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Abstract Background Mesenchymal stem cells (MSCs) hold immense promise for use in immunomodulation and regenerative medicine. However, their inherent heterogeneity makes it difficult to achieve optimal therapeutic outcomes for a specific clinical disease. Primed MSCs containing a certain cytokine can enhance their particular functions, thereby increasing their therapeutic potential for related diseases. Therefore, understanding the characteristic changes and underlying mechanisms of MSCs primed by various cytokines is highly important. Results In this study, we aimed to reveal the cellular heterogeneity, functional subpopulations, and molecular mechanisms of MSCs primed with IFN-γ, TNF-α, IL-4, IL-6, IL-15, and IL-17 using single-cell RNA sequencing (scRNA-seq). Our results demonstrated that cytokine priming minimized the heterogeneity of the MSC transcriptome, while the expression of MSC surface markers exhibited only slight changes. Notably, compared to IL-6, IL-15, and IL-17; IFN-γ, TNF-α, and IL-4 priming, which stimulated a significantly greater number of differentially expressed genes (DEGs). Functional analysis, which included Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, indicated that IFN-γ, TNF-α, and IL-4-primed hUC-MSCs are involved in interferon-mediated immune-related processes, leukocyte migration, chemotaxis potential, and extracellular matrix and cell adhesion, respectively. Moreover, an investigation of various biological function scores demonstrated that IFN-γ-primed hUC-MSCs exhibit strong immunomodulatory ability, TNF-α-primed hUC-MSCs exhibit high chemotaxis potential, and IL-4-primed hUC-MSCs express elevated amounts of collagen. Finally, we observed that cytokine priming alters the distribution of functional subpopulations of MSCs, and these subpopulations exhibit various potential biological functions. Taken together, our study revealed the distinct regulatory effects of cytokine priming on MSC heterogeneity, biological function, and functional subpopulations at the single-cell level. Conclusions These findings contribute to a comprehensive understanding of the inflammatory priming of MSCs, paving the way for their precise treatment in clinical applications.

Lysine succinylation (Ksuc) is a novel protein post-translational modification (PTM) wherein a succinyl group modifies a lysine residue. Ksuc leads to significant chemical and structural changes to the modified protein. Recent studies have shown that Ksuc might play an important role in organism physiology and some pathophysiological processes, such as tumorigenesis and metabolic diseases. To provide an understanding of the molecular mechanism and functions of Ksuc in different organisms, we reviewed the current literature about Ksuc, mainly summarizing the research advances in eukaryotes and prokaryotes based on both traditional study methods and site prediction tools. We also discussed inhibitors or activators associated with Ksuc that may contribute to proteomic studies and could be useful in future clinical practice. A deeper understanding of Ksuc may shed new light on life science at the protein level and could lead to novel therapeutic strategies for various diseases.

Abstract Coronavirus disease 2019 (COVID-19) treatments are still urgently needed for critically and severely ill patients. Human umbilical cord-mesenchymal stem cells (hUC-MSCs) infusion has therapeutic benefits in COVID-19 patients; however, uncertain therapeutic efficacy has been reported in severe patients. In this study, we selected an appropriate cytokine, IL-18, based on the special cytokine expression profile in severe pneumonia of mice induced by H1N1virus to prime hUC-MSCs in vitro and improve the therapeutic effect of hUC-MSCs in vivo. In vitro, we demonstrated that IL-18-primed hUC-MSCs (IL18-hUCMSC) have higher proliferative ability than non-primed hUC-MSCs (hUCMSCcon). In addition, VCAM-1, MMP-1, TGF-β1, and some chemokines (CCL2 and CXCL12 cytokines) are more highly expressed in IL18-hUCMSCs. We found that IL18-hUCMSC significantly enhanced the immunosuppressive effect on CD3+ T-cells. In vivo, we demonstrated that IL18-hUCMSC infusion could reduce the body weight loss caused by a viral infection and significantly improve the survival rate. Of note, IL18-hUCMSC can also significantly attenuate certain clinical symptoms, including reduced activity, ruffled fur, hunched backs, and lung injuries. Pathologically, IL18-hUCMSC transplantation significantly enhanced the inhibition of inflammation, viral load, fibrosis, and cell apoptosis in acute lung injuries. Notably, IL18-hUCMSC treatment has a superior inhibitory effect on T-cell exudation and proinflammatory cytokine secretion in bronchoalveolar lavage fluid (BALF). Altogether, IL-18 is a promising cytokine that can prime hUC-MSCs to improve the efficacy of precision therapy against viral-induced pneumonia, such as COVID-19.

