LncRNA-HMG incites colorectal cancer cells to chemoresistance via repressing p53-mediated ferroptosis.

Upon chemotherapy, excessive reactive oxygen species (ROS) often lead to the production of massive lipid peroxides in cancer cells and induce cell death, namely ferroptosis. The elimination of ROS is pivotal for tumor cells to escape from ferroptosis and acquire drug resistance. Nevertheless, the precise functions of long non-coding RNAs (lncRNAs) in ROS metabolism and tumor drug-resistance remain elusive. In this study, we identify LncRNA-HMG as a chemoresistance-related lncRNA in colorectal cancer (CRC) by high-throughput screening. Abnormally high expression of LncRNA-HMG predicts poorer prognosis in CRC patients. Concurrently, we found that LncRNA-HMG protects CRC cells from ferroptosis upon chemotherapy, thus enhancing drug resistance of CRC cells. LncRNA-HMG binds to p53 and facilitates MDM2-mediated degradation of p53. Decreased p53 induces upregulation of SLC7A11 and VKORC1L1, which contribute to increase the supply of reducing agents and eliminate excessive ROS. Consequently, CRC cells escape from ferroptosis and acquire chemoresistance. Importantly, inhibition of LncRNA-HMG by anti-sense oligo (ASO) dramatically sensitizes CRC cells to chemotherapy in patient-derived xenograft (PDX) model. LncRNA-HMG is also a transcriptional target of ß-catenin/TCF and activated Wnt signals trigger the marked upregulation of LncRNA-HMG. Collectively, these findings demonstrate that LncRNA-HMG promotes CRC chemoresistance and might be a prognostic or therapeutic target for CRC.

Acalabrutinib in Chinese patients with relapsed/refractory chronic lymphocytic leukemia: Primary analysis from an open-label, multicenter phase 1/2 trial.

Acalabrutinib is a highly selective Bruton tyrosine kinase inhibitor approved in the United States and Europe for chronic lymphocytic leukemia (CLL) based on phase 3 trials with limited representation of Asian populations. This phase 1/2 trial evaluates acalabrutinib in Chinese adults with relapsed/refractory (R/R) CLL receiving acalabrutinib 100 mg twice daily in 28-day cycles until disease progression or treatment discontinuation due to adverse events (AEs) presenting substantial clinical risk. The primary endpoint was blinded independent central review (BICR)-assessed overall response rate (ORR). A total of 60 patients from 20 sites in China received acalabrutinib (median age 62 years; median 1 prior therapy line; 21.7% with del(17p) and/or TP53 mutation; 51.7% with unmutated IGHV). Median total treatment duration was 19.4 months (range 0.6-28.2) with 53 patients (88.3%) receiving acalabrutinib at data cutoff; median study follow-up was 20.2 months. BICR-assessed ORR was 85.0% (95% CI, 73.4-92.9). Median duration of response, progression-free survival (PFS), and overall survival (OS) were not reached. Estimated 12-month and 18-month PFS rates were 91.5% (95% CI, 80.9-96.4) and 78.8% (95% CI, 60.9-89.2); OS rates were both 96.7% (95% CI, 87.3-99.2). AEs of grade ≥ 3 occurred in 25 patients (41.7%), most commonly decreased neutrophil count (13.3%, n = 8), pneumonia (6.7%, n = 4), and upper respiratory tract infection (6.7%, n = 4). AEs led to treatment discontinuation in 2 patients (paraneoplastic pemphigus; rectal neoplasm). This study demonstrated high ORR in acalabrutinib-treated Chinese patients with R/R CLL with no unexpected safety concerns. This trial is registered on ClinicalTrials.gov (NCT03932331).

The impact of empowerment theory-based health education on Alzheimer's disease informal caregivers: a randomized controlled trial.

