Ultrathin High-Entropy Fe-Based Spinel Oxide Nanosheets with Metalloid Band Structures for Efficient Nitrate Reduction towards Ammonia.

Spinel oxides with tunable chemical compositions have emerged as versatile electrocatalysts, however their performance is greatly limited by small surface area and low electron conductivity. Here, we rationally design ultrathin high-entropy Fe-based spinel oxides nanosheets (i.e., (Co0.2Ni0.2Zn0.2Mg0.2Cu0.2)Fe2O4; denotes A5Fe2O4) in thickness of ∼4.3 nm with large surface area and highly exposed active sites via a modified sol-gel method. Theoretic and experimental results confirm that the bandgap of A5Fe2O4 nanosheets is significantly smaller than that of ordinary Fe-based spinel oxides, realizing the transformation of binary spinel oxide from semiconductors to metalloids. As a result, such A5Fe2O4 nanosheets manifest excellent performance for the nitrate reduction reaction (NO3 -RR) to ammonia (NH3), with a NH3 yield rate of ∼2.1 mmol h-1 cm-2 at -0.5 V versus Reversible Hydrogen Electrode (RHE), outperforming other spinel-based electrocatalysts. Systematic mechanism investigations reveal that the NO3 -RR is mainly occurred on Fe sites, and introducing high-entropy compositions in tetrahedral sites regulates the adsorption strength of N and O-related intermediates on Fe for boosting the NO3 -RR. The above findings offer a high-entropy platform to regulate the bandgap and enhance the electrocatalytic performance of spinel oxides. This article is protected by copyright. All rights reserved.

Late-Stage C-H Nitration of Unactivated Arenes by Fe(NO3)3·9H2O in Hexafluoroisopropanol.

Operationally simple and generally applicable arene nitration with cheap and easily accessible chemicals has been a long-sought transformation in the synthetic organic community. In this work, we realized this goal with nontoxic and inexpensive Fe(NO3)3·9H2O as the nitro source and easily recyclable solvent hexafluoroisopropanol as the promotor via a network of hydrogen-bonding interactions. As a result of the relative mildness and high reliability of this protocol, late-stage nitration of various highly functionalized natural products and commercially available drugs was realized.

Analysis of health risk factors for older adults living alone in China and establishment and evaluation of a nomogram prediction model.

Objective: To understand the health status of older adults living alone in China and analyze the influencing factors, so as to provide reference for improving the health status of older adults living alone. Methods: Based on CGSS data from China General Social Survey (2017), the influencing factors of health status of older adults living alone were analyzed by unconditional Logistic regression, and the R software was used to develop a nomogram for predicting the risk of self-assessed unhealthy adverse outcomes. Results: Gender, annual income, mandarin listening level and participation in medical insurance were the influencing factors of self-rated health of older adults living alone. Age and annual income are the influencing factors of physiological health. Annual income and Internet use were influential factors for mental health. C-Statistic of nomogram prediction model was 0.645. The calibration curve showed that goodness of fit test (χ2 = 58.09, p < 0.001), and the overall prediction ability of the model was good. Conclusion: The health status of older adults living alone in the home-based older adults care is worrying, and it is affected by various factors. We should pay more attention to older adults living alone, improve the ability of listening and distinguishing mandarin and the use of health information platforms for older adults living alone, and further implement medical insurance policies and health services. Announcing the solution to promote healthy home-based care for older adults living alone.

[Characterization of Microplastic Surface Bacterial Community Structure and Prediction of Ecological Risk in Poyang Lake, China].

