A study on the reasonable dietary trajectory of elderly people in the community and its correlation with body mass index.

Objective: To explore the reasonable dietary trajectory of elderly people in the community and to test the correlation between different dietary trajectories and body mass index (BMI) of the elderly people in the community to provide a reference for these individuals to formulate scientific interventions and cultivate healthy living habits. Methods: The data of The Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2011 to 2018 were used to evaluate the dietary status of elderly people in the community according to their diet, and body mass index was calculated according to height and weight. The latent variable growth mixed (LGMM) model was used to analyze the development trajectory of diet in elderly people, and the multivariate logistic regression model was used to test the relationship between different dietary development trajectories and BMI changes as well as to test the correlation between different dietary trajectories and BMI of the elderly people in the community. Results: The LGMM fit four dietary trajectories of elderly individuals: the continuous reasonable diet group (37.81%), the dietary behavior decline group (28.84%), the continuous unreasonable diet group (20.16%), and the dietary behavior improvement group (13.19%). The results showed that factors including male sex, rural setting, being spouseless, nonformal education status, not being wealthy, living alone, and having tooth loss were more likely to be classified as the "persistently unreasonable diet group" (p < 0.05). The logistic regression results showed that the "continuous reasonable diet group" and the "dietary behavior improvement group" were significantly correlated with the development of obesity to a normal BMI. Conclusion: The dietary behavior of the elderly was significantly correlated with BMI value, and improving the reasonable dietary behavior of the elderly could reduce the high BMI to the normal range, but could not restore the low BMI to the normal range, indicating that reasonable dietary behavior is an important measure to prevent and improve overweight or obesity in the elderly. There is significant heterogeneity in the dietary behavior of the elderly, and community medical staff should identify the risk factors of various dietary behaviors of other groups as soon as possible, and provide corresponding intervention strategies to help them change their poor dietary behaviors and improve their nutritional status.

A systematic review on aquaculture wastewater: Pollutants, impacts, and treatment technology.

Aquaculture is the major way to solve the global food sacrcity. As the global population increases, the demand for aquaculture increases. Fish feed, drugs and chemicals, and metabolic waste or mortalities of aquatic organisms also increase, eventually resulting in the production of a large amount of aquaculture wastewater. These aquaculture discharges contain a variety of pollutants, such as conventional pollutants, organic compounds, heavy metals, and biological contaminants, inducing occupational hazards and risks, food security, the environment pollution. Proper wastewater treatment technologies are required to remove hazardous pollutants for minimizing their impacts on environmental and human health. Recirculating aquaculture systems, some biological and physicochemical methods have been applied to remove some pollutants from the aquaculture wastewater, but their efficiency in removing pollutants still requires to be further improved for achieving zero-waste discharge and ensuring sustainable aquaculture development. Meanwhile, sound regulation and legislation needs to be established for ensuring the normal operation of aquaculture industries and the standard discharge of wastewater. This review aims to provide comprehensive information of aquaculture wastewater for the researchers and promote the healthy development of aquaculture.

Analysis of the liver-gut axis including metabolomics and intestinal flora to determine the protective effects of kiwifruit seed oil on CCl4-induced acute liver injury.

The hepatoprotective effects of kiwifruit seed oil (KSO) were evaluated on acute liver injury (ALI) induced by carbon tetrachloride (CCl4) in vivo. Network pharmacology was used to predict active compounds and targets. Metabolomics and gut microbiota analyses were used to discover the activity mechanism of KSO. KSO improved the liver histological structure, significantly reduced serum proinflammatory cytokine levels, and increased liver antioxidant capacity. The metabolomics analysis showed that KSO may have hepatoprotective effects by controlling metabolites through its participation in signaling pathways like tryptophan metabolism, glycolysis/gluconeogenesis, galactose metabolism, and bile secretion. The gut microbiota analysis demonstrated that KSO improved the composition and quantity of the gut flora. Network pharmacological investigations demonstrated that KSO operated by altering Ptgs2, Nos2, Ppara, Pparg and Serpine1 mRNA levels. All evidence shows that KSO has a hepatoprotective effect, and the mechanism is connected to the regulation of metabolic disorders and intestinal flora.

Role of pterygopalatine ganglion in regulating isoflurane-induced cerebral hyper-perfusion.

