Intestinal lymphatic transport of Smilax china L. pectic polysaccharide via Peyer's patches and its uptake and transport mechanisms in mononuclear phagocytes.

Recently, the intestinal lymphatic transport based on Peyer's patches (PPs) is emerging as a promising absorption pathway for natural polysaccharides. Herein, the aim of this study is to investigate the PP-based oral absorption of a pectic polysaccharide from Smilax china L. (SCLP), as well as its uptake and transport mechanisms in related immune cells. Taking advantages of the traceability of fluorescently labeled SCLP, we confirmed that SCLP could be absorbed into PPs and captured by their mononuclear phagocytes (dendritic cells and macrophages) following oral administration. Subsequently, the systematic in vitro study suggested that the endocytic mechanisms of SCLP by model mononuclear phagocytes (BMDCs and RAW264.7 cells) mainly involved caveolae-mediated endocytosis, macropinocytosis and phagocytosis. More importantly, SCLP directly binds and interacts with toll-like receptor 2 (TLR2) and galectin 3 (Gal-3) receptor, and was taken up by mononuclear phagocytes in receptor-mediated manner. After internalization, SCLP was intracellularly transported primarily through endolysosomal pathway and ultimately localized in lysosomes. In summary, this work reveals novel information and perspectives about the in vivo fate of SCLP, which will contribute to further research and utilization of SCLP and other pectic polysaccharides.

Elucidation of Chalkophomycin Biosynthesis Reveals N-Hydroxypyrrole-Forming Enzymes.

Reactive functional groups, such as N-nitrosamines, impart unique bioactivities to the natural products in which they are found. Recent work has illuminated enzymatic N-nitrosation reactions in microbial natural product biosynthesis, motivating interest in discovering additional metabolites constructed using such reactivity. Here, we use a genome mining approach to identify over 400 cryptic biosynthetic gene clusters (BGCs) encoding homologues of the N-nitrosating biosynthetic enzyme SznF, including the BGC for chalkophomycin, a CuII-binding metabolite that contains a C-type diazeniumdiolate and N-hydroxypyrrole. Characterizing chalkophomycin biosynthetic enzymes reveals previously unknown enzymes responsible for N-hydroxypyrrole biosynthesis, including the first prolyl-N-hydroxylase, and a key step in the assembly of the diazeniumdiolate-containing amino acid graminine. Discovery of this pathway enriches our understanding of the biosynthetic logic employed in constructing unusual heteroatom-heteroatom bond-containing functional groups, enabling future efforts in natural product discovery and biocatalysis.

Influence of genetic polymorphisms on imatinib concentration and therapeutic response in patients with chronic-phase chronic myeloid leukemia.

BACKGROUND: Diminished bioavailability of imatinib in leukemic cells contributes to poor clinical response. We examined the impact of genetic polymorphisms of imatinib on the pharmacokinetics and clinical response in 190 patients with chronic myeloid leukaemia (CML). METHODS: Single nucleotide polymorphisms were genotyped using pyrophosphate sequencing. Plasma trough levels of imatinib were measured using liquid chromatography-tandem mass spectrometry. RESULTS: Patients carrying the TT genotype for ABCB1 (rs1045642, rs2032582, and rs1128503), GG genotype for CYP3A5-rs776746 and AA genotype for ABCG2-rs2231142 polymorphisms showed higher concentration of imatinib. Patients with T allele for ABCB1 (rs1045642, rs2032582, and rs1128503), A allele for ABCG2-rs2231142, and G allele for CYP3A5-rs776746 polymorphisms showed better cytogenetic response and molecular response. In multivariate analysis, carriers of the CYP3A5-rs776746 G allele exhibited higher rates of complete cytogenetic response (CCyR) and major molecular response (MMR). Similarly, patients with the T allele of ABCB1-rs1045642 and rs1128503 demonstrated significantly increased CCyR rates. Patients with the A allele of ABCG2-rs2231142 were associated with higher MMR rates. The AA genotype for CYP3A5-rs776746, and the CC genotype for ABCB1-rs104562, and rs1128503 polymorphisms were associated with a higher risk of imatinib failure. Patients with the G allele for CYP3A5-rs776746 exhibited a higher incidence of anemia, and T allele for ABCB1-rs2032582 demonstrated an increased incidence of diarrhea. CONCLUSIONS: Genotyping of ABCB1, ABCG2, and CYP3A5 genes may be considered in the management of patients with CML to tailor therapy and optimize clinical outcomes.

