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This article examines an epigraphic strategy deployed by the Ming court (1368–1644) in the aftermath of the 1556 Jiajing earthquake. Focusing on two stelae from Shanxi, one dedicated to the Jiao-Long Spirit and the other to Empress Nüwa, it proposes “epigraphic layering” to describe the purposeful division of roles between a stele’s faces. Each stele’s front carries an authoritative imperial proclamation admonishing the deity, while the back envoys prayer that appeases the deity and consoles the populace. By splitting imperial command and contrition between the two faces, the Ming court could assert cosmic order while simultaneously expressing penitence during the crisis. This dual-voice inscription technique was a creative adaptation of established ritual epigraphy to extraordinary circumstances. The study sheds new light on late imperial Chinese ritual practice, epigraphic communication, and state–temple relations, demonstrating how this dual-voice strategy helped navigate tensions between imperial authority and local faith.

Development of practical deuteration reactions is highly valuable for organic synthesis, analytic chemistry and pharmaceutic chemistry. Deuterodehalogenation of organic chlorides tends to be an attractive strategy but remains a challenging task. We here develop a photocatalytic system consisting of an aryl-amine photocatalyst and a disulfide co-catalyst in the presence of sodium formate as an electron and hydrogen donor. Accordingly, many aryl chlorides, alkyl chlorides, and other halides are converted to deuterated products at room temperature in air (>90 examples, up to 99% D-incorporation). The mechanistic studies reveal that the aryl amine serves as reducing photoredox catalyst to initiate cleavage of the C-Cl bond, at the same time as energy transfer catalyst to induce homolysis of the disulfide for consequent deuterium transfer process. This economic and environmentally-friendly method can be used for site-selective D-labeling of a number of bioactive molecules and direct H/D exchange of some drug molecules. Deuterodehalogenation of organic chlorides is a useful strategy to install deuterium atoms at specific positions, however, it has several drawbacks. In this study, the authors report an organophotocatalytic system consisting of an aryl-amine-based photocatalyst and a common disulfide co-catalyst, for efficient deuteration of a wide range of aryl chlorides, alkyl chlorides and other halides, at room temperature in air.

ELONGATED HYPOCOTYL5 (HY5), a bZIP-type transcription factor, acts as a master regulator that regulates various physiological and biological processes in plants such as photomorphogenesis, root growth, flavonoid biosynthesis and accumulation, nutrient acquisition, and response to abiotic stresses. HY5 is evolutionally conserved in function among various plant species. HY5 acts as a master regulator of light-mediated transcriptional regulatory hub that directly or indirectly controls the transcription of approximately one-third of genes at the whole genome level. The transcription, protein abundance, and activity of HY5 are tightly modulated by a variety of factors through distinct regulatory mechanisms. This review primarily summarizes recent advances on HY5-mediated molecular and physiological processes and regulatory mechanisms on HY5 in the model plant Arabidopsis as well as in crops.

Recent work has made substantial progress in understanding the transitions of random constraint satisfaction problems. In particular, for several of these models, the exact satisfiability threshold has been rigorously determined, confirming predictions of statistical physics. Here we revisit one of these models, random regular k-nae-sat: knowing the satisfiability threshold, it is natural to study, in the satisfiable regime, the number of solutions in a typical instance. We prove here that these solutions have a well-defined free energy (limiting exponential growth rate), with explicit value matching the one-step replica symmetry breaking prediction. The proof develops new techniques for analyzing a certain “survey propagation model” associated to this problem. We believe that these methods may be applicable in a wide class of related problems.

Stem cells can differentiate to diverse cell types in our body, and they hold great promises in both basic research and clinical therapies. For specific stem cell types, distinctive nutritional and signaling components are required to maintain the proliferation capacity and differentiation potential in cell culture. Various vitamins play essential roles in stem cell culture to modulate cell survival, proliferation and differentiation. Besides their common nutritional functions, specific vitamins are recently shown to modulate signal transduction and epigenetics. In this article, we will first review classical vitamin functions in both somatic and stem cell cultures. We will then focus on how stem cells could be modulated by vitamins beyond their nutritional roles. We believe that a better understanding of vitamin functions will significantly benefit stem cell research, and help realize their potentials in regenerative medicine.

