Magnetostriction-Driven Muon Localization in an Antiferromagnetic Oxide.

Magnetostriction results from the coupling between magnetic and elastic degrees of freedom. Though it is associated with a relatively small energy, we show that it plays an important role in determining the site of an implanted muon, so that the energetically favorable site can switch on crossing a magnetic phase transition. This surprising effect is demonstrated in the cubic rocksalt antiferromagnet MnO which undergoes a magnetostriction-driven rhombohedral distortion at the Néel temperature T_{N}=118 K. Above T_{N}, the muon becomes delocalized around a network of equivalent sites, but below T_{N} the distortion lifts the degeneracy between these equivalent sites. Our first-principles simulations based on Hubbard-corrected density-functional theory and molecular dynamics are consistent with the experimental data and help to resolve a long-standing puzzle regarding muon data on MnO, as well as having wider applicability to other magnetic oxides.

peu-MIR2916-p3-enriched garlic exosomes ameliorate murine colitis by reshaping gut microbiota, especially by boosting the anti-colitic Bacteroides thetaiotaomicron.

Plant-derived exosome-like nanoparticles (ELNs) have drawn considerable attention for oral treatment of colonic diseases. However, the roles of ELNs derived from garlic on colitis remain unclear. Here, we demonstrate that garlic ELNs (GELNs), with desirable particle sizes (79.60 nm) and trafficking large amounts of functional proteins and microRNAs, stably roam in the gut and confer protection against ulcerative colitis (UC). In mice with DSS-induced colitis, orally administered GELNs effectively ameliorated bloody diarrhea, normalized the production of proinflammatory cytokines, and prevented colonic barrier impairment. Mechanistically, GELNs were taken up by gut microbes and reshaped DSS-induced gut microbiota dysbiosis, in which Bacteroides was the dominant respondent genus upon GELNs treatment. Notably, GELNs-enriched peu-MIR2916-p3 specifically promoted the growth of Bacteroides thetaiotaomicron, an intestinal symbiotic bacterium with palliative effects on colitis. Our findings provide new insights into the medicinal application of GELNs and highlight their potential as natural nanotherapeutic agents for preventing and treating UC.

The association between expressive suppression and anxiety in Chinese left-behind children in middle school: serial mediation roles of psychological resilience and self-esteem.

BACKGROUND: Left-behind children (LBC) have become a special population to be concerned due to the negative consequences of parental absence during their physical and psychological development in China. Expressive suppression (ES) is a response-focused emotion regulation and may be frequently used by LBC to suppress their emotions resulting in different forms of internalizing problems. The objective of the present study was to investigate the role of ES as an emotion regulation strategy on anxiety in Chinese left-behind children in middle school (LBC-MS) by considering the mediating role(s) of psychological resilience and self-esteem. METHODS: 820 middle school students aged between 12 and 17 years from a middle school in Xiangtan, Hunan Province, participated in the study. Screen for Child Anxiety Related Emotional Disorders (SCARED), Emotion Regulation Questionnaire (ERQ), Resilience Scale for Chinese Adolescents (RSCA), and Rosenberg Self-Esteem Scale (SES) were administered. Variables measured using the above scales in left-behind children in middle school (LBC-MS) and non-left-behind children in middle school (non-LBC-MS) were compared, and descriptive statistics were used to present the overall characteristics. Then the PROCESS macro of SPSS was used to conduct regression-based statistical mediation for the data of 211 left-behind children. RESULTS: This study revealed that LBC-MS had higher anxiety and ES scores and lower psychological resilience and self-esteem scores than non-LBC-MS (Ps < 0.01). ES was found positively associated with anxiety in LBC-MS and negatively associated with psychological resilience and self-esteem (Ps < 0.05 - 0.01). Specifically, both psychological resilience and self-esteem significantly mediated the association between ES and anxiety, accounting for 7.50% and 10.68%, respectively, of the total associations. Moreover, psychological resilience and self-esteem had a chain mediating effect between ES and anxiety in LBC-MS. CONCLUSION: The findings indicated that LBC-MS in China may frequently engage in the use of ES which correlated with higher level of anxiety. Psychological interventions should be dedicated to this underserved group. Intervention approaches that improve emotion regulation strategies (i.e., decrease the use of ES) and increase psychological resilience and self-esteem may help to alleviate anxiety in LBC-MS.