Potential Anti-Gouty Arthritis of Citronella Essential Oil and Nutmeg Essential Oil through Reducing Oxidative Stress and Inhibiting PI3K/Akt/mTOR Activation-Induced NLRP3 Activity.

Citronella and Nutmeg are two common spices used for seasoning and medicinal purposes, both of which have significant economic value. This study aimed to investigate whether Citronella essential oil and Nutmeg essential oil (NEO) can ameliorate monosodium urate (MSU)-induced gouty arthritis in rats and the potential mechanisms. The results showed that CEO and NEO reduced swelling and redness at joint sites, inhibited neutrophil infiltration, and limited proinflammatory mediator secretion in mice with MSU-induced gouty arthritis. Based on the results of network pharmacology, molecular docking, and western blotting, CEO and NEO may exert anti-gouty arthritis effects by reducing the expression of reactive oxygen species and oxidative stress and downregulating the phosphorylation of the PI3K/AKT/mTOR signaling pathway, thereby inhibiting the production of the NLRP3 inflammasome and inhibiting the production of inflammatory cytokines. Therefore, these two essential oils show potential for use as adjuvant treatments for gouty arthritis in specific aromatherapy products or food seasonings.

Light-responsive and ultrapermeable two-dimensional metal-organic framework membrane for efficient ionic energy harvesting.

Nanofluidic membranes offer exceptional promise for osmotic energy conversion, but the challenge of balancing ionic selectivity and permeability persists. Here, we present a bionic nanofluidic system based on two-dimensional (2D) copper tetra-(4-carboxyphenyl) porphyrin framework (Cu-TCPP). The inherent nanoporous structure and horizontal interlayer channels endow the Cu-TCPP membrane with ultrahigh ion permeability and allow for a power density of 16.64 W m-2, surpassing state of-the-art nanochannel membranes. Moreover, leveraging the photo-thermal property of Cu-TCPP, light-controlled ion active transport is realized even under natural sunlight. By combining solar energy with salinity gradient, the driving force for ion transport is reinforced, leading to further improvements in energy conversion performance. Notably, light could even eliminate the need for salinity gradient, achieving a power density of 0.82 W m-2 in a symmetric solution system. Our work introduces a new perspective on developing advanced membranes for solar/ionic energy conversion and extends the concept of salinity energy to a notion of ionic energy.

CoNiO2/Co3O4 Nanosheets on Boron Doped Diamond for Supercapacitor Electrodes.

Developing novel supercapacitor electrodes with high energy density and good cycle stability has aroused great interest. Herein, the vertically aligned CoNiO2/Co3O4 nanosheet arrays anchored on boron doped diamond (BDD) films are designed and fabricated by a simple one-step electrodeposition method. The CoNiO2/Co3O4/BDD electrode possesses a large specific capacitance (214 mF cm-2) and a long-term capacitance retention (85.9% after 10,000 cycles), which is attributed to the unique two-dimensional nanosheet architecture, high conductivity of CoNiO2/Co3O4 and the wide potential window of diamond. Nanosheet materials with an ultrathin thickness can decrease the diffusion length of ions, increase the contact area with electrolyte, as well as improve active material utilization, which leads to an enhanced electrochemical performance. Additionally, CoNiO2/Co3O4/BDD is fabricated as the positive electrode with activated carbon as the negative electrode, this assembled asymmetric supercapacitor exhibits an energy density of 7.5 W h kg-1 at a power density of 330.5 W kg-1 and capacity retention rate of 97.4% after 10,000 cycles in 6 M KOH. This work would provide insights into the design of advanced electrode materials for high-performance supercapacitors.

Elucidation of chalkophomycin biosynthesis reveals N-hydroxypyrrole-forming enzymes.

Reactive functional groups, such as N-nitrosamines, impart unique bioactivities to the natural products in which they are found. Recent work has illuminated enzymatic N-nitrosation reactions in microbial natural product biosynthesis, motivating an interest in discovering additional metabolites constructed using such reactivity. Here, we use a genome mining approach to identify over 400 cryptic biosynthetic gene clusters (BGCs) encoding homologs of the N-nitrosating biosynthetic enzyme SznF, including the BGC for chalkophomycin, a CuII-binding metabolite that contains a C-type diazeniumdiolate and N-hydroxypyrrole. Characterizing chalkophomycin biosynthetic enzymes reveals previously unknown enzymes responsible for N-hydroxypyrrole biosynthesis, including the first prolyl-N-hydroxylase, and a key step in assembly of the diazeniumdiolate-containing amino acid graminine. Discovery of this pathway enriches our understanding of the biosynthetic logic employed in constructing unusual heteroatom-heteroatom bond-containing functional groups, enabling future efforts in natural product discovery and biocatalysis.

