Evaporate-casting of curvature gradient graphene superstructures for ultra-high strength structural materials.

In contemporary manufacturing, the processing of structural materials plays a pivotal role in enabling the creation of robust, tailor-made, and precise components suitable for diverse industrial applications. Nonetheless, current material forming technologies face challenges due to internal stress and defects, resulting in a substantial decline in both mechanical properties and processing precision. We herein develop a processing strategy toward graphene superstructure with a curvature gradient, which allows us to fabricate robust structural materials with meticulously designed functional shapes. The structure consists of an arc-shaped assembly of graphene nanosheets positioned at co-axial curvature centers. During the dehydration-based evaporate-casting process, the assembly is tightened via capillary effect, inducing local bending. By precisely tuning the axis-center distance and tilt angle, we achieve accurate control over the shape of obtained structure. Notably, internal stress is harnessed to reinforce a designed mortise and tenon structure, resulting in a high joining strength of up to ~200 MPa. This innovative approach addresses the challenges faced by current material forming technologies and opens up more possibilities for the manufacturing of robust and precisely shaped components.

Derivation of water quality criteria for paraquat, bisphenol A and carbamazepine using quantitative structure-activity relationship and species sensitivity distribution (QSAR-SSD).

The risk assessment of an expanding array of emerging contaminants in aquatic ecosystems and the establishment of water quality criteria rely on species sensitivity distribution (SSD), necessitating ample multi-trophic toxicity data. Computational methods, such as quantitative structure-activity relationship (QSAR), enable the prediction of specific toxicity data, thus mitigating the need for costly experimental testing and exposure risk assessment. In this study, robust QSAR models for four aquatic species (Rana pipiens, Crassostrea virginica, Asellus aquaticus, and Lepomis macrochirus) were developed using leave-one-out (LOO) screening variables and the partial least squares algorithm to predict toxicity data for paraquat, bisphenol A, and carbamazepine. These predicted data can be integrated with experimental data to construct SSD models and derive hazardous concentration for 5 % of species (HC5) for the criterion maximum concentration. The chronic water quality criterion for paraquat, bisphenol A, and carbamazepine were determined at 6.7, 11.1, and 3.5 µg/L, respectively. The QSAR-SSD approach presents a viable and cost-effective method for deriving water quality criteria for other emerging contaminants.

Status quo and factors of depression and anxiety in patients with non-muscle invasive bladder cancer after plasma electrocision.

BACKGROUND: Bladder cancer is a type of cancer with a high incidence in men. Plasma electrosurgery (PES) is often used in the treatment of bladder cancer. Postoperative complications often cause depression and anxiety in patients after surgery. AIM: To investigate the current state of depression and anxiety after PES in patients with non-muscle-invasive bladder cancer and analyze the factors affecting them. METHODS: A retrospective study was conducted to compare the baseline data of patients by collecting their medical history and grouping them according to their mental status into negative and normal groups. Logistic regression analysis was used to explore the risk factors affecting the occurrence of anxiety and depression after surgery in patients with bladder cancer. RESULTS: Comparative analyses of baseline differences showed that the patients in the negative and normal groups differed in terms of their first surgery, economic status, educational level, and marital status. A logistic regression analysis showed that it affected the occurrence of anxiety in patients with bladder cancer, and the results showed that whether the risk factors were whether or not it was the first surgery, monthly income between 3000 and 3000-6000, secondary or junior high school education level, single, divorced, and widowed statuses. CONCLUSION: The risk factors affecting the onset of anxiety and depression in bladder cancer patients after PES are the number of surgeries, economic status, level of education, and marital status. This study provides a reference for the clinical treatment and prognosis of bladder cancer patients in the future.

USP7 upregulated by TGF-ß1 promotes ferroptosis via inhibiting LATS1-YAP axis in sepsis-induced acute lung injury.

