A bibliometric analysis of Oropouche virus.

Objectives: Oropouche virus (OROV) causes systemic infections including the nervous and blood systems, posing a significant and growing public health challenge. However, a comprehensive review of the bibliometric analysis of OROV is still lacking. Therefore, the objective of this study was to provide insight into the research dynamics and current hotspots of OROV. Methods: This study used bibliometric analysis to explore the current status of research related to OROV. 148 publications from 1961 to 2024 were retrieved from the Scopus database. Countries, authors, institutions, journals, references, and keywords were visualized using VOSviewer, CiteSpace, R studio, and Bibliometrix. Microsoft Excel was used for statistical analysis. Results: Brazil is the country with the highest number of publications, total cited frequency, and the most extensive international collaboration. The most popular journal in this field is the American Journal of Tropical Medicine and Hygiene. Instituto Evandro Chagas is the institution with the highest number of publications, and Eurico Arruda is involved in the highest number of publications. Keyword co-occurrence analysis showed that Oropouche bunyavirus, virology, bunyavirus, priority journal, and nucleotide sequence are the main research hotspots in this field. Conclusion: Our study provides a comprehensive overview of the research trends and key areas of focus in OROV. The field is currently experiencing rapid growth, as evidenced by the rising number of annual publications, which not only highlights increased research activity but also lays a solid foundation for further in-depth investigations. This trend offers valuable insights for developing effective strategies for outbreak prevention and control in public health. Presently, researchers are concentrating on the detailed study of Bunyavirus infections, employing both virological and genetic approaches to elucidate their complex pathogenic mechanisms.

Analysis of Aroma Characteristics of 'Binzi' and 'Xiangguo' Apple-Ancient Cultivars in China.

'Binzi' (BZ) (Malus domestica subsp. chinensis var. binzi Li Y.N.) and 'Xiangguo' (XG) (Malus domestica subsp. chinensis var. xiangguo Li Y.N.) are the ancient cultivars in China. The BZ fruits have a low-fragrant flavor on harvest day but a high-fragrant flavor after storage at room temperature, while the XG fruits have a stronger flavor when mature. 'Starking' (SK) and 'Golden Delicious' (GD) fruits have a rich flavor and are recognized by all countries in the world. However, information on the differences between ancient Chinese cultivars and Western apple cultivars in aroma compounds remains unknown. The apple fruits were collected for continuous two years. Aroma compounds in the skin and pulp of the fruits were detected at room temperature (20 ± 1 °C) during storage. The dynamics of VOCs in BZ and SK fruits were more similarly reflected in esters, while those of XG and GD fruits were reflected in aldehydes and alcohols. Ethyl 2-methylbutyrate, with an extremely low odor threshold, was the main source of typical apple flavor in SK, BZ, and XG fruits, while hexyl acetate was the source of the banana flavor in GD fruits. 6-methyl-5-hepten-2-one and ß-damascenone were the important ketones produced in the later stage of storage, derived from the carotenoid metabolism pathway and providing a citrus and rose flavor to the four apple cultivars. SK had the highest number of characteristic aroma components, which were mainly derived from the amino acid metabolism pathway, providing fruits with a sweet and fruity flavor. Although the characteristic aroma components of GD were derived from the fatty acid metabolic pathway, the number of volatile esters was lower. Ethyl butyrate, derived from the saturated fatty acid metabolism, had the highest content in BZ, providing a pineapple flavor; the flavor of XG was mainly derived from ethyl 2-methylbutyrate, 6-methyl-5-hepten-2-one, and ß-damascenone. Therefore, we suggest BZ and XG apples as the aroma-breeding material with which to enrich new cultivars' aroma components, derived from the fatty acid metabolism and carotenoid metabolism pathways, respectively.

Adsorption and separation technologies based on supramolecular macrocycles for water treatment.