Background Health utility measurement is critical for cost-utility analysis (CUA). However, clinical studies often lack direct utility data, and methods of measuring health utility vary across different periods and regions, resulting in missing utility information. Mapping, a method employed to infer utility when direct utility data is absent, has been widely applied in recent years but still faces challenges. This systematic review evaluates the current landscape, trends, and limitations of mapping studies and provides recommendations for improving study design and reporting standards. Methods A literature search was conducted in PubMed, Web of Science, and the HERC Database of Mapping Studies from 2018 to 2024. The study extracted information from the included studies and performed quality assessments based on existing mapping guidelines. Results One hundred thirty-one studies were included, 92 focused on Mapping as the primary objective, five were reviews, 13 focused on methodology, and 21 focused on economic evaluation. The source measure, target measure, and models in mapping functions development remain EORTC-QLQ-C30 ( n  = 13), EQ-5D ( n  = 79), and OLS ( n  = 93). Studies now use larger sample sizes and a higher proportion of response Mapping, and model applications have increased in diversity. However, 32 studies still lack conceptual overlap analysis, and only 16 studies with repeated measurements addressed its issue. Additionally, two studies did not report the region of the sample and value set, while 27 had inconsistencies between the two regions. Conclusions In the last seven years, mapping studies have improved sample size, model application, and result reporting. However, limitations remain in analysing conceptual overlap, ensuring alignment between the sample and value set regions, and processing repeated measurements. To advance the quality of mapping studies, it is necessary to update mapping guidelines and ensure that all mapping functions are developed in compliance with them.

Intrinsically disordered regions (IDRs) play a critical role in phase separation and are essential for the formation of membraneless organelles (MLOs). Mutations within IDRs can disrupt their multivalent interaction networks, altering phase behavior and contributing to various diseases. Therefore, examining the evolutionary constraints of IDRs provides valuable insights into the relationship between protein sequences and phase separation. In this study, we utilized the ESM2 protein language model to map the residue-level mutational tolerance landscapes of IDRs. Our findings reveal that IDRs, particularly those actively participating in phase separation, contain conserved amino acids. This conservation is evident through mutational constraints predicted by ESM2 and supported by direct analyses of multiple sequence alignments. These conserved, disordered amino acids include residues traditionally identified as ‘stickers’ as well as ‘spacers’ and frequently form continuous sequence motifs. The strong conservation, combined with their potential role in phase separation, suggests that these motifs may act as functional units under evolutionary selection to support stable MLO formation. Our findings underscore the insights into phase separation’s molecular grammar made possible through evolutionary analysis enabled by protein language models.

Subretinal fibrosis remains a major obstacle to the management of neovascular age-related macular degeneration. Choroidal pericytes were found to be a significant source of subretinal fibrosis, but the underlying mechanisms of pericyte-myofibroblast transition (PMT) remain largely unknown. The goal of this study was to explore the role and potential mechanisms by which PMT contributes to subretinal fibrosis. Choroidal neovascularization (CNV) was induced by laser photocoagulation in transgenic mice with the collagen1α1-green fluorescent protein (Col1α1-GFP) reporter, and recombinant adeno-associated virus 2 (rAAV2)-mediated TGF-β2 (rAAV2-TGF-β2) was administered intravitreally to further induce PMT. Primary mouse choroidal GFP-positive pericytes were treated with TGF-β2 in combination with siRNAs targeting Smad2/3, the Akt inhibitor MK2206 or the mTOR inhibitor rapamycin to examine cell proliferation, migration, and differentiation into myofibroblasts. The involvement of the Akt/mTOR pathway in PMT in subretinal fibrosis was further investigated in vivo. Intraocular TGF-β2 overexpression induced GFP-positive pericyte infiltration and PMT in subretinal fibrosis, which was mimicked in vitro. Knockdown of Smad2/3 or inhibition of Akt/mTOR decreased cell proliferation, PMT and migration in primary mouse pericytes. Combined inhibition of Smad2/3 and mTOR showed synergistic effects on attenuating α-smooth muscle actin (α-SMA) expression and cell proliferation. In mice with laser-induced CNV, the administration of the Akt/mTOR inhibitors suppressed pericyte proliferation and alleviated the severity of subretinal fibrosis. Our results showed that PMT plays a pivotal role in subretinal fibrosis, which was induced by TGF-β2 through the Smad2/3 and Akt/mTOR pathways. Thus, inhibiting PMT may be a novel strategy for the treatment of subretinal fibrosis.Eye disease: Revealing the mechanisms behind subretinal fibrosisThe identification of a new cell type that plays a crucial role in causing fibrosis under the retina could improve treatment of eye disease. Effective treatments exist for diseases that cause impairment and loss of vision in elderly people, but success can be limited by the development of subretinal fibrosis. Jingfa Zhang at Shanghai Jiao Tong University, China, and co-workers used mice with laser-induced retinal damage to explore how subretinal fibrosis may result from transition of pericytes, multi-functional cells in the capillaries, into myofibroblasts, cells associated with fibrosis. The overexpression of a growth factor called TGF-β2 induced pericytes to infiltrate the subretinal area and pericyte-myofibroblast transition via two signalling pathways. Inhibiting these pathways may help to treat subretinal fibrosis, and one option is the use of inhibitors of AKT/mTOR which may slow the ageing process.