In recent years, the environmental pollution of microplastics in Poyang Lake has received increasing attention. Baisha Lake of Poyang Lake was selected as the study area, and samples of water and sediments of Baisha Lake and the microplastics therein were collected, and the polymer types of microplastics were identified as polyethylene (PE), polyester (PET), polypropylene (PP), and polystyrene (PS) using Fourier infrared spectroscopy. We also analyzed the structural composition of bacterial communities in water, in sediments, and on microplastic surfaces using 16S high-throughput sequencing. The species richness and diversity of bacteria on the microplastic surfaces were lower than those in the surrounding water and sediments. The results of NMDS analysis showed that the bacterial community structures on the microplastic surfaces differed greatly from those in the surrounding sediments and water. The bacterial community composition in water and sediment differed from that on the microplastic surfaces, and the dominant bacterial phyla on the microplastic surfaces were Proteobacteria and Bacteroidota, and their relative abundance on the microplastic surfaces was higher than that in sediment. The relative abundance of Proteobacteria was higher than that in water. The relative abundances of Bacteroidota and Actinobacteriota were significantly lower than that of water. Massilia and Pseudomonas were the dominant genera on the microplastic surfaces, and their relative abundances were significantly higher than those in the surrounding water and sediments. BugBase phenotype prediction revealed that the relative abundance of contains mobile elements, biofilm formation, potential pathogenicity, and stress tolerance phenotypes of microplastic bacterial communities were significantly higher than those of the surrounding water and sediments. The results revealed that microplastics may have contributed to the spread of harmful bacteria, including pathogenic bacteria, and increased the potential pathogenicity of bacterial communities. Additionally, microplastic surface bacterial communities had higher phenotypes of mobile gene element content. Revealing the potential harm of microplastic pollution to wetland ecology at the micro level may provide a scientific reference for maintaining the ecological stability of wetlands.

Resistance mechanisms of SARS-CoV-2 3CLpro to the non-covalent inhibitor WU-04.

Drug resistance poses a significant challenge in the development of effective therapies against SARS-CoV-2. Here, we identified two double mutations, M49K/M165V and M49K/S301P, in the 3C-like protease (3CLpro) that confer resistance to a novel non-covalent inhibitor, WU-04, which is currently in phase III clinical trials (NCT06197217). Crystallographic analysis indicates that the M49K mutation destabilizes the WU-04-binding pocket, impacting the binding of WU-04 more significantly than the binding of 3CLpro substrates. The M165V mutation directly interferes with WU-04 binding. The S301P mutation, which is far from the WU-04-binding pocket, indirectly affects WU-04 binding by restricting the rotation of 3CLpro's C-terminal tail and impeding 3CLpro dimerization. We further explored 3CLpro mutations that confer resistance to two clinically used inhibitors: ensitrelvir and nirmatrelvir, and revealed a trade-off between the catalytic activity, thermostability, and drug resistance of 3CLpro. We found that mutations at the same residue (M49) can have distinct effects on the 3CLpro inhibitors, highlighting the importance of developing multiple antiviral agents with different skeletons for fighting SARS-CoV-2. These findings enhance our understanding of SARS-CoV-2 resistance mechanisms and inform the development of effective therapeutics.

Three Polyoxometalate-Based Ag-Organic Compounds as Heterogeneous Catalysts for the Synthesis of Benzimidazoles.

Three new POM-based compounds, with formulae [Na0.63Ag3(Htba)2.37(tba)0.63(H2O)2(PMo12O40)]·4H2O (Ag3PMo), [Ag4(Htba)4(H2O)2(PMo12O40)](NO3)·H2O (Ag4PMo), and [Ag3(Htba)2(tba)(PW12O40)0.5](NO3)0.5·13H2O (Ag3PW), were prepared with a 3-(4H-1,2,4-triazol-4-yl)benzoic acid (Htba) ligand, Keggin-type anions ([PMo12O40]3-/[PW12O40]3-), and a silver ion (Ag+). The structural features of these compounds are particularly different from the multinuclear subunits, which are [Ag3(tba)3] clusters in Ag3PMo, [Ag4(tba)3] chains in Ag4PMo, and [Ag3(tba)3]2 clusters in Ag3PW, connected by multidonor atom tba ligands and Ag+ ions. Meanwhile, in these compounds, polyanions act as polydentate ligands to link adjacent Ag-tba metal-organic units and expand their spatial dimensions. These compounds, as heterogeneous catalysts, exhibit high stability and excellent catalytic activity to construct benzimidazoles. Ag3PMo could efficiently catalyze the condensation of benzene-1,2-diamines and benzaldehydes and produce benzimidazoles in good yields. In addition, Ag3PMo could be reused up to 7 times and was suitable for gram-scale reactions.