Our work aimed to investigate the interactive roles of transforming growth factor ß1 (TGF-ß1), ubiquitin-specific-processing protease 7 (USP7), and Yes-associated protein (YAP) in ferroptosis during sepsis-secondary acute lung injury (ALI). Our study demonstrated that ferroptosis was aggravated by TGF-ß1 in both cellular and animal models of acute lung injury. Additionally, YAP upregulated glutathione peroxidase 4 (GPX4) and SLC7A11 by regulating the binding of TEAD4 to GPX4/SLC7A11 promoters. Furthermore, large tumor suppressor kinase 1 (LATS1) knockdown resulted in YAP expression stimulation, while USP7 downregulated YAP via deubiquitinating and stabilizing LATS1/2. YAP overexpression or USP7/LATS1 silencing reduced ferroptosis process, which regulated YAP through a feedback loop. However, TGF-ß1 annulled the repression of ferroptosis by YAP overexpression or LATS1/USP7 knockdown. By elucidating the molecular interactions between TGF-ß1, USP7, LATS1/2, and YAP, we identified a new regulatory axis of ferroptosis in sepsis-secondary ALI. Our study sheds light on the pathophysiology of ferroptosis and proposes a potential therapeutic approach for sepsis-induced ALI.

SCARB2 associates with tumor-infiltrating neutrophils and predicts poor prognosis in breast cancer.

BACKGROUND: The tumor microenvironment (TME) plays a crucial role in various aspects of breast cancer development and metastasis. Nevertheless, the expression, prognostic significance, and correlation with clinical features of SCARB2 in breast cancer, as well as the infiltrative characteristics of TME, remain largely unknown. METHODS: We analyzed the differential presentation of SCARB2 mRNA in breast cancer tissues and nontumorous breast tissues and prognosis by The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Additionally, the Tumor Immunity Estimation Resource (TIMER) was taken to evaluate the correlation between SCARB2 mRNA presence and tumor-infiltrating immune cells and immune checkpoints in the TME in breast cancer. We performed multiple immunohistochemical staining to verify the SCARB2 protein expression in breast cancer tissues and its relationship to immune cells and checkpoints and clinicopathological features. RESULTS: We identified elevated SCARB2 expression in breast cancer tissues, and high SCARB2 protein presentation was associated with advanced clinical stage and unfavorable prognosis. In addition, enhanced SCARB2 protein presence was closely correlated with up-regulation CD66b+ neutrophils infiltration in tumor tissues (r = 0.210, P < 0.05) and CD68 + CD163+ M2 macrophages in the interstitium (r = 0.233, P < 0.05), as well as the immune checkpoints, including PD-1 (r = 0.314, P < 0.01) protein expression. CONCLUSION: SCARB2 holds promise for predicting the clinical outcome of breast cancer patients and could serve as a potential therapeutic target.

Structure Factors for Hot Neutron Matter from Ab Initio Lattice Simulations with High-Fidelity Chiral Interactions.

We present the first ab initio lattice calculations of spin and density correlations in hot neutron matter using high-fidelity interactions at next-to-next-to-next-to-leading order in chiral effective field theory. These correlations have a large impact on neutrino heating and shock revival in core-collapse supernovae and are encapsulated in functions called structure factors. Unfortunately, calculations of structure factors using high-fidelity chiral interactions were well out of reach using existing computational methods. In this Letter, we solve the problem using a computational approach called the rank-one operator (RO) method. The RO method is a general technique with broad applications to simulations of fermionic many-body systems. It solves the problem of exponential scaling of computational effort when using perturbation theory for higher-body operators and higher-order corrections. Using the RO method, we compute the vector and axial static structure factors for hot neutron matter as a function of temperature and density. The ab initio lattice results are in good agreement with virial expansion calculations at low densities but are more reliable at higher densities. Random phase approximation codes used to estimate neutrino opacity in core-collapse supernovae simulations can now be calibrated with ab initio lattice calculations.

Causal relationships between gut microbiota, gut metabolites, and diabetic neuropathy: A mendelian randomization study.