Spatial distribution of intangible cultural heritage resources in China and its influencing factors.

Exploring the spatial distribution of China's intangible cultural heritage resources and its influencing factors is an important foundation for their protection and development and a key step toward the integration of culture and tourism. To analyse the geographical distribution patterns of China's 3610 intangible cultural heritage resources and their influencing factors, we comprehensively applied methods such as spatial analysis and geodetectors. The main findings are as follows: (1) In terms of spatial distribution, China's intangible cultural heritage resources are unevenly distributed, with an overall agglomeration-type distribution. The distribution in the north‒south direction is more significant, with more resources in the east than in the west and more resources in the south than in the north. (2) In terms of the spatial distribution of various types of intangible cultural heritage sites, North and East China have always been areas with a high kernel density. (3) In terms of spatial trends, there is a clear correlation between the distribution of intangible cultural heritage resources and the state of economic development and historical and cultural heritage, i.e., the more economically developed and culturally rich a region is, the more resources of intangible cultural heritage there are. (4) The causes of the distribution of China's intangible cultural heritage resources are complicated, the influence of social factors is much greater than that of natural factors, and multidimensional interactions have a relatively significant impact. This study is conducive to the planning and protection of China's intangible cultural heritage resources at the national and regional levels and provides a reference for the sustainable development of China's intangible cultural heritage resources.

Unlocking osmotic energy harvesting potential in challenging real-world hypersaline environments through vermiculite-based hetero-nanochannels.

Nanochannel membranes have demonstrated remarkable potential for osmotic energy harvesting; however, their efficiency in practical high-salinity systems is hindered by reduced ion selectivity. Here, we propose a dual-separation transport strategy by constructing a two-dimensional (2D) vermiculite (VMT)-based heterogeneous nanofluidic system via an eco-friendly and scalable method. The cations are initially separated and enriched in micropores of substrates during the transmembrane diffusion, followed by secondary precise sieving in ultra-thin VMT laminates with high ion flux. Resultantly, our nanofluidic system demonstrates efficient osmotic energy harvesting performance, especially in hypersaline environment. Notably, we achieve a maximum power density of 33.76 W m-2, a 6.2-fold improvement with a ten-fold increase in salinity gradient, surpassing state-of-the-art nanochannel membranes under challenging conditions. Additionally, we confirm practical hypersaline osmotic power generation using various natural salt-lake brines, achieving a power density of 25.9 W m-2. This work triggers the hopes for practical blue energy conversion using advanced nanoarchitecture.

The facilitating effects of KRT80 on chemoresistance, lipogenesis, and invasion of esophageal cancer.

Keratin 80 (KRT80) is a filament protein that makes up one of the major structural fibers of epithelial cells, and involved in cell differentiation and epithelial barrier integrity. Here, KRT80 mRNA expression was found to be higher in esophageal cancer than normal epithelium by RT-PCR and bioinformatics analysis (p < .05), opposite to KRT80 methylation (p < .05). There was a negative relationship between promoter methylation and expression level of KRT80 gene in esophageal cancer (p < .05). KRT80 mRNA expression was positively correlated with the differentiation, infiltration of immune cells, and poor prognosis of esophageal cancer (p < .05). KRT80 mRNA expression was positively linked to no infiltration of immune cells, the short survival time of esophageal cancers (p < .05). The differential genes of KRT80 mRNA were involved in fat digestion and metabolism, peptidase inhibitor, and intermediate filament, desosome, keratinocyte differentiation, epidermis development, keratinization, ECM regulator, complement cascade, metabolism of vitamins and co-factor (p < .05). KRT-80-related genes were classified into endocytosis, cell adhesion molecule binding, cadherin binding, cell-cell junction, cell leading edge, epidermal cell differentiation and development, T cell differentiation and receptor complex, plasma membrane receptor complex, external side of plasma membrane, metabolism of amino acids and catabolism of small molecules, and so forth (p < .05). KRT80 knockdown suppressed anti-apoptosis, anti-pyroptosis, migration, invasion, chemoresistance, and lipogenesis in esophageal cancer cells (p < .05), while ACC1 and ACLY overexpression reversed the inhibitory effects of KRT80 on lipogenesis and chemoresistance. These findings indicated that up-regulated expression of KRT80 might be involved in esophageal carcinogenesis and subsequent progression, aggravate aggressive phenotypes, and induced chemoresistance by lipid droplet assembly and ACC1- and ACLY-mediated lipogenesis.

