Hydrogels underpin many applications in tissue engineering, cell encapsulation, drug delivery and bioelectronics. Methods improving control over gelation mechanisms and patterning are still needed. ...Here we explore a less-known gelation approach relying on sequential electrochemical-chemical-chemical (ECC) reactions. An ionic species and/or molecule in solution is oxidised over a conductive surface at a specific electric potential. The oxidation generates an intermediate species that reacts with a macromolecule, forming a hydrogel at the electrode-electrolyte interface. We introduce potentiostatic control over this process, allowing the selection of gelation reactions and control of hydrogel growth rate. In chitosan and alginate systems, we demonstrate precipitation, covalent and ionic gelation mechanisms. The method can be applied in the polymerisation of hybrid systems consisting of more than one polymer. We demonstrate concomitant deposition of the conductive polymer Poly(3,4-ethylenedioxythiophene) (PEDOT) and alginate. Deposition of the hydrogels occurs in small droplets held between a conductive plate (working electrode, WE), a printing nozzle (counter electrode, CE) and a pseudoreference electrode (reference electrode, RE). We install this setup on a commercial 3D printer to demonstrate patterning of adherent hydrogels on gold and flexible ITO foils. Electro-assisted printing may contribute to the integration of well-defined hydrogels on hybrid electronic-hydrogel devices for bioelectronics applications.
Structurally and genetically, human herpesviruses are among the largest and most complex of viruses. Using cryo-electron microscopy (cryo-EM) with an optimized image reconstruction strategy, we ...report the herpes simplex virus type 2 (HSV-2) capsid structure at 3.1 angstroms, which is built up of about 3000 proteins organized into three types of hexons (central, peripentonal, and edge), pentons, and triplexes. Both hexons and pentons contain the major capsid protein, VP5; hexons also contain a small capsid protein, VP26; and triplexes comprise VP23 and VP19C. Acting as core organizers, VP5 proteins form extensive intermolecular networks, involving multiple disulfide bonds (about 1500 in total) and noncovalent interactions, with VP26 proteins and triplexes that underpin capsid stability and assembly. Conformational adaptations of these proteins induced by their microenvironments lead to 46 different conformers that assemble into a massive quasisymmetric shell, exemplifying the structural and functional complexity of HSV.
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BFBNIB, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK
Potency assays are key to the development, registration, and quality control of biological products. Although previously preferred for clinical relevance, in vivo bioassays have greatly diminished ...with the advent of dependent cell lines as well as due to ethical concerns. However, for some products, the development of in vitro cell-based assay is challenging, or existing method has limitations such as tedious procedure or low sensitivity. The generation of genetically modified (GM) cell line with improved response to the analyte provides a scientific and promising solution. Potency assays based on GM cell lines are currently used for the quality control of biological products including cytokines, hormones, therapeutic antibodies, vaccines and gene therapy products. In this review, we have discussed the general principles of designing and developing GM cells-based potency assays, including identification of cellular signaling pathways and detectable biological effects, generation of responsive cell lines and constitution of test systems, based on the current research progress. In addition, the applications of some novel technologies and the common concerns regarding GM cells have also been discussed. The research presented in this review provides insights for the development and application of novel GM cells-based potency assays for biological products.
•Summarize current progress on genetically modified cells-based potency assays for biological drugs.•Explore general principles of design and development of genetically modified cells-based potency assays.•Discuss concerns on genetically modified cells -based potency assays.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Enterovirus 71 (EV71) is an important cause of hand, foot, and mouth disease, especially in China. In this phase 3 trial involving 10,077 infants and children in China, an EV71 vaccine provided ...protection against EV71-associated disease.
Enterovirus 71 (EV71), an enterovirus that is not associated with poliomyelitis, was one of the major causative agents of outbreaks of hand, foot, and mouth disease or herpangina in Europe,
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Australia,
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and Japan
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between 1972 and 1988, and it has been implicated in a series of outbreaks across the Asia–Pacific region since the 1990s.
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The largest Asia–Pacific epidemic occurred in China in 2008, when approximately 490,000 infections and 126 deaths in infants and young children were reported.