The escalating challenges in water treatment, exacerbated by climate change, have catalyzed the emergence of innovative solutions. Novel adsorption separation and membrane filtration methodologies, achieved through molecular structure manipulation, are gaining traction in the environmental and energy sectors. Separation technologies, integral to both the chemical industry and everyday life, encompass concentration and purification processes. Macrocycles, recognized as porous materials, have been prevalent in water treatment due to their inherent benefits: stability, adaptability, and facile modification. These structures typically exhibit high selectivity and reversibility for specific ions or molecules, enhancing their efficacy in water purification processes. The progression of purification methods utilizing macrocyclic frameworks holds promise for improved adsorption separations, membrane filtrations, resource utilization, and broader water treatment applications. This review encapsulates the latest breakthroughs in macrocyclic host-guest chemistry, with a focus on adsorptive and membrane separations. The aim is to spotlight strategies for optimizing macrocycle designs and their subsequent implementation in environmental and energy endeavors, including desalination, elemental extraction, seawater energy harnessing, and sustainable extraction. Hopefully, this review can guide the design and functionality of macrocycles, offering a significantly promising pathway for pollutant removal and resource utilization.

Polystyrene nanoplastics enhance poxvirus preference for migrasome-mediated transmission.

Since the emergence of a global outbreak of mpox in 2022, understanding the transmission pathways and mechanisms of Orthopoxviruses, including vaccinia virus (VACV), has become paramount. Nanoplastic pollution has become a significant global issue due to its widespread presence in the environment and potential adverse effects on human health. These emerging pollutants pose substantial risks to both living organisms and the environment, raising serious health concerns related to their proliferation. Despite this, the effects of nanoparticles on viral transmission dynamics remain unclear. This study explores how polystyrene nanoparticles (PS-NPs) influence the transmission of VACV through migrasomes. We demonstrate that PS-NPs accelerate the formation of migrasomes early in the infection process, facilitating VACV entry as soon as 15 h post-infection (hpi), compared to the usual onset at 36 hpi. Immunofluorescence and transmission electron microscopy (TEM) reveal significant co-localization of VACV with migrasomes induced by PS-NPs by 15 hpi. This interaction coincides with an increase in lipid droplet size, attributed to higher cholesterol levels influenced by PS-NPs. By 36 hpi, migrasomes exposed to both PS-NPs and VACV exhibit distinct features, such as retraction fibers and larger lipid droplets, emphasizing their critical role in cargo transport during viral infections. These results suggest that PS-NPs may act as modulators of viral transmission dynamics through migrasomes, with potential implications for antiviral strategies and environmental health.

Structural changes and grading mechanism of lignin during solid alkali-active oxygen extraction and grading.

Cooking with active oxygen and solid alkali (CAOSA) is an efficient pretreatment method for biomass. For better grading of the lignin yellow liquor, the different lignin fractions and the recovered solid alkali were obtained using a simultaneous acid-alkali graded separation method. The results indicated that the recovery rate of solid alkali was 67.25 %, and the grading of lignin components was characterized by smaller dispersion coefficients, and more stable properties and structure. Lignin fractions with low dispersion coefficients possess more key structures, including the Phenol hydroxyl group (ArOH), Methoxy (OMe), and ß-aryl ether (ß-O-4), and have better thermal properties. The low molecular weight L4 has the highest ArOH content (2.1 mmol/g), which provides better antioxidant properties. The CAOSA process destroyed the S-unit and prevented lignin from condensation. Furthermore, the CAOSA process protected carbohydrates, which could effectively prevent them from dehydrating and re-polymerizing into pseudo-lignin. This allowed the pulp to remain natural, which was beneficial for subsequent transformation and utilization. Overall, the efficient separation of biomass components and lignin grading method proposed by combining the CAOSA process with the acid-alkali grading separation method has a strong application prospect and provides a theoretical basis for the high-value utilization of biomass and lignin.

Photochemical [2 + 2] Cycloaddition Enables the Synthesis of Highly Thermally Stable and Acid/Base-Resistant Polyesters from a Nonpolymerizable α,ß-Conjugated Valerolactone.

