigate whether miR-29a/b1 affected the expression of beta-secrete enzymes (BACE1) in the process of amyloid ß-protein (Aß) deposition caused by aluminum exposure. The study was performed using two different cell lines. Our results showed that after rat primary cortical neurons were exposed to aluminum, BACE1 gene and protein levels increased to different degrees, and the expression level of Aß1-42 increased. In aluminum-exposed groups, the expression of miR-29a and miR-29b1 decreased, while the expression of amyloid protein Aß1-42 and BACE1 increased. In miRs transfection groups, the expression of amyloid protein Aß1-42 and BACE1 decreased. Aluminum may affect the expression of BACE1 by lowering miR-29a and miR-29b1. AEK293 cells were utilized in this research since they present elevated levels of miR-29a and miR-29b1. After HEK293 cells were exposed to aluminum alone, BACE1 mRNA and BACE1 protein expression levels increased with the increase of aluminum exposure dose (p < 0.05), and the level of Aß1-42 also increased (p < 0.05). Compared with the group exposed to aluminum alone at the same doses, the expression levels of BACE1 mRNA and BACE1 protein in the miRs transfected plus aluminum-exposed groups significantly decreased (p < 0.05), and the level of Aß1-42 also decreased (p < 0.05). This result is consistent with the investigation in rat primary neurons. The results of two types of cells showed that aluminum may cause abnormal down-regulation of the expressions of miR-29a and miR-29b1, thus negatively regulating the increase of BACE1 expression and finally leading to the increase of Aß.


Assuntos
Doença de Alzheimer , MicroRNAs , Alumínio/toxicidade , Secretases da Proteína Precursora do Amiloide/genética , Peptídeos beta-Amiloides , Animais , Ácido Aspártico Endopeptidases/genética , Células HEK293 , Humanos , MicroRNAs/genética , Ratos
8.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34360709

RESUMO

Toxoplasma gondii (T. gondii) is an important human and veterinary pathogen causing life-threatening disease in immunocompromised patients. The UBL-UBA shuttle protein family are important components of the ubiquitin-proteasome system. Here, we identified a novel UBL-UBA shuttle protein DSK2b that is charactered by an N-terminal ubiquitin-like domain (UBL) and a C-terminal ubiquitin-associated domain (UBA). DSK2b was localized in the cytoplasm and nucleus. The deletion of dsk2b did not affect the degradation of ubiquitinated proteins, parasite growth in vitro or virulence in mice. The double-gene knockout of dsk2b and its paralogs dsk2a (ΔΔdsk2adsk2b) results in a significant accumulation of ubiquitinated proteins and the asynchronous division of T. gondii. The growth of ΔΔdsk2adsk2b was significantly inhibited in vitro, while virulence in mice was not attenuated. In addition, autophagy occurred in the ΔΔdsk2adsk2b, which was speculated to degrade the accumulated ubiquitinated proteins in the parasites. Overall, DSK2b is a novel UBL-UBA shuttle protein contributing to the degradation of ubiquitinated proteins and is important for the synchronous cell division of T. gondii.


Assuntos
Divisão Celular , Proteólise , Proteínas de Protozoários/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Toxoplasma/metabolismo , Ubiquitinação , Animais , Deleção de Genes , Humanos , Camundongos , Proteínas de Protozoários/genética , Receptores Citoplasmáticos e Nucleares/genética , Toxoplasma/genética , Toxoplasma/patogenicidade
9.
Parasit Vectors ; 14(1): 400, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384491

