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1.
Environ Sci Technol ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618428

RESUMO

Globally, the consumption of coastal fish is the predominant source of human exposure to methylmercury, a potent neurotoxicant that poses health risks to humans. However, the relative importance of riverine inputs and atmospheric deposition of mercury into coastal oceans remains uncertain owing to a lack of riverine mercury observations. Here, we present comprehensive seasonal observations of riverine mercury and methylmercury loads, including dissolved and particulate phases, to East Asia's coastal oceans, which supply nearly half of the world's seafood products. We found that East Asia's rivers annually exported 95 ± 29 megagrams of mercury to adjacent seas, 3-fold greater than the corresponding atmospheric deposition. Three rivers alone accounted for 71% of East Asia's riverine mercury exports, namely: Yangtze, Yellow, and Pearl rivers. We further conducted a metadata analysis to discuss the mercury burden on seawater and found that riverine export, combined with atmospheric deposition and terrestrial nutrients, quantitatively elevated the levels of total, methylated, and dissolved gaseous mercury in seawater by an order of magnitude. Our observations support that massive amounts of riverine mercury are exported to coastal oceans on a continental scale, intensifying their spread from coastal seawater to the atmosphere, marine sediments, and open oceans. We suggest that the impact of mercury transport along the land-ocean aquatic continuum should be considered in human exposure risk assessments.

2.
Virol J ; 18(1): 203, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635129

RESUMO

BACKGROUND: Chikungunya fever, caused by the Chikungunya virus (CHIKV), has become a major global health concern, causing unexpected large outbreaks in Africa, Asia, Europe, and the Americas. CHIKV is not indigenous to China, and its origin in the country is poorly understood. In particular, there is limited understanding of the recent global spread of CHIKV in the context of the CHIKV epidemic. METHODS: Here we investigated a novel Chikungunya patient who came from Myanmar to China in August, 2019. Direct genome sequencing was performed via combined MinION sequencing and BGISEQ-500 sequencing. A complete CHIKV genome dataset, including 727 CHIKV genomes retrieved from GenBank and the genome sequenced in this study, was constructed. An updated and comprehensive phylogenetic analysis was conducted to understand the virus's origin, evolution, transmission routes and genetic adaptation. RESULTS: All globally distributed CHIKV genomes were divided into West Africa, East/Central/South African and Asian genotypes. The genome sequenced in this study was located in the Indian Ocean lineage, and was closely related to a strain isolated from an Australian patient who returned from Bangladesh in 2017. A comprehensive phylogenetic analysis showed that the Chinese strains mainly originated from the Indian subcontinent and Southeast Asia. Further analyses indicated that the Indian subcontinent and Southeast Asia may act as major hubs for the recent global spread of CHIKV, leading to multiple outbreaks and epidemics. Moreover, we identified 179 distinct sites, including some undescribed sites in the structural and non-structural proteins, which exhibited apparent genetic variations associated with different CHIKV lineages. CONCLUSIONS: Here we report a novel CHIKV isolate from a chikungunya patient who came from Myanmar to China in 2019, and summarize the source and evolution of Chinese CHIKV strains. Our present findings provide a better understanding of the recent global evolution of CHIKV, highlighting the urgent need for strengthened surveillance against viral diversity.

4.
Appl Opt ; 60(21): 6128-6134, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34613276

RESUMO

Based on the vector diffraction theory, this paper investigates the focusing properties of linearly polarized Lorentz-Gaussian vortex beams with sinusoidal phase modulation and discusses the focused light intensity under different parameters in detail. Results show that the focus pattern in the horizontal direction at the focal region can be compressed by increasing the relative Gaussian parameter wx. As the relative Lorentz parameter γy increases, the focus pattern will separate in the vertical direction of the optical field. With the topological charge number m increases, a special tunable optical dark trap focusing mode can be obtained. Through changing the sinusoidal modulation parameter n, the regular trilateral, quadrangle, pentagon, and hexagon shapes of the focusing mode can be correspondingly constructed. Besides, on increasing propagation distance z, the focusing mode in the near focusing region gradually extends outside and always exhibits hexagon-shaped patterns, which reflects that this special focusing mode has a good stability. In addition, the optical gradient force distributions and the field intensity distributions in the longitudinal plane are also investigated to illuminate the applications of these alterable focal patterns. Those novel, to the best of our knowledge, findings may be helpful in applications such as optical manipulation, optical focusing, and imaging.