We report a simple strategy to transform a nonpolymerizable six-membered α,ß-conjugated lactone, 5,6-dihydro-2H-pyran-2-one (DPO), into polymerizable bicyclic lactones via photochemical [2 + 2] cycloaddition. Two bicyclic lactones, M1 and M2, were obtained by the photochemical [2 + 2] cycloaddition of tetramethylethylene and DPO. Ring-opening polymerization (ROP) of M1 and M2 catalyzed by diphenyl phosphate (DPP), La[N(SiMe3)2]3, and 1-tert-butyl-4,4,4-tris(dimethylamino)-2,2-bis[tris (dimethylamino) phosphoranylide-namino]-2λ5, 4λ5-catenadi(phosphazene) (tBu-P4) were conducted. M1 is highly polymerizable, either DPP or La[N(SiMe3)2]3 could catalyze its living ROP under mild conditions, affording the well-defined PM1 with a predictable molar mass and low dispersity. M2 could only be polymerized with tBu-P4 as the catalyst, also generating the same polymer PM1. PM1 has high thermal stability, with a Td,5% being up to 376 °C. Ring-opening copolymerization (ROcP) of M1 and δ-valerolactone (δ-VL) catalyzed by La[N(SiMe3)2]3 afforded a series of random copolymers with enhanced thermal stabilities. Both PM1 and the copolymer containing 10 mol % M1 exhibited excellent resistance to acidic and basic hydrolysis. Our results demonstrate that direct photochemical [2 + 2] cycloaddition of α,ß-conjugated valerolactone is not only a strategy to tune its polymerizability, but also allows for the synthesis of highly thermally stable aliphatic polyesters, inaccessible by other methods.

Activation of α7 nicotinic acetylcholine receptors inhibits hepatic necroptosis and ameliorates acute liver injury in mice.

BACKGROUND: Acute liver injury (ALI) is a disease characterized by severe liver dysfunction, caused by significant infiltration of immune cells and extensive cell death with a high mortality. Previous studies demonstrated that the α7 nicotinic acetylcholine receptor (α7nAChR) played a crucial role in various liver diseases. The hypothesis of this study was that activating α7nAChR could alleviate ALI and investigate its possible mechanisms. METHODS: ALI was induced by intraperitoneal injection of lipopolysaccharide (LPS)/D-galactosamine (D-Gal) in wild type (WT), α7nAChR knockout (α7nAChR -/-) and Sting mutation (Stinggt/gt) mice in the presence or absence of a pharmacological selective α7nAChR agonist (PNU-282987). The effects of α7nAChR on hepatic injury, inflammatory response, mitochondrial damage, necroptosis and infiltration of immune cells during ALI were assessed. RESULTS: The expression of α7nAChR in liver tissue was increased in LPS/D-Gal induced ALI mice. Compared to the age-matched WT mice, α7nAChR deficiency decreased the survival rate, exacerbated the hepatic injury accompanied with enhanced inflammatory response and oxidative stress, and aggravated hepatic mitochondrial damage and necroptosis. Conversely, pharmacological activation of α7nAChR by PNU-282987 displayed the opposite trends. Furthermore, PNU-282987 significantly reduced the proportion of infiltrating monocyte-derived macrophages (CD45+CD11bhiF4/80int), M1 macrophages (CD45+CD11b+F4/80+CD86 hiCD163low), Ly6Chi monocytes (CD45+CD11b+MHCⅡ lowLy6C hi), but increased the resident Kupffer cells (CD45+CD11bintF4/80 hiTIM4 hi) in the damaged hepatic tissues caused by LPS/D-Gal. Interestingly, α7nAChR deficiency promoted the STING signaling pathway under LPS/D-Gal stimulation, while PNU-282987 treatment significantly prevented its activation. Finally, it was found that Sting mutation abolished the protective effects against hepatic injury by activating α7nAChR. CONCLUSIONS: Our study revealed that activating α7nAChR could protect against LPS/D-Gal induced ALI by inhibiting hepatic inflammation and necroptosis possibly via regulating immune cells infiltration and inhibiting STING signaling pathway.

