Owing to their excellent multiplexing ability, high sensitivity, and large dynamic range, immunoassays using surface-enhanced Raman scattering (SERS) as the readout signal have found prosperous ...applications in fields such as disease diagnosis, environmental surveillance, and food safety supervision. Various ever-increasing demands have promoted SERS-based immunoassays from the classical sandwich-type ones to those integrated with fascinating automatic platforms (e.g., test strips and microfluidic chips). As recent years have witnessed impressive progress in SERS immunoassays, we try to comprehensively cover SERS-based immunoassays from their basic working principles to specific applications. Focusing on several basic elements in SERS immunoassays, typical structures of SERS nanoprobes, productive optical spectral encoding strategies, and popular immunoassay platforms are highlighted, followed by their representative biological applications in the last 5 years. Moreover, despite the vast advances achieved to date, SERS immunoassays still suffer from some annoying shortcomings. Thus, proposals on how to improve the SERS immunoassay performance are also discussed, as well as future challenges and perspectives, aiming to give brief and valid guidelines for choosing suitable platforms according to particular applications.
The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We ...report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults.
Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.
In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.
Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.
http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).
Aberrant increases in neuronal network excitability may contribute to cognitive deficits in Alzheimer's disease (AD). However, the mechanisms underlying hyperexcitability of neurons are not fully ...understood. Voltage‐gated sodium channels (VGSC or Nav), which are involved in the formation of excitable cell's action potential and can directly influence the excitability of neural networks, have been implicated in AD‐related abnormal neuronal hyperactivity and higher incidence of spontaneous non‐convulsive seizures. Here, we have shown that the reduction of VGSC α‐subunit Nav1.6 (by injecting adeno‐associated virus (AAV) with short hairpin RNA (shRNA) into the hippocampus) rescues cognitive impairments and attenuates synaptic deficits in APP/PS1 transgenic mice. Concurrently, amyloid plaques in the hippocampus and levels of soluble Aβ are significantly reduced. Interfering with Nav1.6 reduces the transcription level of β‐site APP‐cleaving enzyme 1 (BACE1), which is Aβ‐dependent. In the presence of Aβ oligomers, knockdown of Nav1.6 reduces intracellular calcium overload by suppressing reverse sodium–calcium exchange channel, consequently increasing inactive NFAT1 (the nuclear factor of activated T cells) levels and thus reducing BACE1 transcription. This mechanism leads to a reduction in the levels of Aβ in APP/PS1 transgenic mice, alleviates synaptic loss, improves learning and memory disorders in APP/PS1 mice after downregulating Nav1.6 in the hippocampus. Our study offers a new potential therapeutic strategy to counteract hippocampal hyperexcitability and subsequently rescue cognitive deficits in AD by selective blockade of Nav1.6 overexpression and/or hyperactivity.
In the presence of Aβ oligomers, knockdown of Nav1.6 reduces intracellular calcium overload by suppressing reverse sodium‐calcium exchange channel, consequently increasing inactive NFAT1 (the nuclear factor of activated T cells) levels and thus reducing BACE1 transcription. This mechanism leads to a reduction in the levels of Aβ in APP/PS1 transgenic mice, alleviates synaptic loss, and improves learning and memory disorders in APP/PS1 mice after down‐regulating Nav1.6 in the hippocampus.
Genomic selection is an upgrading form of marker-assisted selection for quantitative traits, and it differs from the traditional marker-assisted selection in that markers in the entire genome are ...used to predict genetic values and the QTL detection step is skipped. Genomic selection holds the promise to be more efficient than the traditional marker-assisted selection for traits controlled by polygenes. Genomic selection for pure breed improvement is based on marker information and thus leads to cost-saving due to early selection before phenotypes are measured. When applied to hybrid breeding, genomic selection is anticipated to be even more efficient because genotypes of hybrids are predetermined by their inbred parents. Hybrid breeding has been an important tool to increase crop productivity. Here we proposed and applied an advanced method to predict hybrid performance, in which a subset of all potential hybrids is used as a training sample to predict trait values of all potential hybrids. The method is called genomic best linear unbiased prediction. The technology applied to hybrids is called genomic hybrid breeding. We used 278 randomly selected hybrids derived from 210 recombinant inbred lines of rice as a training sample and predicted all 21,945 potential hybrids. The average yield of top 100 selection shows a 16% increase compared with the average yield of all potential hybrids. The new strategy of marker-guided prediction of hybrid yields serves as a proof of concept for a new technology that may potentially revolutionize hybrid breeding.