5.
Rev Sci Instrum ; 92(9): 094704, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598536

RESUMO

In this paper, a Ka-band coaxial transit time oscillator (TTO) with internal extraction is proposed. Particle-in-cell simulation of this oscillator is performed to obtain results as follows: under the conditions of a diode voltage of 459 kV, current of 3.9 kA, and guiding magnetic field of 0.5 T, microwaves with an output power of 0.75 GW and a frequency of 31.4 GHz can be achieved with an efficiency of 42% and a saturation time of nearly 25 ns. Moreover, the asymmetric mode competition is suppressed in the preliminary experiments. The study of a Ka-band TTO aims to extend the working frequency of high power microwave sources to a higher level. Such a device has three merits. First, it implements high power and high efficiency. Second, the internal extraction of the microwave output decreases the over-mode ratio in the microwave extraction region. Third, the over-mode ratio of the internal extraction is smaller compared with the external extraction, which can effectively suppress asymmetric mode competition.

6.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(8): 809-813, 2021 Aug 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34565723

RESUMO

OBJECTIVES: To evaluate the effect of anesthetic drugs on the expression of circadian gene Clock and Bmal1 in the brain of New Zealand rabbits, and to explore their change pattern. METHODS: A total of 90 New Zealand rabbits were randomly divided into 5 groups (n=18 in each group): A normal saline group (1 mL/h saline, group S), a propofol group [600 µg/(kg·min-1) propofol, 1 mL/h, group P], a 10% lipid group (1 mL/h lipid, group F), a dexmedetomidine group [1 µg/(kg·min-1) dexmedetomidine, 1 mL/h, group D), a sevoflurane (SEV) group (2.5% SEV, SEV group). Inhaled and intravenous anesthetic drugs were stopped after 24 h. Experimental animals were killed at 0, 24, and 72 h after anesthesia, and their brain tissues were isolated. Western blotting was performed to measure the Clock and Bmal1 protein expression in the brain of rabbits. RESULTS: At 0 and 24 h after anesthesia, compared with the group S, the levels of Clock and Bmal1 proteins were decreased significantly in the group P, the group D, and the group SEV (all P<0.05). At 72 h after anesthesia, compared with the group S, the levels of Clock and Bmal1 proteins showed no significant changes in the group P, the group D, and the SEV group (all P>0.05). Compared with the group S, the levels of Clock and Bmal1 proteins at all time points showed no significant changes in the group F (all P>0.05). CONCLUSIONS: Anesthetic SEV, propofol, and dexmedetomidine can inhibit the expression of clock gene Clock and Bmal1 protein in the brain fissues of the New Zealand rabbits, and the suppression effect continues for at least 24 h after anesthesia, whereas the suppression decreases significantly at 72 h after anesthesia.


Assuntos
Relógios Circadianos , Propofol , Anestesia Geral , Animais , Encéfalo , Propofol/farmacologia , Coelhos , Sevoflurano
7.
Sci Total Environ ; 803: 150068, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34525735