Beneficial Synergistic Intermetallic Effect in ZnCo2O4 for Enhancing the Limonene Oxidation Catalysis.

Utilization of naturally occurring limonene from renewable biomass as a key starting material for the synthesis of valuable chemicals is a promising avenue to reduce both the dependence on nonrenewable fossil fuels and global CO2 emission. Herein, we report a highly active tremella-like ZnCo2O4 catalyst for the selective oxidation of limonene with molecular oxygen under mild reaction conditions. The developed ZnCo2O4 catalyst exhibits an appealing reaction performance with a limonene conversion of 93.5% (reaction rate of 0.0823 mmol gcat-1 h-1) and selectivity of 75.8% for 1,2-limonene oxide (LO), far outperforming the monometallic oxides of ZnO and Co3O4. Detained experimental characterizations and analyses manifest that the substitution of Zn into the Co3O4 framework can facilitate the formation of more unsaturated coordination sites and oxygen vacancies due to the modified chemical environment of Co atoms, inducing a beneficial synergistic intermetallic effect for the limonene oxidation catalysis.

Entanglement between Muon and I>1/2 Nuclear Spins as a Probe of Charge Environment.

We report on the first example of quantum coherence between the spins of muons and quadrupolar nuclei. We reveal that these entangled states are highly sensitive to a local charge environment and thus, can be deployed as a functional quantum sensor of that environment. The quantum coherence effect was observed in vanadium intermetallic compounds which adopt the A15 crystal structure, and whose members include all technologically pertinent superconductors. Furthermore, the extreme sensitivity of the entangled states to the local structural and electronic environments emerges through the quadrupolar interaction with the electric field gradient due to the charge distribution at the nuclear (I>1/2) sites. This case study demonstrates that positive muons can be used as a quantum sensing tool to also probe structural and charge-related phenomena in materials, even in the absence of magnetic degrees of freedom.

The regulation of miR-320a/XBP1 axis through LINC00963 for endoplasmic reticulum stress and autophagy in diffuse large B-cell lymphoma.

BACKGROUND: This study incorporates fundamental research referring to considerable amounts of gene-sequencing data and bioinformatics tools to analyze the pathological mechanisms of diffuse large B-cell lymphoma (DLBCL). METHODS: A lncRNA-miRNA-mRNA ceRNA network of DLBCL was constructed through database analysis combining GTEx and TCGA. qPCR was used to detect the expression of LINC00963 and miR-320a in DLBCL cell lines. After LINC00963 or miR-320a overexpression in vitro, western blot was performed to assess the protein levels of UPR sensors (GRP78, p-IRE1, IRE1, active ATF6, ATF4 and XBP1), along with apoptosis markers (Bcl-2, Bax, caspase 3) and autophagy indicators (Beclin1, LC3II, LC3I and p62). Additionally, the expression of LC3 was analyzed through immunofluorescence (IF) assay.  RESULTS: Following LINC00963 overexpression in vitro, SUDHL4 cell line showed a marked increase in the level of UPR-related GRP78, p-IRE1 and spliced XBP-1/XBP-1(s), apoptosis-related Bax and cleaved caspase 3, as well as autophagy-related Beclin1 and LC3II, whereas miR-320a mimic greatly diminished the effects of LINC00963 overexpression. Moreover, LINC00963 targeted miR-320a while miR-320a bound to the 3'UTR of XBP1. It was also found that LINC00963 overexpression resulted in significantly delayed tumor growth in a xenograft model of DLBCL.  CONCLUSION: Mechanistically, LINC00963/miR-320a regulated XBP1-apoptosis pathway and autophagy, implying the therapeutic potential of this pathway for selective targeting. The data presented here illustrated the mechanism of LINC00963/miR-320a/XBP1 in DLBCL for the first time.

