Bond-selective effect for the dissociative chemisorption of HOD on the Ni(100) surface revealed at the full-dimensional quantum dynamical level.

We present a comprehensive investigation into the dissociative chemisorption of HOD on a rigid Ni(100) surface using an approximate full-dimensional (9D) quantum dynamics approach, which was based on the time-dependent wave-packet calculations on a full-dimensional potential energy surface obtained through neural network fitting to density functional theory energy points. The approximate-9D probabilities were computed by averaging the seven-dimensional (7D) site-specific dissociation probabilities across six impact sites with appropriate relative weights. Our results uncover a distinctive bond-selective effect, demonstrating that the vibrational excitation of a specific bond substantially enhances the cleavage of that excited bond. The product branching ratios are substantially influenced by which bond undergoes excitation, exhibiting a clear preference for the product formed through the cleavage of the excited bond over the alternative product.

Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia: a multicenter, randomized, open-label, phase 3 trial.

Coinfusion of unrelated cord blood (UCB) units in haploidentical hematopoietic cell transplantation (haplo-HCT) (haplo-cord HCT) for hematopoietic malignancies showed promising results in previous reports, but the efficiency of haplo-cord HCT in acute myeloid leukemia (AML) still lacks sufficient evidence. This multicenter, randomized, phase 3 trial (ClinicalTrials.gov NCT03719534) aimed to assess the efficacy and safety of haplo-cord HCT in AML patients. A total of 268 eligible patients aged 18-60 years, diagnosed with measurable residual disease in AML (excluding acute promyelocytic leukemia), with available haploidentical donors and suitable for allotransplantation, were randomly allocated (1:1) to receive haplo-cord HCT (n = 134) or haplo-HCT (n = 134). The 3-year overall survival (OS) was the primary endpoint in this study. Overall median follow-up was 36.50 months (IQR 24.75-46.50). The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group (80.5%, 95% confidence interval [CI]: 73.7-87.9 vs. 67.8% 95% CI 60.0-76.5, p = 0.013). Favorable progression-free survival (70.3%, 95% CI 62.6-78.8 vs. 57.6%, 95% CI 49.6-67.0, p = 0.012) and cumulative incidence of relapse (12.1%, 95% CI 12.0-12.2 vs. 30.3%, 95% CI 30.1-30.4, p = 0.024) were observed in haplo-cord HCT group. Grade 3-4 adverse events (AEs) within two years posttransplantation in the two groups were similar. Haplo-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery (p = 0.026) and increased T-cell reconstitution in the early period posttransplantation. Haplo-cord HCT can improve OS in AML patients without excessive AEs, which may exert additional benefits for recipients of haplo-HCT.

The oncogenic role and regulatory mechanism of ACAA2 in human ovarian cancer.

Acetyl-CoAacyltransferase2 (ACAA2) is a key enzyme in the fatty acid oxidation pathway that catalyzes the final step of mitochondrial ß oxidation, which plays an important role in fatty acid metabolism. The expression of ACAA2 is closely related to the occurrence and malignant progression of tumors. However, the function of ACAA2 in ovarian cancer is unclear. The expression level and prognostic value of ACAA2 were analyzed by databases. Gain and loss of function were carried out to explore the function of ACAA2 in ovarian cancer. RNA-seq and bioinformatics methods were applied to illustrate the regulatory mechanism of ACAA2. ACAA2 overexpression promoted the growth, proliferation, migration, and invasion of ovarian cancer, and ACAA2 knockdown inhibited the malignant progression of ovarian cancer as well as the ability of subcutaneous tumor formation in nude mice. At the same time, we found that OGT can induce glycosylation modification of ACAA2 and regulate the karyoplasmic distribution of ACAA2. OGT plays a vital role in ovarian cancer as a function of oncogenes. In addition, through RNA-seq sequencing, we found that ACAA2 regulates the expression of DIXDC1. ACAA2 regulated the malignant progression of ovarian cancer through the WNT/ß-Catenin signaling pathway probably. ACAA2 is an oncogene in ovarian cancer and has the potential to be a target for ovarian cancer therapy.

