SARS-CoV-2 Omicron variant has presented significant challenges to current antibodies and vaccines. Herein, we systematically compared the efficacy of 50 human monoclonal antibodies (mAbs), covering ...the seven identified epitope classes of the SARS-CoV-2 RBD, against Omicron sub-variants BA.1, BA.1.1, BA.2, and BA.3. Binding and pseudovirus-based neutralizing assays revealed that 37 of the 50 mAbs lost neutralizing activities, whereas the others displayed variably decreased activities against the four Omicron sub-variants. BA.2 was found to be more sensitive to RBD-5 antibodies than the other sub-variants. Furthermore, a quaternary complex structure of BA.1 RBD with three mAbs showing different neutralizing potencies against Omicron provided a basis for understanding the immune evasion of Omicron sub-variants and revealed the lack of G446S mutation accounting for the sensitivity of BA.2 to RBD-5 mAbs. Our results may guide the application of the available mAbs and facilitate the development of universal therapeutic antibodies and vaccines against COVID-19.
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•Immune escape of 50 human mAbs by Omicron sub-variants was assessed•Omicron sub-variants BA.1, BA.1.1, BA.2, and BA.3 have similar immune evasion spectra•BA.2 is more sensitive to RDB-5 mAbs due to the lack of G446S mutation
The evolution of SARS-CoV-2 variants of concern brings new challenges toward host immunity and protection. Huang et al. tested the neutralization potency of 50 human mAbs against Omicron sub-variants BA.1, BA.1.1, BA.2, and BA.3. Structural analysis of three mAbs provides further insight into the immune evasion capacity of Omicron sub-variants.
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•The designs and applications of nanomaterials based on on-demand and precise strategies for combating bacterial infections are summarized.•The antibacterial mechanisms, features and ...bactericidal performances of various nanomaterials based on on-demand and precise strategies are reviewed.•Current challenges and future outlooks of nanomaterials-mediated on-demand and precise antibacterial therapies are discussed.
Bacterial infection is a series of pathological changes caused by bacteria invading the host and interacting with the body. Nowadays, bacterial infection remains a major public health issue and a severe threat to human life and health. Traditional antibiotic therapy is less effective against biofilms and easily causes bacterial resistance, which has urged the development of a substitute antibacterial strategy. Recently, antibacterial nanomaterials have attracted much attention. However, traditional nanomaterials face some problems of insufficient drug concentration at infectious sites and the toxicity of extravasated drug causes damage to healthy tissues. On the contrary, nanomaterials based on advanced on-demand and precise strategies reduce biological toxicity effectively while improving germicidal efficacy, since these type of nanodrugs have higher spatiotemporal controllability. Currently, some smart stimuli-responsive nanomaterials and targeting nanomaterials have been successfully constructed to achieve on-demand and precise antibacterial therapies. This review focuses on the mechanisms, working principles and antimicrobial properties of diverse nanoparticles based on on-demand and precise strategies. Meanwhile, the strengths and inferiorities of different on-demand and precise strategies have been discussed. Finally, this review concludes with our opinions on the future development directions for exploiting next-generation on-demand and precise antibacterial therapies.
Wound healing is a postharvest characteristic of potato tubers through accumulating suberin and lignin, which could reduce decay and water loss during storage. This study aimed to explore the impact ...and mechanisms of sodium silicate on wound healing of potatoes. After being wounded, “Atlantic” potato tubers were treated with water or 50 mM sodium silicate. The results showed that sodium silicate treatment accelerated the formation of wound healing structures and significantly reduced the weight loss and disease index of tubers. Furthermore, sodium silicate induced the genes expression and enzyme activity of phenylalanine ammonia lyase (PAL), 4-coumarate: coenzyme A ligase (4CL), and cinnamyl alcohol dehydrogenase (CAD) involved in the phenylpropane metabolism, enhancing the synthesis of the main precursors of suberin polyphenolic (SPP) and lignin, such as coniferyl alcohol, sinapyl alcohol, and cinnamyl alcohol. Meanwhile, the gene expression of
StPOD
and
StNOX
was activated, and the production of O
2−
and H
2
O
2
was promoted, which could be used for injury signal transmission and oxidative crosslinking of SPP monomers and lignin precursors. Besides, antimicrobial compounds, total phenolics, and flavonoids were also induced. We suggest that sodium silicate could promote wound healing by inducing the deposition of SPP, lignin, and antimicrobial compounds in potato tubers.
In this study, we demonstrated that the widely used cold atmospheric plasma (CAP) jet could significantly inhibit the growth of melanoma cells using a contactless treatment method, The flow rate of ...helium gas was a key operational parameter to modulate electromagnetic (EM) effect on melanoma cells. Metal sheets with different sizes could be used as a strategy to control the strength of EM effect. More attractive, the EM effect from CAP could penetrate glass/polystyrene barriers as thick as 7 mm. All these discoveries presented the profound non-invasive nature of a physically based CAP treatment, which provided a solid foundation for CAP-based cutaneous/subcutaneous tumor therapy.
The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) is phylogenetically closely related to the bat coronaviruses (BatCoVs) HKU4 and HKU5. However, the evolutionary pathway ...of MERS-CoV is still unclear. A receptor binding domain (RBD) in the MERS-CoV envelope-embedded spike protein specifically engages human CD26 (hCD26) to initiate viral entry. The high sequence identity in the viral spike protein prompted us to investigate if HKU4 and HKU5 can recognize hCD26 for cell entry. We found that HKU4-RBD, but not HKU5-RBD, binds to hCD26, and pseudotyped viruses embedding HKU4 spike can infect cells via hCD26 recognition. The structure of the HKU4-RBD/hCD26 complex revealed a hCD26-binding mode similar overall to that observed for MERS-RBD. HKU4-RBD, however, is less adapted to hCD26 than MERS-RBD, explaining its lower affinity for receptor binding. Our findings support a bat origin for MERS-CoV and indicate the need for surveillance of HKU4-related viruses in bats.