Platycodin D (PD) regulates LncRNA-XIST/miR-335 axis to slow down bladder cancer progression in vitro and in vivo.

Recently, increasing evidences indicated that Platycodin D (PD) served as an effective anti-tumor drug for cancer treatment in clinic. However, the molecular mechanisms are still unclear. In the present study, we proved that PD regulated LncRNA-XIST/miR-335 axis to hamper the development of bladder cancer in vitro and in vivo. Mechanistically, PD inhibited malignant phenotypes, including cell proliferation, invasion, migration and epithelial-mesenchymal transition (EMT), and promoted cell apoptosis in bladder cancer cells in a time- and dose-dependent manner. In addition, the following experiments validated that PD inhibited LncRNA-XIST expressions, while increased miR-335 expression levels in bladder cancer cells. Next, by conducting the dual-luciferase reporter gene system assay and RNA pull-down assay, we validated that LncRNA-XIST inhibited miR-335 expressions through acting as RNA sponges, and the promoting effects of PD stimulation on miR-335 levels were abrogated by upregulating LncRNA-XIST. Interestingly, both silencing LncRNA-XIST and miR-335 overexpression enhanced the inhibiting effects of PD on the malignant phenotypes in bladder cancer cells. Consistently, the xenograft tumor-bearing mice models were established, and the data indicated that PD slowed down tumor growth and inhibited tumorigenesis in vivo, which were also aggravated by downregulating LncRNA-XIST. In general, analysis of data proved that targeting LncRNA-XIST/miR-335 axis was novel to enhance the anti-tumor effects of PD in bladder cancer in vitro and in vivo, and this study provided alternative therapeutic strategies for bladder cancer treatment in clinic.

Role of interleukin­32 in cancer progression (Review).

Interleukin (IL)-32 is induced by pro-inflammatory cytokines and promotes the release of inflammatory cytokines. Therefore, it can promote inflammatory responses. The present review article summarized the role of the receptors required for IL-32 action, the biological function of IL-32 and its mechanism of action in tumors. Moreover, it assessed the significance of aberrant IL-32 expression in associated diseases and analyzed the effects of IL-32 on four key types of cancer: Colorectal, gastric, breast and lung. However, the mechanism of action of IL-32 needs to be further demonstrated by assessing the role of this cytokine in cancer to elucidate novel and reliable targets for future cancer treatments.

Symptom networks analysis among people with Meniere's disease: Application for nursing care.

Objectives: This study aimed to explore and visualize the relationships among multiple symptoms in patients with Meniere's disease (MD) and aid clinical nurses in the design of accurate, individualized interventions. Methods: This study included 790 patients with MD at the Eye and ENT Hospital of Fudan University from October 2014 to December 2021. A self-designed symptom checklist was used to assess 15 MD-related symptoms and construct contemporaneous networks with all 15 symptoms in R software. Qgraph package and Fruchterman-Reingold layout were used for network visualization. Bootstrapping methods were performed to assess network accuracy and stability, and three centrality indices were adopted to describe relationships among symptoms. Results: Symptom networks showed good accuracy and stability. "Anxiety and nervousness"(98.2%), "aural fullness"(84.4%) and "tinnitus"(82.7%) were the common symptom in MD patients, while "tinnitus", "aural fullness" and "decline in word recognition", were more serious. MD patients with longer disease duration had higher prevalence and severity for all symptoms (P < 0.05). Symptom networks showed good accuracy and stability. "Decline in word recognition," "fatigue," and "anxiety and nervousness" were at the center of the symptom networks, which had the largest strength values and closeness. "Decline in word recognition," "headache," and "spatial discrimination and poor orientation" were the symptoms with the highest betweenness with the strongest bridging effect. The ≥1-year disease group exhibited higher centralities for "drop attack" and "anxiety and nervousness," and a lower centrality for "headache" compared with the <1-year disease group. Conclusions: The symptom networks of MD patients with varying disease durations were revealed. Clinicians and nurses must provide precision interventions tailored to modifying symptom severity and centrality. Nursing interventions should focus on word recognition issues and associated discomfort in MD patients with multiple symptoms.

