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According to the written records and scores of grain harvest in the official historical documents of the Qing Dynasty in China, the spatial-temporal distribution and the impact caused by the 1759 AD drought in Northwest China were reconstructed, and the response of Chinese society to the drought at that time was summarized. In the spring and summer of 1759, vast areas of northern China suffered from drought, of which that experienced in the northwest region was the most serious. Starting from 27 April 1759, droughts covered Zhili, Shanxi, Shaanxi, and Gansu provinces, and the droughts in Gansu and northern Shaanxi provinces lasted until 23 July 1759. This severe drought caused the worst crop failure in Northwest China during the period 1730–1900. By implementing a series of disaster relief measures, the Qing government managed to ease the adverse societal impact of the drought in the summer of 1760. Among the relief measures, tax reduction and exemption in disaster-stricken areas, grain storage in the northwest region, and bumper agricultural harvests in Henan, Shandong, Jiangsu, and Anhui provinces in 1759 were the main reasons for the rapid recovery from the drought impacts. With better climatic conditions in the 18th century, China had higher agricultural harvest levels in the 18th century than in the 19th century. Favorable financial conditions increased drought relief efforts, which was the background for the greater societal adaptability to the climate disaster of 1759. [ABSTRACT FROM AUTHOR]

Recent studies have shown that DNA methylation is an important epigenetic marker. Two prominent forms are methylation of the C5 position of cytosine and methylation of the C6 position of adenine. Given the vital significance of DNA methylation, investigating the mechanisms that influence protein binding remains a compelling pursuit. This study used molecular dynamics simulations to investigate the binding patterns of R2R3 protein and four differentially methylated DNAs. The alanine scanning combined with interaction entropy method was used to identify key residues that respond to different methylation patterns. The order of protein binding ability to DNA is as follows: unmethylated DNA > A11 methylation (5′-A6mAC-3′) (6m2A system) > A10 methylation (5′-6mAAC-3′) (6m1A system) > both A10 and A11 methylation (5′-6mA6mAC-3′) (6mAA system) > C12 methylation (5′-AA5mC-3′) (5mC system). All methylation systems lead to the sixth α helix (H6) (residues D105 to L116) moving away from the binding interface, and in the 5mC and 6m1A systems, the third α helix (H3) (residues G54 to L65) exhibits a similar trend. When the positively charged amino acids in H3 and H6 move away from the binding interface, their electrostatic and van der Waals interactions with the negatively charged DNA are weakened. Structural changes induced by methylation contributed to the destabilization of the hydrogen bond network near the original binding site, except for the 6m2A system. Moreover, there is a positive correlation between the number of methylated sites and the probability of distorting the DNA structure. Our study explores how different methylation patterns affect binding and structural adaptability, and have implications for drug discovery and understanding diseases related to abnormal methylation. [ABSTRACT FROM AUTHOR]

The Ancient Silk Road has a history of more than 2000 years and gave birth to the diversities of culture between East and West. Climate change may have played a crucial role in this process and in the flourishing and decline of civilizations. In this work, high-resolution temperature reconstructions covering more than 1000 years along the Ancient Silk Road are reviewed, and the main characteristics of temperature and hydroclimatic changes are summarized. Four warm stages occurred that included the 1st–3rd centuries, the late 7th century to the early 11th century, the mid-12th century to the mid-13th century, and since the 20th century, and three cold stages, including the 4th century to the early 7th century, the middle of the 11th century to the early 12th century, and the end of the 13th century to the mid-19th century, occurred. Within these various stages, regional differences existed in amplitudes and starting–ending years of the cold/warm phases. Wetness and dryness variabilities during the Medieval Climate Anomaly (MCA) were greater than during the Little Ice Age in Northwestern China. The climate was dry during the MCA in Central Asia, South Scandinavia, and North-central Europe. In addition, the climate backgrounds of several famous kingdoms flowering and social events that flourished during these times, such as the Roman Empire, the Loulan Kingdom, the Tibetan Kingdom, and the three unprecedented Mongol westward conquests, are discussed. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is characterized by massive cardiomyocytes death and cardiac dysfunction, and effective therapies to achieve cardioprotection are sorely needed. Here we reported that flavin containing monooxygenase 2 (FMO2) level was markedly increased in cardiomyocytes both in ex vivo and in vivo models of ischemia injury. Genetic deletion of FMO2 resulted in reduced cardiomyocyte survival and enhanced cardiac dysfunction, whereas cardiomyocyte-specific FMO2 overexpression exerted a protective effect in infarcted rat hearts. Mechanistically, FMO2 inhibited the activation of endoplasmic reticulum (ER) stress-induced apoptotic proteins, including caspase 12 and C/EBP homologous protein (CHOP), by down-regulating unfolded protein response (UPR) pathway. Furthermore, we identified FMO2 as a chaperone that catalyzed disulfide-bond formation in unfolded/misfolded proteins through its GVSG motif. GVSG-mutated FMO2 failed to catalyze disulfide-bond formation and lost its protection against ER stress and cardiomyocyte death. Finally, we demonstrated the protective effect of FMO2 in human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) model. Collectively, this study highlights FMO2 as a key modulator of oxidative protein folding in cardiomyocytes and underscores its therapeutic potential for treating ischemic heart disease.

Aqueous zinc ion batteries (ZIBs) hold promises as a safer, more cost-effective, and environmental-friendly alternative to lithium-ion batteries, especially for stationary energy storage. Recent advancements in protective anode coatings, which fine-tune zinc ion solvation structure, have yielded significant improvements in the aqueous ZIB performance, addressing dendrite formation and side reactions, thereby prolonging cycle lifetime. Understanding the underlying mechanisms of these coatings as ions sieves is crucial for further optimization and achieving long-term stability, which is a key requirement for practical applications. This concept explores recent developments in ZIB anode coatings from the view of molecular mechanisms and points out future research directions., (© 2024 Wiley-VCH GmbH.)

Convenient and efficient therapeutic agents are urgently needed to block the continued spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, the mechanism for the novel orally targeted SARS-CoV-2 main protease (M pro ) inhibitor S-217622 is revealed through a molecular dynamics simulation. The difference in the movement modes of the S-217622-M pro complex and apo-M pro suggested S-217622 could inhibit the motility intensity of M pro , thus maintaining their stable binding. Subsequent energy calculations showed that the P2 pharmacophore possessed the highest energy contribution among the three pharmacophores of S-217622. Additionally, hot-spot residues H41, M165, C145, E166, and H163 have strong interactions with S-217622. To further investigate the resistance of S-217622 to six mainstream variants, the binding modes of S-217622 with these variants were elucidated. The subtle differences in energy compared to that of the wild type implied that the binding patterns of these systems were similar, and S-217622 still inhibited these variants. We hope this work will provide theoretical insights for optimizing novel targeted M pro drugs.