BACKGROUND: Previous studies have shown a strong correlation between gut microbiota and diabetes and its associated complications. We aimed to evaluate the causal relationships between the gut microbiota, gut metabolites, and diabetic neuropathy. METHODS: Summary statistics of 211 gut microbiota and 12 gut-related metabolites (ß-hydroxybutyric acid, betaine, trimethylamine-N-oxide, carnitine, choline, glutamate, kynurenine, phenylalanine, propionic acid, serotonin, tryptophan, and tyrosine) were obtained from previous genome-wide association studies (GWAS). A two-sample Mendelian randomization (MR) design was used to estimate the effects of gut microbiota and gut metabolites on the risk of diabetic neuropathy based on FinnGen GWAS. RESULTS: Higher levels of Acidaminococcaceae (OR = 0.62; 95%CI = 0.46 to 0.84; P = 0.002), Peptococcaceae (OR = 0.70; 95%CI = 0.54 to 0.90; P = 0.006), and Eubacterium coprostanoligenes group (OR = 0.68; 95%CI = 0.50 to 0.93; P = 0.016) are genetically determined to provide protection against diabetic neuropathy. Conversely, the presence of Alistipes (OR = 1.65; 95%CI = 1.18 to 2.31; P = 0.003), ChristensenellaceaeR7 group (OR = 1.52; 95%CI = 1.03 to 2.23; P = 0.033), Eggerthella (OR = 1.28; 95%CI = 1.05 to 1.55; P = 0.014), RuminococcaceaeUCG013 (OR = 1.35; 95%CI = 1.01 to 1.82; P = 0.046), and Firmicutes (OR = 1.42; 95%CI = 1.05 to 1.93; P = 0.023) increases the risk of diabetic neuropathy. Moreover, a correlation has been identified between diabetic neuropathy and two gut metabolites: betaine (OR = 0.95; 95%CI = 0.90 to 1.00; P = 0.033) and tyrosine (OR = 1.03; 95%CI = 1.01 to 1.06; P = 0.019). Sensitivity analysis indicated robust results with no sign of heterogeneity or pleiotropy. CONCLUSION: The present study elucidated the impact of specific gut microbiota and gut metabolites on the susceptibility to diabetic neuropathy. Interventions targeting the improvement of the gut microbiota diversity and composition hold considerable promise as a potential strategy.

Chemokine ligand 14 correlates with immune cell infiltration in the gastric cancer microenvironment in predicting unfavorable prognosis.

Objective: Gastric cancer (GC) is the world's third-leading cause of cancer-related mortality; the prognosis for GC patients remains poor in terms of a lack of reliable biomarkers for early diagnosis and immune therapy response prediction. Here, we aim to discover the connection between chemokine ligand 14 (CCL14) expression in the gastric tumor microenvironment (TME) and its clinical significance and investigate its correlation with immune cell infiltration. Methods: We assessed CCL14 mRNA expression and its interrelation with tumor-infiltrating immune cells (TILs) using bioinformatics analysis in gastric cancer. CCL14 protein expression, TILs, and immune checkpoints were detected by multiple immunohistochemistry analyses in gastric cancer tissue microarrays. Then, we conducted statistics analysis to determine the association between CCL14-related patient survival and immune cell infiltration (p < 0.05). Results: We found that the CCL14 protein was separately expressed in the carcinoma cells and TILs in stomach cancer tissues. The CCL14 protein was related to tumor differentiation and tumor depth and positively correlated with the presentation of LAG3 and PD-L1 in gastric cancer cells. In addition, the CCL14 protein in the TILs of gastric cancer tissues was related to Lauren's type cells, T cells (CD4+ and CD8+), and CD68+ macrophages in the TME. Kaplan-Meier survival and multivariate analyses showed that the CCL14 expression in gastric cancer cells was an independent prognostic factor. Conclusion: Our study illustrated that CCL14 is a poor prognosis biomarker in gastric cancer, which may be associated with the potential for immunotherapy.

Histamine-related genes participate in the establishment of an immunosuppressive microenvironment and impact the immunotherapy response in hepatocellular carcinoma.