Ubiquitous Order-Disorder Transition in the Mn Antisite Sublattice of the (MnBi2Te4)(Bi2Te3)n Magnetic Topological Insulators.

Magnetic topological insulators (TIs) herald a wealth of applications in spin-based technologies, relying on the novel quantum phenomena provided by their topological properties. Particularly promising is the (MnBi2Te4)(Bi2Te3)n layered family of established intrinsic magnetic TIs that can flexibly realize various magnetic orders and topological states. High tunability of this material platform is enabled by manganese-pnictogen intermixing, whose amounts and distribution patterns are controlled by synthetic conditions. Here, nuclear magnetic resonance and muon spin spectroscopy, sensitive local probe techniques, are employed to scrutinize the impact of the intermixing on the magnetic properties of (MnBi2Te4)(Bi2Te3)n and MnSb2Te4. The measurements not only confirm the opposite alignment between the Mn magnetic moments on native sites and antisites in the ground state of MnSb2Te4, but for the first time directly show the same alignment in (MnBi2Te4)(Bi2Te3)n with n = 0, 1 and 2. Moreover, for all compounds, the static magnetic moment of the Mn antisite sublattice is found to disappear well below the intrinsic magnetic transition temperature, leaving a homogeneous magnetic structure undisturbed by the intermixing. The findings provide a microscopic understanding of the crucial role played by Mn-Bi intermixing in (MnBi2Te4)(Bi2Te3)n and offer pathways to optimizing the magnetic gap in its surface states.

Broccoli-Derived Exosome-like Nanoparticles Alleviate Loperamide-Induced Constipation, in Correlation with Regulation on Gut Microbiota and Tryptophan Metabolism.

Constipation, a common gastrointestinal dysfunction, damages patients' life quality and predisposes them to other serious diseases. Current strategies against constipation often cause drug dependency and side effects. Here, we demonstrated that broccoli-derived exosome-like nanoparticles (BENs), a natural product with high gastrointestinal stability, ameliorated LOP-induced constipation in mice. Specifically, orally administered BENs (17.5 mg/kg/d) effectively shortened defecation time, sped up intestinal propulsion rate, and increased feces amount in constipated mice. BENs also raised excitatory neurotransmitters SP and MTL and reduced inhibitory neurotransmitters VIP and ET-1. Mechanistically, BENs were taken up by gut microbes, restored LOP-disordered gut microbiota, and altered microbial metabolism of SCFAs and tryptophan, as evidenced by the results of fluorescence microscopy, 16S rRNA gene sequencing, and nontargeted metabolomics. Thereinto, BEN-enriched SCFA-producing microorganisms are closely associated with the feces amount and SP and VIP levels and BEN-elevated indole-3-pyruvic acid and 3-indoleacetic acid are highly linked to ET-1, SP, and MTL levels. Conclusively, BENs, mitigating constipation by regulating gut microbiota and microbial tryptophan metabolism, showed high potential to be developed as alternative regimens for constipation.

[Corrigendum] Decreased RNA­binding protein IGF2BP2 downregulates NT5DC2, which suppresses cell proliferation, and induces cell cycle arrest and apoptosis in diffuse large B­cell lymphoma cells by regulating the p53 signaling pathway.

