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1.
Microb Cell Fact ; 19(1): 129, 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32527330

RESUMO

BACKGROUND: L-Alanyl-L-glutamine (AQ) is a functional dipeptide with high water solubility, good thermal stability and high bioavailability. It is widely used in clinical treatment, post-operative rehabilitation, sports health care and other fields. AQ is mainly produced via chemical synthesis which is complicated, time-consuming, labor-intensive, and have a low yield accompanied with the generation of by-products. It is therefore highly desirable to develop an efficient biotechnological process for the industrial production of AQ. RESULTS: A metabolically engineered E. coli strain for AQ production was developed by over-expressing L-amino acid α-ligase (BacD) from Bacillus subtilis, and inactivating the peptidases PepA, PepB, PepD, and PepN, as well as the dipeptide transport system Dpp. In order to use the more readily available substrate glutamic acid, a module for glutamine synthesis from glutamic acid was constructed by introducing glutamine synthetase (GlnA). Additionally, we knocked out glsA-glsB to block the first step in glutamine metabolism, and glnE-glnB involved in the ATP-dependent addition of AMP/UMP to a subunit of glutamine synthetase, which resulted in increased glutamine supply. Then the glutamine synthesis module was combined with the AQ synthesis module to develop the engineered strain that uses glutamic acid and alanine for AQ production. The expression of BacD and GlnA was further balanced to improve AQ production. Using the final engineered strain p15/AQ10 as a whole-cell biocatalyst, 71.7 mM AQ was produced with a productivity of 3.98 mM/h and conversion rate of 71.7%. CONCLUSION: A metabolically engineered strain for AQ production was successfully developed via inactivation of peptidases, screening of BacD, introduction of glutamine synthesis module, and balancing the glutamine and AQ synthesis modules to improve the yield of AQ. This work provides a microbial cell factory for efficient production of AQ with industrial potential.

2.
New Phytol ; 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32583432

RESUMO

Plastid-encoded genes are coordinately transcribed by the nucleus-encoded RNA polymerase (NEP) and the plastid-encoded RNA polymerase (PEP). Resulting primary transcripts are frequently subject to RNA editing by C-to-U conversions at specific sites. The physiological role of many editing events is largely unknown. Here, we have used the CRISPR/Cas9 technique in rice to knock out a member of the PLS-DYW subfamily of pentatricopeptide repeat (PPR) proteins. We found that OsPPR16 is responsible for a single editing event at position 545 in the chloroplast rpoB mRNA, resulting in an amino acid change from serine to leucine in the ß-subunit of the plastid-encoded RNA polymerase. In striking contrast to loss-of-function mutations of the putative orthologue in Arabidopsis, which were reported to have no visible phenotype, knock-out of OsPPR16 leads to impaired accumulation of RpoB, reduced expression of PEP-dependent genes and a pale phenotype during early plant development. Thus, by editing the rpoB mRNA, OsPPR16 is required for faithful plastid transcription, which in turn is required for chlorophyll synthesis and efficient chloroplast development. Our results provide new insights into the interconnection of the finely tuned regulatory mechanisms that operate at the transcriptional and post-transcriptional levels of plastid gene expression.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32520521

RESUMO

Flexible vibration sensors can not only capture broad classes of physiologically relevant information, including mechano-vibration signatures of body processes and precision kinematics of core-body motions, but also detect environmental seismic waves, providing early warning to wearers in time. Spider is one of the most vibration-sensitive creatures because of its hairlike sensilla and lyriform slit structure. Here, a spider-inspired ultrasensitive flexible vibration sensor is designed and fabricated for multifunctional sensing. The vibration sensitivity of the flexible sensor is increased over 2 orders of magnitude from 0.006 to 0.5 mV/g, and the strain sensitivity is hugely enhanced from 0.08 to 150 compared to a plain sensor counterpart. It is shown that the synergistic effect of cilium arrays and cracks is the key for achieving the greatly enhanced vibration and strain sensitivity. The dynamic sensitivity of 0.5 mV/g outperforms the corresponding commercial vibration sensors. The flexible sensor is demonstrated to be generally feasible for detecting vibration signals caused by walk, tumble, and explosion as well as capturing human body motions, indicating its great potential for applications in human health-monitoring devices, posture control in robotics, early earthquake warning, and so forth.