Cerebral perfusion is functionally regulated by neural mechanisms in addition to the systemic hemodynamic variation, vascular reactivity and cerebral metabolism. Although anesthesia is generally esteemed to suppress the overall brain neural activity and metabolism, a few inhalation anesthetics, such as isoflurane, can increase cerebral perfusion, thus heightening the risks of higher intracranial pressure, bleeding, and brain edema during surgery. With the aid of laser speckle contrast imaging, we observed a transient yet limited effect of cerebral perfusion enhancement in mice from awake to anesthetized conditions with different concentration of isoflurane. Retrograde and antegrade tracing revealed a higher proportion of parasympathetic control more than sympathetic innervation for the blood vessels. Surprisingly, isoflurane directly activated pterygopalatine ganglion (PPG) explants and induced FOS expression in the cholinergic neurons. Chemogenetic activation of cholinergic PPG neurons reduced isoflurane-related cerebral perfusion. On the contrary, ablation of the cholinergic PPG neurons resulted in further enhancement of cerebral perfusion induced by isoflurane. While blocking muscarinic cholinergic receptors resulted in the overall reduction upon isoflurane stimulation, the blockage of nicotinic cholinergic receptors enhanced the isoflurane-induced cerebral perfusion only when PPG neurons exist. Collectively, these results suggest that PPG play important roles in regulating cerebral perfusion under isoflurane inhalation.

Machine learning and deep learning approaches for enhanced prediction of hERG blockade: a comprehensive QSAR modeling study.

BACKGROUND: Cardiotoxicity is a major cause of drug withdrawal. The hERG channel, regulating ion flow, is pivotal for heart and nervous system function. Its blockade is a concern in drug development. Predicting hERG blockade is essential for identifying cardiac safety issues. Various QSAR models exist, but their performance varies. Ongoing improvements show promise, necessitating continued efforts to enhance accuracy using emerging deep learning algorithms in predicting potential hERG blockade. STUDY DESIGN AND METHOD: Using a large training dataset, six individual QSAR models were developed. Additionally, three ensemble models were constructed. All models were evaluated using 10-fold cross-validations and two external datasets. RESULTS: The 10-fold cross-validations resulted in Mathews correlation coefficient (MCC) values from 0.682 to 0.730, surpassing the best-reported model on the same dataset (0.689). External validations yielded MCC values from 0.520 to 0.715 for the first dataset, exceeding those of previously reported models (0-0.599). For the second dataset, MCC values fell between 0.025 and 0.215, aligning with those of reported models (0.112-0.220). CONCLUSIONS: The developed models can assist the pharmaceutical industry and regulatory agencies in predicting hERG blockage activity, thereby enhancing safety assessments and reducing the risk of adverse cardiac events associated with new drug candidates.

Impacts of rapidly urbanizing watershed comprehensive management on per- and polyfluoroalkyl substances pollution: Based on PFAS "diversity" assessment.

The impact of watershed comprehensive management (WCM) on per- and polyfluoroalkyl substances (PFAS) pollution in rapidly urbanizing areas remains unclear. In a typical rapidly urbanizing watershed of Shenzhen, China, we investigated temporal variations in contamination level, primary source and ecological risk of 50 emerging and legacy PFAS, as well as the replacement trends of emerging PFAS before and after WCM during a six-year sampling campaign. We found that large-scale dredging was a non-negligible factor in abnormally increased PFAS concentrations (6.43 %-456.16 %) during WCM through their release from river sediments. To better characterize the diverse and complex PFAS contamination, a novel pollution assessment method, PFAS "diversity", was adopted based on a modified Shannon-Weiner diversity index and Pielou evenness index, reflecting numbers of PFAS detected and how evenly each PFAS contributed to the total PFAS concentrations at specific sampling sites. Importantly, we found that the Pielou evenness index can indicate and quantify abnormal pollution sources (especially point sources) along the river. The results revealed that WCM did not effectively reduce total PFAS concentrations and diversity in the rapidly urbanizing watershed but obviously improved point source pollution. Furthermore, 6:2 polyfluorinated phosphate diesters and hexafluoropropylene oxide dimer acid (GenX) that posed high ecological risks emerged and the number of sampling sites with high risk increased from 16 to 20 after WCM. Finally, we summarize several important issues related to PFAS contamination during WCM and propose specific countermeasures, such as adopting environmental dredging and reducing the proportion of ecological water replenished by wastewater treatment plant effluent for better control of PFAS pollution. Our study highlighted the limited effectiveness of WCM in mitigating PFAS pollution and the importance of emerging contaminant regulation in rapidly urbanizing watersheds during WCM.