Subsequently to the publication of this paper, the authors have realized that they included the incorrect data in Fig. 5 for the p21 blots on p. 8. The corrected version of Fig. 5, featuring the data that were intended to have been included in this figure for the p21 blots, is shown on the next page.  Furthermore, the authors wish to make the following changes to the text in the paper (changes are highlighted in bold): i) on p. 2, left­hand column, line 16, the final sentence in the penultimate paragraph of the Introduction should have read as: "However, the functions of RNA­binding protein (RBP) IGF2BP2, and the interactions between IGF2BP2 and NT5DC2 in DLBCL remain to be explored."; ii) In the Materials and methods section, subsection "RNA pull­down assay", the first sentence should be revised to: "An RNA pull down kit (cat. no. P0202: Geneseed) was used to perform RNA pull down assay according to the manufacturer's instructions."; iii) In the Results section on p. 3, the subsection "NT5DC2 is upregulated in DLBC cells and knockdown of NT5DC2 inhibits proliferation of DLBC cells.", the second sentence should be revised as follows: "mRNA and protein expression of NT5DC2 was highest in OCI­Ly7 cells compared with that in the other DLBC cell lines (Fig. 1A)."; iv) The first two sentences in the following paragraph should have read as follows: "mRNA and protein expression levels of NT5DC2 were decreased in DLBC cells transfected with shRNA­NT5DC2#1/2 compared with the untransfected group, and were lower in the shRNA­NT5DC2#2 group compared with the shRNA­NT5DC2#1 group (Fig. 1B)."; and v) On p. 7, left­hand column, the sentence commencing on line 59 should have read as: "The present results indicated that NT5DC2 was increased in DLBCL cells...". Note that these errors did not significantly affect either the results or the conclusions reported in this paper, and all the authors agree with the publication of this corrigendum. Furthermore, the authors thank the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 26: 286, 2022; DOI: 10.3892/mmr.2022.12802].

Effects of ageing time on the properties of polysaccharide in tangerine peel and its bacterial community.

To evaluate the effect of aging time on the quality of tangerine peel (TP) from the perspective of TP polysaccharide (TPP), five polysaccharide samples with different aging times named TPP-0/1/5/10/15 were prepared. Under the conditions of pH 0.5, solid-liquid ratio 1:25 and 80 °C, the TPPs extraction yield ranged from 20.35% to 27.68%. Compared with TPP-0, TPP-1/5/10/15 possesses low molecular weight (Mw) and high methoxy group content. In addition, TPP-15 had the most potent antioxidant activity. And the content of acidic polysaccharides in TPPs was negatively correlated with neutral polysaccharides during aging. Based on the analysis of 16srDNA, the dominant bacteria (Brevundimonas and Pseudomonas) in TP-10 might be critical flora to affect TP quality. This study provided basic information on the relationship between the TPPs and aging time, which could promote a new view to develop TP, and shorten the aging time during TP production.

Partitioning the Two-Leg Spin Ladder in Ba2Cu1 - x Zn x TeO6: From Magnetic Order through Spin-Freezing to Paramagnetism.

Ba2CuTeO6 has attracted significant attention as it contains a two-leg spin ladder of Cu2+ cations that lies in close proximity to a quantum critical point. Recently, Ba2CuTeO6 has been shown to accommodate chemical substitutions, which can significantly tune its magnetic behavior. Here, we investigate the effects of substitution for non-magnetic Zn2+ impurities at the Cu2+ site, partitioning the spin ladders. Results from bulk thermodynamic and local muon magnetic characterization on the Ba2Cu1 - x Zn x TeO6 solid solution (0 ≤ x ≤ 0.6) indicate that Zn2+ partitions the Cu2+ spin ladders into clusters and can be considered using the percolation theory. As the average cluster size decreases with increasing Zn2+ substitution, there is an evolving transition from long-range order to spin-freezing as the critical cluster size is reached between x = 0.1 to x = 0.2, beyond which the behavior became paramagnetic. This demonstrates well-controlled tuning of the magnetic disorder, which is highly topical across a range of low-dimensional Cu2+-based materials. However, in many of these cases, the chemical disorder is also relatively strong in contrast to Ba2CuTeO6 and its derivatives. Therefore, Ba2Cu1 - x Zn x TeO6 provides an ideal model system for isolating the effect of defects and segmentation in low-dimensional quantum magnets.

Non-equilibrium dynamics of spin-lattice coupling.

