The World Health Organization has declared the outbreak of a novel coronavirus (SARS-CoV-2 or 2019-nCoV) as a global pandemic. However, the mechanisms behind the coronavirus infection are not yet ...fully understood, nor are there any targeted treatments or vaccines. In this study, we identified high-binding-affinity aptamers targeting SARS-CoV-2 RBD, using an ACE2 competition-based aptamer selection strategy and a machine learning screening algorithm. The K d values of the optimized CoV2-RBD-1C and CoV2-RBD-4C aptamers against RBD were 5.8 nM and 19.9 nM, respectively. Simulated interaction modeling, along with competitive experiments, suggests that two aptamers may have partially identical binding sites at ACE2 on SARS-CoV-2 RBD. These aptamers present an opportunity for generating new probes for recognition of SARS-CoV-2 and could provide assistance in the diagnosis and treatment of SARS-CoV-2 while providing a new tool for in-depth study of the mechanisms behind the coronavirus infection.
The Anthropocene is defined by human‐driven environmental change, with one consequence being the modern dramatic decline in biodiversity globally. This is especially worrisome given the ...long‐acknowledged causal linkage between biodiversity and ecosystem functioning and the delivery of ecosystem services. However, the exact mechanisms driving biodiversity–ecosystem function (BEF) relationships remain unclear, specifically the linkages between species differences, measured by trait and phylogenetic distances, and how interactions, such as competitive inequality and stable coexistence via niche partitioning, influence these relationships. Using complementary plant biodiversity experiments, a synthetic‐assembled one that combined species in different phylogenetic distance treatments with a semi‐natural functional group removal experiment, we assessed how species differences influence the mechanisms underpinning BEF relationships. We calculated the net biodiversity effect (ΔY) of biomass production and partitioned it into two additive parts: the complementarity and selection effects at species and functional group level to test how phylogenetic diversity and functional diversity capture the influences of the complementarity and selection effects. For both experiments, we found that phylogenetic and functional diversity explained biodiversity effects through similar mechanisms, with a positive relationship with the complementarity effect, and a negative relationship with the selection effect. However, we found that the selection effect was best predicted by a negative relationship with functional dispersion (FDis) of height where the selection effect was strongest in plots with similarly tall species and weakest with a greater diversity of heights, while higher complementary effects were best explained by increasing phylogenetic diversity (i.e. high MPDa). Our work revealed that the mechanisms underpinning biodiversity–ecosystem function relationships are dependent on species differences and how these differences influence competitive inequalities and niche differences.
Tumor‐derived exosomal proteins have emerged as promising biomarkers for cancer diagnosis, but the quantitation accuracy is hindered by large numbers of normal cell‐derived exosomes. Herein, we ...developed a dual‐target‐specific aptamer recognition activated in situ connection system on exosome membrane combined with droplet digital PCR (ddPCR) (TRACER) for quantitation of tumor‐derived exosomal PD‐L1 (Exo‐PD‐L1). Leveraging the high binding affinity of aptamers, excellent selectivity of dual‐aptamer recognition, and the high sensitivity of ddPCR, this method exhibits significant sensitivity and selectivity for tracing tumor‐derived Exo‐PD‐L1 in a wash‐free manner. Due to the excellent sensitivity, the level of tumor‐derived Exo‐PD‐L1 detected by TRACER can distinguish cancer patients from healthy donors, and for the first time was identified as a more reliable tumor diagnostic marker than total Exo‐PD‐L1. The TRACER strategy holds great potential for converting exosomes into reliable clinical indicators and exploring the biological functions of exosomes.
We developed a dual‐target‐specific aptamer recognition system combined with droplet digital PCR for precise quantitative analysis of exosomal PD‐L1 (Exo‐PD‐L1). This method can distinguish tumor‐derived from non‐tumor‐derived Exo‐PD‐L1, holding great potential for the analysis of exosome subtypes and offering unprecedented opportunities for the study of the biological functions of exosomes and their conversion into reliable clinical indicators.
Circulating tumor cell (CTC)‐enrichment by using aptamers has a number of advantages, but the issue of compromised binding affinities and stabilities in real samples hinders its wide applications. ...Inspired by the high efficiency of the prey mechanism of the octopus, we engineered a deterministic lateral displacement (DLD)‐patterned microfluidic chip modified with multivalent aptamer‐functionalized nanospheres (AP‐Octopus‐Chip) to enhance capture efficiency. The multivalent aptamer–antigen binding efficiency improves 100‐fold and the capture efficiency is enhanced more than 300 % compared with a monovalent aptamer‐modified chip. Moreover, the captured cancer cells can be released through a thiol exchange reaction with up to 80 % efficiency and 96 % viability, which is fully compatible with downstream mutation detection and CTC culture. Using the chip, we were able to find CTCs in all cancer samples analyzed.
