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This paper discusses Dai Zhen’s 戴震 (1724–1777) interpretation of human nature against the backdrop of Mencius’s claim that human nature is good. I argue that Dai Zhen ingeniously reinterprets the “shan” 善 (good; goodness) in terms of “fen” 分 (allotments; distinction) to view the claimed “goodness” as the unique and finest physical makeup of human nature that possesses the potential ability to know moral goodness, viz. liyi 理義 (principle & righteousness). Nonetheless, rather than a transcendental principle or some heavenly endowed virtue, liyi is present in human relationships and everyday life. At the crux of the issue is how to activate the given ability and advance our intelligent mind for principle and righteousness. By ridding “xingshan” 性善 (human nature is good) of its inherent moral properties as Mencius posits in his theory of human nature, Dai Zhen, from a naturalistic and empirical stance, proposes an unconventional approach to the longstanding debate over whether human nature is good or evil in Confucian discourse. While his interpretation may unsettle us that are accustomed to the traditional view of the “goodness” of human nature as one’s innate moral feelings of ren yi li zhi 仁義禮智 (benevolence, righteousness, wisdom, and propriety), Dai Zhen’s reading has undoubtedly thrown a new light on this famed Mencian thesis.

Host cellular receptors play key roles in the determination of virus tropism and pathogenesis. However, little is known about SARS-CoV-2 host receptors with the exception of ACE2. Furthermore, ACE2 alone cannot explain the multi-organ tropism of SARS-CoV-2 nor the clinical differences between SARS-CoV-2 and SARS-CoV, suggesting the involvement of other receptor(s). Here, we performed genomic receptor profiling to screen 5054 human membrane proteins individually for interaction with the SARS-CoV-2 capsid spike (S) protein. Twelve proteins, including ACE2, ASGR1, and KREMEN1, were identified with diverse S-binding affinities and patterns. ASGR1 or KREMEN1 is sufficient for the entry of SARS-CoV-2 but not SARS-CoV in vitro and in vivo. SARS-CoV-2 utilizes distinct ACE2/ASGR1/KREMEN1 (ASK) receptor combinations to enter different cell types, and the expression of ASK together displays a markedly stronger correlation with virus susceptibility than that of any individual receptor at both the cell and tissue levels. The cocktail of ASK-related neutralizing antibodies provides the most substantial blockage of SARS-CoV-2 infection in human lung organoids when compared to individual antibodies. Our study revealed an interacting host receptome of SARS-CoV-2, and identified ASGR1 and KREMEN1 as alternative functional receptors that play essential roles in ACE2-independent virus entry, providing insight into SARS-CoV-2 tropism and pathogenesis, as well as a community resource and potential therapeutic strategies for further COVID-19 investigations.

TF-IDF (term frequency-inverse document frequency) is one of the traditional text similarity calculation methods based on statistics. Because TF-IDF does not consider the semantic information of words, it cannot accurately reflect the similarity between texts, and semantic information enhanced methods distinguish between text documents poorly because extended vectors with semantic similar terms aggravate the curse of dimensionality. Aiming at this problem, this paper advances a hybrid with the semantic understanding and TF-IDF to calculate the similarity of texts. Based on term similarity weighting tree (TSWT) data structure and the definition of semantic similarity information from the HowNet, the paper firstly discusses text preprocess and filter process and then utilizes the semantic information of those key terms to calculate similarities of text documents according to the weight of the features whose weight is greater than the given threshold. The experimental results show that the hybrid method is better than the pure TF-IDF and the method of semantic understanding at the aspect of accuracy, recall, and F1-metric by different K-means clustering methods.

Defective cholesterol biosynthesis in eye lens cells is often associated with cataracts; however, how genes involved in cholesterol biosynthesis are regulated in lens cells remains unclear. Here, we show that Quaking (Qki) is required for the transcriptional activation of genes involved in cholesterol biosynthesis in the eye lens. At the transcriptome level, lens-specific Qki-deficient mice present downregulation of genes associated with the cholesterol biosynthesis pathway, resulting in a significant reduction of total cholesterol level in the eye lens. Mice with Qki depletion in lens epithelium display progressive accumulation of protein aggregates, eventually leading to cataracts. Notably, these defects are attenuated by topical sterol administration. Mechanistically, we demonstrate that Qki enhances cholesterol biosynthesis by recruiting Srebp2 and Pol II in the promoter regions of cholesterol biosynthesis genes. Supporting its function as a transcription co-activator, we show that Qki directly interacts with single-stranded DNA. In conclusion, we propose that Qki-Srebp2–mediated cholesterol biosynthesis is essential for maintaining the cholesterol level that protects lens from cataract development. Eye lens cells are highly enriched in cholesterol that sustains lens transparency, and disruption of cholesterol biosynthesis leads to cataracts. The authors show that cholesterol biosynthesis regulated by Qki is essential for maintenance of membrane integrity of lens cells and proper protein folding.

