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•The introduced Mn on Fe2O3 improved the interfacialconductivity and adsorption.•The kinetic degradation rate of BPA was increased by 235 times through Mn-Fe2O3.•Surface active ...complexes, O2− and 1O2 were the main reactive species.•Mn-Fe2O3 could operate continuously in the reactor for 23 days.
Intrinsically inferior electron transfer rate between catalyst and oxidant was considered as a limiting factor to inhibit the catalytic efficiency of peroxymonosulfate (PMS). In this work, the introduction of Mn atoms into iron oxide (Fe2O3) (Mn-Fe2O3) effectively altered the electronic structure of catalyst surface and promoted the adsorption of PMS, which increased the removal rate of Bisphenol A (BPA) by 235 times, with an extensive pH range (3–11). The main active species contained surface active complexes, superoxide radical (O2−), and singlet oxygen (1O2). The reactor unit could operate continuously for 23 days and still maintain a removal rate of more than 95%. In addition, it had good adaptability to actual water bodies and could effectively reduce the toxicity of BPA. This work shed new light on the regulation of the interfacial electron transfer process between catalyst and oxidant.
Oral cancer is 1 of the 6 most common human cancers, with an annual incidence of >300,000 cases worldwide. This study aimed to investigate potential biomarkers in human saliva to facilitate the early ...diagnosis of oral squamous cell carcinoma (OSCC).
Unstimulated whole saliva obtained from OSCC patients (n=30) and apparently healthy individuals (n=30) were assayed with ultra-performance liquid chromatography–mass spectrometry (UPLC–MS) in hydrophilic interaction chromatography mode. The data were analyzed using a nonparametric Mann–Whitney U test, logistic regression, and the receiver operating characteristic (ROC) to evaluate the predictive power of each of 4 biomarkers, or combinations of biomarkers, for OSCC screening.
Four potential salivary biomarkers demonstrated significant differences (P<0.05) in concentrations between patients at stages I–II and the healthy individuals. The area under the curve (AUC) values in control vs OSCC I–II mode based on choline, betaine, pipecolinic acid, and l-carnitine were 0.926, 0.759, 0.994, and 0.708, respectively. Four salivary biomarkers in combination yielded satisfactory accuracy (0.997), sensitivity (100%), and specificity (96.7%) in distinguishing OSCC I–II from control.
Salivary metabolite biomarkers for the early diagnosis of OSCC were verified in this study. The proposed approach is expected to be applied as a potential technique of preclinical screening of OSCC.
•Salivary choline, betaine and pipecolinic acid levels were higher in OSCC.•Low level of salivary l-carnitine correlates with OSCC.•Salivary biomarkers for OSCC early diagnosis were successfully verified.•These biomarkers have important diagnostic clinical value.
Multiple SARS-CoV-2 variants of concern (VOCs) have been emerging and some have been linked to an increase in case numbers globally. However, there is yet a lack of understanding of the molecular ...basis for the interactions between the human ACE2 (hACE2) receptor and these VOCs. Here we examined several VOCs including Alpha, Beta, and Gamma, and demonstrate that five variants receptor-binding domain (RBD) increased binding affinity for hACE2, and four variants pseudoviruses increased entry into susceptible cells. Crystal structures of hACE2-RBD complexes help identify the key residues facilitating changes in hACE2 binding affinity. Additionally, soluble hACE2 protein efficiently prevent most of the variants pseudoviruses. Our findings provide important molecular information and may help the development of novel therapeutic and prophylactic agents targeting these emerging mutants.