Decoding the κ Opioid Receptor (KOR): Advancements in Structural Understanding and Implications for Opioid Analgesic Development.

The opioid crisis in the United States is a significant public health issue, with a nearly threefold increase in opioid-related fatalities between 1999 and 2014. In response to this crisis, society has made numerous efforts to mitigate its impact. Recent advancements in understanding the structural intricacies of the κ opioid receptor (KOR) have improved our knowledge of how opioids interact with their receptors, triggering downstream signaling pathways that lead to pain relief. This review concentrates on the KOR, offering crucial structural insights into the binding mechanisms of both agonists and antagonists to the receptor. Through comparative analysis of the atomic details of the binding site, distinct interactions specific to agonists and antagonists have been identified. These insights not only enhance our understanding of ligand binding mechanisms but also shed light on potential pathways for developing new opioid analgesics with an improved risk-benefit profile.

Prevention of cyclophosphamide-induced immune suppression by polysaccharides from Apocynum venetum flowers via enhancing immune response, reducing oxidative stress, and regulating gut microbiota in mice.

Introduction: Emerging proof suggests that Apocynum venetum flowers polysaccharide (AVFP) has immunomodulatory effects in vitro. However, the action mechanism of AVFA is still unclear in vivo. The purpose of this study is to probe into the potential mechanism of AVFA in immunosuppressed mice by investigating organ index, cytokine levels, anti-oxidative stress capacity, transcriptomics, and gut microbiota. Methods: Immunocompromised mice induced by cyclophosphamide (CTX) were divided into six groups. The enzyme-labeled method, hematoxylin and eosin, transcriptomics, and high-throughput sequencing were used to detect the regulatory effects of AVFP on immunocompromised mice and the function of AVFP on the concentration of short-chain fatty acids (SCFAs) by high-performance liquid chromatography (HPLC) analysis. The Spearman correlation analysis was used to analyze the correlation between the intestinal microbiota and biochemical indexes. Results: The experimental results illustrated that AVFP has protective effects against CTX-induced immunosuppression in mice by prominently increasing the organ index and levels of anti-inflammatory factors in serum in addition to enhancing the antioxidant capacity of the liver. Meanwhile, it could also signally decrease the level of pro-inflammatory cytokines in serum, the activity of transaminase in serum, and the content of free radicals in the liver, and alleviate the spleen tissue damage induced by CTX. Transcriptomics results discovered that AVFP could play a role in immune regulation by participating in the NF-κB signaling pathway and regulating the immune-related genes Bcl3, Hp, Lbp, Cebpd, Gstp2, and Lcn2. Gut microbiota results illustrated that AVFP could increase the abundance of beneficial bacteria, reduce the abundance of harmful bacteria, and regulate the metabolic function of intestinal microorganisms while dramatically improving the content of SCFAs, modulating immune responses, and improving the host metabolism. The Spearman analysis further evaluated the association between intestinal microbiota and immune-related indicators. Conclusion: These findings demonstrated that AVFP could enhance the immune effects of the immunosuppressed mice and improve the body's ability to resist oxidative stress.

The First Discovery of Spherical Carborane Molecular Ferroelectric Crystals.

Carborane compounds, known for their exceptional thermal stability and non-toxic attributes, have garnered widespread utility in medicine, supramolecular design, coordination/organometallic chemistry, and others. Although there is considerable interest among chemists, the integration of suitable carborane molecules into ferroelectric materials remains a formidable challenge. In this study, we employ the quasi-spherical design strategy to introduce functional groups at the boron vertices of the o-carborane cage, aiming to reduce molecular symmetry. This approach led to the successful synthesis of the pioneering ferroelectric crystals composed of cage-like carboranes: 9-OH-o-carborane (1) and 9-SH-o-carborane (2), which undergo above-room ferroelectric phase transitions (Tc) at approximately 367 K and 347 K. Interestingly, 1 and 2 represent uniaxial and multiaxial ferroelectrics respectively, with 2 exhibiting six polar axes and as many as twelve equivalent polarization directions. As the pioneering instance of carborane ferroelectric crystals, this study introduces a novel structural archetype for molecular ferroelectrics, thereby providing fresh insights into the exploration of molecular ferroelectric crystals with promising applications.

Rice Origin Tracing Technology Based on Fluorescence Spectroscopy and Stoichiometry.