Octopus chip cell capture: Inspired by the high efficiency of the prey mechanism of the octopus, an aptamer‐tailed octopus chip (AP‐Octopus‐Chip) for CTC enrichment was developed. The design of the chip and the high binding affinity of the multivalent structures against the target cells significantly improved the CTC capture efficiency and enrichment. The enriched cancer cells can be released through a thiol exchange reaction, which is fully compatible with downstream mutation detection and CTC culture.
Immunotherapy has revolutionized cancer treatment, but its efficacy is severely hindered by the lack of effective predictors. Herein, we developed a homogeneous, low‐volume, efficient, and sensitive ...exosomal programmed death‐ligand 1 (PD‐L1, a type of transmembrane protein) quantitation method for cancer diagnosis and immunotherapy response prediction (HOLMES‐ExoPD‐L1). The method combines a newly evolved aptamer that efficiently binds to PD‐L1 with less hindrance by antigen glycosylation than antibody, and homogeneous thermophoresis with a rapid binding kinetic. As a result, HOLMES‐ExoPD‐L1 is higher in sensitivity, more rapid in reaction time, and easier to operate than existing enzyme‐linked immunosorbent assay (ELISA)‐based methods. As a consequence of an outstanding improvement of sensitivity, the level of circulating exosomal PD‐L1 detected by HOLMES‐ExoPD‐L1 can effectively distinguish cancer patients from healthy volunteers, and for the first time was found to correlate positively with the metastasis of adenocarcinoma. Overall, HOLMES‐ExoPD‐L1 brings a fresh approach to exosomal PD‐L1 quantitation, offering unprecedented potential for early cancer diagnosis and immunotherapy response prediction.
An aptamer‐induced thermophoresis quantitation of exosomal programmed death‐ligand 1 (PD‐L1, a transmembrane protein) was developed, which integrates effective recognition of aptamer and homogeneous thermophoresis. The facile technique is more sensitive and efficient than the current enzyme‐linked immunosorbent assay (ELISA)‐based methods. Translation of the method into standard clinical practice for immunotherapy prediction and monitoring is anticipated.
The COVID‐19 pandemic caused by SARS‐CoV‐2 is threating global health. Inhibiting interaction of the receptor‐binding domain of SARS‐CoV‐2 S protein (SRBD) and human ACE2 receptor is a promising ...treatment strategy. However, SARS‐CoV‐2 neutralizing antibodies are compromised by their risk of antibody‐dependent enhancement (ADE) and unfavorably large size for intranasal delivery. To avoid these limitations, we demonstrated an aptamer blocking strategy by engineering aptamers’ binding to the region on SRBD that directly mediates ACE2 receptor engagement, leading to block SARS‐CoV‐2 infection. With aptamer selection against SRBD and molecular docking, aptamer CoV2‐6 was identified and applied to prevent, compete with, and substitute ACE2 from binding to SRBD. CoV2‐6 was further shortened and engineered as a circular bivalent aptamer CoV2‐6C3 (cb‐CoV2‐6C3) to improve the stability, affinity, and inhibition efficacy. cb‐CoV2‐6C3 is stable in serum for more than 12 h and can be stored at room temperature for more than 14 days. Furthermore, cb‐CoV2‐6C3 binds to SRBD with high affinity (Kd=0.13 nM) and blocks authentic SARS‐CoV‐2 virus with an IC50 of 0.42 nM.
We propose an aptamer blocking strategy to inhibit SARS‐CoV‐2 infection. With the advantages of small size, rapid kinetics, high stability, sophisticated programmability and high security, our aptamers have great potential as prophylactic and therapeutic agents, which could greatly assist in the intervention of prevailing and emerging infectious diseases other than COVID‐19.
There is mounting evidence from experimental studies that drought and nutrient enrichment can interact to impact the biodiversity and productivity of terrestrial ecosystems. Whether such interactive ...effect influences plant diversity and the temporal stability of community productivity of natural ecosystems is unknown. To fill this knowledge gap, we combined a field survey of plant diversity and soil conditions with remote sensing temporal estimates of primary productivity in grasslands along a natural gradient in northern China. We found that aridity and soil ammonium (NH
4
+
‐N) interacted to influence temporal stability of NDVI. That is, the relationship between ammonium and temporal stability of NDVI shifted from positive to negative due to increased standard deviation of NDVI with increasing aridity. Species richness was not related to temporal stability because it influenced the mean and standard deviation of NDVI proportionally. As a result, soil fertility outweighed the contribution of species richness to temporal stability. Our study demonstrates the synergistic effect of aridity and soil fertility, but not species richness, on temporal stability along a large natural gradient. Predicting how environmental drivers affect diversity and the stable provisioning of ecosystem services in real‐world ecosystems therefore requires a better understanding of the complex interactions among environmental drivers.