The newly-emerging Middle East respiratory syndrome coronavirus （MERS-CoV） can cause severe and fatal acute respiratory disease in humans. Despite global efforts, the potential for an associated ...pandemic in the future cannot be excluded. The development of effective counter-measures is urgent. MERS-CoV-specific anti-viral drugs or vac- cines are not yet available. Using the spike receptor-binding domain of MERS-CoV （MERS-RBD） to immunize mice, we identified two neutralizing monoclonal antibodies （mAbs） 4C2 and 2E6. Both mAbs potently bind to MERS-RBD and block virus entry in vitro with high efficacy. We further investigated their mechanisms of neutralization by crys- tallizing the complex between the Fab fragments and the RBD, and solved the structure of the 4C2 Fab/MERS-RBD complex. The structure showed that 4C2 recognizes an epitope that partially overlaps the receptor-binding footprint in MERS-RBD, thereby interfering with the virus/receptor interactions by both steric hindrance and interface-resi- due competition. 2E6 also blocks receptor binding, and competes with 4C2 for binding to MERS-RBD. Based on the structure, we further humanized 4C2 by preserving only the paratope residues and substituting the remaining amino acids with the counterparts from human immunoglobulins. The humanized 4C2 （4C2h） antibody sustained similar neutralizing activity and biochemical characteristics to the parental mouse antibody. Finally, we showed that 4C2h can significantly abate the virus titers in lungs of Ad5-hCD26-transduced mice infected with MERS-CoV, therefore representing a promising agent for prophylaxis and therapy in clinical settings.
The rapid expansion of the COVID-19 pandemic has made the development of a SARS-CoV-2 vaccine a global health and economic priority. Taking advantage of versatility and rapid development, three ...SARS-CoV-2 mRNA vaccine candidates have entered clinical trials with a two-dose immunization regimen. However, the waning antibody response in convalescent patients after SARS-CoV-2 infection and the emergence of human re-infection have raised widespread concerns about a possible short duration of SARS-CoV-2 vaccine protection. Here, we developed a nucleoside-modified mRNA vaccine in lipid-encapsulated form that encoded the SARS-CoV-2 RBD, termed as mRNA-RBD. A single immunization of mRNA-RBD elicited both robust neutralizing antibody and cellular responses, and conferred a near-complete protection against wild SARS-CoV-2 infection in the lungs of hACE2 transgenic mice. Noticeably, the high levels of neutralizing antibodies in BALB/c mice induced by mRNA-RBD vaccination were maintained for at least 6.5 months and conferred a long-term notable protection for hACE2 transgenic mice against SARS-CoV-2 infection in a sera transfer study. These data demonstrated that a single dose of mRNA-RBD provided long-term protection against SARS-CoV-2 challenge.
Cancer immunotherapy by targeting of immune checkpoint molecules has been a research 'hot-spot' in recent years. Nivolumab, a human monoclonal antibody targeting PD-1, has been widely used clinically ...since 2014. However, the binding mechanism of nivolumab to PD-1 has not yet been shown, despite a recent report describing the complex structure of pembrolizumab/PD-1. It has previously been speculated that PD-1 glycosylation is involved in nivolumab recognition. Here we report the complex structure of nivolumab with PD-1 and evaluate the effects of PD-1 N-glycosylation on the interactions with nivolumab. Structural and functional analyses unexpectedly reveal an N-terminal loop outside the IgV domain of PD-1. This loop is not involved in recognition of PD-L1 but dominates binding to nivolumab, whereas N-glycosylation is not involved in binding at all. Nivolumab binds to a completely different area than pembrolizumab. These results provide the basis for the design of future inhibitory molecules targeting PD-1.
Compared with many chemotherapy and radiotherapy modalities, selective killing of cancer cells is a pivotal feature of cold atmospheric plasma (CAP). Understanding its underlying mechanism will build ...the foundation of CAP‐based cancer treatment. Additionally, we provided forward‐looking thinking to extend the definition of selectivity from conventional cases involving a single‐cell line to a coculture case. Finally, the newly established physically based treatment strategy provides unprecedented visions to realize selectivity beyond the previously established concepts based on reactive species and direct killing effect.