A Conductive Two-dimensional Trimetallic FeCoNi-Benzenehexathiol π-d Conjugated Metal-organic Framework for Highly Efficient Oxygen Evolution Reaction.

The poor electrically conductivity of metal-organic frameworks (MOFs) is the main factor hinder their application in electrocatalysis field. In this work, we synthesize a conductive two-dimensional (2D) trimetallic π-d conjugated metal-organic framework (MOF) FeCoNi-BHT (BHT = 1,2,3,4,5,6-benzenehexathiol) through coordinating Co, Fe and Ni ions with 1,2,3,4,5,6-benzenehexathiol ligands. FeCoNi-BHT is demonstrated possessing homogeneously dispersed abundant Co-S4, Fe-S4, Ni-S4 single-atom active sites (14.26 wt% of the metal elements) and a large specific surface area (267.05 m2g-1). The room temperature conductivity of FeCoNi-BHT is measured to be 92 S m-1, indicating its metallic behavior. DFT theoretical calculation reveals that the π-d conjugation structure of FeCoNi-BHT is responsible for its metallic behavior. In addition, FeCoNi-BHT exhibits prominent oxygen evolution reaction (OER) activity (an overpotential of 266 mV vs. RHE at 10 mA cm-2 and a Tafel value of 58 mV dec-1) in alkaline media. The combined experimental and DFT studies reveal that the synergistic effect of Co, Fe, Ni sites of FeCoNi-BHT contribute to its prominent OER activity. This work paves a new avenue of developing 2D π-d conjugated MOFs with different metal centers as highly efficient eletrocatalysts.

Sn-doped ZnO for efficient and stable quantum dot light-emitting diodes via a microchannel synthesis strategy.

ZnO nanocrystals (NCs) are widely employed as an electron transport layer (ETL) in quantum-dot light-emitting diodes (QLEDs). However, the excessive electron mobility, abundant surface defects and poor reproducibility of ZnO NC synthesis are currently the primary restrictive factors influencing the development of QLEDs. In this study, we developed Sn(IV)-doped ZnO NCs as the ETL for constructing highly efficient and long lifetime QLEDs. The introduction of Sn can reduce the surface hydroxyl oxygen defects and alter the electron transport properties of NCs, and thus is beneficial for improving the efficiency of hole-electron recombination in the emitting layer. Meanwhile, a microchannel (MC) reactor is utilized to finely control the synthesis of Zn0.96Sn0.04O NCs, enabling us to achieve uniform size distribution and consistent production reproducibility. Using the Sn(IV)-doped ZnO NCs as the ETL has led to a remarkable enhancement of external quantum efficiency (EQE) for the fabricated red QLED, from 9.2% of the ZnO only device to 15.5% of the Zn0.96Sn0.04O device. Furthermore, the T70 (@1000 cd m-2) of the Zn0.96Sn0.04O device reached 78 h, which is 1.77-fold higher than that of the ZnO only device (44 h). The present work provides an alternative ETL for efficient and stable QLEDs.