Quantifying the dynamics of normal modes and how they interact with other excitations is of central importance in condensed matter. Spin-lattice coupling is relevant to several sub-fields of condensed matter physics; examples include spintronics, high-Tc superconductivity, and topological materials. However, experimental approaches that can directly measure it are rare and incomplete. Here we use time-resolved X-ray diffraction to directly access the ultrafast motion of atoms and spins following the coherent excitation of an electromagnon in a multiferroic hexaferrite. One striking outcome is the different phase shifts relative to the driving field of the two different components. This phase shift provides insight into the excitation process of such a coupled mode. This direct observation of combined lattice and magnetization dynamics paves the way to access the mode-selective spin-lattice coupling strength, which remains a missing fundamental parameter for ultrafast control of magnetism and is relevant to a wide variety of materials.

The non-destructive investigation of a late antique knob bow fibula (Bügelknopffibel) from Kaiseraugst/CH using Muon Induced X-ray Emission (MIXE).

A knob bow fibula (Bügelknopffibel) of the Leutkirch type, which typologically belongs to the second half of the 4th and early 5th century CE, was excavated in 2018 in the Roman city of Augusta Raurica, present-day Kaiseraugst (AG, Switzerland). This was analyzed for the first time for its elemental composition by using the non-destructive technique of Muon Induced X-ray Emission (MIXE) in the continuous muon beam facility at the Paul Scherrer Institute (PSI). In the present work, the detection limit is 0.4 wt% with ∼ 1.5 hours of measurement time. The fibula was measured at six different positions, at a depth of 0.3-0.4 mm inside the material. The experimental results show that the fibula is made of bronze, containing the main elements copper (Cu), zinc (Zn), tin (Sn) and lead (Pb). The compositional similarities/differences between different parts of the fibula reveal that it was manufactured as two "workpieces". One workpiece consists of the knob (13.0±0.6 wt% Pb), bow (11.9±0.4 wt% Pb) and foot (12.5 ± 0.9 wt% Pb). These show a higher Pb content, suggesting a cast bronze. The spiral (3.2 ± 0.2 wt% Pb), which is part of the other workpiece, has a comparatively lower Pb content, suggesting a forged bronze.

Bibliometric Analysis of Network Pharmacology in Traditional Chinese Medicine.

Aim: We evaluated the developmental process, research status, and existing challenges of network pharmacology. Moreover, we elucidated the corresponding solutions to improve and develop network pharmacology. Methods: Research data for the current study were retrieved from the Web of Science. The developmental process of network pharmacology was analyzed using HisCite, whereas cooccurrence analysis of countries, institutions, keywords, and references in literature was conducted using CiteSpace. Results: In literature, there was a trend of annual increase of studies on network pharmacology and China was found to be the country with the most published literature on network pharmacology. The main publishing research institutions were universities of traditional Chinese medicine (TCM). The keywords with more research frequency were TCM, mechanisms, molecular docking, and quercetin, among others. Conclusion: Currently, studies on network pharmacology are mainly associated with the exploration of action mechanisms of TCM. The main active ingredient in many Chinese medicines is quercetin. This ingredient may lead to deviation of research results, inability to truly analyze active ingredients, and even mislead the research direction of TCM. Such deviation may be because the database fails to reflect the content and composition changes of Chinese medicinal components. The database does not account for interactions among components, targets, and diseases, and it ignores the different pathological states of the disease. Therefore, network pharmacology should be improved from the databases and research methods.

[Cross-cultural adaptation and clinical application of Meniere's disease outcomes questionnaire].