Background: There is a lack of evidence regarding the effectiveness of empowerment healthy education for caregivers of Alzheimer's patients. Objective: To explore the effectiveness of the intervention of health education guided by empowerment theory on dementia knowledge, caregiving readiness, positive caregiving emotions, anxiety, and depression in informal Alzheimer's disease caregivers. Design: A single-blinded, randomized controlled trial. Setting: A teaching hospital in Tianjin, China. Participants: Eighty caregivers of Alzheimer's disease patients. Methods: Participants were recruited from the hospital and randomly assigned to either experimental or control group. The experimental group underwent a 12-weeks, one-to-one intervention of six session lasting 45-60 min each. The control group received conventional health education. Outcome measures included dementia knowledge, caregiver readiness (primary outcomes), positive caregiving emotions, anxiety, and depression (secondary outcomes). Results: After 12 weeks, the intervention group exhibited significantly higher levels of dementia knowledge, caregiver readiness, and positive caregiving emotions compared with the control group. Furthermore, levels of hospitalization-related anxiety and depression were lower in the intervention group. All study results of this study showed statistically significant differences (p < 0.05). Discussion: Empowerment theory-based health education appears to be an effective intervention for improving caregiver and readiness to care for caregivers of Alzheimer's disease individuals. The intervention may help reduce caregivers' anxiety and depression levels.

Investigating muscle coordination patterns with Granger causality analysis in protrusive motion from tagged and diffusion MRI.

The human tongue exhibits an orchestrated arrangement of internal muscles, working in sequential order to execute tongue movements. Understanding the muscle coordination patterns involved in tongue protrusive motion is crucial for advancing knowledge of tongue structure and function. To achieve this, this work focuses on five muscles known to contribute to protrusive motion. Tagged and diffusion MRI data are collected for analysis of muscle fiber geometry and motion patterns. Lagrangian strain measurements are derived, and Granger causal analysis is carried out to assess predictive information among the muscles. Experimental results suggest sequential muscle coordination of protrusive motion among distinct muscle groups.

Speech Motion Anomaly Detection via Cross-Modal Translation of 4D Motion Fields from Tagged MRI.

Understanding the relationship between tongue motion patterns during speech and their resulting speech acoustic outcomes-i.e., articulatory-acoustic relation-is of great importance in assessing speech quality and developing innovative treatment and rehabilitative strategies. This is especially important when evaluating and detecting abnormal articulatory features in patients with speech-related disorders. In this work, we aim to develop a framework for detecting speech motion anomalies in conjunction with their corresponding speech acoustics. This is achieved through the use of a deep cross-modal translator trained on data from healthy individuals only, which bridges the gap between 4D motion fields obtained from tagged MRI and 2D spectrograms derived from speech acoustic data. The trained translator is used as an anomaly detector, by measuring the spectrogram reconstruction quality on healthy individuals or patients. In particular, the cross-modal translator is likely to yield limited generalization capabilities on patient data, which includes unseen out-of-distribution patterns and demonstrates subpar performance, when compared with healthy individuals. A one-class SVM is then used to distinguish the spectrograms of healthy individuals from those of patients. To validate our framework, we collected a total of 39 paired tagged MRI and speech waveforms, consisting of data from 36 healthy individuals and 3 tongue cancer patients. We used both 3D convolutional and transformer-based deep translation models, training them on the healthy training set and then applying them to both the healthy and patient testing sets. Our framework demonstrates a capability to detect abnormal patient data, thereby illustrating its potential in enhancing the understanding of the articulatory-acoustic relation for both healthy individuals and patients.

The impact of histone lactylation on the tumor microenvironment and metabolic pathways and its potential in cancer therapy.

BACKGROUND: The complexity of cancer is intricately linked to its multifaceted biological processes, including the roles of the tumor microenvironment (TME) as well as genetic and metabolic regulation. Histone lactylation has recently emerged as a novel epigenetic modification mechanism that plays a pivotal role in regulating cancer initiation, proliferation, invasion, and metastasis. OBJECTIVE: This review aims to elucidate the role of histone lactylation in modulating various aspects of tumor biology, including DNA repair mechanisms, glycolytic metabolic abnormalities, functions of non-tumor cells in the TME, and the promotion of tumor inflammatory responses and immune escape. Additionally, the review explores potential therapeutic strategies targeting histone lactylation. METHODS: A comprehensive literature review was performed, analyzing recent findings on histone lactylation and its impact on cancer biology. This involved a systematic examination of studies focusing on biochemical pathways, cellular interactions, and clinical implications related to histone lactylation. RESULTS: Histone lactylation was identified as a critical regulator of tumor cell DNA repair mechanisms and glycolytic metabolic abnormalities. It also significantly influences the functions of non-tumor cells within the TME, promoting tumor inflammatory responses and immune escape. Moreover, histone lactylation acts as a multifunctional biological signaling molecule impacting immune responses within the TME. Various cell types within the TME, including T cells and macrophages, were found to regulate tumor growth and immune escape mechanisms through lactylation. CONCLUSION: Histone lactylation offers a novel perspective on tumor metabolism and its role in cancer development. It presents promising opportunities for the development of innovative cancer therapies. This review underscores the potential of histone lactylation as a therapeutic target, paving the way for new strategies in cancer treatment.