A Short Review of Advances in MOF Glass Membranes for Gas Adsorption and Separation.

The phenomenon of melting in metal-organic frameworks (MOFs) has recently garnered attention. Crystalline MOF materials can be transformed into an amorphous glassy state through melt-quenching treatment. The resulting MOF glass structure eliminates grain boundaries and retains short-range order while exhibiting long-range disorder. Based on these properties, it emerges as a promising candidate for high-performance separation membranes. MOF glass membranes exhibit permanent and accessible porosity, allowing for selective adsorption of different gas species. This review summarizes the melting mechanism of MOFs and explores the impact of ligands and metal ions on glassy MOFs. Additionally, it presents an analysis of the diverse classes of MOF glass composites, outlining their structures and properties, which are conducive to gas adsorption and separation. The absence of inter-crystalline defects in the structures, coupled with their distinctive mechanical properties, renders them highly promising for industrial gas separation applications. Furthermore, this review provides a summary of recent research on MOF glass composite membranes for gas adsorption and separation. It also addresses the challenges associated with membrane production and suggests future research directions.

Thermally Stable and Chemically Recyclable Poly(ketal-ester)s Regulated by Floor Temperature.

Chemical recycling to monomers (CRM) offers a promising closed-loop approach to transition from current linear plastic economy toward a more sustainable circular paradigm. Typically, this approach has focused on modulating the ceiling temperature (Tc) of monomers. Despite considerable advancements, polymers with low Tc often face challenges such as inadequate thermal stability, exemplified by poly(γ-butyrolactone) (PGBL) with a decomposition temperature of ∼200 °C. In contrast, floor temperature (Tf)-regulated polymers, particularly those synthesized via the ring-opening polymerization (ROP) of macrolactones, inherently exhibit enhanced thermodynamic stability as the temperature increases. However, the development of those Tf regulated chemically recyclable polymers remains relatively underexplored. In this context, by judicious design and efficient synthesis of a biobased macrocyclic diester monomer (HOD), we developed a type of Tf -regulated closed-loop chemically recyclable poly(ketal-ester) (PHOD). First, the entropy-driven ROP of HOD generated high-molar mass PHOD with exceptional thermal stability with a Td,5% reaching up to 353 °C. Notably, it maintains a high Td,5% of 345 °C even without removing the polymerization catalyst. This contrasts markedly with PGBL, which spontaneously depolymerizes back to the monomer above its Tc in the presence of catalyst. Second, PHOD displays outstanding closed-loop chemical recyclability at room temperature within just 1 min with tBuOK. Finally, copolymerization of pentadecanolide (PDL) with HOD generated high-performance copolymers (PHOD-co-PPDL) with tunable mechanical properties and chemical recyclability of both components.

Comparing Business, Innovation, and Platform Ecosystems: A Systematic Review of the Literature.

In recent decades, the term "ecosystem" has garnered substantial attention in scholarly and managerial discourse, featuring prominently in academic and applied contexts. While individual scholars have made significant contributions to the study of various types of ecosystem, there appears to be a research gap marked by a lack of comprehensive synthesis and refinement of findings across diverse ecosystems. This paper systematically addresses this gap through a hybrid methodology, employing bibliometric and content analyses to systematically review the literature from 1993 to 2023. The primary research aim is to critically examine theoretical studies on different ecosystem types, specifically focusing on business, innovation, and platform ecosystems. The methodology of this study involves a content review of the identified literature, combining quantitative bibliometric analyses to differentiate patterns and content analysis for in-depth exploration. The core findings center on refining and summarizing the definitions of business, innovation, and platform ecosystems, shedding light on both commonalities and distinctions. Notably, the research unveils shared characteristics such as openness and diversity across these ecosystems while highlighting significant differences in terms of participants and objectives. Furthermore, the paper delves into the interconnections within these three ecosystem types, offering insights into their dynamics and paving the way for discussions on future research directions. This comprehensive examination not only advances our understanding of business, innovation, and platform ecosystems but also lays the groundwork for future scholarly inquiries in this dynamic and evolving field.