Down-regulation of A20 mRNA expression in peripheral blood mononuclear cells from MDS patients.

Myelodysplastic syndrome (MDS) is characterized by activated inflammatory signaling and affects prognosis. Targeting inflammatory signaling may provide a way to treat the disease. We were curious whether there were changes in A20 in peripheral blood mononuclear cells (PBMC) of MDS patients. Therefore, we conducted a study with 60 clinical samples, including 30 MDS patients and 30 healthy controls. All patients with MDS were diagnosed and classified according to the criteria of the 2016 World Health Organization. The study was performed in accordance with the guidelines of the Declaration of Helsinki. Using Quantitative Real-Time RT-PCR, we discovered that A20 mRNA expression in PBMC of the MDS group was significantly lower than that in the control group (P < 0.001). Additionally, using Luminex Liquid Suspension Chip, we observed elevated plasma levels of pro-inflammatory IL-8 and TNF-α in the MDS group compared to the healthy control group (P < 0.001). We did not find a significant correlation between A20 mRNA and clinical characteristics (age, sex, concentration of hemoglobin, neutrophils count, platelets count, percent of blasts, and WHO classification) of the patients, nor between A20 mRNA and plasma cytokines (data not shown). Our study found down-regulated of A20 and increased levels of pro-inflammatory cytokines in the peripheral blood of MDS patients, providing further evidence for the activation of inflammatory signals in MDS.

Genotype characterization of tetrahydrobiopterin deficiency in two Tibetan children.

Background: Tetrahydrobiopterin (BH4) deficiency is a rare cause of hyperphenylalaninemia (HPA). The incidence of this condition varies based on region and ethnicity. In the early stages, patients typically do not exhibit any symptoms, and HPA is identified only through newborn screening for diseases. It is important to distinguish BH4 deficiency from phenylketonuria (PKU, MIM # 261600). Timely diagnosis and treatment of BH4 deficiency are crucial for the prognosis of patients. Case presentation: We present two rare cases of Chinese Tibetan children with BH4D, diagnosed through biochemical tests and genetic sequencing. Case 1 is a male infant, 2 months old, with a newborn screening (NBS) Phe level of 1212 µmol/L (reference range <120 µmol). The biopterin(B) level was 0.19 mmol/molCr (reference range: 0.42-1.92 mmol/molCr), with a B% of 5.67% (reference range: 19.8%-50.3%). Gene sequencing revealed a homozygous missense variant [NM_000317.3 (PTS): c.259C > T (p.Pro87Ser), rs104894276, ClinVar variation ID: 480]. The patient was treated with a Phe-reduced diet and oral sapropterin, madopar and is currently 3 years and 4 months old, showing mild global developmental delay. Case 2 is a 40-day-old female infant with a Phe level of 2442.11 µmol/L and dihydropteridine reductase (DHPR) activity of 0.84 nmol/(min. 5 mm disc) (reference range: 1.02-3.35 nmol/min.5 mm disc. Gene sequencing revealed a compound heterozygous genotype [NM_000320.3(QDPR): c.68G > A (p.Gly23Asp), rs104893863, ClinVar Variation ID: 490] and [NM_000320.3(QDPR) c.419C > A (p. Ala140Asp), ClinVar ID: 2444501]. The patient was treated with a Phe-reduced diet and oral madopar, 5-hydroxytryptophan. At the age of 1 year, she exhibited severe global developmental delay with seizures. Conclusion: We identified and treated two cases of BH4D in Tibetan populations in China, marking the first confirmed instances. Our report emphasizes the significance of conducting differential diagnosis tests for BH4D.