Impact of peptic ulcer bleeding on the in-hospital outcomes of cirrhotic patients with acute gastrointestinal bleeding: an international multicenter study.

OBJECTIVES: Peptic ulcer is the most common source of non-variceal bleeding. However, it remains controversial whether the outcomes of cirrhotic patients with peptic ulcer bleeding differ from those with variceal bleeding. METHODS: Cirrhotic patients with acute gastrointestinal bleeding (AGIB) who underwent endoscopy and had an identifiable source of bleeding were retrospectively screened from an international multicenter cohort. Logistic regression analyses were performed to explore the impact of peptic ulcer bleeding on in-hospital death and 5-day failure to control bleeding. Propensity score matching (PSM) analysis was performed by matching age, gender, Child-Pugh score, and model for end-stage liver disease score between the peptic ulcer bleeding and variceal bleeding groups. RESULTS: Overall, 1535 patients were included, of whom 73 (4.7%) had peptic ulcer bleeding. Multivariate logistic regression analyses showed that peptic ulcer bleeding was not independently associated with in-hospital death (OR = 2.169, p = 0.126) or 5-day failure to control bleeding (OR = 1.230, p = 0.680). PSM analyses demonstrated that both in-hospital mortality (9.7% vs. 6.3%, p = 0.376) and rate of 5-day failure to control bleeding (6.9% vs. 5.4%, p = 0.787) were not significantly different between the two groups. CONCLUSIONS: The impact of peptic ulcer bleeding on the in-hospital outcomes of cirrhotic patients is similar to that of variceal bleeding.

In this international multicenter study, we included 1535 patients with acute gastrointestinal bleeding (AGIB) and divided them into peptic ulcer bleeding and variceal bleeding groups. We found that only a minority of AGIB episodes in cirrhotic patients was attributed to peptic ulcer. Additionally, after adjusting for the severity of liver dysfunction, the in-hospital mortality and the rate of 5-day failure to control bleeding should be similar between cirrhotic patients with peptic ulcer bleeding and those with variceal bleeding.

Complete chloroplast genomes of two Ainsliaea species and the phylogenetic analysis in the tribe Pertyeae.

The genus Ainsliaea DC. is one of the major groups within the tribe Pertyeae (Asteraceae). It comprises several important Chinese medicinal species. However, the phylogenetic position has undergone a long process of exploration. The complete chloroplast (cp) genome sequences data has not been employed in species identification and phylogeny of Ainsliaea. In this study, the complete cp genomes of two Ainsliaea species (A. gracilis and A. henryi) were reported, followed by structural, comparative, and phylogenetic analyses within the tribe Peryteae. Both cp genomes displayed a typical quadripartite circular structure, with the LSC and SSC regions separated by the IR regions. The genomes were 152,959 (A. gracilis) and 152,805 (A. henryi) base pairs (bp) long, with a GC content of 37.6%. They were highly conserved, containing 134 genes, including 87 protein-coding genes, 37 tRNA genes, 8 rRNA genes, and 2 pseudogenes (rps19 and ycf1). Moreover, thirteen highly polymorphic regions (e.g., trnK-UUU, trnG-UCC, trnT-GGU, accD-psaI, and rpl22-rps19) were identified, indicating their potential as DNA barcodes. The phylogenetic analysis confirmed the placement of Ainsliaea in the tribe Pertyeae, revealing close relationships with the genera Myripnois and Pertya. In comparison with Ainsliaea, Myripnois was more closely related to Pertya. This study lays a theoretical foundation for future research on species identification, population genetics, resource conservation, and sustainable utilization within Ainsliaea and Pertyeae.

Strong interaction between promoter and metal in Pd-Ba/TiO2 catalysts for formaldehyde oxidation.