Spatio-temporal variation and drivers of blue carbon sequestration in Hainan Island, China.

Blue carbon ecosystems, such as mangrove, seagrass bed and salt marsh, have attracted increasing attention due to their remarkable capacity for efficient carbon sequestration. However, the current threat posed by human activities to these ecosystems necessitates the characterization of their changes and identification of the primary driving factors in order to facilitate the gradual restoration of blue carbon ecosystems. In this study, we present an analysis of the spatio-temporal characteristics and primary influencing factors governing carbon sequestration in mangrove and seagrass beds located in Hainan Island. The findings revealed a 40% decline in carbon sequestration by mangroves from 1976 to 2017, while seagrass beds exhibited a 13% decrease in carbon sequestering between 2009 and 2016. The decline in carbon sequestration was primarily concentrated in Wenchang city, with aquaculture and population growth identified as the primary driving factors. Despite the implementation of measures aimed at reducing aquaculture in Hainan Island to promote blue carbon sequestration over the past two decades, the resulting recovery remains insufficient in achieving macro-level goals for carbon sequestration. This study emphasizes the necessity of safeguarding blue carbon ecosystems in Hainan Island by effectively mitigating anthropogenic disturbances.

Enabling Closed-Loop Circularity of "Non-Polymerizable" α, ß-Conjugated Lactone Towards High-Performance Polyester with the Assistance of Cyclopentadiene.

Chemical recycling of polymers to monomers presents a promising solution to the escalating crisis associated with plastic waste. Despite considerable progress made in this field, the primary efforts have been focused on redesigning new monomers to produce readily recyclable polymers. In contrast, limited research into the potential of seemingly "non-polymerizable" monomers has been conducted. Herein, we propose a paradigm that leverages a "chaperone"-assisted strategy to establish closed-loop circularity for a "non-polymerizable" α, ß-conjugated lactone, 5,6-dihydro-2H-pyran-2-one (DPO). The resulting PDPO, a structural analogue of poly(δ-valerolactone) (PVL), exhibits enhanced thermal properties with a melting point (Tm) of 114 °C and a decomposition temperature (Td,5%) of 305 °C. Notably, owing to the structural similarity between DPO and δ-VL, the copolymerization generates semi-crystalline P(DPO-co-VL)s irrespective of the DPO incorporation ratio. Intriguingly, the inherent C=C bonds in P(DPO-co-VL)s enable their convenient post-functionalization via Michael-addition reaction. Lastly, PDPO was demonstrated to be chemically recyclable via ring-closing metathesis (RCM), representing a significant step towards the pursuit of enabling the closed-loop circularity of "non-polymerizable" lactones without altering the ultimate polymer structure.

Energy-dependent photoion angular distributions in two-body Coulomb explosions of molecules.

We experimentally study two-body Coulomb explosions of CO2, O2, and CH3Cl molecules in intense femtosecond laser pulses. We observe an obvious variation in the ionic angular distribution of the fragments with respect to the kinetic energy releases (KERs). Using a classical model based on ab initio potential energy curves, we find that the dependence of the ionic angular distribution on the KER is relevant to the fact that the accurate potential energy deviates significantly from the value determined by applying the Coulomb interaction approximation at a relatively small internuclear distance of the molecule. We show that the KER-dependent ionic angular distribution provides an effective way to determine the critical internuclear distance at which the Coulomb interaction approximation holds or breaks down without relying on the knowledge of the accurate potential energy curves.

A role for tunneling nanotubes in virus spread.