4.
Sleep Med ; 72: 1-4, 2020 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-32502844

RESUMO

OBJECTIVE: To evaluate sleep disturbances of Chinese frontline medical workers (FMW) under the outbreak of coronavirus disease 2019 (COVID-19), and make a comparison with non-FMW. METHODS: The medical workers from multiple hospitals in Hubei Province, China, volunteered to participate in this cross-sectional study. An online questionnaire, including Pittsburgh Sleep Quality Index (PSQI), Athens Insomnia Scale (AIS) and Visual Analogue Scale (VAS), was used to evaluate sleep disturbances and mental status. Sleep disturbances were defined as PSQI>6 points or/and AIS>6 points. We compared the scores of PSQI, AIS, anxiety and depression VAS, as well as prevalence of sleep disturbances between FMW and non-FMW. RESULTS: A total of 1306 subjects (801 FMW and 505 non-FMW) were enrolled. Compared to non-FMW, FMW had significantly higher scores of PSQI (9.3 ± 3.8 vs 7.5 ± 3.7; P < 0.001; Cohen's d = 0.47), AIS (6.9 ± 4.3 vs 5.3 ± 3.8; P < 0.001; Cohen's d = 0.38), anxiety (4.9 ± 2.7 vs 4.3 ± 2.6; P < 0.001; Cohen's d = 0.22) and depression (4.1 ± 2.5 vs 3.6 ± 2.4; P = 0.001; Cohen's d = 0.21), as well as higher prevalence of sleep disturbances according to PSQI > 6 points (78.4% vs 61.0%; relative risk [RR] = 1.29; P < 0.001) and AIS > 6 points (51.7% vs 35.6%; RR = 1.45; P < 0.001). CONCLUSION: FMW have higher prevalence of sleep disturbances and worse sleep quality than non-FMW. Further interventions should be administrated for FMW, aiming to maintain their healthy condition and guarantee their professional performance in the battle against COVID-19.

5.
J Colloid Interface Sci ; 579: 119-127, 2020 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-32574729

RESUMO

Antibiotics as newly emerging organic pollutants are arousing more and more serious environmental issues. Meantime, metal-organic frameworks (MOFs) are considered as promising adsorbents to remove antibiotics. To overcome the limitations of large-scale applications for MOFs in the powder form, herein, we proposed a strategy of in-situ growth ZIF-67 onto polyaniline (PANI) modified regenerated cellulose aerogel (RCA). First, RCA was obtained by chemical cross-linking and physical cross-linking method. Then, PANI played the role of metal chelated layers, which were coated on RCA by in-situ polymerization. Finally, ZIF-67 nanocrystals were in-situ growth on the surface of the PANI coated regenerated cellulose aerogel to synthesise the composite adsorbent ZIF-67/PANI/RCA. The loading mass ratios of ZIF-67 on RCA and PANI/RCA were 25.39% and 42.38%, respectively, which indicates that PANI as interface layers can effectively promote the in-situ growth of ZIF-67 compared with pure RCA. The obtained composite adsorbent (ZIF-67/PANI/RCA) was applied for the adsorption of tetracycline (TC) with high adsorption capacity (409.55 mg·g-1) and good recycling ability. After six cycles of adsorption-desorption, the removal efficiency toward TC was still over 94%. This strategy may provide an effective and versatile pathway to increase MOF loading mass on aerogel and sequentially branch out their applications in pollutant treatment fields.