As our previous works found, alkali metals have a common promotion effect on supported noble metals catalysts for formaldehyde (HCHO) oxidation. As second-group elements, alkaline earth metals (AEMs) are neighbors to the first-group elements and share some properties in common. However, detailed investigations into the specific mechanisms underlying AEMs' effects on HCHO oxidation remain limited. In this study, we found that Ba addition showed a similar promotion effect on HCHO oxidation for Pd/TiO2. Ba species stabilized Pd groups, improved the dispersion, and even caused a large number of monatomic-like Pd sites to appear, which may be attributed to the electronic interaction between promoter and metal (EIPM) between Ba and Pd. Besides, AEM loading had the important effect of increasing the electron density of metallic Pd nanoparticles, which further improved the ability for O2 activation and so enhanced the mobility of chemisorbed oxygen on the catalyst surface. For Pd/TiO2, the HCHO oxidation path is mainly HCHO→HCOOH→HCOO→H2O+CO2. By contrast, for Pd-Ba/TiO2, with more surface-active species, the formate intermediate was more likely to be directly oxidized into H2O and CO2, which is a more effective reaction pathway. The details of the EIPM between Pd and Ba were investigated by GPAW (DFT calculation module) in ASE (Atomic Simulation Environment). The AEM Ba acted as an electron donor and could interact with Pd d orbital electrons through BaO sp orbital electrons. Ba species were highly dispersed on the carrier due to the Ba-Ti interaction. Ba species dispersed over large areas stabilized the Pd particles and donated electrons to Pd. Therefore, adding an AEM is an efficacious strategy to improve the performance of the catalytic oxidation of HCHO.

An Integrated Micro-Heating System for On-Chip Isothermal Amplification of African Swine Fever Virus Genes.

The loop-mediated isothermal amplification (LAMP) is widely used in the laboratory to facilitate rapid DNA or RNA detection with a streamlined operational process, whose properties are greatly dependent on the uniformity and rise rate of temperature in the reaction chambers and the design of the primers. This paper introduces a planar micro-heater equipped with an embedded micro-temperature sensor to realize temperature tunability at a low energy cost. Moreover, a control system, based on the Wheatstone bridge and proportional, integral, and derivative (PID) control, is designed to measure and adjust the temperature of the micro-heater. The maximum temperature rise rate of the designed micro-heater is ≈8 °C s-1, and it only takes ≈60 s to reach the target temperature. Furthermore, a designed plasmid, containing the B646L gene of African Swine Fever Virus (ASFV), and a set of specific primers, are used to combine with the designed micro-heating system to implement the LAMP reaction. Finally, the lateral flow assay is used to interpret the amplification results visually. This method can achieve highly sensitive and efficient detection of ASFV within 40 min. The sensitivity of this on-chip gene detection method is 8.4 copies per reaction, holding great potential for applications in DNA and RNA amplification.

Metabolic characteristic profiling of 1-amino-3,3-dimethyl-1-oxobutan-2-yl-derived indole and indazole synthetic cannabinoids in vitro.

Characterizing the metabolic profiles of synthetic cannabinoids (SCs), a type of new psychoactive substances, is of particular importance for forensic detection and analysis. Although the metabolism of individual SCs derived from 1-amino-3,3-dimethyl-1-oxobutan-2-yl (ADB-SCs) has been reported, their metabolites also undergo a continuous change and combination of their tail and core regions. Therefore, elucidating the metabolic characteristics and effects of these structures is essential to enhance our understanding. In this study, the human liver microsome was used as the model for studying the in vitro phase I metabolism of 12 ADB-SCs, and the metabolites obtained were analyzed using ultra-high performance liquid chromatography-tandem four-level rod-electrostatic field orbital ion trap mass spectrometry to determine type, structure, and relative contents. The results indicated that hydroxylation and N-dealkylation were the major metabolic pathways in 12 ADB-SCs. The effects of the core and tail on the metabolism of these ADB-SCs were studied using theoretical calculations. For N-dealkylation metabolism, the strong electron-withdrawing conjugative effect of the -N= moiety in the pyrazole ring, steric hindrance of the tail, and electronic effect of substituents on the tail significantly affected metabolism. Further, it changed the relative contents of N-dealkylation metabolites. For hydroxylation, the reaction types were inconsistent at different parts. For instance, the phenyl group of the core is electrophilic, and its electron cloud density determines whether the phenyl group can be hydroxylated at the specific metabolic sites. Meanwhile, hydroxylation of the neopentyl moiety of the linked group involves the oxidation of aliphatic C-H bonds, whereas amide-hydroxylamine tautomerism affects hydroxylation metabolism. When the alkyl chain in the tail contains functional groups (such as -F and >CC<), oxidative defluorination or dihydrodiol metabolites are produced. Taken together, we systematically determined d the effect of functional groups in the core and tail of ADB-SCs on their metabolism, validating confirmed the feasibility of ADB-SC metabolism prediction based on their structural characteristics.