Eco-friendly bacterial cellulose/MXene aerogel with excellent photothermal and electrothermal conversion capabilities for efficient separation of crude oil/seawater mixture.

Developing novel absorbent materials targeting high-efficiency, low-energy-consumption, and environmental-friendly oil spill cleanup is still a global issue. Porous absorbents endowed with self-heating function are an attractive option because of that they are able to in-situ heat crude oil and dramatically reduce oil viscosity for efficient remediation. Herein, we facilely prepared an eco-friendly multifunctional bacterial cellulose/MXene aerogel (P-SBC/MXene aerogel) for rapid oil recovery. Thanks to excellent full solar spectrum absorption (average absorbance = 96.6 %), efficient photo-thermal conversion, and superior electrical conductivity (electrical resistance = 36 Ω), P-SBC/MXene aerogel exhibited outstanding photothermal and electrothermal capabilities. Its surface temperature could quickly reach 93 °C under 1.0 kW/m2 solar irradiation and 124 °C under 3.0 V voltage respectively, enabling effective heat transfer toward spilled oil. The produced heat significantly decreased crude oil viscosity, allowing P-SBC/MXene aerogel to rapidly absorb oil. By combining solar heating and Joule heating, P-SBC/MXene aerogel connected to a pump-assisted absorption device was capable of achieving all-weather crude oil removal from seawater (crude oil flux = 630 kg m-2 h-1). More notably, P-SBC/MXene aerogel showed splendid outdoor crude oil separation performance. Based on remarkable crude oil/seawater separation ability, the versatile aerogel provides a promising way to deal with large-area oil spills.

The oncogenic role and regulatory mechanism of PGK1 in human non-small cell lung cancer.

BACKGROUND: Phosphoglycerate kinase 1 (PGK1) is a metabolic enzyme that participates in various biological and pathological processes. Dysregulated PGK1 has been observed in numerous malignancies. However, whether and how PGK1 affects non-small cell lung cancer (NSCLC) is not yet fully elucidated. METHODS: Herein, the non-metabolic function of PGK1 in NSCLC was explored by integrating bioinformatics analyses, cellular experiments, and nude mouse xenograft models. The upstream regulators and downstream targets of PGK1 were examined using multiple techniques such as RNA sequencing, a dual-luciferase reporter assay, Co-immunoprecipitation, and Western blotting. RESULTS: We confirmed that PGK1 was upregulated in NSCLC and this upregulation was associated with poor prognosis. Further in vitro and in vivo experiments demonstrated the promoting effects of PGK1 on NSCLC cell growth and metastasis. Additionally, we discovered that PGK1 interacted with and could be O-GlcNAcylated by OGT. The inhibition of PGK1 O-GlcNAcylation through OGT silencing or mutation at the T255 O-GlcNAcylation site could weaken PGK1-mediated NSCLC cell proliferation, colony formation, migration, and invasion. We also found that a low miR-24-3p level led to an increase in OGT expression. Additionally, PGK1 exerted its oncogenic properties by augmenting ERK phosphorylation and MCM4 expression. CONCLUSIONS: PGK1 acted as a crucial mediator in controlling NSCLC progression. The miR-24-3p/OGT axis was responsible for PGK1 O-GlcNAcylation, and ERK/MCM4 were the downstream effectors of PGK1. It appears that PGK1 might be an attractive therapeutic target for the treatment of NSCLC.

Six-dimensional quantum dynamics study for the dissociative chemisorption of H2 on pure and alloyed AgAu surfaces.