RESUMO

Phenacetin (PNCT), a common antipyretic and analgesic drug, is often used to treat fever and headache. However, the effect of PNCT on nitrifiers in wastewater treatment processes remains unclear. The practicability of attaining partial nitrification (PN) through inhibitor-PNCT was investigated in this study. The optimal treatment conditions of soaking once for 18 h with 2.50 × 10-3 g PNCT/(g MLSS) were applied to the PN stability experiment. The results showed that ammonia oxidation activity recovered quickly after 3 cycles of operation, while nitrite oxidation activity was suppressed steadily. In addition, average ammonium removal efficiency and nitrite accumulation ratio during 138 cycles could reach 94.94% and 85.38%, respectively. Complimentary DNA high-throughput sequencing and oligotyping analysis showed that the activity of Nitrosomonas would gradually surpass Nitrospira after PNCT treatment only once. The decrease of Nitrospira activity was accompanied by the simplification of oligotypes after PNCT treatment, while Nitrosomonas could adapt to PNCT stress by reducing the differences between oligotypes. Metagenomics revealed that the decrease in the number of NXR in the nitrogen metabolism pathways was the key reason for achieving PN. The potential mechanisms might be that the dominant nitrite-oxidizing bacteria and complete ammonia oxidizers were bio-killed by PNCT.

8.
Nat Commun ; 12(1): 5262, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489456

RESUMO

TFE3-translocation renal cell carcinoma (TFE3-tRCC) is a rare and heterogeneous subtype of kidney cancer with no standard treatment for advanced disease. We describe comprehensive molecular characteristics of 63 untreated primary TFE3-tRCCs based on whole-exome and RNA sequencing. TFE3-tRCC is highly heterogeneous, both clinicopathologically and genotypically. ASPSCR1-TFE3 fusion and several somatic copy number alterations, including the loss of 22q, are associated with aggressive features and poor outcomes. Apart from tumors with MED15-TFE3 fusion, most TFE3-tRCCs exhibit low PD-L1 expression and low T-cell infiltration. Unsupervised transcriptomic analysis reveals five molecular clusters with distinct angiogenesis, stroma, proliferation and KRAS down signatures, which show association with fusion patterns and prognosis. In line with the aggressive nature, the high angiogenesis/stroma/proliferation cluster exclusively consists of tumors with ASPSCR1-TFE3 fusion. Here, we describe the genomic and transcriptomic features of TFE3-tRCC and provide insights into precision medicine for this disease.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Adolescente , Adulto , Idoso , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Criança , Pré-Escolar , Feminino , Regulação Neoplásica da Expressão Gênica , Fusão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Análise de Sequência de RNA , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Sequenciamento Completo do Exoma , Adulto Jovem
9.
ACS Nano ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34553906

RESUMO

Chirality involved reactions enable to probe features in the fields of asymmetric synthesis and catalysis, which allow to gain insight into the fundamental mechanisms of topochemically controlled reactions. However, in situ observation of the chirality-associated reaction dynamics with simultaneous structural determination of microscopic features has been lacking. Here, we report the direct visualization of the electron-beam-stimulated reaction dynamics of HgS nanostructures with chiral and achiral morphologies simultaneously in both real and reciprocal space. Under the electron-beam excitation of HgS nanostructures, the formation and evaporation dynamics of Hg nanodroplets were vividly pictured, while the reciprocal space imaging revealed the structural transformation from monocrystalline to polycrystalline. Interestingly, such induced changes were size dependent, which were slowed when involving the chirality in the nanostructures. The finding offers a fundamental understanding of topochemically controlled reaction mechanisms and holds promise of tuning asymmetric synthesis for catalysis-related applications.

10.
ACS Appl Mater Interfaces ; 13(38): 45269-45278, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34520159

RESUMO

Rationally constructing single-atom enzymes (SAEs) with superior activity, robust stability, and good biocompatibility is crucial for tumor therapy but still remains a substantial challenge. In this work, we adopt biocompatible carbon dots as the carrier material to load Ru single atoms, achieving Ru SAEs with superior multiple enzyme-like activity and stability. Ru SAEs behave as oxidase, peroxidase, and glutathione oxidase mimics to synchronously catalyze the generation of reactive oxygen species (ROS) and the depletion of glutathione, thus amplifying the ROS damage and finally causing the death of cancer cells. Notably, Ru SAEs exhibit excellent peroxidase-like activity with a specific activity of 7.5 U/mg, which surpasses most of the reported SAEs and is 20 times higher than that of Ru/C. Theoretical results reveal that the electrons of the Ru 4d orbital in Ru SAEs are transferred to O atoms in H2O2 and then efficiently activate H2O2 to produce •OH. Our work may provide some inspiration for the design of SAEs for cancer therapy.