6.
Parasitol Res ; 119(7): 2287-2298, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32468190

RESUMO

Toxoplasma gondii is an important zoonotic protozoan of the phylum Apicomplexa that can infect nearly all warm-blooded animals. The parasite can exist as the interconvertible tachyzoite or bradyzoite forms, leading to acute or latent infection, respectively. No drug has been reported to penetrate the cyst wall and reduce bradyzoite survival and proliferation till now. The transcriptional level of metacaspases 2 (TgMCA2) in T. gondii is significantly upregulated during the formation of bradyzoites in the Pru strain, indicating that it may play an important role in the formation of bradyzoites. To further explore the function of TgMCA2, we constructed a TgMCA2 gene-knockout variant of the Pru strain (Δmca2). Comparative analysis revealed that the proliferative capacity of Pru Δmca2 increased, while the invasion and egressing properties were not affected by the knockout. Further data shows that the tachyzoites of Δmca2 failed to induce differentiation and form bradyzoites in vitro, and the transcriptional levels of some of the bradyzoite-specific genes (such as BAG1, LDH2, and SAG4A) in Δmca2 were significantly lower compared with that in the Pru strain at the bradyzoite stage. In vivo, no cysts were detected in Δmca2-infected mice. Further determination of parasite burden in Δmca2- and Pru-infected mice brain tissue at the genetic level showed that the gene load was significantly lower than that in Pru. In summary, we confirmed that TgMCA2 contributes to the formation of bradyzoites, and could provide an important foundation for the development of attenuated vaccines for the prevention of T. gondii infection.

7.
J Nat Prod ; 83(6): 1751-1765, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32468815

RESUMO

Eighteen new limonoids, including eight methyl angolensates (1-8) and 10 cipadesins (9-18), were isolated from the leaves of Cipadessa baccifera. Their structures were characterized by means of spectroscopic data analyses, single-crystal X-ray diffraction, and quantum chemistry computational methods. The C-6 configurations in those compounds possessing a C-6 hydroxy group were all assigned as S regardless of the magnitude of J5,6, and the C-2' configuration in those bearing a 2-methylbutyryl residue was defined by single-crystal X-ray diffraction and NMR data. Compounds 1, 5, 6, 7, 11, and 12 showed moderate antimalarial activities with IC50 values ranging from 12 to 28 µM.

8.
J Trace Elem Med Biol ; 61: 126551, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32470791

RESUMO

BACKGROUND: Aluminium is an environmental neurotoxin to which human beings are extensively exposed. However, the molecular mechanism of aluminium toxicity remains unclear. METHODS: The changes in cognitive function of aluminum exposed workers under long-term occupational exposure were evaluated, and the relationship between cognitive changes, plasma memory related BDNF and EGR1 protein expression, and variations of epigenetic markers H3K4me3, H3K9me2, H3K27me3 expression levels in blood was explored. RESULTS: MMSE, DSFT, DST scores in cognitive function and the levels of plasma BDNF and EGR1 protein expression decreased with the increase of blood aluminum level. H3K4me3, H3K9me2, H3K27me3 expression levels in peripheral blood lymphocytes of aluminum exposed workers were statistically different (all P<0.05). H3K4me3, H3K9me2 and H3K27me3 expression levels in lymphocytes were correlated with blood aluminum level. BDNF, EGR1 protein level and H3K4me3, H3K9me2, H3K27me3 expression levels have different degrees of correlation. There was a linear regression relationship between plasma BDNF, H3K4me3 and H3K9me2. H3K9me2 had a greater effect on BDNF than H3K4me3. There is a linear regression relationship between EGR1, H3K4me3 and H3K27me3, and the influence of H3K4me3 on EGR1 is greater than that of H3K27me3 on EGR1. CONCLUSION: Alummnum may regulate the expression of BDNF and EGR1 by regulating H3K4me3, H3K27me3 and H3K9me2, and affect the cognitive function of workers by affecting the expression of BDNF and EGR1.