Due to the polygenic nature of most diseases, simultaneous correction or introduction of single nucleotide variants is needed. Here, the authors demonstrated the feasibility of multiplex base editing for polygenes disease modeling in cynomolgus monkey embryos with high specificity.

Mesenchymal stromal cells (MSCs) show potential for treating preclinical models of newborn bronchopulmonary dysplasia (BPD), but studies of their therapeutic effectiveness have had mixed results, in part due to the use of different media supplements for MSCs expansion in vitro. The current study sought to identify an optimal culture supplement of umbilical cord-derived MSCs (UC-MSCs) for BPD therapy. In this study, we found that UC-MSCs cultured with human platelet lysate (hPL-UCMSCs) were maintained a small size from Passage 1 (P1) to P10, while UC-MSCs cultured with fetal bovine serum (FBS-UCMSCs) became wide and flat. Furthermore, hPL was associated with lower levels of senescence in UC-MSCs during in vitro expansion compared with FBS, as indicated by the results of β-galactosidase staining and measures of senescence-related genes (CDKN2A, CDKN1A, and mTOR). In addition, hPL enhanced the proliferation and cell viability of the UC-MSCs and reduced their doubling time in vitro. Compared with FBS-UCMSCs, hPL-UCMSCs have a greater potential to differentiate into osteocytes and chondrocytes. Moreover, using hPL resulted in greater expression of Nestin and specific paracrine factors (VEGF, TGF-β1, FGF2, IL-8, and IL-6) in UC-MSCs compared to using FBS. Critically, we also found that hPL-UCMSCs are more effective than FBS-UCMSCs for the treatment of BPD in a rat model, with hPL leading to improvements in survival rate, lung architecture and fibrosis, and lung capillary density. Finally, qPCR of rat lung mRNA demonstrated that hPL-UCMSCs had lower expression levels of inflammatory factors (TNF-α and IL-1β) and a key chemokine (MCP-1) at postnatal day 10, and there was significant reduction of CD68+ macrophages in lung tissue after hPL-UCMSCs transplantation. Altogether, our findings suggest that hPL is an optimal culture supplement for UC-MSCs expansion in vitro, and that hPL-UCMSCs promote lung repair in rat BPD disease.

As Leslie’s advisee for seven years in the 1990s, I had the privilege of studying with a master teacher, caring mentor, and brilliant researcher who, over time, also became a cherished friend. Leslie’s compassion, sense of humor, passion for her subject matter as well as for life, and her academic vitality—or charisma—have impressed me more than she will ever know. I am indeed grateful for the foundation she gave me in sociolinguistics and second language (L2) pragmatics. I have never known a professor who could engage her students in such a powerful, enlightening, and entertaining way, as I experienced in the many captivating three-hour doctoral seminars I took with Leslie over the years.