Circumventing the Theoretical Scaling Relation Limit for the Oxygen Evolution Reaction.

Transition metal hydr(oxy)oxides (TMHs) are considered efficient electrocatalysts for the oxygen evolution reaction (OER) under alkaline conditions. Toward identification of potential descriptors to circumvent the scaling relation limit for the OER, first-principles calculations were used to quantify the effects on the overpotential of different s (Mg), p (Al), and d (Ti, V, Cr, Fe, Co, Sc, and Zn) electron dopants in Ni-based TMHs. Both the adsorbate evolution mechanism (AEM) and the lattice oxygen-mediated mechanism (LOM) were examined. The results demonstrate that the formation energy of oxygen vacancies (EVO) is strongly affected by the chemical nature of the dopants. A linear relationship is identified between EVO and the free energy difference for the oxygen-oxygen coupling. A descriptor could be employed to discriminate whether the LOM is energetically favored over the AEM. These findings fill existing gaps in appropriate yet computationally light descriptors for direct identification between the AEM and LOM.

Enhancing Efficacy and Quality of Life in Patients with Herpes Zoster Infection in Hairy Cell Leukemia.

Hairy cell leukemia (HCL) is an infrequent and persistent B-cell inert lymphoid leukemia. In this study, we present the case of a 71-year-old female patient with a previous diagnosis of variant HCL who experienced a severe herpes zoster infection leading to an extensive skin eruption. The patient's initial diagnosis of HCL occurred 7 years ago, and she underwent treatment with cladribine, interferon, COP (cyclophosphamide, vincristine, and prednisone), benztropine tablets + clarithromycin dispersible, and ibrutinib. Immune disorders resulting from repeated prior chemotherapy and targeted therapy may potentially precipitate herpes zoster infection. Despite an initial two-week period of unresponsiveness to antivirals and nerve nutrition treatments, the introduction of topical Coptis liquid to the treatment regimen yielded significant efficacy. This case report underscores the potential of Chinese medicine as an adjunct to conventional antiviral therapy in the management of herpes zoster infection in immunocompromised patients. This treatment protocol has the potential to enhance efficacy, enhance quality of life, and serve as a more robust foundation for clinical diagnosis and improved treatments.

Identification of a conserved α-helical domain at the N terminus of human DNA methyltransferase 1.

In vertebrates, DNA methyltransferase 1 (DNMT1) contributes to preserving DNA methylation patterns, ensuring the stability and heritability of epigenetic marks important for gene expression regulation and the maintenance of cellular identity. Previous structural studies have elucidated the catalytic mechanism of DNMT1 and its specific recognition of hemimethylated DNA. Here, using solution nuclear magnetic resonance spectroscopy and small-angle X-ray scattering, we demonstrate that the N-terminal region of human DNMT1, while flexible, encompasses a conserved globular domain with a novel α-helical bundle-like fold. This work expands our understanding of the structure and dynamics of DNMT1 and provides a structural framework for future functional studies in relation with this new domain.

Single-cell transcriptome analysis of aging mouse liver.