11.
Biofactors ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34570919

RESUMO

Trimethyltin chloride (TMT) is a stabilizer for polyvinyl chloride plastics that causes serious health hazards in nontarget organisms. Melatonin (MT) exhibits powerful protective effects in cardiac diseases. As a new environmental pollutant, TMT-induced cardiotoxicity and the protective effects of MT remain unclear. To explore this, the mice were treated with TMT (2.8 mg/kg) and/or MT (10 mg/kg) for 7 days. Firstly, the histopathological and ultrastructural evaluation showed that TMT induced cardiac damage, tumescent rupture and nuclear pyknosis. Moreover, TMT elevated the expressions of pyroptosis genes NLRP3, ASC and Cas1 and inflammation factors IL-6, IL-17 and TNFα. Secondly, TMT reduced antioxidant enzymes (GSH, CAT and T-AOC) via decreasing the expression of genes associated with the Keap1-Nrf2/ARE pathway to increase oxidative stress. Thirdly, TMT decreased the expression of genes associated with the ARE-driven drug metabolizing enzymes (DMEs), including Akr7a3, Akr1b8, and Akr1b10. Besides, TMT upregulated the mRNA expression of nuclear Xenobiotic metabolism on cytochrome P450s enzymes via increasing the expression of CAR, PXP, and AHR genes. Furthermore, MT treatment mitigated the aforementioned adverse changes induced by TMT. Overall, these results demonstrated that TMT caused pyroptosis and inflammation to aggravate cardiac damage via inducing excessive oxidative stress, imbalance of DMEs homeostasis, and nuclear Xenobiotic metabolism disorder, which could be alleviated by MT.

12.
J Hazard Mater ; 423(Pt A): 126866, 2021 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-34482079

RESUMO

Antibiotic resistant bacteria (ARB) and the antibiotic resistance genes (ARGs) dissemination via plasmid-mediated conjugation have attracted considerable attentions. In this research, sulfidated nanoscale zerovalent iron (S-nZVI)/peroxymonosulfate (PMS) and S-nZVI/peroxydisulfate (PDS) process were investigated to inactivate ARB (Escherichia coli DH5α with RP4 plasmid, Pseudomonas. HLS-6 contains sul1 and intI1 on genome DNA sequence). S-nZVI/PMS system showed higher efficiency than S-nZVI/PDS on ARB inactivation. Thus, the optimal condition 28 mg/L S-nZVI coupled with 153.7 mg/L (0.5 mM) PMS was applied to remove both intracellular ARGs (iARGs) and ARB. The oxidative damage of ARB cell was systemically studied by cell viability, intracellular Mg2+ levels, the changes of extracellular and internal structure, integrity of cell walls and membranes and enzymatic activities. S-nZVI/PMS effectively inactivated ARB (~7.32 log) within 15 min. These effects were greatly higher than those achieved individually. Moreover, removal efficiencies of iARGs sul1, intI1 and tetA were 1.52, 1.79 and 1.56 log, respectively. These results revealed that S-nZVI and PMS have a synergistic effect against ARB and iARGs. The regrowth assays illustrated that the ARB were effectively inactivated. By verifying the inhibitory impacts of S-nZVI/PMS treatment on conjugation transfer, this work highlights a promising alternative technique for inhibiting the horizontal gene transfer.

