Cocirculation and coinfection of multiple respiratory viruses during autumn and winter seasons of 2023 in Beijing, China: A retrospective study.

China experienced severe epidemics of multiple respiratory pathogens in 2023 after lifting "Zero-COVID" policy. The present study aims to investigate the changing circulation and infection patterns of respiratory pathogens in 2023. The 160 436 laboratory results of influenza virus and respiratory syncytial virus (RSV) from February 2020 to December 2023, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from June 2020 to December 2023, Mycoplasma pneumoniae, adenovirus, and human rhinovirus from January 2023 to December 2023 were analyzed. We observed the alternating epidemics of SARS-CoV-2 and influenza A virus (IAV), as well as the out-of-season epidemic of RSV during the spring and summer of 2023. Cocirculation of multiple respiratory pathogens was observed during the autumn and winter of 2023. The susceptible age range of RSV in this winter epidemic (10.5, interquartile range [IQR]: 5-30) was significantly higher than previously (4, IQR: 3-34). The coinfection rate of IAV and RSV in this winter epidemic (0.695%) was significantly higher than that of the last cocirculation period (0.027%) (p < 0.001). Similar trend was also found in the coinfection of IAV and SARS-CoV-2. The present study observed the cocirculation of multiple respiratory pathogens, changing age range of susceptible population, and increasing coinfection rates during the autumn and winter of 2023, in Beijing, China.

Symmetry breaking and chiral amplification in prebiotic ligation reactions.

The single chirality of biological molecules is a signature of life. Yet, rationalizing how single chirality emerged remains a challenging goal1. Research has commonly focused on initial symmetry breaking and subsequent enantioenrichment of monomer building blocks-sugars and amino acids-that compose the genetic polymers RNA and DNA as well as peptides. If these building blocks are only partially enantioenriched, however, stalling of chain growth may occur, whimsically termed in the case of nucleic acids as "the problem of original syn"2. Here, in studying a new prebiotically plausible route to proteinogenic peptides3-5, we discovered that the reaction favours heterochiral ligation (that is, the ligation of L monomers with D monomers). Although this finding seems problematic for the prebiotic emergence of homochiral L-peptides, we demonstrate, paradoxically, that this heterochiral preference provides a mechanism for enantioenrichment in homochiral chains. Symmetry breaking, chiral amplification and chirality transfer processes occur for all reactants and products in multicomponent competitive reactions even when only one of the molecules in the complex mixture exhibits an imbalance in enantiomer concentrations (non-racemic). Solubility considerations rationalize further chemical purification and enhanced chiral amplification. Experimental data and kinetic modelling support this prebiotically plausible mechanism for the emergence of homochiral biological polymers.

Prebiotic access to enantioenriched amino acids via peptide-mediated transamination reactions.

The kinetic resolution of racemic amino acids mediated by dipeptides and pyridoxal provides a prebiotically plausible route to enantioenriched proteinogenic amino acids. The enzymatic transamination cycles that are key to modern biochemical formation of enantiopure amino acids may have evolved from this half of the reversible reaction couple. Kinetic resolution of racemic precursors emerges as a general route to enantioenrichment under prebiotic conditions.

TLR2 regulates Moraxella catarrhalis adhesion to and invasion into alveolar epithelial cells and mediates inflammatory responses.

Moraxella catarrhalis is a major cause of chronic obstructive pulmonary disease. Toll-like receptor 2 (TLR2) plays an important role in the inflammatory response in host respiratory epithelial cells. M. catarrhalis induces an inflammatory immune response in respiratory epithelial cells that is mostly dependent on TLR2. However, the mechanisms by which this pathogen adheres to and invades the respiratory epithelium are not well understood. The present study aimed to reveal the role of TLR2 in M. catarrhalis adhesion to and invasion into alveolar epithelial cells, using molecular techniques. Pretreatment with the TLR2 inhibitor TLR2-IN-C29 enhanced M. catarrhalis adhesion to A549 cells but reduced its invasion, whereas the agonist Pam3CSK4 reduced both M. catarrhalis adhesion and invasion into A549 cells. Similarly, M. catarrhalis 73-OR strain adhesion and invasion were significantly reduced in TLR2-/- A549 cells. Moreover, the lung clearance rate of the 73-OR strain was significantly higher in TLR2-/- C57/BL6J mice than in wild-type (WT) mice. Histological analysis showed that inflammatory responses were milder in TLR2-/- C57/BL6J mice than in WT mice, which was confirmed by a decrease in cytokine levels in TLR2-/- C57/BL6J mice. Overall, these results indicate that TLR2 promoted M. catarrhalis adhesion and invasion of A549 cells and lung tissues and mediated inflammatory responses in infected lungs. This study provides important insights into the development of potential therapeutic strategies against M. catarrhalis and TLR2-induced inflammatory responses.