10.
Chin J Integr Med ; 2020 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-32388822

RESUMO

OBJECTIVE: To investigate the effects of different acupuncture manipulations on Deqi sensations and surface myoelectricity, and explore the correlation between Deqi sensations and needling manipulations. METHODS: Forty-five healthy participants accepted twirling, lifting-thrusting, and twirling plus lifting-thrusting manipulanions at right Zusanli (ST 36), respectively. The acupuncturist's and participants' Deqi sensations were collected by MGH Acupuncture Sensation Scale (MASS). The intensity and occurrence rate of soreness, dull pain, pressure, heaviness, fullness, numbness, sharp pain, warmth, coolness, and throbbing feelings of participants, and tightness, smooth, and tangle feelings of acupuncturist were measured. The correlation between the acupuncturist's and participant's Deqi sensations was analyzed. Surface electromyogram (EMG) were recorded before, during and after needling in 30 participants. The integrated EMG (iEMG), mean power frequency (MPF) and media frequency (MF) were analyzed. RESULT: Both fullness and soreness of participants and tightness of acupuncturist were the most frequently occurred ones. A positive correlation between participants' fullness and acupuncturist's tightness was observed during the three aforementioned needling manipulations (P<0.05, OR>1). Almost all the needling sensations measured in the present study could be induced by the three needling manipulations. However, strength of Deqi sensations was exhibited as lifting-thrusting > twirling plus lifting-thrusting > twirling according to MASS index. The iEMG values were increased and MPF, MF values were decreased during needling compaired to those before needling, especially during lifting-thrusting (P<0.01). CONCLUSIONS: The intensity and occurrence rate of the different Deqi sensations induced by different needling manipulations were basically similar. The fullness and soreness were both the most frequently induced Deqi sensations. The strongest Deqi sensation could be induced by lifting-thrusting manipulation. There is a positive correlation between participants' fullness and acupuncturist's tightness during the three needling manipulations. The myoelectricity around the acupoint is related to Deqi responses. (Registration No. AMCTR-IOR-20000314).

11.
Ann Palliat Med ; 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32389019

RESUMO

BACKGROUND: Over half of patients with advanced cancer report appetite loss or anorexia. Previous studies have shown the benefit of acupuncture for cancer-related nausea and vomiting, but limited evidence exists for its role in appetite improvement. Our study aimed to evaluate the feasibility and safety of auricular acupuncture to improve appetite for cancer patients with advanced disease. METHODS: We performed a two-arm parallel, pilot randomized controlled trial (RCT) of auricular acupuncture versus usual care control in patients with stage III or IV cancer who experienced appetite loss. The primary outcome was changed in the Simplified Nutritional Appetite Questionnaire (SNAQ; score range, 4-20) between two groups from baseline to weeks 2 and 4, with secondary outcomes including change in weight, as well as an additional evaluation at week 8 for durability of treatment effects. We used independent two-sample t-test for the change in mean score for each outcome during or after treatment. We assessed the interaction between time and treatment from baseline to weeks 2, 4, and 8 using mixed-effects models by ANOVA test. RESULTS: We randomized 55 patients to auricular acupuncture (N=27) or control group (N=28). By week 4, the auricular acupuncture group had a significantly higher escalation in the SNAQ score than the control group compared with baseline [mean difference 3.69; 95% confidential interval (95% CI): 2.5, 4.8; P<0.001] and experienced a 51.4% improvement in appetite. From baseline to weeks 2 and 4, patients lost a little weight in the control group but gained weight in the auricular acupuncture group. Between baseline and week 4, change in the SNAQ score was significantly associated with change in weight (P=0.001). No adverse events (AEs) were reported during the study. CONCLUSIONS: Compared to usual care, auricular acupuncture is feasible and safe to improve appetite and help patients with advanced cancer gain weight.