13.
Orthop Surg ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477308

RESUMO

OBJECTIVE: To clarify the morphological, biochemical, and biomechanical effects of peracetic acid-ethanol sterilization processing to human hamstring tendon allografts for different time periods. METHODS: Thirty-two fresh-frozen human hamstring tendon allografts obtained from an allograft supplier were prepared and incubated in peracetic acid-ethanol solution (PES) containing 1% v/v peracetic acid and 24% v/v ethanol. Specimens were randomly classified into four groups according to the PES processing time (untreated as the control group, 30 min as the PES30 group, 120 min as the PES120 group, and 240 min as the PES240group). Light microscopy with hematoxylin-eosin and toluidine blue were performed, along with transmission electron microscopy (TEM) to measure the collagen fibril diameters and their distributions, from which the collagen fibril index (CFI) and mass average diameter (MAD) were calculated. The thermal stability and collagen denaturation were analyzed by differential scanning calorimetry (DSC) and collagen denaturation test by α-chymotrypsin. Cyclic loading and failure testing were applied on five tendons from each group, from which the cyclic creep strain, elastic modulus, maximum stress, maximum strain, and strain energy density were calculated. RESULTS: Tendons in the control, PES30, PES120 groups showed similar regularly aligned collagen fibers in light microscopy images, while the images from the PES240 group revealed relatively disordered and heterogeneous collagen bundles with larger interfiber spaces. TEM analysis showed that the mean diameter (F = 3.09, P = 0.04) was lower in the PES120 group (87.15 ± 4.76 nm) than it was in the control group (99.39 ± 9.19 nm) but not statistically (P = 0.05). Moreover, the CFI value in the PES30 group (65.37 ± 4.14%) was the lowest among groups (all P ≤ 0.01), while no variance existed in density and MAD among groups (F = 2.09, P = 0.13, and F = 0.27, P = 0.85, respectively). The onset temperature (H = 8.74, P = 0.03) and peak temperature (H = 9.97, P = 0.02) were decreased in the PES30 group compared to the control group (P = 0.02 and P = 0.01, respectively), but there were no differences in enthalpy of denaturation among groups (F = 2.20, P = 0.17). The collagen denaturation test revealed lower hydroxyproline concentrations in PES-treated specimens with no statistical differences among groups (H = 8.86, P = 0.07). The maximum stress showed variance (F = 10.52, P < 0.01) that it was higher in PES30 group (68.29 ± 10.86 MPa) compared to the PES120 and the PES240 group, while it was lower in the PES120 group (19.40 ± 4.94 MPa) compared to the control and the PES30 group (all P < 0.05). The strain energy density (F = 7.34, P < 0.01) was over 4 times higher in the PES30 group (7.39 ± 2.51 MPa) than it was in the PES120 group (1.56 ± 0.64 MPa, P < 0.01). CONCLUSION: PES treatment for 30 min has no adverse effect on the properties of human hamstring tendon allografts, longer processing time could not promise better properties preservation.

14.
Small ; 17(39): e2102699, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34396696

RESUMO

g-C3 N4 /CdS heterojunctions are potential photocatalysts for hydrogen production but their traditional type-II configuration generally leads to weak oxidative and reductive activity. How to construct the novel Z-scheme g-C3 N4 /CdS counterparts to address this issue remains a great challenge in this field. In this work, a new direct Z-scheme heterojunction of defective g-C3 N4 /CdS is designed by introducing cyano groups (NC-) as the active bridge sites. Experimental observations in combination with density functional theory (DFT) calculations reveal that the unique electron-withdrawing feature of cyano groups in the defective g-C3 N4 /CdS heterostructure can endow this photocatalyst with numerous advantageous properties including high light absorption ability, strong redox performance, satisfactory charge separation efficiency, and long lifetime of charge carriers. Consequently, the resultant photocatalytic system exhibits more active performance than CdS and g-C3 N4 under visible light and reaches an excellent hydrogen evolution rate of 1809.07 µmol h-1 g-1 , which is 6.09 times higher than pristine g-C3 N4 . Moreover, the defective g-C3 N4 /CdS photocatalyst maintains good stability after 40 h continuous test. This work provides new insights into design and construction of Z-scheme heterojunctions for regulating the visible-light-induced photocatalytic activity for H2 evolution.