RBMS3-induced circHECTD1 encoded a novel protein to suppress the vasculogenic mimicry formation in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is a highly vascularized malignant cancer of the central nervous system, and the presence of vasculogenic mimicry (VM) severely limits the effectiveness of anti-vascular therapy. In this study, we identified downregulated circHECTD1, which acted as a key VM-suppressed factor in GBM. circHECTD1 elevation significantly inhibited cell proliferation, migration, invasion and tube-like structure formation in GBM. RIP assay was used to demonstrate that the flanking intron sequence of circHECTD1 can be specifically bound by RBMS3, thereby inducing circHECTD1 formation to regulate VM formation in GBM. circHECTD1 was confirmed to possess a strong protein-encoding capacity and the encoded functional peptide 463aa was identified by LC-MS/MS. Both circHECTD1 and 463aa significantly inhibited GBM VM formation in vivo and in vitro. Analysis of the 463aa protein sequence revealed that it contained a ubiquitination-related domain and promoted NR2F1 degradation by regulating the ubiquitination of the NR2F1 at K396. ChIP assay verified that NR2F1 could directly bind to the promoter region of MMP2, MMP9 and VE-cadherin, transcriptionally promoting the expression of VM-related proteins, which in turn enhanced VM formation in GBM. In summary, we clarified a novel pathway for RBMS3-induced circHECTD1 encoding functional peptide 463aa to mediate the ubiquitination of NR2F1, which inhibited VM formation in GBM. This study aimed to reveal new mechanisms of GBM progression in order to provide novel approaches and strategies for the anti-vascular therapy of GBM. The schematic illustration showed the inhibitory effect of circHECTD1-463aa in the VM formation in GBM.

Regenerating gene 4 promotes chemoresistance of colorectal cancer by affecting lipid droplet synthesis and assembly.

BACKGROUND: Regenerating gene 4 (REG4) has been proved to be carcinogenic in some cancers, but its manifestation and possible carcinogenic mechanisms in colorectal cancer (CRC) have not yet been elucidated. Our previous study found that the drug resistance of CRC cells may be closely linked to their fat metabolism. AIM: To explore the role of REG4 in CRC and its association with lipid droplet formation and chemoresistance. METHODS: We conducted a meta-analysis and bioinformatics and pathological analyses of REG4 expression in CRC. The effects of REG4 on the phenotypes and related protein expression were also investigated in CRC cells. We detected the impacts of REG4 on the chemoresistance and lipid droplet formation in CRC cells. Finally, we analyzed how REG4 regulated the transcription and proteasomal degradation of lipogenic enzymes in CRC cells. RESULTS: Compared to normal mucosa, REG4 mRNA expression was high in CRC (P < 0.05) but protein expression was low. An inverse correlation existed between lymph node and distant metastases, tumor-node-metastasis staging or short overall survival and REG4 mRNA overexpression (P < 0.05), but vice versa for REG4 protein expression. REG4-related genes included: Chemokine activity; taste receptors; protein-DNA and DNA packing complexes; nucleosomes and chromatin; generation of second messenger molecules; programmed cell death signals; epigenetic regulation and DNA methylation; transcription repression and activation by DNA binding; insulin signaling pathway; sugar metabolism and transfer; and neurotransmitter receptors (P < 0.05). REG4 exposure or overexpression promoted proliferation, antiapoptosis, migration, and invasion of DLD-1 cells in an autocrine or paracrine manner by activating the epidermal growth factor receptor-phosphoinositide 3-kinase-Akt-nuclear factor-κB pathway. REG4 was involved in chemoresistance not through de novo lipogenesis, but lipid droplet assembly. REG4 inhibited the transcription of acetyl-CoA carboxylase 1 (ACC1) and ATP-citrate lyase (ACLY) by disassociating the complex formation of anti-acetyl (AC)-acetyl-histone 3-AC-histone 4-inhibitor of growth protein-5-si histone deacetylase;-sterol-regulatory element binding protein 1 in their promoters and induced proteasomal degradation of ACC1 or ACLY. CONCLUSION: REG4 may be involved in chemoresistance through lipid droplet assembly. REG4 reduces expression of de novo lipid synthesis key enzymes by inhibiting transcription and promoting ubiquitination-mediated proteasomal degradation.

Physiological response mechanism of heavy metal-resistant endophytic fungi isolated from the roots of Polygonatum kingianum.

This study aims to evaluate the tolerance of endophytic fungi isolated from the fibrous roots of Polygonatum kingianum to arsenic (As) and cadmium (Cd) and their physiological response mechanisms. Five isolated strains were obtained with EC50 values for As(V) ranging from 421 to 1281 mg/L, while the other three strains tolerated Cd(II) with an EC50 range of 407-1112 mg/L. Morphological and molecular identification indicated that these eight strains were Cladosporium spp. belonging to dark septate endophytes (DSEs). The contents of metal ions in mycelium sharply increased, reaching 38.87 mg/kg for strain MZ-11 under As(V) stress and 0.33 mg/kg for fungus PR-2 under Cd(II). The physiological response revealed that the biomass decreased with increasing concentrations of As(V) or Cd(II), and the activity of superoxide dismutase significantly improved under the corresponding EC50 -concentration As/Cd of the strains, as well as the contents of antioxidant substances, including metallothionein, glutathione, malondialdehyde, melanin, and proline. Taken together, the filamentous fungi of Cladosporium spp. accounted for a high proportion of fungi isolated from the fibrous roots of P. kingianum and had a strong capacity to tolerate As(V) or Cd(II) stress by improving antioxidase activities and the content of antioxidant substances, and immobilization of metal ions in hyphae.