The origin of agricultural products is crucial to their quality and safety. This study explored the differences in chemical composition and structure of rice from different origins using fluorescence detection technology. These differences are mainly affected by climate, environment, geology and other factors. By identifying the fluorescence characteristic absorption peaks of the same rice seed varieties from different origins, and comparing them with known or standard samples, this study aims to authenticate rice, protect brands, and achieve traceability. The study selected the same variety of rice seed planted in different regions of Jilin Province in the same year as samples. Fluorescence spectroscopy was used to collect spectral data, which was preprocessed by normalization, smoothing, and wavelet transformation to remove noise, scattering, and burrs. The processed spectral data was used as input for the long short-term memory (LSTM) model. The study focused on the processing and analysis of rice spectra based on NZ-WT-processed data. To simplify the model, uninformative variable elimination (UVE) and successive projections algorithm (SPA) were used to screen the best wavelengths. These wavelengths were used as input for the support vector machine (SVM) prediction model to achieve efficient and accurate predictions. Within the fluorescence spectral range of 475-525 nm and 665-690 nm, absorption peaks of nicotinamide adenine dinucleotide (NADPH), riboflavin (B2), starch, and protein were observed. The origin tracing prediction model established using SVM exhibited stable performance with a classification accuracy of up to 99.5%.The experiment demonstrated that fluorescence spectroscopy technology has high discrimination accuracy in tracing the origin of rice, providing a new method for rapid identification of rice origin.

BERT-based language model for accurate drug adverse event extraction from social media: implementation, evaluation, and contributions to pharmacovigilance practices.

Introduction: Social media platforms serve as a valuable resource for users to share health-related information, aiding in the monitoring of adverse events linked to medications and treatments in drug safety surveillance. However, extracting drug-related adverse events accurately and efficiently from social media poses challenges in both natural language processing research and the pharmacovigilance domain. Method: Recognizing the lack of detailed implementation and evaluation of Bidirectional Encoder Representations from Transformers (BERT)-based models for drug adverse event extraction on social media, we developed a BERT-based language model tailored to identifying drug adverse events in this context. Our model utilized publicly available labeled adverse event data from the ADE-Corpus-V2. Constructing the BERT-based model involved optimizing key hyperparameters, such as the number of training epochs, batch size, and learning rate. Through ten hold-out evaluations on ADE-Corpus-V2 data and external social media datasets, our model consistently demonstrated high accuracy in drug adverse event detection. Result: The hold-out evaluations resulted in average F1 scores of 0.8575, 0.9049, and 0.9813 for detecting words of adverse events, words in adverse events, and words not in adverse events, respectively. External validation using human-labeled adverse event tweets data from SMM4H further substantiated the effectiveness of our model, yielding F1 scores 0.8127, 0.8068, and 0.9790 for detecting words of adverse events, words in adverse events, and words not in adverse events, respectively. Discussion: This study not only showcases the effectiveness of BERT-based language models in accurately identifying drug-related adverse events in the dynamic landscape of social media data, but also addresses the need for the implementation of a comprehensive study design and evaluation. By doing so, we contribute to the advancement of pharmacovigilance practices and methodologies in the context of emerging information sources like social media.

Strong Homology Between Colonizing and Bloodstream Carbapenem-Resistant Acinetobacter Spp.: Implications for Empiric Antibiotic Therapy in Hematological Patients.

Objective: This study aimed to assess the impact of colonization status on the outcomes of Acinetobacter spp. bloodstream infection (BSI) and investigate the homology and within-host evolution between colonizing and bloodstream carbapenem-resistant Acinetobacter spp. (CRA) to inform antibiotic therapeutic decisions. Methods: We analyzed clinical outcomes of 46 hematological patients with Acinetobacter spp. BSI and performed whole-genome sequencing on the remaining CRA isolates. Results: Among the patients, 39.1% (n=18) had prior Acinetobacter spp. colonization. Colonized patients had higher rates of polymicrobial BSI (50.0% vs 21.4%, P=0.044) and CRA BSI (72.2% vs 17.9%, P<0.001), resulting in elevated inflammatory markers and increased 30-day mortality. Each of the eight pairs of the remaining respiratory colonizing and bloodstream CRA strains belonged to the same genomospecies. Each pair exhibited definitive agreement in at least 21 of the 22 most representative antibiotic susceptibility tests. The minimum spanning tree based on multilocus sequence typing (MLST) and phylogenetic trees based on MLST and single nucleotide polymorphism (SNP) all indicated that each pair shared the same minimum branch. Very few non-synonymous SNPs in genic regions were identified during the transition from respiratory colonization to bloodstream infection, with minimal changes in virulence genes. Homology analysis suggested that CRA BSI originated from colonizing isolates in the respiratory tract. Conclusion: Strict infection control measures are needed to manage Acinetobacter spp. colonisation in hematological patients. Appropriate empirical therapy can be administered for suspected CRA BSI based on the antimicrobial minimum inhibitory concentration of CRA colonising the respiratory tract.