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•The bat coronavirus HKU4 is phylogenetically closely related to MERS-CoV•The BatCoV HKU4, but not HUK5, spike protein binds to the MERS-CoV human receptor hCD26•Virus particles pseudotyped with BatCoV HKU4 spike infect cells by engaging hCD26•HKU4-RBD/hCD26 structure delineates the recognition basis and interaction details
Bat origin has been suggested for the recently identified MERS coronavirus (CoV). Wang et al. provide structural and functional evidence that bat coronavirus HKU4 can utilize the MERS-CoV human receptor CD26 for cell entry. These studies support the possible adaptation of HKU4 coronavirus to infect humans and the need for continued surveillance.
SARS-CoV-2 can infect many domestic animals, including dogs. Herein, we show that dog angiotensin-converting enzyme 2 (dACE2) can bind to the SARS-CoV-2 spike (S) protein receptor binding domain ...(RBD), and that both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells. We solved the crystal structure of RBD in complex with dACE2 and found that the total number of contact residues, contact atoms, hydrogen bonds and salt bridges at the binding interface in this complex are slightly fewer than those in the complex of the RBD and human ACE2 (hACE2). This result is consistent with the fact that the binding affinity of RBD to dACE2 is lower than that of hACE2. We further show that a few important mutations in the RBD binding interface play a pivotal role in the binding affinity of RBD to both dACE2 and hACE2. Our work reveals a molecular basis for cross-species transmission and potential animal spread of SARS-CoV-2, and provides new clues to block the potential transmission chains of this virus.
Cold atmospheric plasma (CAP) is a near room-temperature ionized gas composed of highly reactive species. CAP also generates thermal radiation, ultraviolet radiation, and electromagnetic (EM) waves. ...So far, nearly all biological effects of CAP have relied on the chemical factors in CAP. Here, we first show that the EM emission from CAP can lead to the death of melanoma cells via a transbarrier contactless method. Compared with reactive species, the effect of the physical factors causes much stronger growth inhibition on a reactive species-resistant melanoma cell line B16F10. Such a physically triggered growth inhibition is due to a new cell death type, characterized by the rapid leakage of bulk solutions from the cells, resulting in cytoplasm shrinkage and bubbling on the cell membrane. The physically based CAP-triggered cell death can occur even there is a macroscale gap between the bulk CAP and cells, which includes an air gap (∼8 mm) and a dielectric material of the dish or plate (∼1 mm). Either a too large or a too small gap will inhibit such cell death. The physically triggered cellular pressure may cause the bubbling on cells, which can be inhibited in a hypotonic environment via the extracellular osmotic pressure. This study builds a foundation to use CAP as a physically based noninvasive cancer treatment.
Old age identity is the self-perception of when old age begins, reflects public age values and acceptance of aging. Not all elderly people aged 60 and above identify with their old age status. The ...aging society in the traditional sense may not be "aging". Therefore, redefining old age is crucial. Different from Western countries, China is a country with a long-standing culture of respect for the elderly and filial piety norms, and the influence of the cultural background on the old age identity is worthy of attention.
Data were drawn from the 2014 China Longitudinal Aging Social Survey (CLASS). A total of 7400 participants answered questions about old age identity. Based on old age identity, we obtained two other types of indicators of perceived old age: elderly group identity and aging degree. For the continuous variable old age identity and aging degree, an OLS linear regression model was established. A binary logistic regression model was established for the binary variable elderly group identity.
The average old age identity of Chinese people aged 60 and above is 70 years. Health status, psychological status, behavior, socioeconomic status, and some demographic characteristics significantly affect the old age identity of the Chinese elderly.
The traditional Chinese cultural background of respect for the elderly and the norms of filial piety have an impact on the old age identity of the Chinese elderly through family intergenerational support. The various forms of support provided by children to the elderly can help them achieve a positive age identity-enter old age later, raise the likelihood of identification with non-elderly groups, and reduce aging degree. The number of children of the elderly, the children's economic conditions and care support for grandchildren have negative effects. A positive old age identity can help the elderly improve their self-esteem.
The brain is particularly susceptible to oxidative damage which is a key feature of several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's ...disease. The shuttling of glutathione (GSH) precursors from astrocytes to neurons has been shown to be instrumental for the neuroprotective activity. Here, we revealed that short chain fatty acids (SCFA), which have been related to AD and PD, could promote glutamate-glutamine shuttle to potentially resist oxidative damage in neurons at cellular level. Furthermore, we performed nine-month-long dietary SCFA supplementations in APPswe/PS1dE9 (APP/PS1) mice, and showed that it reshaped the homeostasis of microbiota and alleviated the cognitive impairment by reducing Aβ deposition and tau hyperphosphorylation. Single-cell RNA sequencing analysis of the hippocampus revealed SCFA can enhance astrocyte-neuron communication including glutamate-glutamine shuttle, mainly by acting on astrocyte in vivo. Collectively, our findings indicate that long-term dietary SCFA supplementations at early aging stage can regulate the neuroenergetics to alleviate AD, providing a promising direction for the development of new AD drug.
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•SCFA contribute to the glutamate-glutamine shuttle by acting on glutamine synthetase.•Long-term SCFA diet alleviates cognitive and spatial memory defeat in APP/PS1 mice.•Long-term SCFA diet reduces Aβ deposition and abnormal phosphorylation of tau.•SCFA promote astrocyte-neuron metabolic coupling to reduce oxidative damage.
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