RESUMO

BACKGROUND: Metacaspases are multifunctional proteins found in plants, fungi and protozoa, and are involved in processes such as insoluble protein aggregate clearance and cell proliferation. Our previous study demonstrated that metacaspase-1 (MCA1) contributes to parasite apoptosis in Toxoplasma gondii. Deletion of MCA1 from T. gondii has no effect on the growth and virulence of the parasites. Three metacaspases were identified in the ToxoDB Toxoplasma Informatics Resource, and the function of metacaspase-2 (MCA2) and metacaspase-3 (MCA3) has not been demonstrated. METHODS: In this study, we constructed MCA1, MCA2 and MCA1/MCA2 transgenic strains from RHΔku80 (Δku80), including overexpressing strains and knockout strains, to clarify the function of MCA1 and MCA2 of T. gondii. RESULTS: MCA1 and MCA2 were distributed in the cytoplasm with punctuated aggregation, and part of the punctuated aggregation of MCA1 and MCA2 was localized on the inner membrane complex of T. gondii. The proliferation of the MCA1/MCA2 double-knockout strain was significantly reduced; however, the two single knockout strains (MCA1 knockout strain and MCA2 knockout strain) exhibited normal growth rates as compared to the parental strain, Δku80. In addition, endodyogeny was impaired in the tachyzoites whose MCA1 and MCA2 were both deleted due to multiple nuclei and abnormal expression of IMC1. We further found that IMC1 of the double-knockout strain was detergent-soluble, indicating that MCA1 and MCA2 are associated with IMC1 maturation. Compared to the parental Δku80 strain, the double-knockout strain was more readily induced from tachyzoites to bradyzoites in vitro. Furthermore, the double-knockout strain was less pathogenic in mice and was able to develop bradyzoites in the brain, which formed cysts and established chronic infection. CONCLUSION: MCA1 and MCA2 are important factors which participate in IMC1 maturation and endodyogeny of T. gondii. The double-knockout strain has slower proliferation and was able to develop bradyzoites both in vitro and in vivo.

10.
Zhen Ci Yan Jiu ; 46(7): 570-4, 2021 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-34369676

RESUMO

OBJECTIVE: To observe the influence of electroacupuncture(EA) combined with aconitine on the hemodyna-mics, echocardiogram, and arrhythmias in heart failure rats, so as to explore the facilitation and attenuation effects of EA combined with aconitine. METHODS: SD rats were randomly divided into control, model, aconitine and aconitine+EA groups, with 6 rats in each group. Propranolol hydrochloride was used to establish the heart failure model. Rats in the aconitine group were trea-ted with aconitine continuously for 1 h (40 µg/kg). Rats in the aconitine +EA group were given the same treatment as the aconitine group, meanwhile, EA (3 mA, 2 Hz/15 Hz) was applied at "Neiguan"(PC6) for 30 min. Left ventricular catheter and small animal ultrasound imaging system were used to observe the heart hemodynamic indexes such as left ventricular systolic pressure(LVSP), maximal rate for left ventricular pressure rising (+dp/dtmax), and maximal rate for left ventricular pressure declining (-dp/dtmax), ejection fraction (EF) and fractional shortening (FS). The incidence rate of arrhythmia and arrhythmia score was observed by electrocardiogram. RESULTS: Following modeling and compared with the control group, LVSP, +dp/dtmax, -dp/dtmax, EF and FS in the aconitine group all decreased(P<0.01) and maintained in the model group. The LVSP of rats in the aconitine group was higher than that of the model group at 15 min after administration of aconitine (P<0.05), and +dp/dtmax was higher at 15, 60 min after administration (P<0.05). Since 15 min after administration, EF and FS in the aconitine group were significantly higher than those of the model group (P<0.01, P<0.05). After EA intervention, compared with the aconitine group, LVSP, +dp/dtmax, -dp/dtmax in the aconitine+EA group were significantly increased (P<0.01, P<0.05) during administration and EF and FS in the aconitine+EA group significantly increased at the beginning of administration of aconitine and 30 and 60 min during administration (P<0.05, P<0.01). The incidence rate of arrhythmia was 100% in the aconitine group, and 50.0% in the rats of aconitine + EA group. The arrhythmia score of aconitine + EA group was significantly lower than that of aconitine group (P<0.05). CONCLUSION: Aconitine has a certain inotropic effect, but it is easy to cause arrhythmia. The combination of EA and aconitine can not only improve the contractile function of the heart in rats with heart failure, but also reduce the toxic reaction of aconitine.


Assuntos
Eletroacupuntura , Insuficiência Cardíaca , Aconitina , Animais , Coração , Insuficiência Cardíaca/terapia , Humanos , Ratos , Ratos Sprague-Dawley
11.
Mol Cell ; 81(19): 3919-3933.e7, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34453889

RESUMO

Heat-shock proteins of 70 kDa (Hsp70s) are vital for all life and are notably important in protein folding. Hsp70s use ATP binding and hydrolysis at a nucleotide-binding domain (NBD) to control the binding and release of client polypeptides at a substrate-binding domain (SBD); however, the mechanistic basis for this allostery has been elusive. Here, we first characterize biochemical properties of selected domain-interface mutants in bacterial Hsp70 DnaK. We then develop a theoretical model for allosteric equilibria among Hsp70 conformational states to explain the observations: a restraining state, Hsp70R-ATP, restricts ATP hydrolysis and binds peptides poorly, whereas a stimulating state, Hsp70S-ATP, hydrolyzes ATP rapidly and has high intrinsic substrate affinity but rapid binding kinetics. We support this model for allosteric regulation with DnaK structures obtained in the postulated stimulating state S with biochemical tests of the S-state interface and with improved peptide-binding-site definition in an R-state structure.