Comparative analysis of complete chloroplast genomes of Synotis species (Asteraceae, Senecioneae) for identification and phylogenetic analysis.

BACKGROUND: The Synotis (C. B. Clarke) C. Jeffrey & Y. L. Chen is an ecologically important genus of the tribe Senecioneae, family Asteraceae. Because most species of the genus bear similar morphology, traditional morphological identification methods are very difficult to discriminate them. Therefore, it is essential to develop a reliable and effective identification method for Synotis species. In this study, the complete chloroplast (cp.) genomes of four Synotis species, S. cavaleriei (H.Lév.) C. Jeffrey & Y.L. Chen, S. duclouxii (Dunn) C. Jeffrey & Y.L. Chen, S. nagensium (C.B. Clarke) C. Jeffrey & Y.L. Chen and S. erythropappa (Bureau & Franch.) C. Jeffrey & Y. L. Chen had been sequenced using next-generation sequencing technology and reported here. RESULTS: These four cp. genomes exhibited a typical quadripartite structure and contained the large single-copy regions (LSC, 83,288 to 83,399 bp), the small single-copy regions (SSC, 18,262 to 18,287 bp), and the inverted repeat regions (IR, 24,837 to 24,842 bp). Each of the four cp. genomes encoded 134 genes, including 87 protein-coding genes, 37 tRNA genes, 8 rRNA genes, and 2 pseudogenes (ycf1 and rps19). The highly variable regions (trnC-GCA-petN, ccsA-psaC, trnE-UUC-rpoB, ycf1, ccsA and petN) may be used as potential molecular barcodes. The complete cp. genomes sequence of Synotis could be used as the potentially effective super-barcode to accurately identify Synotis species. Phylogenetic analysis demonstrated that the four Synotis species were clustered into a monophyletic group, and they were closed to the Senecio, Crassocephalum and Dendrosenecio in tribe Senecioneae. CONCLUSIONS: This study will be useful for further species identification, evolution, genetic diversity and phylogenetic studies within this genus Synotis and the tribe Senecioneae.

Point-supervised Brain Tumor Segmentation with Box-prompted MedSAM.

Delineating lesions and anatomical structure is important for image-guided interventions. Point-supervised medical image segmentation (PSS) has great potential to alleviate costly expert delineation labeling. However, due to the lack of precise size and boundary guidance, the effectiveness of PSS often falls short of expectations. Although recent vision foundational models, such as the medical segment anything model (MedSAM), have made significant advancements in bounding-box-prompted segmentation, it is not straightforward to utilize point annotation, and is prone to semantic ambiguity. In this preliminary study, we introduce an iterative framework to facilitate semantic-aware point-supervised MedSAM. Specifically, the semantic box-prompt generator (SBPG) module has the capacity to convert the point input into potential pseudo bounding box suggestions, which are explicitly refined by the prototype-based semantic similarity. This is then succeeded by a prompt-guided spatial refinement (PGSR) module that harnesses the exceptional generalizability of MedSAM to infer the segmentation mask, which also updates the box proposal seed in SBPG. Performance can be progressively improved with adequate iterations. We conducted an evaluation on BraTS2018 for the segmentation of whole brain tumors and demonstrated its superior performance compared to traditional PSS methods and on par with box-supervised methods.

Purification of acidic wastewater containing Cd(II) using a red mud-loess mixture: Column test, breakthrough curve, and speciation of Cd.

In this study, the safety of a red mud-loess mixture (RM-L) for the remediation of groundwater polluted by acid mine drainage (AMD) containing Cd(II) in mining areas was systematically analyzed and clarified. The effects of the initial concentration, flow rate, and packing height on the breakthrough performance and longevity of RM-L as a permeable reactive barrier (PRB) packing material were explored by column tests. The results show that the breakthrough time, saturation time, and adsorption capacity of Cd(II) in RM-L increased with decreasing initial concentration and flow rate, as well as increasing packing height. Moreover, RM-L had a long-term effective acid buffering capacity for acidic wastewater containing Cd(II). An increase in the packing height led to a longer longevity of the PRB than the theoretical value. In addition, the speciation of Cd on RM-L was dominated by carbonate form and iron-manganese oxide form. The surface of the RM-L particles evolved from a dense lamellar structure to small globular clusters after purifying the acidic wastewater containing Cd(II), due to the corrosion of H+ and the reoccupation and coverage by increasingly enriched adsorbates and precipitates of heavy metal ions.

