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The spike (S) protein is the main handle for SARS-CoV-2 to enter host cells via surface angiotensin-converting enzyme 2 (ACE2) receptors. How ACE2 binding activates proteolysis of S protein is unknown. Here, using amide hydrogen–deuterium exchange mass spectrometry and molecular dynamics simulations, we have mapped the S:ACE2 interaction interface and uncovered long-range allosteric propagation of ACE2 binding to sites necessary for host-mediated proteolysis of S protein, critical for viral host entry. Unexpectedly, ACE2 binding enhances dynamics at a distal S1/S2 cleavage site and flanking protease docking site ~27 Å away while dampening dynamics of the stalk hinge (central helix and heptad repeat [HR]) regions ~130 Å away. This highlights that the stalk and proteolysis sites of the S protein are dynamic hotspots in the prefusion state. Our findings provide a dynamics map of the S:ACE2 interface in solution and also offer mechanistic insights into how ACE2 binding is allosterically coupled to distal proteolytic processing sites and viral–host membrane fusion. Thus, protease docking sites flanking the S1/S2 cleavage site represent alternate allosteric hotspot targets for potential therapeutic development.

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The scale and duration of neutralizing antibody responses targeting SARS-CoV-2 viral variants represents a critically important serological parameter that predicts protective immunity for COVID-19. In this study, we describe the development and employment of a new functional assay that measures neutralizing antibodies for SARS-CoV-2 and present longitudinal data illustrating the impact of age, sex and comorbidities on the kinetics and strength of vaccine-induced antibody responses for key variants in an Asian volunteer cohort. We also present an accurate quantitation of serological responses for SARS-CoV-2 that exploits a unique set of in-house, recombinant human monoclonal antibodies targeting the viral Spike and nucleocapsid proteins and demonstrate a reduction in neutralizing antibody titres across all groups 6 months post-vaccination. We also observe a marked reduction in the serological binding activity and neutralizing responses targeting recently newly emerged Omicron variants including XBB 1.5 and highlight a significant increase in cross-protective neutralizing antibody responses following a third dose (boost) of vaccine. These data illustrate how key virological factors such as immune escape mutations combined with host demographic factors such as age and sex of the vaccinated individual influence the strength and duration of cross-protective serological immunity for COVID-19. [ABSTRACT FROM AUTHOR]

The perovskite-type La(0.5+x)Sr(0.5−x)FeO3−δ (x = 0.00, 0.10, 0.20) oxides for the electrocatalytic oxygen reduction reaction (ORR) were synthesized by a facile reaction-EDTA/citric acid mixed complex sol–gel method. The cubic single-phase perovskite structure of the as-prepared oxides is demonstrated using powder X-ray diffraction (XRD). Scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM–EDX), transmission electron microscopy/selected area electron diffraction (TEM–SAED), and X-ray photoelectron spectroscopy (XPS) characterizations were also conducted for the perovskite-type La(0.5+x)Sr(0.5−x)FeO3−δ (x = 0.00, 0.10, 0.20) oxides. Furthermore, the electrochemical ORR properties of the as-prepared oxides in alkaline media were studied, with the oxides exhibiting good electrocatalytic ORR performance. [ABSTRACT FROM AUTHOR]

Fermentation is an important strategy for food preservation, and fermented foods are the result of the joint action of a diverse range of microorganisms that impart a special flavor to the product. Quorum sensing system (QS) is a highly targeted and universal microbial regulation mechanism, which is based on population density and regulates the behavior of multiple gene expressions by sensing the concentration of autoinducers (AI). According to different types of AIs, QS systems are classified into three major categories. The article provided an overview of fermented foods and the three major types of QS systems. The positive effects of QS systems on microbial co-culture, the prevention and control of harmful microorganisms, and the effects on fermented food quality were described. From the perspective of QS, the article broadens the research ideas of microorganisms in fermented foods, and lays the foundation for further improving the application of microorganisms in food production. [ABSTRACT FROM AUTHOR]

Background: Fasting is known to influence the immune functions of leukocytes primarily by regulating their mobilization and redistribution between the bone marrow and the peripheral tissues or circulation, in particular via relocalization of leukocytes back in the bone marrow. However, how the immune system responds to the increased risk of invasion by infectious pathogens with fewer leukocytes in the peripheral blood during fasting intervention remains an open question. Results: We used proteomic, biochemical and flow cytometric tools to evaluate the impact of short-term intensive fasting (STIF), known as beego, on red blood cells by profiling the cells from the STIF subjects before and after 6 days of fasting and 6 days of gradual refeeding. We found that STIF, by triggering the activation of the complement system via the complement receptor on the membrane of red blood cells, boosts fairly sustainable function of red blood cells in immune responses in close relation to various pathogens, including viruses, bacteria and parasites, particularly with the pronounced capacity to defend against SARS-CoV-2, without compromising their oxygen delivery capacity and viability. Conclusion: STIF fosters the immune function of red blood cells and therefore, it may be considered as a nonmedical intervention option for the stronger capacity of red blood cells to combat infectious diseases. Keypoints: STIF fosters the immune response of red blood cells to various pathogens, in particular SARS-CoV-2, via activation of the complement receptor on their membranes. STIF does not compromise the oxygen transport capacity or viability of red blood cells. [ABSTRACT FROM AUTHOR]