12.
J Biochem Mol Toxicol ; : e22909, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34463003

RESUMO

Circular RNAs have participated in oncology progress. Nevertheless, the potential mechanisms are not completely understood. We intended to inspect the functions of hsa_circ_0088088 on breast malignancy, together with the possible mechanism(s). hsa_circ_0088088 expression in breast malignancy was studied using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). The overall survival was studied by the Kaplan-Meier curve. The biological functions of hsa_circ_0088088 aberrant expression on cell growth and metastasis were evaluated in MDA-MB-231 cells. Bioinformatics analysis, RNA immunoprecipitation (RIP), and qRT-PCR were accomplished to confirm the possible regulatory effects of eukaryotic initiation factor 4A3 (EIF4A3) on the biogenesis of hsa_circ_0088088. Furthermore, a dual-luciferase reporter assay, qRT-PCR, and RNA pull-down assay were used to confirm the association between the hsa_circ_0088088 and miR-135-5p in MDA-MB-231 cells. hsa_circ_0088088 was upregulated in the tumor tissues and cells, and higher expression presented an unfavorable prognosis. hsa_circ_0088088 overexpression promoted cell growth and metastasis in MDA-MB-231 cells. EIF4A3 was found to positively regulate hsa_circ_0088088. Furthermore, we confirmed that hsa_circ_0088088 sponges miR-135-5p and directly targets miR-135-5p with respect to the cell growth and metastasis in MDA-MB-231 cells. Our data suggest that EIF4A3-induced hsa_circ_0088088 stimulates the carcinogenic effects of breast tumors by sponging miR-135-5p.

13.
Int J Biol Macromol ; 188: 678-688, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34343590

RESUMO

As high-efficiency, safe, and low-drug resistant antibacterial agents, silver nanoparticles (AgNPs) have been widely applied in food and biomedicine. AgNPs was prepared using mango peel extract (MPE) as green and cheap reducing agent and stabilizer. In addition, a novel of preservative film material was developed with polylactic acid (PLA) as protective and substrate. AgNPs was characterized by XPS, XRD and TEM, and the size of AgNPs were in the range of 2.5-6.5 nm. The addition of AgNPs improved the mechanical properties of the film and its barrier ability to water vapor and oxygen. The film exhibited excellent antibacterial properties, and the inhibition rate against Escherichia coli and Staphylococcus aureus were above 95%. Furthermore, in terms of safety, the silver migration and cytotoxicity of the film met the relevant standards, and the shelf life of strawberries was significantly extended.

14.
Zool Res ; 42(5): 548-561, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34327887

RESUMO

The genetic adaptations of various organisms to heterogeneous environments in the northwestern Pacific remain poorly understood. Heterogeneous genomic divergence among populations may reflect environmental selection. Advancing our understanding of the mechanisms by which organisms adapt to different temperatures in response to climate change and predicting the adaptive potential and ecological consequences of anthropogenic global warming are critical. We sequenced the whole genomes of Japanese whiting ( Sillago japonica) specimens collected from different latitudinal locations along the coastal waters of China and Japan to detect possible thermal adaptations. Using population genomics, a total of 5.48 million single nucleotide polymorphisms (SNPs) from five populations revealed a complete genetic break between the Chinese and Japanese groups, which was attributed to both geographic distance and local adaptation. The shared natural selection genes between two isolated populations (i.e., Zhoushan and Ise Bay/Tokyo Bay) indicated possible parallel evolution at the genetic level induced by temperature. These genes also indicated that the process of temperature selection on isolated populations is repeatable. Moreover, we observed natural candidate genes related to membrane fluidity, possibly underlying adaptation to cold environmental stress. These findings advance our understanding of the genetic mechanisms underlying the rapid adaptations of fish species. Species distribution projection models suggested that the Chinese and Japanese groups may have different responses to future climate change, with the former expanding and the latter contracting. The findings of this study enhance our understanding of genetic differentiation and adaptation to changing environments.