15.
Prostate ; 81(15): 1191-1201, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34435696

RESUMO

BACKGROUND: To explore whether metastatic castration-resistant prostate cancer (mCRPC) patients with distinct intraductal carcinoma of the prostate (IDC-P) subtypes respond differently to abiraterone and docetaxel treatment. METHODS: We retrospectively analyzed data of 170 mCRPC patients receiving abiraterone or docetaxel as first-line therapy. PSA response, PSA progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed based on the presence of IDC-P and its subpatterns. RESULTS: IDC-P was confirmed in 91/170 (53.5%) patients. Among them 36/91 (39.6%) and 55/91 (60.4%) harbored IDC-P patterns 1 and 2, respectively. Patients with IDC-P pattern 1 shared similar clinical outcomes to those without IDC-P in both abiraterone and docetaxel treatment. However, against cases without IDC-P or with IDC-P pattern 1, patients with IDC-P pattern 2 had markedly poorer prognosis in either abiraterone (mPSA-PFS: 11.9 vs. 11.1 vs. 6.1 months, p < 0.001; mrPFS: 18.9 vs. 19.4 vs. 9.6 months, p < 0.001) or docetaxel (mPSA-PFS: 6.2 vs. 6.6 vs. 3.0 months, p < 0.001; mrPFS: 15.1 vs. 12.6 vs. 5.5 months, p < 0.001) treatment. For patients without IDC-P, docetaxel had comparable therapeutic efficacy with abiraterone. However, the efficacy of docetaxel was significantly inferior to abiraterone in patients with either IDC-P pattern 1 (mPSA-PFS: 6.6 vs. 11.1 months, p = 0.021; mrPFS: 12.6 vs. 19.4 months, p = 0.027) or pattern 2 (mPSA-PFS: 3.0 vs. 6.1 months, p = 0.003; mrPFS: 5.5 vs. 9.6 months, p = 0.007). CONCLUSION: Compared to docetaxel, abiraterone exhibited better efficacy in patients with IDC-P of either pattern. However, IDC-P pattern 2 responded unsatisfactorily to either abiraterone or docetaxel therapy. Novel therapeutic strategies for IDC-P pattern 2 need further investigations.

17.
ACS Appl Mater Interfaces ; 13(33): 39446-39457, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34387085

RESUMO

Step-scheme (S-scheme) photocatalysts have been proposed for highly efficient charge separation and strong redox activity in the photocatalysis field. Here, we reported a facile strategy to obtain the S-scheme heterojunction composite TiO2/chlorophyll (Chl). The S-scheme heterojunction enables the significant improvement of electron transfer efficiency at the interfacial heterojunction of TiO2/Chl. Also, the lifted conduction band and valence band of TiO2/Chl resulted in more than 1.61 times generation of reactive oxidizing species, compared to that of bare TiO2. In addition, TiO2/Chl was applied as a photocatalytic bactericidal material to fabricate commercial masks for prolonged life span of the mask. The TiO2/Chl-coated mask filter exhibited excellent bactericidal effect on Escherichia coli under light illumination (2.94 × 107 cfu E. coli were killed by 1 cm-2 coated mask filters within illumination of 3 h), while commercial mask filters showed no bactericidal effect. After three circulation-sterilization tests, the TiO2/Chl-made mask filter maintained the initial bactericidal effect, which greatly extended the life span of the mask that presents a promising strategy to alleviate the supply stress of masks.