13.
Nat Commun ; 11(1): 2249, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32382010

RESUMO

Plant metacaspases mediate programmed cell death in development, biotic and abiotic stresses, damage-induced immune response, and resistance to pathogen attack. Most metacaspases require Ca2+ for their activation and substrate processing. However, the Ca2+-dependent activation mechanism remains elusive. Here we report the crystal structures of Metacaspase 4 from Arabidopsis thaliana (AtMC4) that modulates Ca2+-dependent, damage-induced plant immune defense. The AtMC4 structure exhibits an inhibitory conformation in which a large linker domain blocks activation and substrate access. In addition, the side chain of Lys225 in the linker domain blocks the active site by sitting directly between two catalytic residues. We show that the activation of AtMC4 and cleavage of its physiological substrate involve multiple cleavages in the linker domain upon activation by Ca2+. Our analysis provides insight into the Ca2+-dependent activation of AtMC4 and lays the basis for tuning its activity in response to stresses for engineering of more sustainable crops for food and biofuels.

16.
Carbohydr Polym ; 237: 116112, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32241407

RESUMO

Chitosan has attracted much attention in drug delivery, however, carboxymethyl chitosan (CMC)-based self-aggregated nanocarriers are seldom reported. In this paper, two kinds of CMC-based pH-responsive amphiphilic chitosan derivatives, N-2-hydroxylpropyl-3-butyl ether-O-carboxymethyl chitosan (HBCC) and N-2-hydroxylpropyl-3-(2-ethylhexyl glycidyl ether)-O-carboxymethyl chitosan (H2ECC), have been synthesized by the homogeneous reaction. The molecular structures were characterized by FTIR, 1H NMR and 13C NMR. The optimum reaction condition was obtained based on the data of 1H NMR spectrum: reaction time of 4 h, reaction temperature of 80 °C and nepoxyn-NH2 of 3/1, respectively. The XRD patterns showed the crystallinity of HBCC and H2ECC decreased due to the introduction of hydrophobic segments. The thermostability of HBCC and H2ECC was improved for the formation of heat-resistant stereo-complexed structures. The intermolecular hydrophobic interaction hindered the intermolecular mobility by increasing glass transition temperature of ca. 10 °C. Both HBCC and H2ECC have very low critical aggregation concentrations (HBCC: 0.66-1.56 g/L, H2ECC: 0.57-1.07 g/L) and moderate aggregate particle size, which is advantageous for utilization as a drug carrier. The curcumin loaded HBCC and H2ECC aggregates showed nontoxicity, meanwhile, HBCC and H2ECC showed good antibacterial activity against Staphylococcus aureus and Escherichia coli. As a result of these two favorable properties, HBCC and H2ECC could be used as curcumin nanocarriers as well as antibacterial agents.

17.
Zhen Ci Yan Jiu ; 45(4): 264-8, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32333529

RESUMO

OBJECTIVE: To investigate the autonomic nervous mechanism of acupuncture therapy in the treatment of ischemic cardiomyopathy by observing the influence of electroacupuncture (EA) at "Neiguan"(PC6) on the superior cervical cardiac nerve activity and cardiac function in chronic myocardial ischemia (CMI) rats. METHODS: Male SD rats were randomly divided into control, model and EA groups (n=8 in each group). The CMI model was established by ligating the anterior descending branch of the left coronary artery. EA (15 Hz, 1.5 mA) was applied to bilateral PC6 for 20 min, once a day for 28 consecutive days. Cardiac sympathetic nerve electrical activities (CSNEA), electrocardiogram (ECG) of the standard limb lead Ⅱ and ultrasonic cardiogram (UCG) were recorded for observing changes of ST segment height, left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS).. RESULTS: The CSNEA was significantly increased(P<0.001), and the hight of ECG-STⅡ, LVEF and LVFS were considerably decreased in the model group relevant to the control group (P<0.01, P<0.001), while after the intervention, modeling induced increase of CSNEA and decrease of ECG-STⅡ, LVEF and LVFS were obviously suppressed in the EA group in comparison with the model group (P<0.01, P<0.05, P<0.001). CONCLUSION: EA of PC6 can improve cardiac function and myocardial ischemia in CMI rats, which is possibly related to its effect in decreasing cardiac sympathetic hyperactivity.