Aging has a great impact on the liver, which causes a loss of physiological integrity and an increase in susceptibility to injury, but many of the underlying molecular and cellular processes remain unclear. Here, we performed a comprehensive single-cell transcriptional profiling of the liver during aging. Our data showed that aging affected the cellular composition of the liver. The increase in inflammatory cells including neutrophils and monocyte-derived macrophages, as well as in inflammatory cytokines, could indicate an inflammatory tissue microenvironment in aged livers. Moreover, aging drove a distinct transcriptional course in each cell type. The commonly significant up-regulated genes were S100a8, S100a9, and RNA-binding motif protein 3 across all cell types. Aging-related pathways such as biosynthesis, metabolism, and oxidative stress were up-regulated in aged livers. Additionally, key ligand-receptor pairs for intercellular communication, primarily linked to macrophage migration inhibitory factor, transforming growth factor-ß, and complement signaling, were also elevated. Furthermore, hepatic stellate cells (HSCs) serve as the prominent hub for intrahepatic signaling. HSCs acquired an "activated" phenotype, which may be involved in the increased intrahepatic vascular tone and fibrosis with aging. Liver sinusoidal endothelial cells derived from aged livers were pseudocapillarized and procontractile, and exhibited down-regulation of genes involved in vascular development and homeostasis. Moreover, the aging-related changes in cellular composition and gene expression were reversed by caloric restriction. Collectively, the present study suggests liver aging is linked to a significant liver sinusoidal deregulation and a moderate pro-inflammatory state, providing a potential concept for understanding the mechanism of liver aging.

Highly selective detection of 2,4-dinitrophenol by fluorescent NH2-MIL-125(Ti) via dual-parameter sensing technology.

The organic contaminant 2,4-dinitrophenol (2,4-DNP) is widely prevalent and poses significant risks to human health. Although numerous in-depth studies having been reported on the highly sensitive detection of 2,4-DNP, there are still challenges to its selective detection. Here, the fluorescence intensity ratio (I0/I) and emission peak shift (Δλ) were utilized for selective detection of 2,4-DNP by NH2-MIL-125(Ti). Notably, the emission peak of the NH2-MIL-125(Ti) suspension exhibited a remarkable red shift in the presence of 2,4-DNP (Δλ = 26 nm), accompanied by the blue shift or weak red shift of analogs, which provided a solid basis for selective detection of 2,4-DNP. Meanwhile, the I0/I ratio of the NH2-MIL-125(Ti) suspension exhibited a robust linear correlation with 2,4-DNP at the low concentration range (0-70 µM). The interaction of the analyte with NH2-MIL-125(Ti) was revealed to involve intermolecular charge transfer (ICT) and fluorescence resonance energy transfer (FRET) through XPS, FTIR, and UV-vis absorption spectroscopy. Additionally, we achieved the detection of 2,4-DNP using a smartphone by recognizing both the blue (B) values and the luminance (L) values. The obtained results demonstrated that the NH2-MIL-125(Ti) probe based on dual-parameter sensing technology exhibited excellent potential for selectively detecting 2,4-DNP in water environments, thereby offering significant prospects for its application in water quality assessment.

Economic growth effects of public health expenditure in OECD countries: An empirical study using the dynamic panel threshold model.

Background: Member countries of the Organization for Economic Co-operation and Development (OECD) have experienced a downward trend in capital and macro investment returns. Countries rely on investments in healthcare and health-related sectors to ensure continuous input and an efficient labor market. Public healthcare coverage is a social welfare policy implemented by governments, which contributes to improving human capital quality and ensuring stable economic growth. Methods: This study employs a method that combines theoretical modeling and empirical testing examining 33 OECD countries from 2001 to 2017. We first construct a nonlinear dynamic panel threshold model to examine the impact of public health spending on economic growth. We then employ the model to empirically analyze the threshold effect of public health expenditure on economic growth, validating the effectiveness of our theoretical model. Results: When the level of household consumption is below the 9.63 threshold, the effect of public health expenditure on economic growth is significantly negative (p < 0.1); however, when consumption exceeds the 9.63 threshold, the effect becomes significantly positive (p < 0.05). Similarly, when employee wages are below the 10.57 threshold, the effect of public health expenditure on economic growth is significantly negative (p > 0.1), and it becomes significantly positive when it exceeds 10.57 (p < 0.5). Finally, when the level of physical capital investment falls below the 8.73 threshold, the effect of public health expenditure on economic growth is significantly negative (p < 0.5), and it becomes significantly positive when it exceeds 8.73 (p < 0.5). The positive impact of public health expenditure on economic growth gradually strengthens as household consumption, employee wages, and per capita physical capital investment continue to rise. Conclusions: In an economic environment with higher household consumption, employee wages, and physical capital investment, public health expenditure will significantly promote economic growth.