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The vast majority of severe cases and fatal cases occurred in children younger than 3 years of age. EV71 . . .
Enterovirus 71 (EV71), a cause of hand, foot, and mouth disease, may be associated with poliomyelitis-like paralysis. In this report from China, a vaccine was shown to significantly decrease ...EV71-associated illness in children.
Epidemics of hand, foot, and mouth disease in children have emerged recently in Asia and have been caused primarily by enterovirus 71 (EV71) and coxsackievirus A16,
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which typically show two peak epidemic incidences each year, in May and October.
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An important clinical concern regarding hand, foot, and mouth disease is central nervous system injury, which occurs during the disease course in some severe cases and may result in a poor outcome.
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Infection with the EV71 C4 genotype accounts for 40.1 to 55.4% of cases of hand, foot, and mouth disease, with considerable associated mortality, including thousands of deaths . . .
Abstract
Deuterated molecules are valuable probes for investigating the evolution and the kinematics in the earliest stages of star formation. In this study, we conduct a comprehensive investigation ...by performing a single-point survey of 101 starless clump candidates, and carrying out on-the-fly (OTF) observations of 11 selected sources, focusing on deuterated molecular lines using the IRAM 30 m telescope. In the single-point observation, we make 46 detections for DCO
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J
= 1−0, 12 for DCN
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= 1−0, 51 for DNC
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= 1−0, 7 for N
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D
+
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= 1−0, 20 for DCO
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= 2−1, and 10 for DCN
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= 2−1. The starless clump candidates with deuterated molecule detections exhibit lower median kinetic temperatures and a narrower H
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CO (1
(0,1)
−0
(0,0)
) median full width at half maximum compared to those without such detections, while simultaneously displaying similar median values of 1.1 mm intensity, mass, and distance. Furthermore, our OTF observations reveal that deuterated molecules predominantly have peaks near the 1.1 mm continuum peaks, with the DCO
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J
= 1−0 emission demonstrating higher intensity in the deuterated peak region compared to the DCN and DNC
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= 1−0 emissions. Additionally, the majority of emissions from deuterated molecules and
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C isotopologues exhibit peak positions close to those of the 1.1 mm continuum peaks. By analyzing the 20″ × 20″ regions with strongest deuterated emissions in the OTF observations, we estimated deuterated abundances of 0.004−0.045, 0.011−0.040, and 0.004−0.038 for
D
frac
(HCN),
D
frac
(HCO
+
), and
D
frac
(HNC), respectively. The differential detection of deuterated molecular lines in our OTF observations could be attributed to variations in critical densities and formation pathways.
The world has entered the second wave of the COVID-19 pandemic, and its intensity is significantly higher than that of the first wave of early 2020. Many countries or regions have been forced to ...start the second round of lockdowns. To respond rapidly to this global pandemic, dozens of COVID-19 vaccine candidates have been developed and many are undergoing clinical testing. Evaluating and defining effective vaccine candidates for human use is crucial for prioritizing vaccination programs against COVID-19. In this review, we have summarized and analyzed the efficacy, immunogenicity and safety data from clinical reports on different COVID-19 vaccines. We discuss the various guidelines laid out for the development of vaccines and the importance of biological standards for comparing the performance of vaccines. Lastly, we highlight the key remaining challenges, possible strategies for addressing them and the expected improvements in the next generation of COVID-19 vaccines.
COVID-19 vaccines emerging from different platforms differ in efficacy, duration of protection, and side effects. To maximize the benefits of vaccination, we explored the utility of employing a ...heterologous prime-boost strategy in which different combinations of the four types of leading COVID-19 vaccine candidates that are undergoing clinical trials in China were tested in a mouse model. Our results showed that sequential immunization with adenovirus vectored vaccine followed by inactivated/recombinant subunit/mRNA vaccine administration specifically increased levels of neutralizing antibodies and promoted the modulation of antibody responses to predominantly neutralizing antibodies. Moreover, a heterologous prime-boost regimen with an adenovirus vector vaccine also improved Th1-biased T cell responses. Our results provide new ideas for the development and application of COVID-19 vaccines to control the SARS-CoV-2 pandemic.
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