Tunneling nanotubes (TNTs) are actin-rich intercellular conduits that mediate distant cell-to-cell communication and enable the transfer of various cargos, including proteins, organelles, and virions. They play vital roles in both physiological and pathological processes. In this review, we focus on TNTs in different types of viruses, including retroviruses such as HIV, HTLV, influenza A, herpesvirus, paramyxovirus, alphavirus and SARS-CoV-2. We summarize the viral proteins responsible for inducing TNT formation and explore how these virus-induced TNTs facilitate intercellular communication, thereby promoting viral spread. Furthermore, we highlight other virus infections that can induce TNT-like structures, facilitating the dissemination of viruses. Moreover, TNTs promote intercellular spread of certain viruses even in the presence of neutralizing antibodies and antiviral drugs, posing significant challenges in combating viral infections. Understanding the mechanisms underlying viral spread via TNTs provides valuable insights into potential drug targets and contributes to the development of effective therapies for viral infections.

Robust machine-learning based prognostic index using cytotoxic T lymphocyte evasion genes highlights potential therapeutic targets in colorectal cancer.

BACKGROUND: A minute fraction of patients stands to derive substantial benefits from immunotherapy, primarily attributable to immune evasion. Our objective was to formulate a predictive signature rooted in genes associated with cytotoxic T lymphocyte evasion (CERGs), with the aim of predicting outcomes and discerning immunotherapeutic response in colorectal cancer (CRC). METHODS: 101 machine learning algorithm combinations were applied to calculate the CERGs prognostic index (CERPI) under the cross-validation framework, and patients with CRC were separated into high- and low-CERPI groups. Relationship between immune cell infiltration levels, immune-related scores, malignant phenotypes and CERPI were further analyzed. Various machine learning methods were used to identify key genes related to both patient survival and immunotherapy benefits. Expression of HOXC6, G0S2, and MX2 was evaluated and the effects of HOXC6 and G0S2 on the viability and migration of a CRC cell line were in-vitro verified. RESULTS: The CERPI demonstrated robust prognostic efficacy in predicting the overall survival of CRC patients, establishing itself as an independent predictor of patient outcomes. The low-CERPI group exhibited elevated levels of immune cell infiltration and lower scores for tumor immune dysfunction and exclusion, indicative of a greater potential benefit from immunotherapy. Moreover, there was a positive correlation between CERPI levels and malignant tumor phenotypes, suggesting that heightened CERPI expression contributes to both the occurrence and progression of tumors. Thirteen key genes were identified, and their expression patterns were scrutinized through the analysis of single-cell datasets. Notably, HOXC6, G0S2, and MX2 exhibited upregulation in both CRC cell lines and tissues. Subsequent knockdown experiments targeting G0S2 and HOXC6 resulted in a significant suppression of CRC cell viability and migration. CONCLUSION: We developed the CERPI for effectively predicting survival and response to immunotherapy in patients, and these results may provide guidance for CRC diagnosis and precise treatment.

Multi-replicas integrity checking scheme with supporting probability audit for cloud-based IoT.

Nowadays, more people are choosing to use cloud storage services to save space and reduce costs. To enhance the durability and persistence, users opt to store important data in the form of multiple copies on cloud servers. However, outsourcing data in the cloud means that it is not directly under the control of users, raising concerns about security and integrity. Recent research has found that most existing multicopy integrity verification schemes can correctly perform integrity verification even when multiple copies are stored on the same Cloud Service Provider (CSP), which clearly deviates from the initial intention of users wanting to store files on multiple CSPs. With these considerations in mind, this paper proposes a scheme for synchronizing the integrity verification of copies, specifically focusing on strongly privacy Internet of Things (IoT) electronic health record (EHR) data. First, the paper addresses the issues present in existing multicopy integrity verification schemes. The scheme incorporates the entity Cloud Service Manager (CSM) to assist in the model construction, and each replica file is accompanied with its corresponding homomorphic verification tag. To handle scenarios where replica files stored on multiple CSPs cannot provide audit proof on time due to objective reasons, the paper introduces a novel approach called probability audit. By incorporating a probability audit, the scheme ensures that replica files are indeed stored on different CSPs and guarantees the normal execution of the public auditing phase. The scheme utilizes identity-based encryption (IBE) for the detailed design, avoiding the additional overhead caused by dealing with complex certificate issues. The proposed scheme can withstand forgery attack, replace attack, and replay attack, demonstrating strong security. The performance analysis demonstrates the feasibility and effectiveness of the scheme.