Chronic inflammation is pivotal in the pathogenesis of hepatocellular carcinoma (HCC). Histamine is a biologically active substance that amplifies the inflammatory and immune response and serves as a neurotransmitter. However, knowledge of histamine's role in HCC and its effects on immunotherapy remains lacking. We focused on histamine-related genes to investigate their potential role in HCC. The RNA-seq data and clinical information regarding HCC were obtained from The Cancer Genome Atlas (TCGA). After identifying the differentially expressed genes, we constructed a signature using the univariate Cox proportional hazard regression and least absolute shrinkage and selection operator (LASSO) analyses. The signature's predictive performance was evaluated using a receiver operating characteristic curve (ROC) analysis. Furthermore, drug sensitivity, immunotherapy effects, and enrichment analyses were conducted. Histamine-related gene expression in HCC was confirmed using quantitative real-time polymerase chain reaction (qRT-PCR). A histamine-related gene prognostic signature (HRGPS) was developed in TCGA. Time-dependent ROC and Kaplan-Meier survival analyses demonstrated the signature's strong predictive power. Importantly, patients in high-risk groups exhibited a higher frequency of TP53 mutations, elevated immune checkpoint-related gene expression, and increased infiltration of immunosuppressive cells-indicating a potentially favorable response to immunotherapy. In addition, drug sensitivity analysis revealed that the signature could effectively predict chemotherapy efficacy and sensitivity. qRT-PCR results validated histamine-related gene overexpression in HCC. Our findings demonstrate that inhibiting histamine-related genes and signaling pathways can impact the therapeutic effect of anti-PD-1/PD-L1. The precise predictive ability of our signature in determining the response to different therapeutic options highlights its potential clinical significance.

Reduced sensitivity to thyroid hormones is associated with lung function in euthyroid individuals.

Background: The thyroid gland exhibits a subtle interconnection with the lungs. We further investigated the correlation between thyroid hormone sensitivity and lung function in euthyroid individuals. Methods: Data on spirometry and mortality for participants aged 19-79 years were extracted from the NHANES database. Obstructive lung function was defined as a forced expiratory volume in 1 s to forced vital capacity ratio (FEV1/FVC) < 0.70, while restrictive lung function was considered when FEV1/FVC ≥0.70 and baseline FVC <80 % predicted. Central and peripheral sensitivities to thyroid hormones were mainly evaluated by Thyroid Feedback Quantile-based Index (TFQI) and Free Triiodothyronine/Free thyroxine (FT3/FT4) ratio. Logistic regression and subgroup analysis were used to examine potential associations between thyroid hormone sensitivity and lung function. The association between TFQI and all-cause mortality risk was also investigated. Results: A total of 6539 participants were analyzed, 900 with obstructive lung function and 407 with restrictive lung function. The prevalence of impaired lung function, both obstructive and restrictive, increased with higher TFQI levels. Logistic regression analysis showed that increased TFQI and decreased FT3/FT4 levels were independent risk factors for obstructive and restrictive lung function (P < 0.05). After adjusting for the impact of lung function, TFQI (HR = 1.25, 95 % CI 1.00-1.56, P = 0.048) was an independent risk factor for all-cause mortality. Conclusion: Reduced sensitivity to thyroid hormones has been linked to impaired lung function. TFQI and FT3/FT4 are potential epidemiological tools to quantify the role of central and peripheral thyroid resistance in lung function.

PD-1 Inhibitor Aggravate Irradiation-Induced Myocardial Fibrosis by Regulating TGF-ß1/Smads Signaling Pathway via GSDMD-Mediated Pyroptosis.

Cancer therapy has entered a new era with the use of programmed cell death protein 1 (PD-1) immune checkpoint inhibitors. When combined with thoracic radiotherapy, it demonstrates synergistic anti-tumor effects and potentially worsens radiation-induced myocardial fibrosis (RIMF). RIMF is the final stage of radiation-induced heart disease (RIHD) and a potentially fatal clinical complication of chest radiotherapy. It is characterized by decreased ventricular elasticity and distensibility, which can result in decreased ejection fraction, heart failure, and even sudden cardiac death. Pyroptosis, a type of programmed cell death, is mediated by members of the gasdermin (GSDM) family and has been associated with numerous cardiac disorders. The effect of pyroptosis on myocardial fibrosis caused by a combination of radiotherapy and PD-1 inhibitors remains uncertain. In this study, a 6MV X-ray of 20 Gy for local heart irradiation was used in the RIHD mouse model. We noticed that PD-1 inhibitors aggravated radiation-induced cardiac dysfunction and RIMF, concurrently enhancing the presence of CD8+ T lymphocytes in the cardiac tissue. Additionally, our findings indicated that the combination of PD-1 inhibitor and thoracic radiation can stimulate caspase-1 to cleave GSDMD, thereby regulating pyroptosis and liberating interleukin-8 (IL-18). In the myocardium of mice, the manifestation of pyroptosis mediated by GSDMD is accompanied by the buildup of proteins associated with fibrosis, such as collagen I, transforming growth factor ß1 (TGF-ß1), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor α (TNF-α). Moreover, it was discovered that TFG-ß1 induced the phosphorylation of Smad2/Smad3 when the cardiac underwent PD-1 inhibitor in conjunction with thoracic irradiation (IR). The findings of this research indicate that PD-1 inhibitor worsen RIMF in mice by triggering GSDMD-induced pyroptosis and influencing the TGF-ß1/Smads pathway. While using the caspase-1 inhibitor Z-YVAD-FMK, RIMF can be alleviated. Blocking GSDMD may be a viable strategy for managing myocardial fibrosis caused by the combination of PD-1 inhibitors and radiotherapy.