Background: Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system. Angiogenesis is a main contributing factor for tumorigenesis. E74-like transcription factor 5 (ELF5) has been verified to participate in the progression of different cancers and can regulate angiogenesis. This study was aimed to explore the functions of ELF5 in RCC. Methods: Bioinformatics tools were used to predict the expression of ELF5 in RCC. RT-qPCR was applied for testing ELF5 expression in RCC cells. Cell behaviors were evaluated by colony formation, CCK-8, and transwell assays. The tube formation assay was used for determining angiogenesis. Methylation-specific PCR (MSP) was utilized for measuring the methylation level of ELF5 in RCC cells. ChIP and luciferase reporter assays were applied for assessing the binding of ELF5 and ubiquitin-specific protease 3 (USP3). Co-IP and GST pull-down were utilized for detecting the interaction of WD40 and tetratricopeptide repeats 1 (WDTC1) and USP3. Ubiquitination level of WDTC1 was determined by ubiquitination assay. Results: ELF5 was lowly expressed in RCC cells and tissues. High expression of ELF5 expression notably suppressed RCC cell proliferative, migratory, and invasive capabilities, and inhibited angiogenesis. The tumor growth in mice was inhibited by ELF5 overexpression. ELF5 was highly methylated in RCC samples, and DNA methyltransferases (DNMTs) can promote hypermethylation level of ELF5 in RCC cells. ELF5 was further proved to transcriptionally activate USP3 in RCC. Moreover, USP3 inhibited WDTC1 ubiquitination. ELF5 can promote USP3-mediated WDTC1 stabilization. Additionally, WDTC1 silencing reversed the functions of ELF5 overexpression on RCC progression. Conclusion: Downregulation of ELF5 due to DNA hypermethylation inhibits RCC development though the USP3/WDTC1axis in RCC. [ABSTRACT FROM AUTHOR]

Despite being a convenient clinical substrate for biomonitoring, saliva's widespread utilization has not yet been realized. The non‐Newtonian, heterogenous, and highly viscous nature of saliva complicate the development of automated fluid handling processes that are vital for accurate diagnoses. Furthermore, conventional saliva processing methods are resource and/or time intensive precluding certain testing capabilities, with these challenges aggravated during a pandemic. The conventional approaches may also alter analyte structure, reducing application opportunities in point‐of‐care diagnostics. To overcome these challenges, we introduce the SHEAR saliva collection device that mechanically processes saliva, in a rapid and resource‐efficient way. We demonstrate the device's impact on reducing saliva's viscosity, improving sample's uniformity, and increasing diagnostic performance of a COVID‐19 rapid antigen test. Additionally, a formal user experience study revealed generally positive comments. SHEAR saliva collection device may support realization of the saliva's potential, particularly in large‐scale and/or resource‐limited settings for global and community diagnostics. [ABSTRACT FROM AUTHOR]

The changing landscape of SARS-CoV-2 Spike protein is linked to the emergence of variants, immune-escape and reduced efficacy of the existing repertoire of anti-viral antibodies. The functional activity of neutralizing antibodies is linked to their quaternary changes occurring as a result of antibody-Spike trimer interactions. Here, we reveal the conformational dynamics and allosteric perturbations linked to binding of novel human antibodies and the viral Spike protein. We identified epitope hotspots, and associated changes in Spike dynamics that distinguish weak, moderate and strong neutralizing antibodies. We show the impact of mutations in Wuhan-Hu-1, Delta, and Omicron variants on differences in the antibody-induced conformational changes in Spike and illustrate how these render certain antibodies ineffective. Antibodies with similar binding affinities may induce destabilizing or stabilizing allosteric effects on Spike, with implications for neutralization efficacy. Our results provide mechanistic insights into the functional modes and synergistic behavior of human antibodies against COVID-19 and may assist in designing effective antiviral strategies. Here, Tulsian et al. identified the effect of biologically relevant full-length IgG binding on the Spike protein from different SARS-CoV-2 variants to comprehensively understand the mechanisms of antibody evasion, towards the development of better antiviral strategies. [ABSTRACT FROM AUTHOR]