Crescent calculator: A webtool enabling objective decision-making for assessment of IgA nephropathy immune activity throughout the disease course.

IgA nephropathy (IgAN) is an immune-mediated glomerulonephritis, posing a challenge for the long-term management. It is crucial to monitor the disease's activity over the disease course. Crescent lesions have been known as an active lesion associated with immune activity. We aimed to develop the Crescent Calculator to aid clinicians in making timely and well-informed decisions throughout the long-term disease course, such as renal biopsies and immunosuppressive therapy. 1,761 patients with biopsy-proven IgAN were recruited from four medical centers in Zhejiang Province, China. 16.9% presented crescent lesions. UPCR, URBC, eGFR and C4 were independently associated with the crescent lesions. By incorporating these variables, the Crescent Calculator was constructed to estimate the likelihood of crescent lesions. The predictor achieved AUC values of over 0.82 in two independent testing datasets. In addition, to fulfill varied clinical needs, multiple classification modes were established. The Crescent Calculator was developed to estimate the risk of crescent lesions for patients with IgAN, assisting clinicians in making timely, objective, and well-informed decisions regarding the need for renal biopsies and more appropriate use of immunosuppressive therapy in patients with IgAN.

Accelerating the Discovery of Anticancer Peptides through Deep Forest Architecture with Deep Graphical Representation.

Cancer is one of the leading diseases threatening human life and health worldwide. Peptide-based therapies have attracted much attention in recent years. Therefore, the precise prediction of anticancer peptides (ACPs) is crucial for discovering and designing novel cancer treatments. In this study, we proposed a novel machine learning framework (GRDF) that incorporates deep graphical representation and deep forest architecture for identifying ACPs. Specifically, GRDF extracts graphical features based on the physicochemical properties of peptides and integrates their evolutionary information along with binary profiles for constructing models. Moreover, we employ the deep forest algorithm, which adopts a layer-by-layer cascade architecture similar to deep neural networks, enabling excellent performance on small datasets but without complicated tuning of hyperparameters. The experiment shows GRDF exhibits state-of-the-art performance on two elaborate datasets (Set 1 and Set 2), achieving 77.12% accuracy and 77.54% F1-score on Set 1, as well as 94.10% accuracy and 94.15% F1-score on Set 2, exceeding existing ACP prediction methods. Our models exhibit greater robustness than the baseline algorithms commonly used for other sequence analysis tasks. In addition, GRDF is well-interpretable, enabling researchers to better understand the features of peptide sequences. The promising results demonstrate that GRDF is remarkably effective in identifying ACPs. Therefore, the framework presented in this study could assist researchers in facilitating the discovery of anticancer peptides and contribute to developing novel cancer treatments.

Evaluation of Anti-Helicobacter pylori IgG Antibodies for the Detection of Helicobacter pylori Infection in Different Populations.

Serological testing (immunoassay) for Helicobacter pylori (H. pylori) is widely available and inexpensive, and does not require medication modifications before testing. It can also determine the type of infection, which helps with clinical diagnosis and treatment, and guides the use of medication. However, the performance of immunoblotting for the detection of H. pylori infections in different populations has still not been fully evaluated. We performed a retrospective analysis of patients in the Health Examination Center and Outpatient Department, from November 2017 to September 2020, at Peking Union Medical College Hospital. All the subjects were tested with the 13C-urea breath test (13C-UBT) and for IgG antibodies. A total of 1678 participants, including 1377 individuals who had undergone physical examinations, were recruited. The results of the immunoassay were significantly different from those of the 13C-UBT for all the subjects and outpatients (p < 0.001). For the physical examinations of individuals, the agreement between the immunoassay and the 13C-UBT was 0.64 (95%CI: 0.59−0.68; p < 0.001), and the H. pylori immunoassay demonstrated a sensitivity and specificity of 74.24% and 90.45%, respectively, with a positive predictive value of 71.01% and negative predictive value of 91.76%. In addition, in patients with gastric mucosal atrophy or early gastric cancer, antibody typing tests can also detect infected patients with missed UBT. The prevalence of H. pylori in Beijing was 26.8%, and the serological positivity rate for H. pylori in the population of Beijing was about 31.7% (25.1% in the physical examination population). The rate of H. pylori antibody positivity among patients with allergic diseases was 73.5%, which is significantly higher than that of the non-allergic disease population (29.3%, p < 0.001). In conclusion, H. pylori antibody typing testing can be applied as a specific test in the healthy physical examination population, and the test can be performed with the remaining serum during the physical examination.