With the rapid development of machine learning, challenging question and answer datasets have also emerged, and the machine reading comprehension technology has emerged. Traditional machine reading comprehension methods mostly focus on the understanding word level semantics, with the weak ability to extract logical relationships from text, resulting in the lower ability of logical reasoning. In order to strengthen the ability of machine reading comprehension method to extract the logical relationship of text and the ability of logical reasoning, a neural symbol model based on logical reasoning was proposed, and the logical expressions captured by the neural symbol model were converted into text input and trained in a mixed reasoning reading comprehension model based on symbolic logic. The mixed reasoning reading comprehension model based on symbolic logic is different from the traditional machine reading comprehension model. It uses symbolic definition and logical capture to extract logical symbols and generate logical expressions. The research results show that the accuracy and F-measure values of the neural symbol model based on the logical reasoning are 70.08% and 70.05%, respectively, when the training set sample size is 4000. The accuracy of the mixed reasoning reading comprehension model based on symbolic logic in the logical reasoning data set of the standard postgraduate entrance examination is 88.31%, which is higher than the 58.74% of the language perception map network model. The accuracy rate in the four-choice and one-choice question-and-answer data set is 40.92%, which is 1.58% higher than that of the language awareness graph network model. In summary, the neural symbol model and hybrid inference reading comprehension model proposed in the study have superior performance, which can capture the logical relationship of text in data sets well, improve the model feature abstraction and reasoning ability, effectively shorten the training time and improve the model efficiency.

Sidewalk autonomous delivery robots (SADRs) share sidewalks with pedestrians and may affect their perceived safety. In outdoor nighttime environments, the color of the lights on SADRs serves as a noticeable form of communication that can influence human emotions. Therefore, this study investigated whether the perceived safety of SADRs varied with the colors of their lighting. In this study, an experiment (n = 30) was conducted where participants walked towards a robot from opposite directions to interact. The perceived safety of five different lighting colors (red, yellow, blue, green, and white) on SADRs was measured before and after the interaction using two perceived safety scales. The results showed significant differences in participants’ perceived safety for the robot’s red, green, blue, and yellow lighting before and after the interaction. Red lighting was rated the least perceived safe, while white and yellow lighting were rated the most perceived safe. Additionally, gender significantly influenced the perceived safety assessments, with females reporting lower perceived safety than males. These findings are valuable when designing SADRs that enhance pedestrians’ perceived safety, thereby facilitating their integration into broader environments in the future.

Hydrogen production by electrolyzing water is an important technique to store energy from renewables into chemical energy. Many efforts have been made to improve the energy conversion efficiency. In this review article, we mainly summarized the emerging ideas on water oxidation by multi-energy coupling. First, the physicochemical nature of electrolyzing water reaction is described. Then, we conceptually proposed the physical basis of energy coupling with a goal to maximize the energy conversion efficiency and showed the methods to achieve heat–electricity and magnetism–electricity coupling to drive water splitting. Finally, the material requirements for creating efficient energy coupling water splitting system were proposed. These new ideas unlock a big potential direction for developing multi-energy coupling hydrogen production devices to efficiently store the intermittent and fluctuating renewables.

Abstract A Ni- and Co- sulfide co-doped g-C3N4 photocatalyst (g-C3N4/NixCo1−xS2) was prepared by hydrothermal method and this photocatalyst, namely, g-C3N4/NixCo1−xS2 shown excellent photocatalytic properties due to the special structure of Ni-Co-S with boundary different exposure to active site of transition metal-metal (Ni-Co) active planes. With the introduction of Co atoms, the H2 production amount reached the maximum about 400.81 μmol under continuous visible light irradiation for 4 hours based on the efficiently charge separation and greatly improved electron transfer resulted from the presence of sufficient active exposure at the boundary. The serial studies shown that the existence of Ni-Co-S structure over g-C3N4 active surface is the key factor of activity affections by means of several characterizations such as SEM, XRD, XPS diffuse reflectance etc. and the results of which were in good agreement with each other. A possible reaction mechanism over eosin Y-sensitized g-C3N4/NixCo1−xS2 photocatalyst under visible light irradiation was proposed.

The rapid development of the internet has led to the accumulation of massive amounts of data, and thus we find ourselves entering the age of big data. Obtaining useful information from these big data is a crucial issue. The aim of this article is to solve the problem of recommending experts to provide peer reviews for universities and other scientific research institutions. Our proposed recommendation method has two stages. An information filtering method is first offered to identify proper experts as a candidate set. Then, an aggregation model with various constraints is suggested to recommend appropriate experts for each applicant. The proposed method has been implemented in an online research community, and the results exhibit that the proposed method is more effective than existing ones.