Selective killing of cancer cells by cold atmospheric plasma treatment may be due to multiple factors. At least, the biological impact of reactive species on the cellular membrane and their cross‐membrane diffusion, intracellular antioxidant systems, and redox balance, as well as genome repairing systems need to be considered in terms of their specific expression in cancer cells and normal cells.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading worldwide, causing a global pandemic. Bat-origin RaTG13 is currently the most phylogenetically related virus. Here we ...obtained the complex structure of the RaTG13 receptor binding domain (RBD) with human ACE2 (hACE2) and evaluated binding of RaTG13 RBD to 24 additional ACE2 orthologs. By substituting residues in the RaTG13 RBD with their counterparts in the SARS-CoV-2 RBD, we found that residue 501, the major position found in variants of concern (VOCs) 501Y.V1/V2/V3, plays a key role in determining the potential host range of RaTG13. We also found that SARS-CoV-2 could induce strong cross-reactive antibodies to RaTG13 and identified a SARS-CoV-2 monoclonal antibody (mAb), CB6, that could cross-neutralize RaTG13 pseudovirus. These results elucidate the receptor binding and host adaption mechanisms of RaTG13 and emphasize the importance of continuous surveillance of coronaviruses (CoVs) carried by animal reservoirs to prevent another spillover of CoVs.
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•The complex structure of RaTG13 RBD with hACE2 was determined•Binding of RaTG13 RBD to 24 additional ACE2 orthologs was evaluated•Residue 501 plays a key role in determining the potential host range of RaTG13•SARS-CoV-2 induces strong cross-protective antibodies to RaTG13 RBD
Structural and molecular analysis of the receptor binding domain of RaTG13, a coronavirus phylogenetically closely related to SARS-CoV-2, bound to the human receptor ACE2 as well as ACE2 orthologs in 24 other species provides a framework to understand its host range as well as the basis of antibody cross-reactivity between the two viruses.
Corrosion is the process of damaging materials, and corrosion of metallic materials frequently results in serious consequences. The addition of corrosion inhibitors is the most effective means of ...preventing metal corrosion. Until now, researchers have made unremitting efforts in the research of high-efficiency green corrosion inhibitors, and research on biomass corrosion inhibitors in a class of environmentally friendly corrosion inhibitors is currently quite promising. This work presents the classification of green biomass corrosion inhibitors in detail, including plant-based corrosion inhibitors, amino acid corrosion inhibitors, and biosurfactant corrosion inhibitors, based on the advantages of easy preparation, environmental friendliness, high corrosion inhibition efficiency, and a wide application range of biomass corrosion inhibitors. This work also introduces the preparation methods of biomass corrosion inhibitors, including hydrolysis, enzymatic digestion, the heating reflux method, and microwave extraction. In addition, the corrosion inhibition mechanisms of green biomass corrosion inhibitors, including physical adsorption, chemisorption, and film-forming adsorption, and evaluation methods of biomass corrosion inhibitors are also explicitly described. This study provides valuable insights into the development of green corrosion inhibitors.
Abstract
Omicron SARS-CoV-2 is rapidly spreading worldwide. To delineate the impact of emerging mutations on spike’s properties, we performed systematic structural analyses on apo Omicron spike and ...its complexes with human ACE2 or S309 neutralizing antibody (NAb) by cryo-EM. The Omicron spike preferentially adopts the one-RBD-up conformation both before and after ACE2 binding, which is in sharp contrast to the orchestrated conformational changes to create more up-RBDs upon ACE2 binding as observed in the prototype and other four variants of concern (VOCs). Furthermore, we found that S371L, S373P and S375F substitutions enhance the stability of the one-RBD-up conformation to prevent exposing more up-RBDs triggered by ACE2 binding. The increased stability of the one-RBD-up conformation restricts the accessibility of S304 NAb, which targets a cryptic epitope in the closed conformation, thus facilitating the immune evasion by Omicron. These results expand our understanding of Omicron spike’s conformation, receptor binding and antibody evasion mechanism.
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