Vehicle path planning is a key issue for car navigation systems. When path planning, considering the time spent at intersections is more in line with the actual situation, so it is of practical ...significance to study the path planning problem take account intersection attributes. In this article, we study the problem in a deterministic network, taking the minimization of travel time from the origin to the destination as the optimization goal. For this purpose, we construct a mathematical model for the problem. This paper proposes a reverse labeling Dijkstra algorithm (RLDA) based on traditional Dijkstra algorithm to solve the problem, it is proved that the correctness of the RLDA algorithm theoretically, and analyze that the RLDA algorithm has a lower polynomial time complexity. Finally, we selected the actual road network as the simulation experiment object to verify the effectiveness of the algorithm searching for the optimal path. And select 10 groups of networks of different sizes and conduct extensive experiments to compare the convergence efficiency and calculation speed between RLDA and PSO, GA, ACO, NNA, OPABRL. The statistical results show that the convergence rate of the RLDA algorithm is better than that of ACO, NNA, and GA. When the number of network nodes is less than 350, the algorithm has the smallest running time.
Recent advances with the type II clustered regularly interspaced short palindromic repeats （CRISPR） system promise an improved approach to genome editing. However, the applicability and efficiency of ...this system in model organisms, such as zebrafish, are little studied. Here, we report that RNA-guided Cas9 nuclease efficiently facilitates genome editing in both mammalian cells and zebrafish embryos in a simple and robust manner. Over 35% of site- specific somatic mutations were found when specific Cas/gRNA was used to target either etsrp, gata4 or gata5 in zebrafish embryos in vivo. The Cas9/gRNA efficiently induced biallelic conversion of etsrp or gata5 in the resulting somatic cells, recapitulating their respective vessel phenotypes in etsrpv11 mutant embryos or cardia bifida phenotypes in fautm236a mutant embryos. Finally, we successfully achieved site-specific insertion of mloxP sequence induced by Cas9/gRNA system in zebrafish embryos. These results demonstrate that the Cas9/gRNA system has the potential of becoming a simple, robust and efficient reverse genetic tool for zebrafish and other model organisms. Together with other genome-engineering technologies, the Cas9 system is promising for applications in biology, agriculture, envi- ronmental studies and medicine.
Ferns are primitive vascular plants with diverse morphologies and structures. Plant anatomical traits and their linkages can reflect adaptation to the environment; however, these remain are still ...poorly understood in ferns. The main objective of this study was to explore whether there was structural coordination among and within organs in fern species. We measured 16 hydraulically related anatomical traits of pinnae, petioles, and roots of 24 representative fern species from the tropical and subtropical forest understory and analyzed trait correlation networks. In addition, we examined phylogenetic signals for the anatomical traits and analyzed co‐evolutionary relationships. These results indicated that stomatal density and all petiole anatomical traits exhibited significant phylogenetic signals. Evolutionary correlations were observed between the tracheid diameter and wall thickness of the petiole and between the water transport capacity of the petiole and stomatal density. Conversely, anatomical traits of roots (e.g., root diameter) showed no phylogenetic signals and were not significantly correlated with those of the pinnae and petioles, indicating a lack of structural coordination between the below‐ and above‐ground organs. Unlike angiosperms, vein density is unrelated to stomatal density or pinna thickness in ferns. As root diameter decreased, the cortex‐to‐stele diameter ratio decreased significantly (enhanced water absorption) in angiosperms but remained unchanged in ferns. These differences lead to different responses of ferns to climate change and improve our knowledge of the water adaptation strategies of ferns.
COVID-19 poses a severe threat worldwide. This study analyzes its propagation and evaluates statistically the effect of mobility restriction policies on the spread of the disease.
We apply a ...variation of the stochastic Susceptible-Infectious-Recovered model to describe the temporal-spatial evolution of the disease across 33 provincial regions in China, where the disease was first identified. We employ Bayesian Markov Chain Monte-Carlo methods to estimate the model and to characterize a dynamic transmission network, which enables us to evaluate the effectiveness of various local and national policies.
The spread of the disease in China was predominantly driven by community transmission within regions, which dropped substantially after local governments imposed various lockdown policies. Further, Hubei was only the epicenter of the early epidemic stage. Secondary epicenters, such as Beijing and Guangdong, had already become established by late January 2020. The transmission from these epicenters substantially declined following the introduction of mobility restrictions across regions.
The spatial transmission network is able to differentiate the effect of the local lockdown policies and the cross-region mobility restrictions. We conclude that both are important policy tools for curbing the disease transmission. The coordination between central and local governments is important in suppressing the spread of infectious diseases.
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