Characterization of mechanical stress in the occurrence of cortical opacification in age-related cataracts using three-dimensional finite element model of the human lens and RNA-seq.

Cataract is the leading cause of blindness across the world. Age-related cataract (ARC) is the most common type of cataract, but its pathogenesis is not fully understood. Using three-dimensional finite element modeling combining experimental biotechnology, our study demonstrates that external forces during accommodation cause mechanical stress predominantly in lens cortex, basically matching the localization of opacities in cortical ARCs. We identified the cellular senescence and upregulation of PIEZO1 mRNA in HLECs under mechanical stretch. This mechano-induced senescence in HLECs might be mediated by PIEZO1-related pathways, portraying a potential biomechanical cause of cortical ARCs. Our study updates the fundamental insight towards cataractogenesis, paving the way for further exploration of ARCs pathogenesis and nonsurgical treatment.

Modulation of long noncoding RNAs by polyphenols as a novel potential therapeutic approach in lung cancer: A comprehensive review.

Lung cancer stands as a formidable global health challenge, necessitating innovative therapeutic strategies. Polyphenols, bioactive compounds synthesized by plants, have garnered attention for their diverse health benefits, particularly in combating various cancers, including lung cancer. The advent of whole-genome and transcriptome sequencing technologies has illuminated the pivotal roles of long noncoding RNAs (lncRNAs), operating at epigenetic, transcriptional, and posttranscriptional levels, in cancer progression. This review comprehensively explores the impact of polyphenols on both oncogenic and tumor-suppressive lncRNAs in lung cancer, elucidating on their intricate regulatory mechanisms. The comprehensive examination extends to the potential synergies when combining polyphenols with conventional treatments like chemotherapy, radiation, and immunotherapy. Recognizing the heterogeneity of lung cancer subtypes, the review emphasizes the need for the integration of nanotechnology for optimized polyphenol delivery and personalized therapeutic approaches. In conclusion, we collect the latest research, offering a holistic overview of the evolving landscape of polyphenol-mediated modulation of lncRNAs in lung cancer therapy. The integration of polyphenols and lncRNAs into multidimensional treatment strategies holds promise for enhancing therapeutic efficacy and navigating the challenges associated with lung cancer treatment.

Wavefunction matching for solving quantum many-body problems.

Ab initio calculations have an essential role in our fundamental understanding of quantum many-body systems across many subfields, from strongly correlated fermions1-3 to quantum chemistry4-6 and from atomic and molecular systems7-9 to nuclear physics10-14. One of the primary challenges is to perform accurate calculations for systems where the interactions may be complicated and difficult for the chosen computational method to handle. Here we address the problem by introducing an approach called wavefunction matching. Wavefunction matching transforms the interaction between particles so that the wavefunctions up to some finite range match that of an easily computable interaction. This allows for calculations of systems that would otherwise be impossible owing to problems such as Monte Carlo sign cancellations. We apply the method to lattice Monte Carlo simulations15,16 of light nuclei, medium-mass nuclei, neutron matter and nuclear matter. We use high-fidelity chiral effective field theory interactions17,18 and find good agreement with empirical data. These results are accompanied by insights on the nuclear interactions that may help to resolve long-standing challenges in accurately reproducing nuclear binding energies, charge radii and nuclear-matter saturation in ab initio calculations19,20.