Assuntos
Antibacterianos/química , Clorofila/química , Nanocompostos/química , Titânio/química , Antibacterianos/farmacologia , Catálise , Escherichia coli/efeitos dos fármacos , Humanos , Luz , Máscaras , Oxirredução , Processos Fotoquímicos , Esterilização/métodos , Nanomedicina Teranóstica
18.
Nat Biomed Eng ; 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34341535

RESUMO

Approximately 11% of monogenic diseases involve nonsense mutations that are caused by premature termination codons. These codons can in principle be read-through via the site-specific incorporation of unnatural amino acids to generate full-length proteins with minimal loss of function. Here we report that aminoacyl-tRNA-synthase-tRNA pairs specific for the desired unnatural amino acids can be used to read through a nonsense mutation in the dystrophin gene. We show partial restoration of dystrophin expression in differentiated primary myoblasts (from a mdx mouse model and a patient with Duchenne muscular dystrophy), and restoration of muscle function in two mouse models: mdx mice, via viral delivery of the engineered tRNA-synthase-tRNA pair intraperitoneally or intramuscularly and of the associated unnatural amino acid intraperitoneally; and mice produced by crossing mdx mice and transgenic mice with a chromosomally integrated pair, via intraperitoneal delivery of the unnatural amino acid. The incorporation of unnatural amino acids to restore endogenous protein expression could be explored for therapeutic use.

19.
Nano Lett ; 21(16): 6882-6890, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34387492

RESUMO

Through its ability to image liquid-phase dynamics at nano/atomic-scale resolution, liquid-cell electron microscopy is essential for a wide range of applications, including wet-chemical synthesis, catalysis, and nanoparticle tracking, for which involved structural features are critical. However, statistical investigations by usual techniques remain challenging because of the difficulty in fabricating substantial liquid cells with appreciable efficiency. Here, we report a general approach for efficiently printing huge numbers of ready-to-use liquid cells (∼9000) within 30 s by electrospinning, with the unique feature of statistical liquid-phase studies requiring only one experimental time slot. Our solution efficiently resolves a complete transition picture of bubble evolution and also the induced nanoparticle motion. We statistically quantify the effect of the electron dose rate on the bubble variation and conclude that the bubble-driven nanoparticle motion is a ballistic-like behavior insignificant to morphological asymmetries. The versatile approach here is critical for statistical research, offering great opportunities in liquid-phase-associated dynamic studies.


Assuntos
Nanopartículas , Catálise , Microscopia Eletrônica , Movimento (Física) , Impressão Tridimensional
20.
Microb Cell Fact ; 20(1): 154, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348711

RESUMO

BACKGROUND: Indigo is a color molecule with a long history of being used as a textile dye. The conventional production methods are facing increasing economy, sustainability and environmental challenges. Therefore, developing a green synthesis method converting renewable feedstocks to indigo using engineered microbes is of great research and application interest. However, the efficiency of the indigo microbial biosynthesis is still low and needs to be improved by proper metabolic engineering strategies. RESULTS: In the present study, we adopted several metabolic engineering strategies to establish an efficient microbial biosynthesis system for converting renewable carbon substrates to indigo. First, a microbial co-culture was developed using two individually engineered E. coli strains to accommodate the indigo biosynthesis pathway, and the balancing of the overall pathway was achieved by manipulating the ratio of co-culture strains harboring different pathway modules. Through carbon source optimization and application of biosensor-assisted cell selection circuit, the indigo production was improved significantly. In addition, the global transcription machinery engineering (gTME) approach was utilized to establish a high-performance co-culture variant to further enhance the indigo production. Through the step-wise modification of the established system, the indigo bioproduction reached 104.3 mg/L, which was 11.4-fold higher than the parental indigo producing strain. CONCLUSION: This work combines modular co-culture engineering, biosensing, and gTME for addressing the challenges of the indigo biosynthesis, which has not been explored before. The findings of this study confirm the effectiveness of the developed approach and offer a new perspective for efficient indigo bioproduction. More broadly, this innovative approach has the potential for wider application in future studies of other valuable biochemicals' biosynthesis.

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