Bu-Sui-Dan Enhances Osteoblast Differentiation by Upregulating VGLL4 to Counteract TEAD4-Mediated RUNX2 Transcription Suppression in Ovariectomized Rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Postmenopausal osteoporosis (PMOP) has been considered as a major causative factor for bone-joint pain and inducing pathologic fractures. Bu-Sui-Dan (BSD), a classic ancient herbal formula, has been shown to exhibit osteoprotective effects by promoting bone marrow development and bone growth. However, the exact mechanism of BSD are still unexplored. AIM OF STUDY: The study aimed to investigate the protective effect of BSD against osteoporotic injury, and to explore whether BSD regulated BMSCs' osteogenic differentiation by targeting VGLL4, which in turn improved PMOP. MATERIALS AND METHODS: The anti-osteoporotic effect of BSD was studied in ovariectomized (OVX) rats and bone marrow mesenchymal stem cells (BMSCs). Micro-CT imaging and HE staining were performed, and the levels of osteogenic protein RUNX2 and osteogenesis-related factor VGLL4 were determined. Co-immunoprecipitation (Co-IP) was further employed to delve into the effects of BSD on the interactions between TEAD4 and RUNX2. The key osteogenic factors 1ALP, COLl1A1, and Osterix expression were detected by RT-qPCR. Co-IP and proximity ligation assay (PLA) were employed to scrutinize the influence of BSD on TEAD4 and RUNX2 inter-binding. Moreover, VGLL4 knockdown in BMSCs was conducted to confirm the role of VGLL4 in the therapeutic mechanism of BSD. RESULTS: BSD showed a dose-dependent protective effect against osteoporotic injury, as evidenced by improvement in bone volume, bone microarchitecture, and histomorphometry. Additionally, BSD treatment increased the levels of RUNX2 and its downstream target genes including ALP, COL1A1, and Osterix. Moreover, BSD upregulated VGLL4 expression and lessened TEAD4-RUNX2 interactions. In BMSCs experiment, BSD-containing serum could promote osteogenic differentiation of BMSCs, boosted the expression of osteogenesis-related factors and VGLL4 level. The knockdown of VGLL4 in BMSCs diminished the promotion effect of BSD in osteoblast differentiation, suggesting that VGLL4 play a vital role in the therapeutic effects exerted by BSD. CONCLUSION: BSD ameliorated osteoporosis injury and promoted osteoblast differentiation through upregulation of VGLL4 levels, which in turn antagonized TEAD4-mediated RUNX2 transcriptional repression. Our study implied that BSD may be an osteoporosis therapeutic agent.

Chemotherapy-induced acetylation of ACLY by NAT10 promotes its nuclear accumulation and acetyl-CoA production to drive chemoresistance in hepatocellular carcinoma.

Chemotherapeutic efficacy is seriously impeded by chemoresistance in more than half of hepatocellular carcinoma (HCC) patients. However, the mechanisms involved in chemotherapy-induced upregulation of chemoresistant genes are not fully understood. Here, this study unravels a novel mechanism controlling nuclear acetyl-CoA production to activate the transcription of chemoresistant genes in HCC. NAT10 is upregulated in HCC tissues and its upregulation is correlated with poor prognosis of HCC patients. NAT10 is also upregulated in chemoresistant HCC cells. Targeting NAT10 increases the cytotoxicity of chemotherapy in HCC cells and mouse xenografts. Upon chemotherapy, NAT10 translocates from the nucleolus to the nucleus to activate the transcription of CYP2C9 and PIK3R1. Additionally, nuclear acetyl-CoA is specifically upregulated by NAT10. Mechanistically, NAT10 binds with ACLY in the nucleus and acetylates ACLY at K468 to counteract the SQSTM1-mediated degradation upon chemotherapy. ACLY K468-Ac specifically accumulates in the nucleus and increases nuclear acetyl-CoA production to activate the transcription of CYP2C9 and PIK3R1 through enhancing H3K27ac. Importantly, K468 is required for nuclear localization of ACLY. Significantly, ACLY K468-Ac is upregulated in HCC tissues, and ablation of ACLY K468-Ac sensitizes HCC cells and mouse xenografts to chemotherapy. Collectively, these findings identify NAT10 as a novel chemoresistant driver and the blockage of NAT10-mediated ACLY K468-Ac possesses the potential to attenuate HCC chemoresistance.