Treatment of neuropathic pain by traditional Chinese medicine: An updated review on their effect and putative mechanisms of action.

Neuropathic pain (NP) is a common chronic pain with heterogeneous clinical features, and consequent lowering of quality of life. Currently, although conventional chemical drugs can effectively manage NP symptoms in the short term, their long-term efficacy is limited, and they come with significant side effects. In this regard, traditional Chinese medicine (TCM) provides a promising avenue for treating NP. Numerous pharmacological and clinical studies have substantiated the effectiveness of TCM with multiple targets and mechanisms. We aimed to outline the characteristics of TCM, including compound prescriptions, single Chinese herbs, active ingredients, and TCM physical therapy, for NP treatment and discussed their efficacy by analyzing the pathogenesis of NP. Various databases, such as PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang database, were searched. We focused on recent research progress in NP treatment by TCM. Finally, we proposed the future challenges and emerging trends in the treatment of NP. TCM demonstrates significant clinical efficacy in NP treatment, employing multi-mechanisms. Drawing from the theory of syndrome differentiation, four types of dialectical treatments for NP by compound TCM prescriptions were introduced: promoting blood circulation and removing blood stasis; promoting blood circulation and promote Qi flow; warming Yang and benefiting Qi; soothing the liver and regulating Qi. Meanwhile, 33 single Chinese herbs and 25 active ingredients were included. In addition, TCM physical therapy (e.g., acupuncture, massage, acupoint injection, and fumigation) also showed good efficacy in NP treatment. TCM, particularly through the use of compound prescriptions and acupuncture, holds bright prospects in treating NP owing to its diverse holistic effects. Nonetheless, the multi-targets of TCM may result in possible disadvantages to NP treatment, and the pharmacological mechanisms of TCM need further evaluation. Here, we provide an overview of NP treatment via TCM, based on the pathogenesis and the potential therapeutic mechanisms, thus providing a reference for further studies.

Evaluation of Rhododendri Mollis Flos and its representative component as a potential analgesic.

Rhododendri Mollis Flos (R. mole Flos), the dried flowers of Rhododendron mole G. Don, have the ability to relieve pain, dispel wind and dampness, and dissolve blood stasis, but they are highly poisonous. The significance of this study is to explore the analgesic application potential of R. mole Flos and its representative component. According to the selected processing methods recorded in ancient literature, the analgesic activities of wine- and vinegar-processed R. mole Flos, as well as the raw product, were evaluated in a writhing test with acetic acid and a formalin-induced pain test. Subsequently, the HPLC-TOP-MS technique was utilized to investigate the changes in active components before and after processing once the variations in activities were confirmed. Based on the results, rhodojaponin VI (RJ-Vl) was chosen for further study. After processing, especially in vinegar, R. mole Flos did not only maintain the anti-nociception but also showed reduced toxicity, and the chemical composition corresponding to these effects also changed significantly. Further investigation of its representative components revealed that RJ-VI has considerable anti-nociceptive activity, particularly in inflammatory pain (0.3 mg/kg) and peripheral neuropathic pain (0.6 mg/kg). Its toxicity was about three times lower than that of rhodojaponin III, which is another representative component of R. mole Flos. Additionally, RJ-VI mildly inhibits several subtypes of voltage-gated sodium channels (IC50 > 200 µM) that are associated with pain or cardiotoxicity. In conclusion, the chemical substances and biological effects of R. mole Flos changed significantly before and after processing, and the representative component RJ-VI has the potential to be developed into an effective analgesic.

Based on Virtual Screening and Simulation Exploring the Mechanism of Plant-Derived Compounds with PINK1 to Postherpetic Neuralgia.

