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.
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.
Enterovirus 71 (EV71) is one of the major causative agents of outbreaks of hand, foot, and mouth disease or herpangina worldwide. This phase 3 trial was designed to evaluate the efficacy, safety, and ...immunogenicity of an EV71 vaccine.
We conducted a randomized, double-blind, placebo-controlled, multicenter trial in which 10,007 healthy infants and young children (6 to 35 months of age) were randomly assigned in a 1:1 ratio to receive two intramuscular doses of either EV71 vaccine or placebo, 28 days apart. The surveillance period was 12 months. The primary end point was the occurrence of EV71-associated hand, foot, and mouth disease or herpangina.
During the 12-month surveillance period, EV71-associated disease was identified in 0.3% of vaccine recipients (13 of 5041 children) and 2.1% of placebo recipients (106 of 5028 children) in the intention-to-treat cohort. The vaccine efficacy against EV71-associated hand, foot, and mouth disease or herpangina was 94.8% (95% confidence interval CI, 87.2 to 97.9; P<0.001) in this cohort. Vaccine efficacies against EV71-associated hospitalization (0 cases vs. 24 cases) and hand, foot, and mouth disease with neurologic complications (0 cases vs. 8 cases) were both 100% (95% CI, 83.7 to 100 and 42.6 to 100, respectively). Serious adverse events occurred in 111 of 5044 children in the vaccine group (2.2%) and 131 of 5033 children in the placebo group (2.6%). In the immunogenicity subgroup (1291 children), an anti-EV71 immune response was elicited by the two-dose vaccine series in 98.8% of participants at day 56. An anti-EV71 neutralizing antibody titer of 1:16 was associated with protection against EV71-associated hand, foot, and mouth disease or herpangina.
The EV71 vaccine provided protection against EV71-associated hand, foot, and mouth disease or herpangina in infants and young children. (Funded by Sinovac Biotech; ClinicalTrials.gov number, NCT01507857.).
Enterovirus 71 (EV71) is a major cause of hand, foot, and mouth disease in children and may be fatal. A vaccine against EV71 is needed.
We conducted a randomized, double-blind, placebo-controlled ...phase 3 trial involving healthy children 6 to 71 months of age in Guangxi Zhuang Autonomous Region, China. Two doses of an inactivated EV71 vaccine or placebo were administered intramuscularly, with a 4-week interval between doses, and children were monitored for up to 11 months. The primary end point was protection against hand, foot, and mouth disease caused by EV71.
A total of 12,000 children were randomly assigned to receive vaccine or placebo. Serum neutralizing antibodies were assessed in 549 children who received the vaccine. The seroconversion rate was 100% 4 weeks after the two vaccinations, with a geometric mean titer of 170.6. Over the course of two epidemic seasons, the vaccine efficacy was 97.4% (95% confidence interval CI, 92.9 to 99.0) according to the intention-to-treat analysis and 97.3% (95% CI, 92.6 to 99.0) according to the per-protocol analysis. Adverse events, such as fever (which occurred in 41.6% of the participants who received vaccine vs. 35.2% of those who received placebo), were significantly more common in the week after vaccination among children who received the vaccine than among those who received placebo.
The inactivated EV71 vaccine elicited EV71-specific immune responses and protection against EV71-associated hand, foot, and mouth disease. (Funded by the National Basic Research Program and others; ClinicalTrials.gov number, NCT01569581.).
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
+
J
= 1−0, 12 for DCN
J
= 1−0, 51 for DNC
J
= 1−0, 7 for N
2
D
+
J
= 1−0, 20 for DCO
+
J
= 2−1, and 10 for DCN
J
= 2−1. The starless clump candidates with deuterated molecule detections exhibit lower median kinetic temperatures and a narrower H
2
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
+
J
= 1−0 emission demonstrating higher intensity in the deuterated peak region compared to the DCN and DNC
J
= 1−0 emissions. Additionally, the majority of emissions from deuterated molecules and
13
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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