Generation and emission mechanism of polycyclic aromatic hydrocarbon (PAHs) during the coking process in Shanxi, China.

Although coking process is the important source of polycyclic aromatic hydrocarbons (PAHs) in the environment, the generation and emission of PAHs during this process is unclear. It is crucial to clarify the formation mechanism of PAHs in coal pyrolysis during the coking process for effectively identifying and controlling the emission of these organic pollutants. In this study, the combination of laboratory simulation and field sampling was used to analyze the mechanism of PAHs formation and emission in coking process. The release of PAHs from the pyrolysis process of coal blends used in coking plants was 1778.20 ± 111.95 µg · g-1, which was much higher than the content of free PAHs in raw coal (76.50 ± 12.46 µg · g-1). 3-ring PAHs were the most abundant components of free PAHs and pyrolysis-generated PAHs. PAH formation during pyrolysis of coal blends was primarily attributed to the cracking of the macromolecular structure of coal, with minimal influence of free PAHs in blended coal. The emission of PAHs from coal-charging was higher (62.93 ± 17.75 µg · m-3) than that from pushing of coke (11.79 ± 1.91 µg · m-3·, PC) and combustion of coke oven gas (5.53 ± 1.20 µg · m-3, CG), and was mainly related to free PAHs in coal. In contrast, the characteristics of PAHs in the flue gas of PC and CG were similar to those from blended coal pyrolysis. PAHs in fugitive emission from coke oven were primarily affected by flue gas leakage and were mainly related to coal pyrolysis and free PAHs in blended coal.

Nucleobase-modulated copper nanomaterials with laccase-like activity for high-performance degradation and detection of phenolic pollutants.

Laccases are the most commonly used agents for the treatment of phenolic pollutants. To address the instability and high cost of natural laccases, we investigated nucleobase-modulated copper nanomaterial with laccase-like activity. Various nucleobases, including adenine, guanine, cytosine, and thymine, were investigated as templates for Cu2+ reduction and copper nanomaterials formation due to their coordination capacity. By comparing structure and catalytic activity, the cytosine-mediated copper nanomaterial (C-Cu) had the best laccase-like activity and other nucleobase-templated copper nanomaterials exhibited low catalytic activity under the same conditions. The mechanism of nucleobase regulation of the catalytic activity of copper nanomaterials was further analyzed using X-ray photoelectron spectroscopy and density functional theory. The possible catalytic mechanisms of C-Cu, including substrate adsorption, substrate oxidation, oxygen binding, and oxygen reduction, were proposed. Remarkably, nucleobase-modulated copper nanozymes showed high stability and catalytic oxidation performance at various pH values, temperatures, long-term storage, and high salinity. In combination with electrochemical techniques, a portable electrochemical sensor for measuring phenolic pollutants was developed. This novel sensor exhibited a good linear response to catechol (10-1000 µM) with a limit of detection of 1.8 µM and excellent selectivity and anti-interference ability. This study provides not only a new strategy for the regulation of the laccase-like activity of copper nanomaterials but also a novel tool for the effective removal and low-cost detection of phenolic pollutants.

Pillar[5]arene-Based Ion-Pair Recognition for Encapsulation of a Stilbazolium-Type Dye with Enhanced Photophysical Properties and Nonlinear Optical Activity.

Constructing organic composite materials through molecular recognition has emerged as an important theme in materials science. Here we report an ion-pair recognition system involving the use of a propoxylated pillar[5]arene (PrP5) to modulate the solid-state photophysical properties of dye trans-4'-(dimethylamino)-N-methyl-4-stilbazolium hexafluorophosphate (DMASP). Single crystal X-ray diffraction analysis reveals that the dye guest DMASP is encapsulated by PrP5 to form a 2 : 1 host-guest complex 2PrP5⸧DMASP in the crystalline state. The macrocyclic skeleton of PrP5 imposes restrictions on the intramolecular motions of the dye guest, leading to a significant enhancement of its fluorescence emission. Additionally, within the 2PrP5⸧DMASP complex crystal structure, DMASP molecules are found to display two possible opposite orientations in the one-dimensional channels formed by PrP5 molecules. This arrangement is believed to alter the overall solid-state packing structure of DMASP, thereby activating its nonlinear optical activity. This work not only reports a novel ion-pair molecular recognition system based on pillararenes but also provides valuable insights into the modulation of the crystalline state photophysical properties of organic dyes via cocrystal engineering.