It has been extensively studied that the gut microbiome provides animals flexibility to adapt to food variability. Yet, how gut phageome responds to diet variation of wild animals remains unexplored. Here, we analyze the eco-evolutionary dynamics of gut phageome in six wild gibbons ( Hoolock tianxing ) by collecting individually-resolved fresh fecal samples and parallel feeding behavior data for 15 consecutive months. Application of complementary viral and microbial metagenomics recovers 39,198 virulent and temperate phage genomes from the feces. Hierarchical cluster analyses show remarkable seasonal diet variations in gibbons. From high-fruit to high-leaf feeding period, the abundances of phage populations are seasonally fluctuated, especially driven by the increased abundance of virulent phages that kill the Lachnospiraceae hosts, and a decreased abundance of temperate phages that piggyback the Bacteroidaceae hosts. Functional profiling reveals an enrichment through horizontal gene transfers of toxin-antitoxin genes on temperate phage genomes in high-leaf season, potentially conferring benefits to their prokaryotic hosts. The phage-host ecological dynamics are driven by the coevolutionary processes which select for tail fiber and DNA primase genes on virulent and temperate phage genomes, respectively. Our results highlight complex phageome-microbiome interactions as a key feature of the gibbon gut microbial ecosystem responding to the seasonal diet. The significance of gut phageome for wild animals with seasonal diets remains unexplored. Here, the authors use complementary metagenomics to analyze the phage-host dynamics and its implications for diet variations in wild skywalker hoolock gibbons.

Adult stem cell identity, plasticity, and homeostasis are precisely orchestrated by lineage-restricted epigenetic and transcriptional regulatory networks. Here, by integrating super-enhancer and chromatin accessibility landscapes, we delineate core transcription regulatory circuitries (CRCs) of limbal stem/progenitor cells (LSCs) and find that RUNX1 and SMAD3 are required for maintenance of corneal epithelial identity and homeostasis. RUNX1 or SMAD3 depletion inhibits PAX6 and induces LSCs to differentiate into epidermal-like epithelial cells. RUNX1, PAX6, and SMAD3 (RPS) interact with each other and synergistically establish a CRC to govern the lineage-specific cis -regulatory atlas. Moreover, RUNX1 shapes LSC chromatin architecture via modulating H3K27ac deposition. Disturbance of RPS cooperation results in cell identity switching and dysfunction of the corneal epithelium, which is strongly linked to various human corneal diseases. Our work highlights CRC TF cooperativity for establishment of stem cell identity and lineage commitment, and provides comprehensive regulatory principles for human stratified epithelial homeostasis and pathogenesis. Corneal epithelium shares similar molecular signatures to other stratified epithelia. Here, the authors map super-enhancers and accessible chromatin in corneal epithelium, identifying a transcription regulatory circuit, including RUNX1, PAX6, and SMAD3, required for corneal epithelial identity and homeostasis.

Meiotic recombination is initiated by the formation of double-strand breaks (DSBs), which are repaired as either crossovers (COs) or noncrossovers (NCOs). In most mammals, PRDM9-mediated H3K4me3 controls the nonrandom distribution of DSBs; however, both the timing and mechanism of DSB fate control remain largely undetermined. Here, we generated comprehensive epigenomic profiles of synchronized mouse spermatogenic cells during meiotic prophase I, revealing spatiotemporal and functional relationships between epigenetic factors and meiotic recombination. We find that PRDM9-mediated H3K4me3 at DSB hotspots, coinciding with H3K27ac and H3K36me3, is intimately connected with the fate of the DSB. Our data suggest that the fate decision is likely made at the time of DSB formation: earlier formed DSBs occupy more open chromatins and are much more competent to proceed to a CO fate. Our work highlights an intrinsic connection between PRDM9-mediated H3K4me3 and the fate decision of DSBs, and provides new insight into the control of CO homeostasis.