The promoting effects of GPR176 expression on proliferation, chemoresistance, lipogenesis and invasion of oesophageal cancer.

PURPOSE: As a member of the G-protein-coupled receptor 1 family, the G-protein-coupled receptor 176 (GPR176) gene encodes a glycosylated protein made up of 515 amino acids. The current study was performed to evaluate the impact of GPR176 on the clinicopathology and prognosis of oesophageal cancer, as well as uncover its molecular mechanisms. METHODS: Bioinformatics and clinical tissue samples were used to detect the expression and clinicopathological significance of GPR176 in oesophageal cancer. The expression, proliferation, migration and invasion, apoptosis and lipid droplet formation of GPR176 gene in oesophageal cancer were performed as phenotypic readouts. RESULTS: Here, RT-PCR and bioinformatic analyses revealed that GPR176 mRNA expression was significantly higher in oesophageal cancer than in normal mucosa (p < 0.05). GPR176 mRNA expression was associated with low weight and BMI, low T stage, low N and clinicopathological stage, low histological grade and favourable clinical outcome of oesophageal cancer (p < 0.05). The differential genes of GPR176 mRNA were involved in protein digestion and absorption, extracellular matrix constituent, endoplasmic reticulum lumen, among others (p < 0.05). GPR176-related genes were classified as being involved in oxidoreductase activity, actin and myosin complexes, lipid localisation and transport, among others (p < 0.05). GPR176 knockdown suppressed proliferation, anti-apoptotic and anti-pyroptotic properties, migration, invasion, chemoresistance and lipid droplet formation in oesophageal cancer cells (p < 0.05), while ACC1 and ACLY overexpression reversed the inhibitory effects of GPR176 silencing on lipid droplet formation and chemoresistance. CONCLUSION: These findings indicated that upregulated expression of GPR176 might be involved in oesophageal carcinogenesis and subsequent progression, aggressiveness, and induced chemoresistance by ACC1- and ACLY-mediated lipogenesis and lipid droplet assembly.

FAM64A aggravates proliferation, invasion, lipid droplet formation, and chemoresistance in gastric cancer: A biomarker for aggressiveness and a gene therapy target.

FAM64A is a mitogen-induced regulator of the metaphase and anaphase transition. Here, we found that FAM64A messenger RNA (mRNA) and protein expression levels were higher in gastric cancer tissue than in normal mucosa (p < .05). FAM64A methylation was negatively correlated with FAM64A mRNA expression (p < .05). The differentially expressed genes of FAM64A were mainly involved in digestion, potassium transporting or exchanging ATPase, contractile fibers, endopeptidase, and pancreatic secretion (p < .05). The FAM64A-related genes were principally categorized into ubiquitin-mediated proteolysis, cell cycle, chromosome segregation and mitosis, microtubule binding and organization, metabolism of amino acids, cytokine receptors, lipid droplet, central nervous system, and collagen trimer (p < .05). FAM64A protein expression was lower in normal gastric mucosa than intestinal metaplasia, adenoma, and primary cancer (p < .05), negatively correlated with older age, T stage, lymphatic and venous invasion, tumor, node, metastasis stage, and dedifferentiation (p < .05), and associated with a favorable overall survival of gastric cancer patients. FAM64A overexpression promoted proliferation, antiapoptosis, migration, invasion, and epithelial-mesenchymal transition via the EGFR/Akt/mTOR/NF-κB, while the opposite effect was observed for FAM64A knockdown. FAM64A also induced chemoresistance directly or indirectly through lipid droplet formation via ING5. These results suggested that upregulation of FAM64A expression might induce aggressive phenotypes, leading to gastric carcinogenesis and its subsequent progression. Thus, FAM64A could be regarded as a prognosis biomarker and a target for gene therapy.

Nanoscale Investigation of Bubble Nucleation and Boiling on Random Rough Surfaces.