The 6D time-dependent wave packet calculations were performed to explore H2 dissociation on Ag, Au, and two AgAu alloy surfaces, using four newly fitted potential energy surfaces based on the neural network fitting to density functional theory energy points. The ligand effect resulting from the Ag-Au interaction causes a reduction in the barrier height for H2+Ag/Au(111) compared to H2+Ag(111). However, the scenario is reversed for H2+Au/Ag(111) and H2+Au(111). The 6D dissociation probabilities of H2 on Ag/Au(111) surfaces are significantly higher than those on the pure Ag(111) surface, but the corresponding results for H2 on Au/Ag(111) surfaces are substantially lower than those on the pure Au(111) surface. The reactivity of H2 on Au(111) is larger than that on Ag(111), despite Ag(111) having a slightly lower static barrier height. This can be attributed to the exceptionally small dissociation probabilities at the hcp and fcc regions, which are at least 100 times smaller compared to those at the bridge or top site for H2+Ag(111). Due to the late barrier being more pronounced, the vibrational excitation of H2 on Ag(111) is more effective in promoting the reaction than on Au(111). Moreover, a high degree of alignment dependence is detected for the four reactions, where the H2 dissociation has the highest probability at the helicopter alignment, as opposed to the cartwheel alignment.

Multifunctional In-MOF and Its S-Scheme Heterojunction toward Pollutant Decontamination via Fluorescence Detection, Physical Adsorption, and Photocatalytic REDOX.

A novel doubly interpenetrated indium-organic framework of 1 has been assembled by In3+ ions and highly conjugated biquinoline carboxylate-based bitopic connectors (H2L). The isolated 1 exhibits an anionic framework possessing channel-type apertures repleted with exposed quinoline N atoms and carboxyl O atoms. Owing to the unique architecture, 1 displays a durable photoluminescence effect and fluorescence quenching sensing toward CrO42-, Cr2O72-, and Cu2+ ions with reliable selectivity and anti-interference properties, fairly high detection sensitivity, and rather low detection limits. Ligand-to-ligand charge transition (LLCT) was identified as the essential cause of luminescence by modeling the ground state and excited states of 1 using DFT and TD-DFT. In addition, the negatively charged framework has the ability to rapidly capture single cationic MB, BR14, or BY24 and their mixture, including the talent to trap MB from the (MB + MO) system with high selectivity. Moreover, intrinsic light absorption capacity and band structure feature endow 1 with effective photocatalytic decomposition ability toward reactive dyes RR2 and RB13 under ultraviolet light. Notably, after further polishing the band structure state of 1 by constructing the S-scheme heterojunction of In2S3/1, highly efficient photocatalytic detoxification of Cr(VI) and degradation of reactive dyes have been fully achieved under visible light. This finding may open a new avenue for designing novel multifunctional MOF-based platforms to address some intractable environmental issues, i.e., detection of heavy metal ions, physical capture of pony-sized dyes, and photochemical decontamination of ultrastubborn reactive dyes and highly toxic Cr(VI) ions from water.

A mitochondria-regulated p53-CCF circuit integrates genome integrity with inflammation.

Genomic instability and inflammation are distinct hallmarks of aging, but the connection between them is poorly understood. Understanding their interrelationship will help unravel new mechanisms and therapeutic targets of aging and age-associated diseases. Here we report a novel mechanism directly linking genomic instability and inflammation in senescent cells, through a mitochondria-regulated molecular circuit that connects the p53 tumor suppressor and cytoplasmic chromatin fragments (CCF), a driver of inflammation through the cGAS-STING pathway. Activation or inactivation of p53 by genetic and pharmacologic approaches showed that p53 suppresses CCF accumulation and the downstream inflammatory senescence-associated secretory phenotype (SASP), independent of its effects on cell cycle arrest. p53 activation suppressed CCF formation by promoting DNA repair, reflected in maintenance of genomic integrity, particularly in subtelomeric regions, as shown by single cell genome resequencing. Activation of p53 by pharmacological inhibition of MDM2 in old mice decreased features of SASP in liver, indicating a senomorphic role in vivo . Remarkably, mitochondria in senescent cells suppressed p53 activity by promoting CCF formation and thereby restricting ATM-dependent nuclear DNA damage signaling. These data provide evidence for a mitochondria-regulated p53-CCF circuit in senescent cells that controls DNA repair, genome integrity and inflammatory SASP, and is a potential target for senomorphic healthy aging interventions.