Genomic Insights into the First Emergence of blaNDM-5-Carrying Carbapenem-Resistant Salmonella enterica Serovar London Strain in China.

Carbapenem-resistant Salmonella enterica (S. enterica) pose a significant threat to public health, causing gastroenteritis and invasive infections. We report the first emergence of a carbapenem-resistant S. enterica serovar London strain, A132, carrying the blaNDM-5 gene in China. Whole-genome sequencing and bioinformatics analysis assigned A132 to be ST155, a multidrug-resistant clone frequently reported in China. The strain A132 exhibited resistance to multiple antibiotics, with 20 acquired antibiotic resistance genes (ARGs) identified, predominantly located on the IncFIB plasmid (pA132-1-NDM). Notably, the blaNDM-5 gene was located within an IS26 flanked-class 1 integron-ISCR1 complex, comprising two genetic cassettes. One cassette is the class 1 integron, which may facilitate the transmission of the entire complex, while the other is the blaNDM-5-containing ISCR1-IS26-flanked cassette, carrying multiple other ARGs. Genbank database search based on the blaNDM-5-carrying cassette identified a similar genetic context found in transmissible IncFIA plasmids from Escherichia coli (p91) and Enterobacter hormaechei (p388) with a shared host range, suggesting the potential for cross-species transmission of blaNDM-5. To our knowledge, this is the first reported case of Salmonella serovar London ST155 harboring blaNDM-5 gene. Phylogenetic analysis indicated a close relationship between A132 and eight S. London ST155 strains isolated from the same province. However, A132 differed by carrying the blaNDM-5 gene and four unique ARGs. Given the high transmissibility of the F-type plasmid harboring blaNDM-5 and 18 other ARGs, it is imperative to implement vigilant surveillance and adopt appropriate infection control measures to mitigate the threat to public health.

Radiomic features of the medial meniscus predicts incident destabilizing meniscal tears: Data from the osteoarthritis initiative.

The objective of this study was to determine the optimal meniscal radiomic features to classify people who will develop an incident destabilizing medial meniscal tear. We used magnetic resonance (MR) images from an existing case-control study that includes images from the first 4 years of the Osteoarthritis Initiative (OAI). For this exploratory analysis (n = 215), we limited our study sample to people with (1) intact menisci at the OAI baseline visit, (2) 4-year meniscal status data, and (3) complete meniscal data from each region of interest. Incident destabilizing meniscal tear was defined as progressing from an intact meniscus to a destabilizing tear by the 48-month visit using intermediate-weighted fat-suppressed MR images. One reader manually segmented each participant's anterior and posterior horn of the medial menisci at the OAI baseline visit. Next, 61 different radiomic features were extracted from each medial meniscus horn. We performed a classification and regression tree (CART) analysis to determine the classification rules and important variables that predict incident destabilizing meniscal tear. The CART correctly classified 24 of the 34 cases and 172 out of 181 controls with a sensitivity of 70.6% and a specificity of 95.0%. The CART identified large zone high gray level emphasis (i.e., more coarse texture) from the posterior horn as the most important variable to classify who would develop an incident destabilizing medial meniscal tear. The use of radiomic features provides sensitive and quantitative measures of meniscal alterations, allowing us to intervene and prevent destabilizing meniscal tears.

LncRNA PCED1B-AS1 mediates miR-3681-3p/MAP2K7 axis to promote metastasis, invasion and EMT in gastric cancer.