Assuntos
Eletroacupuntura , Isquemia Miocárdica , Pontos de Acupuntura , Animais , Doença Crônica , Modelos Animais de Doenças , Masculino , Extratos Vegetais , Ratos , Ratos Sprague-Dawley , Volume Sistólico , Função Ventricular Esquerda
18.
Artigo em Inglês | MEDLINE | ID: mdl-32144129

RESUMO

OBJECTIVE: Pancreatic beta cells proliferate in response to metabolic requirements during pregnancy, while failure of this response may cause gestational diabetes. A member of the vascular endothelial growth factor family, placental growth factor (PlGF), typically plays a role in metabolic disorder and pathological circumstance. The expression and function of PlGF in the endocrine pancreas have not been reported and are addressed in the current study. RESEARCH DESIGN AND METHODS: PlGF levels in beta cells were determined by immunostaining or ELISA in purified beta cells in non-pregnant and pregnant adult mice. An adeno-associated virus (AAV) serotype 8 carrying a shRNA for PlGF under the control of a rat insulin promoter (AAV-rat insulin promoter (RIP)-short hairpin small interfering RNA for PlGF (shPlGF)) was prepared and infused into mouse pancreas through the pancreatic duct to specifically knock down PlGF in beta cells, and its effects on beta-cell growth were determined by beta-cell proliferation, beta-cell mass and insulin release. A macrophage-depleting reagent, clodronate, was coapplied into AAV-treated mice to study crosstalk between beta cells and macrophages. RESULTS: PlGF is exclusively produced by beta cells in the adult mouse pancreas. Moreover, PlGF expression in beta cells was significantly increased during pregnancy. Intraductal infusion of AAV-RIP-shPlGF specifically knocked down PlGF in beta cells, resulting in compromised beta-cell proliferation, reduced growth in beta-cell mass and impaired glucose tolerance during pregnancy. Mechanistically, PlGF depletion in beta cells reduced islet infiltration of trophic macrophages, which appeared to be essential for gestational beta-cell growth. CONCLUSIONS: Our study suggests that increased expression of PlGF in beta cells may trigger gestational beta-cell growth through recruited macrophages.

19.
J Phys Chem Lett ; : 2322-2329, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32141759

RESUMO

Li-rich layered oxides (LLOs) are promising cathodes for lithium-ion batteries because of their high energy density provided by anionic redox. Although great improvements have been achieved in electrochemical performance, little attention has been paid to the energy density stability during fast charging. Indeed, LLOs have severe capacity fading and voltage decay especially at a high state of charge (SOC), disabling the application of the frequently used constant-current-constant-voltage mode for fast charging. Herein, we address this problem by manipulating the external electric field and tensile strain induced by lattice expansion effect in nanomaterials under the guidance of theoretical calculations, which indicate that LLOs at high SOC have almost a zero band gap and a low oxygen formation energy. This strategy will weaken polarization, stabilize lattice oxygen, and restrict phase transition simultaneously. Thus, the energy density during fast charging can be highly stabilized. Therefore, it may be of great value for the practical application of layered cathodes.

20.
Int J Infect Dis ; 94: 44-48, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32171952

RESUMO

There is a current worldwide outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; the pathogen called SARS-CoV-2; previously 2019-nCoV), which originated from Wuhan in China and has now spread to 6 continents including 66 countries, as of 24:00 on March 2, 2020. Governments are under increased pressure to stop the outbreak from spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak site and from laboratories supporting the investigation. This paper aggregates and consolidates the epidemiology, clinical manifestations, diagnosis, treatments and preventions of this new type of coronavirus.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Betacoronavirus/genética , China/epidemiologia , Surtos de Doenças , Saúde Global , Humanos , Pandemias , Filogenia
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