Charge-Transfer-Controlled Quantum Dynamics of HCl Dissociation on the Ag/Au(111) Bimetallic Alloy Surface.

Understanding polar molecule dynamics on bimetallic surfaces, especially electropositivity and electronegativity, remains a challenge. Here, we report the reactivity of HCl on a strained Ag monolayer on Au(111) using six-dimensional quantum dynamics with a new machine-learning-based potential energy surface. Surprisingly, HCl reactivity is significantly suppressed by the Ag-Au interaction despite a lower HCl+Ag/Au(111) barrier than pure Ag(111). This arises from charge transfer between Ag and Au, where electronegative Au makes the top Ag layer on Ag/Au(111) electropositive, unlike that on pure Ag(111). Electropositive Ag in HCl+Ag/Au(111) attracts Cl, yielding an unfavorable H-Cl configuration and reduced reactivity. These findings deepen our understanding of polar molecule interactions on bimetallic surfaces, highlighting the role of charge transfer in dissociative chemisorption and the implications for catalyst design in heterogeneous catalysis.

Post-translational modifications of ATG8 proteins - an emerging mechanism of autophagy control.

Autophagy is a recycling mechanism involved in cellular homeostasis with key implications for health and disease. The conjugation of the ATG8 family proteins, which includes LC3B (also known as MAP1LC3B), to autophagosome membranes, constitutes a hallmark of the canonical autophagy process. After ATG8 proteins are conjugated to the autophagosome membranes via lipidation, they orchestrate a plethora of protein-protein interactions that support key steps of the autophagy process. These include binding to cargo receptors to allow cargo recruitment, association with proteins implicated in autophagosome transport and autophagosome-lysosome fusion. How these diverse and critical protein-protein interactions are regulated is still not well understood. Recent reports have highlighted crucial roles for post-translational modifications of ATG8 proteins in the regulation of ATG8 functions and the autophagy process. This Review summarizes the main post-translational regulatory events discovered to date to influence the autophagy process, mostly described in mammalian cells, including ubiquitylation, acetylation, lipidation and phosphorylation, as well as their known contributions to the autophagy process, physiology and disease.

Modulation of cancer-associated fibroblasts by nanodelivery system to enhance efficacy of tumor therapy.

Cancer-associated fibroblasts (CAFs) are the most common cells in the tumor stroma and are essential for tumor development and metastasis. While decreasing the release and infiltration of nanomedicine through nonspecific internalization, CAFs specifically increase solid tumor pressure and interstitial fluid pressure by secreting tumor growth- and migration-promoting cytokines, which increases vascular and organ pressure caused by solid tumor pressure. Nanoparticles have good permeability and can penetrate tumor tissue to reach the lesion area, inhibiting tumor growth. Thus, CAFs are used as modifiable targets. Here, the authors review the biological functions, origins and biomarkers of CAFs and summarize strategies for modulating CAFs in nanodelivery systems. This study provides a prospective guide to modulating CAFs to enhance oncology treatment.

Cancer-associated fibroblasts (CAFs) participate in the growth and metastasis of cancer and also suppress the penetration of antitumor drugs into the deep tumor tissue. Therefore, many researchers have sought to improve the therapeutic efficacy of nanomedicine through the regulation of CAFs. Some nanoparticles that can precisely target CAFs can slow their growth while also assisting the immune system in fighting cancer cells and releasing pressure within the tumor. These nanoparticles may pass through tumors and inhibit the growth of cancer cells. Therefore, the modulation of CAFs with nanomedicines to enhance tumor therapy is essential.

Mode specificity of water dissociating on Ni(100): An approximate full-dimensional quantum dynamics study.