Global environmental changes are reducing the diversity and affecting the functioning of natural ecosystems as well as their ability to reliably provide ecosystem functions and services to mankind. ...Many studies have shown that a greater plant diversity can stabilize community productivity against environmental fluctuations. However, most of these studies focused on plant species richness, thus overlooking the potential role of functional traits in stabilizing community productivity against environmental fluctuations. Whether and how functional trait mean and variability influence community stability in response to environmental changes and their relative contributions to community stability are largely unknown. Here, we used a 10‐year experiment to investigate the role of species richness, as well as functional mean and intra‐ and interspecific variability of specific leaf area (SLA) of plants within‐ and among communities in driving community stability in response to nitrogen (N) addition and warming. We found that both N addition and warming reduced the temporal stability of community productivity by reducing species richness and its contribution to species asynchrony and species stability. In contrast, changes in the mean and variability of SLA in response to N addition and warming mitigated the reduction of community stability. Specifically, N addition reduced variation in SLA both by reducing interspecific differences in SLA within communities and differences in mean values of SLA among communities. Warming increased intraspecific differences in SLA among communities, leading to higher species stability that partly buffered the reduction of community stability. Our study demonstrates the role of trait mean and variability in mitigating the reduction of community stability in response to two pervasive global environmental changes. Gaining a deeper understanding of the processes linking global changes and the stability of our ecosystems requires integrating both trait mean values and trait variability.
The gamma coronavirus infectious bronchitis virus (IBV) is known to cause an acute and highly contagious infectious disease in poultry. Here, this study aimed to investigate the impact of virulent or ...avirulent IBV infection on the avian host by conducting proteomics with data-independent acquisition mass spectrometry (DIA-MS) in the kidneys of IBV-infected chickens. The results revealed 267, 489, and 510 differentially expressed proteins (DEPs) in the chicken kidneys at 3, 5, and 7 days postinfection (dpi), respectively, when infected with the GD17/04 strain, which is a highly nephrogenic strain and belongs to the 4/91 genotype. In contrast, the attenuated 4/91 vaccine resulted in the identification of 144, 175, and 258 DEPs at 3, 5, and 7 dpi, respectively. Functional enrichment analyses indicated distinct expression profiles between the 2 IBV strains. Upon GD17/04 infection, metabolic pathways respond initially in the early stage (3 dpi) and immune-related signaling pathways respond in the middle and late stages (5 and 7 dpi). The 4/91 vaccine elicited a completely opposite response compared to the GD17/04 infection. Among all DEPs, 62 immune-related DEPs were focused on and found to be mainly enriched in the type I interferon (IFN-I) signaling pathway and involved in humoral and cellular immunity. Notably, key molecules in the IFN-I signaling pathway including MDA5, LGP2, and TBK1 may serve as regulatory targets of IBV. Overall, this study highlights similarities and discrepancies in the patterns of protein expression at different stages of infection with virulent and avirulent IBV strains, with the IFN-I signaling pathway emerging as a critical response to IBV infection.
The analysis of circulating tumor cells (CTCs) holds great significance for cancer diagnosis, prognosis, and personalized therapy. However, the rarity, vulnerability and heterogeneity of CTCs bring ...daunting technical challenges to their isolation, release and analysis. Recent exciting advances in microfluidics have greatly promoted CTC isolation and analysis due to its merits of precise control of fluid behavior, integration, and automation. Especially, aptamer-based microfluidic chip is considered as promising platform, because aptamers as recognition ligands have inherent superiority in CTC isolation and release for their convenient modification and controllable recognition ability. This review focuses on recent progresses in aptamer-based microfluidics for isolation, release and analysis of CTCs. First, existing CTC-related aptamers and their selection methods are briefly introduced. Strategies for conjugating aptamers onto microfluidic chips are also reviewed. Then, aptamer-based microfluidic chips for CTC isolation, release and analysis are summarized. Finally, future research directions and challenges in this field are discussed.
•CTC analysis is important for cancer diagnosis, prognosis, and personalized therapy.•Microfluidic chip is emerged as powerful CTC analysis platform.•Aptamers are considered as ideal recognition tools for CTC isolation and release.•Aptamer-based microfluidics for CTC isolation, release, and analysis is summarized.
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