Investigation of volatile compounds during fermentation of Elaeagnus moorcroftii Wall.ex schlecht. juice by Bifidobacterium animalis subsp. lactis HN-3 and Lacticaseibacillus paracasei YL-29.

The influence on and biotransformation of volatile compounds (VOCs) during fermentation of Elaeagnus moorcroftii Wall.ex Schlecht. juice (EWSJ) through single inoculation and co-inoculation of Bifidobacterium animalis subsp. lactis HN-3 (B.an3) and Lacticaseibacillus paracasei YL-29 (L.cp29) were analyzed through headspace-solid phase microextraction-gas chromatography-mass spectrometry. Compared with the B.an3- and L.cp29-fermented EWSJ, the B.an3 + L.cp29-fermented EWSJ had more increased 9 desirable flavor compositions and less decreased in or even elimination of 12 undesirable flavor compositions, and 3 new characteristic VOCs, formed through the interaction between B.an3 and L.cp29 were detected. In addition, biotransformations that led to an increase and a decrease in VOCs mainly involved 3 oxidation, 3 reduction, 1 hydrolysis, and 1 isomerization reactions. This study offers a theoretical basis for investigating the interaction effect of Lactobacillus and Bifidobacterium species on VOCs and developing lactic acid bacteria-fermented plant-based juices with lower sugar content and better flavor.

Effects of Multi-Mechanism Complementary Therapy on Pain and Anxiety During Labor Latency in Primiparous Women.

Objective: Evaluate the efficacy of single and mixed complementary therapies, with different analgesic mechanisms, in relieving pain and anxiety during the late labor period. Design and method: In this study, 145 primiparous women with 2-3 cm dilation of the cervix were randomly assigned to one of five groups: control group (psychological comfort), comprehensive group, aroma group, auricular acupuncture group, and music group. The groups were distributed equally (1:1:1:1 ratio), and pain and anxiety scores were assessed at 30, 60, and 120 minutes post-intervention in each group. Outcomes and measures: Compared to the control group, all intervention groups showed lower pain scores. The comprehensive group had the largest reduction in pain scores at 30, 60, and 120 minutes post-intervention. The auricular point, aroma, and music groups also demonstrated significant reductions in pain scores at different time points. Only the comprehensive group had a statistically significant reduction in anxiety at 30 minutes post-intervention compared to the control group. However, at 60 and 120 minutes post-intervention, all intervention groups showed lower anxiety scores compared to the control group. Conclusion: The optimal effects of each therapy varied in terms of timing and duration. Combination therapy showed a greater effect size than single complementary therapy.

Effects of Neolamarckia cadamba leaves extract on microbial community and antibiotic resistance genes in cecal contents and feces of broilers challenged with lipopolysaccharides.