The mode-specific dynamics for the dissociative chemisorption of H2O on rigid Ni(100) is investigated by approximate nine-dimensional (9D) quantum dynamics calculations. The vibrational state-specific 9D dissociation probabilities are obtained by site-averaging the site-specific seven-dimensional results based on an accurate full-dimensional potential energy surface newly developed by neural network fitting to density functional theory energy points with the revised version of the Perdew, Burke, and Ernzerhof functional. The mode specificity of H2O/Ni(100) is very different from that of H2O/Ni(111) or H2O/Cu(111) whose reactivity enhancement by vibrational excitations is quite efficient. For H2O/Ni(100), it is found that the excitation in the symmetric stretching mode is more efficacious than increasing the translational energy in promoting the reaction, while the excitations in the asymmetric stretching mode and bending mode are less efficacious than the translational energy at low collision energies. These interesting observations can be attributed to the near central-barrier reaction for H2O/Ni(100), as well as large discrepancies between the site-specific mode specificities at different impact sites. The mode-specific dynamics obtained in this study is different from that obtained with the reaction path Hamiltonian approach, indicating the importance of full-dimensional quantum dynamics for gas-surface reactions.

Anisotropic Growth of One-Dimensional Carbides in Single-Walled Carbon Nanotubes with Strong Interaction for Catalysis.

Tungsten and molybdenum carbides have shown great potential in catalysis and superconductivity. However, the synthesis of ultrathin W/Mo carbides with a controlled dimension and unique structure is still difficult. Here, inspired by the host-guest assembly strategy with single-walled carbon nanotubes (SWCNTs) as a transparent template, we reported the synthesis of ultrathin (0.8-2.0 nm) W2C and Mo2C nanowires confined in SWCNTs deriving from the encapsulated W/Mo polyoxometalate clusters. The atom-resolved electron microscope combined with spectroscopy and theoretical calculations revealed that the strong interaction between the highly carbophilic W/Mo and SWCNT resulted in the anisotropic growth of carbide nanowires along a specific crystal direction, accompanied by lattice strain and electron donation to the SWCNTs. The SWCNT template endowed carbides with resistance to H2O corrosion. Different from normal modification on the outer surface of SWCNTs, such M2C@SWCNTs (M = W, Mo) provided a delocalized and electron-enriched SWCNT surface to uniformly construct the negatively charged Pd catalyst, which was demonstrated to inhibit the formation of active PdHx hydride and thus achieve highly selective semihydrogenation of a series of alkynes. This work could provide a nondestructive way to design the electron-delocalized SWCNT surface and expand the methodology in synthesizing unusual 1D ultrathin carbophilic-metal nanowires (e.g., TaC, NbC, ß-W) with precise control of the anisotropy in SWCNT arrays.

Electrochemical Preparation of Crystalline Hydrous Iridium Oxide and Its Use in Oxygen Evolution Catalysis.

Even the most stable Ir-based oxides inevitably encounter a severe degradation problem during the oxygen evolution reaction (OER) in acid, resulting in quick formation of amorphous IrOx layers on the catalyst surface. Unfortunately, there is still a lack of fundamental understanding of such hydrous IrOx layers, including the atomic arrangement, key active structure, compositions, chemical stability, and so on. In this work, we demonstrate an electrochemical strategy to prepare two types of protonated iridium oxides with well-defined crystalline structures: one possesses a 2D layered structure (denoted as α-HxIrO3) and the other consists of 3D interconnected polymorphs (denoted as ß-HxIrO3). Both protonated iridium oxides demonstrate superior electrochemical stabilities with 6 times suppressed Ir dissolution comparing to the initial Li2IrO3 and rutile IrO2. It is hypothesized that the enriched protons and fast diffusions in these two protonated HxIrO3 crystal oxides may promote surface structural stability by suppressing the formation of high-valence Ir species at the solid-liquid interfaces during OER. Overall, the results of this work shed light on the role of proton dynamics toward the OER processes on the catalyst surface in acid media.

Clinical characteristics and predictive model of pulmonary tuberculosis patients with pulmonary fungal coinfection.