Assuntos
Adaptação Fisiológica/genética , Peixes/genética , Peixes/fisiologia , Distribuição Animal , Animais , Evolução Biológica , China , Mudança Climática , Ecossistema , Japão , Oceano Pacífico , Polimorfismo de Nucleotídeo Único , Temperatura , Sequenciamento Completo do Genoma
15.
Ecotoxicol Environ Saf ; 222: 112479, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34224968

RESUMO

Lead is a widely distributed priority controlled heavy metals in aquatic system, its toxicity to aquatic organisms affected by water quality parameters. This study investigated the acute toxicity of lead (Pb) to the aquatic organisms in Taihu Lake under various water hardness, corresponding regional water quality criteria were derived. The acute toxicity experimental results revealed that the toxicity of Pb to aquatic organisms increased with water hardness. The Pb toxicity has a highest toxicity at water hardness 50 mg/L (expressed as CaCO3), especially for Palaemon modestus where the 96 h LC50 value was 0.024 mg/L. The hazardous concentration for 5% of biological species (HC5) values were determined via species sensitivity distribution (SSD) method as 94.0 µg/L, 222.3 µg/L and 375.8 µg/L for Pb at water hardness 50, 150, and 250 mg/L, respectively. The assessment factor (AF) value was set at 2, followed by the current SSD framework where European commission recommend a fixed AF of 5-1. Thus, the predicted no effect concentration (PNEC) values was 47.0 µg/L, 111.2 µg/Land 187.9 µg/L at water hardness 50, 150, and 250 mg/L, respectively. Meanwhile, the short-term water quality criteria of Pb for Taihu lake aquatic organisms were derived as 111.2 µg/L at water hardness 150 mg CaCO3/L. The long-term water quality criteria were derived as 4.3 µg/L by using acute/chronic ratio 51.29. When the derived value was used for Taihu Lake, 2.7% of the sampling sites in Taihu Lake was exceeded this criterion. The results of this study can provide technical methods and basic information for deriving Pb regional water quality criteria for protecting native aquatic organisms, in China.


Assuntos
Poluentes Químicos da Água , Qualidade da Água , Organismos Aquáticos , China , Lagos , Chumbo/toxicidade , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
16.
Nat Commun ; 12(1): 3433, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103506

RESUMO

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has created global health and economic emergencies. SARS-CoV-2 viruses promote their own spread and virulence by hijacking human proteins, which occurs through viral protein recognition of human targets. To understand the structural basis for SARS-CoV-2 viral-host protein recognition, here we use cryo-electron microscopy (cryo-EM) to determine a complex structure of the human cell junction protein PALS1 and SARS-CoV-2 viral envelope (E) protein. Our reported structure shows that the E protein C-terminal DLLV motif recognizes a pocket formed exclusively by hydrophobic residues from the PDZ and SH3 domains of PALS1. Our structural analysis provides an explanation for the observation that the viral E protein recruits PALS1 from lung epithelial cell junctions. In addition, our structure provides novel targets for peptide- and small-molecule inhibitors that could block the PALS1-E interactions to reduce E-mediated virulence.


Assuntos
Proteínas do Envelope de Coronavírus/química , Proteínas do Envelope de Coronavírus/metabolismo , Junções Intercelulares/metabolismo , Proteínas de Membrana/metabolismo , Núcleosídeo-Fosfato Quinase/metabolismo , Sequência de Aminoácidos , Proteínas do Envelope de Coronavírus/ultraestrutura , Microscopia Crioeletrônica , Humanos , Domínios Proteicos , SARS-CoV-2/fisiologia , Homologia Estrutural de Proteína , Relação Estrutura-Atividade
17.
Stem Cell Res Ther ; 12(1): 355, 2021 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-34147136

RESUMO

BACKGROUND: The adverse health effects of fine particulate matter (PM2.5) exposure are associated with marked inflammatory responses. Adipose-derived stem cells (ADSCs) have immunosuppressive effects, and ADSC transplantation could attenuate pulmonary fibrosis in different animal disease models. However, whether ADSCs affect PM2.5-induced lung injury has not been investigated. METHOD: C57BL/6 mice were exposed to PM2.5 every other day via intratracheal instillation for 4 weeks. After that, the mice received tail vein injections of ADSCs every 2 weeks. RESULTS: ADSC transplantation significantly attenuated systemic and pulmonary inflammation, cardiac dysfunction, fibrosis, and cell death in PM2.5-exposed mice. RNA-sequencing results and bioinformatic analysis suggested that the downregulated differentially expressed genes (DEGs) were mainly enriched in inflammatory and immune pathways. Moreover, ADSC transplantation attenuated PM2.5-induced cell apoptosis and pyroptosis in the lungs and hearts. CONCLUSION: ADSCs protect against PM2.5-induced adverse health effects through attenuating pulmonary inflammation and cell death. Our findings suggest that ADSC transplantation may be a potential therapeutic approach for severe air pollution-associated diseases.