Economies-of-scale have always been a significant concern, but previous theoretical studies have primarily focused on the traditional manufacturing industry. Consequently, their findings are not directly applicable to the tertiary sector, particularly the hospitality service industry. The hospitality service operates in a high-risk environment and is susceptible to market exits. Therefore, it becomes even more crucial to effectively leverage economies of scale for improving survival rates and long-term operations. This study aims to explore the effectiveness of economies of scale theory in the hospitality industry by examining how sharing accommodation’s economies-of-scale impact personalized and professionalized homestay businesses’ survival. To achieve this objective, we analyze a panel dataset comprising 551,605 properties located in New York City, Los Angeles, Chicago, and Austin using panel survival analysis techniques such as the Cox model and the exponential model. The findings indicate that economies-of-scale can confer short-term survival advantages to professional homestay businesses in comparison with personalized ones. However, in the long run, the social benefits of personalized homestay businesses surpass the impacts of economies-of-scale, thereby enabling them to achieve better sustainability than professional homestay businesses. The likelihood of survival for professional homestay businesses increases with a greater number of listings in operation, referred to as the advantage of economies-of-scale on professionalization; conversely, this is not true for personalized homestay businesses. Moreover, effective host–guest communication both facilitates the attainment of benefits for personalized businesses and amplifies its impact on professionalized enterprises; high-quality products offered by personalized hosts can derive more advantages from scales compared to low-quality products, while superhost-certified professionalized hosts experience less business benefit than uncertificated hosts. This study is one of the pioneering efforts to investigate how economies-of-scale can contribute to the professionalization and personalization of homestay properties, thereby enhancing their business survival. It significantly contributes to the existing literature on hospitality business survival and expands upon the economies-of-scale theory by elucidating its advantages and potential pitfalls in relation to homestay businesses.

Background The characteristics and therapeutic potential of subtypes of mesenchymal stem cells (MSCs) are largely unknown. In this study, CD146 + and CD146 – MSCs were separated from human umbilical cords, and their effects on regulatory T cells (Tregs), Th17 cells, chondrogenesis, and osteogenesis were investigated. Methods Flow cytometry was used to quantify IL-6 and TGF-β1 expressed on CD146 + and CD146 – MSCs. The therapeutic potential of both subpopulations was determined by measuring the clinical score and joint histology after intra-articular (IA) transfer of the cells into mice with collagen-induced arthritis (CIA). Results Compared with CD146 – MSCs, CD146 + MSCs expressed less IL-6 and had a significantly greater effect on chondrogenesis. After T lymphocyte activation, Th17 cells were activated when exposed to CD146 – cells but not when exposed to CD146 + cells both in vitro and in vivo . IA injection of CD146 + MSCs attenuated the progression of CIA. Immunohistochemistry showed that only HLA-A + CD146 + cells were detected in the cartilage of CIA mice. These cells may help preserve proteoglycan expression. Conclusions This study suggests that CD146 + cells have greater potency than CD146 – cells for cartilage protection and can suppress Th17 cell activation. These data suggest a potential therapeutic application for CD146 + cells in treating inflammatory arthritis.

Cervical cancer is widely known as one of the most common types of cancer diagnosed in women, and microRNAs (miRNAs) has been characterized as an important regulator in tumor progression, such as cervical cancer. MiR‐636 was found to play a tumor suppressor role in hepatocellular carcinoma tumorigenesis. However, the tumorigenic mechanism of miR‐636 on cervical cancer has not yet been found. In the present study, we first found that miR‐636 was significantly downregulated in cervical cancer tissues and cell lines. in vitro gain‐ and loss‐of‐function assays revealed that overexpression of miR‐636 inhibited cell proliferation and induced cell apoptosis, while knockdown of miR‐636 reversed the effect on cervical tumorigenesis. Furthermore, cyclin‐dependent kinase 6 (CDK6) and B‐cell lymphoma 2 (Bcl‐2) were characterized as targets of miR‐636. Notably, overexpression of CDK6 or Bcl‐2 could reverse the inhibitory effect of miR‐636 on cervical cancer progression. Mechanistically, miR‐636 repressed cell survival by targeting CDK6/Bcl‐2 in cervical cancer, which may be the underlying mechanism of miR‐636‐inhibited cervical progression. In conclusion, our findings clarified the biologic significance of miR‐636/CDK6/Bcl‐2 axis in cervical cancer progression and suggested the potential therapeutic target ability of miR‐636 in treatment of cervical cancer.