BACKGROUND: In clinical settings, pulmonary tuberculosis (PTB) patients were often found to have pulmonary fungal coinfection. This study aimed to assess the clinical characteristics of patients suffering from coinfection with TB and pulmonary fungal and construct a predictive model for evaluating the probability of pulmonary fungal coinfection in patients with pulmonary tuberculosis. METHODS: The present case-control study retrospectively collected information from 286 patients affected by PTB who received treatment from December 6,2016- December 6,2021 at Beijing Chest Hospital, Capital Medical University. As control subjects, patients with sex and address corresponding to those of the case subjects were included in the study in a ratio of 1:1. These 286 patients were randomly divided into the training and internal validation sets in a ratio of 3:1. Chi-square test and logistic regression analysis were performed for the training set, and a predictive model was developed using the selected predictors. Bootstrapping was performed for internal validation. RESULTS: Seven variables [illness course, pulmonary cavitation, broad-spectrum antibiotics use for at least 1 week, chemotherapy or immunosuppressants, surgery, bacterial pneumonia, and hypoproteinemia] were validated and used to develop a predictive model which showed good discrimination capability for both training set [area under the curve (AUC) = 0.860, 95% confidence interval (CI) = 0.811-0.909] and internal validation set (AUC = 0.884, 95% CI = 0.799-0.970). The calibration curves also showed that the probabilities predicted using the predictive model had satisfactory consistency with the actual probability for both training and internal validation sets. CONCLUSIONS: We developed a predictive model that can predict the probability of pulmonary fungal coinfection in pulmonary tuberculosis patients. It showed potential clinical utility.

Detoxification of Fumonisins by Three Novel Transaminases with Diverse Enzymatic Characteristics Coupled with Carboxylesterase.

Fumonisin (FB) is one of the most common mycotoxins contaminating feed and food, causing severe public health threat to human and animals worldwide. Until now, only several transaminases were found to reduce FB toxicity, thus, more fumonisin detoxification transaminases with excellent catalytic properties required urgent exploration for complex application conditions. Herein, through gene mining and enzymatic characterization, three novel fumonisin detoxification transaminases-FumTSTA, FumUPTA, FumPHTA-were identified, sharing only 61-74% sequence identity with reported fumonisin detoxification transaminases. Moreover, the recombinant proteins shared diverse pH reaction ranges, good pH stability and thermostability, and the recombinant protein yields were also improved by condition optimum. Furthermore, the final products were analyzed by liquid chromatography-mass spectrometry. This study provides ideal candidates for fumonisin detoxification and meets diverse required demands in food and feed industries.

Diethyldithiocarbamate inhibits the activation of hepatic stellate cells via PPARα/FABP1 in mice with non-alcoholic steatohepatitis.

Activation of hepatic stellate cells (HSCs) is the main course of liver fibrosis which is positively correlated with adverse clinical outcomes in non-alcoholic steatohepatitis (NASH). Diethyldithiocarbamate (DDC) attenuates NASH related liver fibrosis in mice, but its underlying mechanisms remains unclear. In this study, the data showed that DDC inhibited the activation of HSCs in high fat choline-deficient, L-amino acid-defined (CDAA) diet induced NASH. Double Immunofluorescence analysis showed that the baseline expression of peroxisome proliferator-activated receptor α (PPARα) is high in HSCs in normal mouse liver and notably decreases in the NASH liver, indicating that PPARα might be associated with the activation of HSCs. While, DDC upregulated PPARα in HSCs in the NASH liver. Mixture of free fatty acid was used to induce steatosis of hepatocytes. Human HSCs (LX-2 cells) were activated after co-cultured with steatotic hepatocytes, and DDC inhibited the activation of LX-2 cells. Meanwhile, DDC upregulated PPARα and FABP1, and promoted the accumulation of LDs in LX-2 cells. PPARα small interfering RNA blocked these effect of DDC. These findings suggest that PPARα is associated with the activation of HSCs in the context of NASH. DDC improves NASH related fibrosis through inhibiting the activation of HSCs via PPARα/FABP1.