Surface roughness is one of the significant factors affecting liquid-vapor phase change heat transfer. This paper explores the effect of surface roughness on bubble nucleation and boiling heat transfer, as well as the microscopic mechanism, by constructing random rough surfaces using molecular dynamics (MD) simulation. Bubbles randomly nucleate on a flat surface and tend to nucleate in pits on rough surfaces. The pits on the random rough surface gather more argon atoms than the protrusions, forming low potential energy regions on the surface, thus providing stable nucleation sites for bubbles. As the surface roughness increases, bubble generation, merging, and growth are advanced. In addition, rough surfaces offer a larger effective heat transfer area for the heat transfer process, increase the strength of solid-liquid coupling, and obtain smaller solid-liquid interaction energy. The critical heat flux (CHF) value positively correlates with surface roughness. As the roughness increases, the surface superheat at the onset of CHF decreases accordingly. This paper provides new insights into the mechanism of heat transfer enhancement on rough surfaces and surface design in thermal management.

Adherence to tyrosine kinase inhibitor and clinical outcomes in patients with chronic myeloid leukemia.

PURPOSE: To ensure optimal care for patients with chronic myeloid leukemia (CML), adherence to tyrosine kinase inhibitors (TKIs) has emerged as a critical component. The objective of this study was to assess the impact of TKIs adherence on clinical outcomes in a cohort of Chinese CML patients who received treatment with TKIs. METHODS: This retrospective study employed a cross-sectional design utilizing questionnaires to assess adherence to TKIs in a sample of 398 patients diagnosed with CML. Adherence was measured using the Morisky Medication Adherence Scale (MMAS-8), which dichotomizes patients into low, medium, and high adherence groups. RESULTS: Of the patients included in this study, 34.2% were classified as highly adherent, with 43.2% and 22.6% of patients categorized as having medium and low adherence, respectively. Compared to the low-adherence group, patients in the medium- and high-adherence groups exhibited significantly higher rates of achieving major molecular response (MMR) and lower rates of switching TKIs. Moreover, patients who failed to adhere to TKIs treatment demonstrated significantly lower event-free survival and failure-free survival compared to those in the high-adherence group. Notably, regular molecular monitoring and utilization of the "CML Academy" mobile application were positively associated with increased TKI adherence. On the other hand, patients receiving third-generation or above first-line TKIs treatment displayed reduced adherence. CONCLUSION: The findings suggest that high adherence to TKIs treatment confers clinical benefits to patients with CML. Accordingly, the implementation of effective guidance and intervention measures aimed at promoting adherence to TKIs therapy in real-world settings is imperative.

IGF2BP3 drives gallbladder cancer progression by m6A-modified CLDN4 and inducing macrophage immunosuppressive polarization.

INTRODUCTION: N6-methyladenosine (m6A) is an emerging epigenetic modification, which plays a crucial role in the development of cancer. Nevertheless, the underlying mechanism of m6A-associated proteins and m6A modification in gallbladder cancer remains largely unknown. MATERIALS AND METHODS: The Gene Expression Omnibus database and tissue microarray were used to identify the key m6A-related gene in gallbladder cancer. The function and mechanism of IGF2BP3 were further investigated by knockdown and overexpression techniques in vitro and in vivo. RESULTS: We found that IGF2BP3 was elevated and correlated with poor prognosis in gallbladder cancer, which can be used as an independent prognostic factor for gallbladder cancer. IGF2BP3 accelerated the proliferation, invasion and migration of gallbladder cancer cells in vitro and in vivo. Mechanistically, IGF2BP3 interacted with and augmented the stability of CLDN4 mRNA by m6A modification. Enhancement of CLDN4 reversed the inhibitory effect of IGF2BP3 deficiency on gallbladder cancer. Furthermore, we demonstrated that IGF2BP3 promotes the activation of NF-κB signaling pathway by up-regulation of CLDN4. Overexpression of IGF2BP3 in gallbladder cancer cells obviously promoted the polarization of immunosuppressive phenotype in macrophages. Besides, Gallbladder cancer cells-derived IGF2BP3 up-regulated the levels of STAT3 in M2 macrophages, and promoted M2 polarization. CONCLUSIONS: We manifested IGF2BP3 promotes the aggressive phenotype of gallbladder cancer by stabilizing CLDN4 mRNA in an m6A-dependent manner and induces macrophage immunosuppressive polarization, which might offer a new theoretical basis for against gallbladder cancer.