Assuntos
Lesão Pulmonar , Tecido Adiposo , Animais , Pulmão , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/genética , Lesão Pulmonar/terapia , Camundongos , Camundongos Endogâmicos C57BL , Material Particulado/toxicidade , Células-Tronco
18.
Org Lett ; 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34109797

RESUMO

A visible-light-induced intermolecular sulfur-alkenylation of alkenes, including both activated and unactivated alkenes, is described. This sulfur-alkenylation reaction proceed in a highly regio- and stereospecific manner involving the visible-light-induced conversion of a ketene dithioacetal to the thiavinyl 1,3-dipole intermediate, followed by a formal [3 + 2] cycloaddition and C-S bond cleavage. Furthermore, it is also an efficient approach for the late-stage functionalization of natural products and complex molecules, even being induced by sunlight under ambient conditions.

19.
Nat Commun ; 12(1): 3702, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-34140491

RESUMO

Versatile methods to organize proteins in space are required to enable complex biomaterials, engineered biomolecular scaffolds, cell-free biology, and hybrid nanoscale systems. Here, we demonstrate how the tailored encapsulation of proteins in DNA-based voxels can be combined with programmable assembly that directs these voxels into biologically functional protein arrays with prescribed and ordered two-dimensional (2D) and three-dimensional (3D) organizations. We apply the presented concept to ferritin, an iron storage protein, and its iron-free analog, apoferritin, in order to form single-layers, double-layers, as well as several types of 3D protein lattices. Our study demonstrates that internal voxel design and inter-voxel encoding can be effectively employed to create protein lattices with designed organization, as confirmed by in situ X-ray scattering and cryo-electron microscopy 3D imaging. The assembled protein arrays maintain structural stability and biological activity in environments relevant for protein functionality. The framework design of the arrays then allows small molecules to access the ferritins and their iron cores and convert them into apoferritin arrays through the release of iron ions. The presented study introduces a platform approach for creating bio-active protein-containing ordered nanomaterials with desired 2D and 3D organizations.


Assuntos
Apoferritinas/química , Bioengenharia/métodos , Citoesqueleto/química , DNA/química , Ferritinas/química , Nanoestruturas/química , Apoferritinas/ultraestrutura , Microscopia Crioeletrônica , Citoesqueleto/ultraestrutura , Ferritinas/ultraestrutura , Processamento de Imagem Assistida por Computador , Microscopia Eletrônica de Transmissão , Modelos Moleculares , Conformação Molecular
20.
Aging (Albany NY) ; 13(11): 15013-15031, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34031268

RESUMO

Fat storage is one of the important strategies employed in regulating energy homeostasis. Impaired lipid storage causes metabolic disorders in both mammals and Drosophila. In this study, we report CG9911, the Drosophila homolog of ERp44 (endoplasmic reticulum protein 44) plays a role in regulating adipose tissue fat storage. Using the CRISPR/Cas9 system, we generated a CG9911 mutant line deleting 5 bp of the coding sequence. The mutant flies exhibit phenotypes of lower bodyweight, fewer lipid droplets, reduced TAG level and increased expression of lipolysis related genes. The increased lipolysis phenotype is enhanced in the presence of ER stresses and suppressed by a reduction of the ER Ca2+. Moreover, loss of CG9911 per se results in a decrease of ER Ca2+ in the fat body. Together, our results reveal a novel function of CG9911 in promoting fat storage via regulating ER Ca2+ signal in Drosophila.


Assuntos
Adipócitos/metabolismo , Adiposidade , Cálcio/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/metabolismo , Retículo Endoplasmático/metabolismo , Homeostase , Proteínas de Membrana/metabolismo , Chaperonas Moleculares/metabolismo , Animais , Sequência de Bases , Proteínas de Drosophila/genética , Estresse do Retículo Endoplasmático , Espaço Intracelular/metabolismo , Lipólise , Proteínas de Membrana/genética , Modelos Biológicos , Chaperonas Moleculares/genética , Mutação/genética , Fenótipo
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