Accumulating evidence strongly supports that PINK1 mutation can mediate mitochondrial autophagy dysfunction in dopaminergic neurons. This study was conducted to determine the role of PINK1 in the pathogenesis of postherpetic neuralgia (PHN) and find new targets for its treatment. A rigorous literature review was conducted to identify 2801 compounds from more than 200 plants in Asia. Virtual screening was used to shortlist the compounds into 20 groups based on their binding energies. MM/PBSA was used to further screen the compound dataset, and vitexin, luteoloside, and 2'-deoxyadenosine-5'-monophosphate were found to have a score of - 59.439, - 52.421, and - 47.544 kcal/mol, respectively. Pain behavioral quantification, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, western blotting, and transmission electron microscopy were used to confirm the effective mechanism. Vitexin had the most significant therapeutic effect on rats with PHN followed by luteoloside; 2'-deoxyadenosine-5'-monophosphate had no significant effect. Our findings suggested that vitexin could alleviate PHN by regulating mitochondrial autophagy through PINK1.

The treatment of petrochemical wastewater via ozone-persulfate coupled catalytic oxidation: mechanism of removal of soluble organic matter.

Petrochemical wastewater contains a variety of organic pollutants. Advanced oxidation processes (AOPs) are used for deep petrochemical wastewater treatment with distinct advantages, including the complete mineralization of organic substances, minimal residual byproducts, and compatibility with biological treatment systems. This work evaluates the effectiveness of three methods, namely, ozone, persulfate, and O3-PMS (ozone-persulfate) processes, which were compared to remove soluble organic matter. The O3-PMS process offered significant advantages in terms of organic matter removal efficiency. This process involves ozone dissolution in an aqueous persulfate solution, producing a more significant amount of hydroxyl radicals in comparison to single AOPs. The production of hydroxyl radicals and the synergistic effect of hydroxyl radicals and persulfate radicals were investigated. In the O3-PMS process, transition metal ions were added to understand the mechanism of the O3-PMS coupled catalytic oxidation system. The results showed that when the ozone concentration was in the range of 5 ~ 25 mg/L, the dosage of persulfate was in the range of 0.01 ~ 0.05 mol/L, the dosage of metal compounds was in the range of 0:0 ~ 2:1, and the reaction time was in the range of 0 ~ 2 h; the optimum chemical oxygen demand (CODCr) and total organic content (TOC) removal effect was achieved under the coupled system with an ozone concentration of 10 mg/L, a persulfate dosage of 0.02 mol/L, a 1:2 dosage ratio of between Fe2+ and Cu2+ compounds, and a reaction time of 2 h. Under optimal reaction conditions, the rates of CODCr and TOC removal reached 70% and 79.3%, respectively. Furthermore, the removal kinetics of the O3-PMS coupled catalytic oxidation system was analyzed to optimize the removal conditions of COD and TOC, and the mechanism regulating the degradation of dissolved organic matter was explored by three-dimensional fluorescence and GC-MS technology. Thus, O3-PMS coupled catalytic oxidation is an effective process for the deep treatment of wastewater. The careful selection of transition metal ions serves as a theoretical foundation for the subsequent preparation of catalysts for the ozone persulfate oxidation system, and this study provides a suitable reference for removing organic matter from petrochemical wastewater.

Key mechanistic features of the trade-off between antibody escape and host cell binding in the SARS-CoV-2 Omicron variant spike proteins.

Since SARS-CoV-2 Omicron variant emerged, it is constantly evolving into multiple sub-variants, including BF.7, BQ.1, BQ.1.1, XBB, XBB.1.5 and the recently emerged BA.2.86 and JN.1. Receptor binding and immune evasion are recognized as two major drivers for evolution of the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein. However, the underlying mechanism of interplay between two factors remains incompletely understood. Herein, we determined the structures of human ACE2 complexed with BF.7, BQ.1, BQ.1.1, XBB and XBB.1.5 RBDs. Based on the ACE2/RBD structures of these sub-variants and a comparison with the known complex structures, we found that R346T substitution in the RBD enhanced ACE2 binding upon an interaction with the residue R493, but not Q493, via a mechanism involving long-range conformation changes. Furthermore, we found that R493Q and F486V exert a balanced impact, through which immune evasion capability was somewhat compromised to achieve an optimal receptor binding. We propose a "two-steps-forward and one-step-backward" model to describe such a compromise between receptor binding affinity and immune evasion during RBD evolution of Omicron sub-variants.

Corrigendum: Pyruvate kinase M2 promotes prostate cancer metastasis through regulating ERK1/2-COX-2 signaling.

[This corrects the article DOI: 10.3389/fonc.2020.544288.].