The purpose of this study is to discover and evaluate the feasibility of travel live streaming (TLS) for social media (TikTok). Inspired by the uses and gratifications theory, stimulus-organism-response (S-O-R) model, and the compensatory internet usage model (CIUM), this study develops a theoretical framework of social interaction, telepresence, immersion, user satisfaction, and behavioral intention. The originality of this study is mainly reflected in the innovation of the chosen topic and research results. This is one of the first studies to empirically examine and discuss the immersion and behavioral intentions of users watching travel live streaming. The immersion brings some new meaningful information and extends the application of the ‘S-O-R model’ and ‘the uses and gratifications theory’. This study utilized a quantitative research approach, with data collected online and analyzed from 274 Chinese users. We found that social interaction and telepresence are positively correlated with immersion and user satisfaction. Further, Immersion also positively influences user satisfaction and behavioral intentions. The findings provide valuable insights to users, potential tourists, live streamers, and destination managers. However, there are some limitations to this study. For example, there is a lack of assessment of the anchor persona (looks, personality presentation style, etc.). In addition, there are differences between user-host interactions and user-user interactions, which should be distinguished and studied in more detail in future studies. Plain language summary The emergence of travel live streaming has transformed how people live and travel. This study is among the first to empirically examine and discuss the immersion and behavioral intentions of users watching travel live streaming. Immersion offers new and meaningful insights. Uses and Gratifications Theory is an important communication theory that explains the relationship between users’ needs and satisfaction and is now fully integrated into the study of social media. The emergence of the Compensatory Internet Use Model (CIUM) has deepened our understanding of webcasting, vividly explaining why people become immersed in live travel streams. Additionally, the S-O-R model, which explains the relationship between “stimulus, organism, and response,” has informed the derivation of this study’s model and contributed to the development of a theoretical framework encompassing “social interaction, telepresence, immersion, user satisfaction, and behavioral intention.” A quantitative approach was adopted for this study. Data were collected from 274 Chinese users who watched travel live streaming on TikTok and had not yet visited the destinations featured in the live streams. We found that social interaction and telepresence were positively associated with immersion and user satisfaction. Additionally, immersion positively influenced user satisfaction and behavioral intentions. These findings enhance the understanding of related theories and offer valuable insights for users, potential visitors, and destination managers alike.

An increasing body of research indicates that the circulating microbiome plays a significant role in cancer initiation and progression and the treatment response. The genomic characteristics of circulating microorganisms may influence the tumor immune microenvironment, thereby affecting cancer progression and therapeutic outcomes. However, whether the circulating microbiome can serve as a prognostic biomarker for cervical cancer patients and its mechanistic role in the tumor immune microenvironment still requires further investigation. Univariate, Lasso, and multivariate Cox regression analyses were utilized to identify the circulating microbial signatures associated with overall survival (OS) in patients with cervical cancer. A circulating Microbial Abundance Prognostic Score (MAPS) model was constructed based on these findings. A nomogram that integrated clinical features and MAPSs was developed to predict the OS rates in patients with cervical cancer. Blood microbiome data were combined with matched tumor RNA-seq data to analyze the differences in the tumor microenvironment between high- and low-MAPS groups, elucidating the impact of the MAPS on the tumor immune microenvironment. Finally, the potential application of the circulating MAPS to predicting the efficacy of immunotherapy and chemotherapy was assessed. The MAPS predictive model, which includes 15 circulating microorganisms, has shown independent prognostic value for patients with cervical cancer. Integrating the MAPS into a nomogram improved the accuracy of the prognostic predictions. Combined microbial and gene analyses revealed potential interactions between prognostic tumor microbiomes and the tumor immune microenvironment. The drug sensitivity analysis indicated the potential of MAPS as a predictor of chemotherapy’s efficacy. Our findings suggest that circulating microbial signatures hold promise as novel prognostic biomarkers and may inform personalized treatment strategies in cervical cancer. Further large-scale and multicenter studies are warranted to validate the clinical utility of the MAPS.