Synthesis and antibacterial properties of fluorinated biodegradable cationic polyesters.

Antimicrobial peptide-mimicking antibacterial polymers represent a practical strategy to conquer the ever-growing threat of antimicrobial resistance. Herein, we report the syntheses and antibacterial performance of degradable amphiphilic cationic polyesters containing pendent quaternary ammonium motifs and hydrophobic alkyl or fluoroalkyl groups. These polyesters were conveniently prepared from poly(3-methylene-1,5-dioxepan-2-one) via highly efficient one-pot successive thiol-Michael addition reactions. The antibacterial activity of these polyesters against S. aureus and E. coli and their hemolytic activity toward red blood cells were evaluated; some of them showed moderate antibacterial activity and selectivity against Gram-positive S. aureus. The membrane disruption mechanism of these cationic polyesters was briefly explored by monitoring the bacteria killing kinetics and SEM observations. Moreover, the effects of cationic/hydrophobic ratio and the incorporation of fluoroalkyl groups on the antibacterial activity and selectivity of the polyesters were demonstrated.

Sting mutation attenuates acetaminophen-induced acute liver injury by limiting NLRP3 activation.

Acetaminophen (N-acetyl-p-aminophenol; APAP), a widely used effective nonsteroidal anti-inflammatory drug, leads to acute liver injury at overdose worldwide. Evidence showed that the severity of liver injury associated with the subsequent involvement of inflammatory mediators and immune cells. The innate immune stimulator of interferon genes protein (STING) pathway was critical in modulating inflammation. Here, we show that STING was activated and inflammation was enhanced in the liver in APAP-overdosed C57BL/6J mice, and Sting mutation (Stinggt/gt) mice exhibited less liver damage. Multiplexing flow cytometry displayed that Sting mutation changed hepatic recruitment and replacement of macrophages/monocytes in APAP-overdosed mice, which was inclined to anti-inflammation. In addition, Sting mutation limited NLRP3 activation in the liver in APAP-overdosed mice, and inhibited the expression of inflammatory cytokines. Finally, MCC950, a potent and selective NLRP3 inhibitor, significantly ameliorated APAP-induced liver injury and inflammation. Besides, pretreatment of MCC950 in C57 mice resulted in changes of immune cells infiltration in the liver similar to Stinggt/gt mice. Our study revealed that STING played a crucial role in APAP-induced acute liver injury, possibly by maintaining liver immune cells homeostasis and inhibiting NLRP3 inflammasome activation, suggesting that inhibiting STING-NLRP3 pathway might be a potential therapeutic strategy for acute liver injury.

The expedient, CAET-assisted synthesis of dual-monoubiquitinated histone H3 enables evaluation of its interaction with DNMT1.

Site-selective conjugation chemistry has proven effective to synthesize homogenously ubiquitinated histones. Recently, a powerful strategy using 2-((2-chloroethyl) amino) ethane-1-thiol (CAET) as a bifunctional handle was developed to generate chemically stable ubiquitin chains without racemization and homodimerization. Herein, we extend this strategy to the expedient synthesis of ubiquitinated histones, exemplifying its utility to not only synthesize single-monoubiquitinated histones, but dual-monoubiquitinated histones as well. The synthetic histones enabled us to evaluate the binding of DNMT1 to ubiquitinated nucleosomes and map the hotspots of this interaction. Our work highlights the potential of modern chemical protein synthesis to synthesize ubiquitinated histones for epigenetic studies.