The effects of Neolamarckia cadamba leaves extract (NCLE), with effective ingredients of flavonoids, on antibiotic resistance genes (ARGs) and relevant microorganisms in cecal contents and feces of broilers treated with or without lipopolysaccharide stimulation (LPS) were investigated. LPS stimulation increased (P < 0.05) the relative abundance of ARGs and mobile genetic elements (MGEs), such as tet(W/N/W), APH(3')-IIIa, ErmB, tet (44), ANT (6)-Ia, tet(O), tet (32), Vang_ACT_CHL, myrA, ANT (6)-Ib, IncQ1, tniB, and rep2 in cecal contents. However, the difference disappeared (P > 0.05) when NCLE was added at the same time. These differential ARGs and MGEs were mainly correlated (P < 0.01) with Clostridiales bacterium, Lachnospiraceae bacterium, and Candidatus Woodwardibium gallinarum. These species increased in LPS-stimulated broilers and decreased when NCLE was applied at the same time. In feces, LPS stimulation decreased (P < 0.05) the relative abundance of tet(Q), adeF, ErmF, Mef(En2), OXA-347, tet (40), npmA, tmrB, CfxA3, and ISCrsp1, while the LPS + NCLE treated group showed no significant effect (P > 0.05) on these ARGs. These differential ARGs and MGEs in feces were mainly correlated (P < 0.01) with Clostridiales bacterium, Pseudoflavonifractor sp. An184, Flavonifractor sp. An10, Ruminococcaceae bacterium, etc. These species increased in LPS-stimulated broilers and increased when NCLE was applied at the same time. In conclusion, LPS stimulation and NCLE influenced microbial communities and associated ARGs in both cecal contents and feces of broilers. NCLE alleviated the change of ARGs and MGEs in LPS-induced broilers by maintaining the microbial balance.IMPORTANCEAntibiotics showed a positive effect on gut health regulation and growth performance improvement in livestock breeding, but the antimicrobial resistance threat and environment pollution problem are increasingly severe with antibiotics abuse. As alternatives, plant extract containing bioactive substances are increasingly used to improve immunity and promote productivity. However, little is known about their effects on diversity and abundance of ARGs. Here, we investigated the effects of NCLE, with effective ingredients of flavonoids, on ARGs and relevant microorganisms in cecal contents and feces of broilers treated with or without lipopolysaccharide stimulation. We found that NCLE reduced the abundance of ARGs in cecal contents of lipopolysaccharide-induced broilers by maintaining the microbial balance. This study provides a comprehensive view of cecal and fecal microbial community, ARGs, and MGEs of broiler following LPS stimulation and NCLE treatment. It might be used to understand and control ARGs dissemination in livestock production.

Mechanisms of RNF168 nucleosome recognition and ubiquitylation.

RNF168 plays a central role in the DNA damage response (DDR) by ubiquitylating histone H2A at K13 and K15. These modifications direct BRCA1-BARD1 and 53BP1 foci formation in chromatin, essential for cell-cycle-dependent DNA double-strand break (DSB) repair pathway selection. The mechanism by which RNF168 catalyzes the targeted accumulation of H2A ubiquitin conjugates to form repair foci around DSBs remains unclear. Here, using cryoelectron microscopy (cryo-EM), nuclear magnetic resonance (NMR) spectroscopy, and functional assays, we provide a molecular description of the reaction cycle and dynamics of RNF168 as it modifies the nucleosome and recognizes its ubiquitylation products. We demonstrate an interaction of a canonical ubiquitin-binding domain within full-length RNF168, which not only engages ubiquitin but also the nucleosome surface, clarifying how such site-specific ubiquitin recognition propels a signal amplification loop. Beyond offering mechanistic insights into a key DDR protein, our study aids in understanding site specificity in both generating and interpreting chromatin ubiquitylation.

Regulation of RAS palmitoyltransferases by accessory proteins and palmitoylation.

Palmitoylation of cysteine residues at the C-terminal hypervariable regions in human HRAS and NRAS, which is necessary for RAS signaling, is catalyzed by the acyltransferase DHHC9 in complex with its accessory protein GCP16. The molecular basis for the acyltransferase activity and the regulation of DHHC9 by GCP16 is not clear. Here we report the cryo-electron microscopy structures of the human DHHC9-GCP16 complex and its yeast counterpart-the Erf2-Erf4 complex, demonstrating that GCP16 and Erf4 are not directly involved in the catalytic process but stabilize the architecture of DHHC9 and Erf2, respectively. We found that a phospholipid binding to an arginine-rich region of DHHC9 and palmitoylation on three residues (C24, C25 and C288) were essential for the catalytic activity of the DHHC9-GCP16 complex. Moreover, we showed that GCP16 also formed complexes with DHHC14 and DHHC18 to catalyze RAS palmitoylation. These findings provide insights into the regulatory mechanism of RAS palmitoyltransferases.