BACKGROUND: LncRNA PCED1B-AS1 is abnormally expressed in multiple cancers and has been confirmed as an oncogene. Our study aimed to investigate the regulatory mechanism of lncRNA PCED1B-AS1 in gastric cancer. METHODS: TCGA database was used to analyze the abnormal expression of lncRNA PCED1B-AS1 in gastric cancer. By database prediction and mass spectrometric analysis, miR-3681-3p and MAP2K7 are potential downstream target molecules of lncRNA PCED1B-AS1 and verified by dual-luciferase report assay. RT-qPCR analysis and western blot were performed to detect the expressions of PCED1B-AS1 and MAP2K7 in gastric cancer cell lines and tissues. CCK-8 kit was applied to measure the cell viability. Wound healing and Transwell experiment were used to detect the migration and invasion. Western blot and immunohistochemical staining were performed to detect the expressions of EMT-related proteins in tissues. The changes of tumor proliferation were detected by xenograft experiment in nude mice. RESULTS: PCED1B-AS1 expression was higher but miR-3681-3 expression was lower in gastric cancer cell lines or tissues, compared to normal group. Function analysis verified PCED1B-AS1 promoted cell proliferation and inhibited cell apoptosis in gastric cancer cells in vitro and in vivo. LncRNA PCED1B-AS1 could bind directly to miR-3681-3p, and MAP2K7 was found to be a downstream target of miR-3681-3p. MiR-3681-3p mimics or si-MAP2K7 could partly reverse the effect of PCED1B-AS1 on gastric cancer cells. CONCLUSION: PCED1B-AS1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-3681-3p to upregulate MAP2K7 expression in gastric cancer, which indicated PCED1B-AS1/miR-3681-3p/MAP2K7 axis may serve as a potential therapeutic target for gastric cancer.

The DNA damage-independent ATM signalling maintains CBP/DOT1L axis in MLL rearranged acute myeloid leukaemia.

The long-term maintenance of leukaemia stem cells (LSCs) is responsible for the high degree of malignancy in MLL (mixed-lineage leukaemia) rearranged acute myeloid leukaemia (AML). The DNA damage response (DDR) and DOT1L/H3K79me pathways are required to maintain LSCs in MLLr-AML, but little is known about their interplay. This study revealed that the DDR enzyme ATM regulates the maintenance of LSCs in MLLr-AML with a sequential protein-posttranslational-modification manner via CBP-DOT1L. We identified the phosphorylation of CBP by ATM, which confers the stability of CBP by preventing its proteasomal degradation, and characterised the acetylation of DOT1L by CBP, which mediates the high level of H3K79me2 for the expression of leukaemia genes in MLLr-AML. In addition, we revealed that the regulation of CBP-DOT1L axis in MLLr-AML by ATM was independent of DNA damage activation. Our findings provide insight into the signalling pathways involoved in MLLr-AML and broaden the understanding of the role of DDR enzymes beyond processing DNA damage, as well as identigying them as potent cancer targets.

Inorganic Pyrophosphate at Serum Concentration May Not Be Able to Inhibit Mineralization: A Study in Aqueous Solutions and Serum.

The constituent ions of calcium phosphate in body fluids are in the supersaturated state and tend to form minerals physiologically or pathologically. Inorganic pyrophosphate (PPi) has been considered as one of the most important inhibitors against the formation of calcium phosphate minerals. However, serum PPi concentrations in humans are maintained at a level of several µmol/L, and its effectiveness and mechanism for mineralization inhibition remain ambiguous. Therefore, this work studied the mineralization process in an aqueous solution, explored the effective inhibitory concentration of PPi by titration, and characterized the species during the reactions. We find that PPi at a normal serum concentration does not inhibit mineralization significantly. Such a conclusion was further confirmed in the PPi-added serum. This work indicates that PPi may not be a major direct inhibitor of mineralization in serum and possibly functions via alternative mechanisms.

Numerical simulation study on the evolution law of mechanical properties of different metamorphic coals after heat treatment.

In order to study the effect of temperature on the structure and mechanical properties of coal with different metamorphic degree. Three coal samples with varying degrees of metamorphism were chosen for analysis. The discrete element software PFC2D is used to simulate the heat treatment and compression of coal. The findings indicate that during the heating process, low-order coal exhibits noticeable thermal cracks at an early stage, while thermal crack development in middle-order coal is concentrated in the later stages. In contrast, high-order coal demonstrates a more stable macroscopic structure. The strength and stiffness of low rank coal show the lowest value and decrease significantly within 135 °C. However, the strength and stiffness of medium rank coal decrease significantly after 135 °C. The changes of mechanical properties and damage modes of coal caused by thermal damage are often ignored, which may lead to the deviation of design and research results from the actual situation. Therefore, this study is of great significance to the prevention and control of coal mine disasters.