Objective:To cross-culturally adapt the Meniere's Disease Outcomes Questionnaire（MDOQ） into Chinese language, to evaluate its reliability and validity, and to apply in clinical. Methods:The MDOQ was translated according to the Brislin model. Cross-cultural adaption was done by expert discussion and pilot study. The MDOQ was applied to 101 patients to test its reliability and validity. The quality of life（QOL） of 272 patients was measured by MDOQ-C, analyzing the influence factors of QOL of patients with Meniere's disease. Results:The CR value of each item of MDOQ-C exceeded 3.00, the Cronbach's α coefficient was 0.88, and the Spearman Brown coefficient was 0.90. The Pearson correlation coefficient of MDOQ-C and the DHI was 0.803（P<0.01）. Three factors were extracted by factor analysis, which could explain 60.503% of the total variance. The dimension composition was different from the original scale. The average QOL score of Meniere's disease patients was 52.94±13.87. The main influence factors were age, marital status, work status, with tinnitus and the number of vertigo attacks. Conclusion:The MDOQ-C is reliable and valid. After dimension reconstruction, MDOQ-C can be used to evaluate the QOL of patients with Meniere's disease. Through the preliminary clinical application, the influence factors of quality of life of patients with Meniere's disease were identified, thus providing reference for optimizing clinical management strategies.

HOXD3 Up-regulating KDM5C Promotes Malignant Progression of Diffuse Large B-Cell Lymphoma by Decreasing p53 Expression

Background: Diffuse large B-cell lymphoma is a type of B-cell non-Hodgkin lymphoma with a high incidence. About one-third of patients are resistant or eventually relapse. The prognosis for patients with relapsed/resistant diffuse large B-cell lymphoma who need salvage therapy is not optimistic. Aims: To explore whether homebox D3 binding to lysine (K)-specific demethylase 5C promoted malignant progression of diffuse large B-cell lymphoma by decreasing p53 expression. Study Design: Cell culture study. Methods: The mRNA and protein expression of lysine (K)-specific demethylase 5C and homebox D3 in cells were respectively detected by real-time quantitative polymerase chain reaction analysis and Western blot. Real-time quantitative polymerase chain reaction analysis and Western blot were also applied to determine the transfection effects of shRNA-KDM5C or OeHOXD3 in OCI-Ly7 cells. After transfection, the cell viability, proliferation, and apoptosis were respectively analyzed by Cell Counting Kit-8 assay, EdU staining, and acridine orange­ethidium bromide staining. The interaction between homebox D3 and lysine (K)-specific demethylase 5C promoter was verified by the dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay. Results: Lysine (K)-specific demethylase 5C mRNA expression (HBL1 2.84 ± 0.29; SUDHL4 3.53 ± 0.21; OCI-Ly8 4.06 ± 0.24; OCI-Ly7 5.03 ± 0.28 vs. GM12878 1.00 ± 0.07; all P < .001) and protein expression (HBL1 1.52 ± 0.06; SUDHL4 1.77 ± 0.10; OCI-Ly8 2.34 ± 0.07; OCI-Ly7 2.78 ± 0.07 vs. GM12878 1.00 ± 0.07; all P < .001) in DLBCL cells were higher than that in GM12878 cells and showed the highest in OCI-Ly7 cells. Homebox D3 mRNA (OCI-Ly7 3.85 ± 0.17 vs. GM12878 1.00 ± 0.05; P < .001) and protein (OCI-Ly7 1.73 ± 0.10 vs. GM12878 1.00 ± 0.06; P < .001) expression were also highly expressed in OCI-Ly7 cells. Moreover, down-regulation of lysine (K)-specific demethylase 5C suppressed the viability and proliferation and enhanced the apoptosis of OCI-Ly7 cells. Knockdown of lysine (K)-specific demethylase 5C decreased the B-cell lymphoma 2 expression while increased the expression of Bax, cleaved caspase 3, cytochrome C, p53, and p21. The transcription factor homebox D3 was confirmed to interact with the lysine (K)-specific demethylase 5C promoter. Homebox D3 overexpression could reverse the regulating effect of down-regulation of lysine (K)-specific demethylase 5C on the OCI-Ly7 cells. Conclusion: Homebox D3 up-regulating lysine (K)-specific demethylase 5C promotes malignant progression of diffuse large B-cell lymphoma by decreasing p53 expression.

Decreased RNA­binding protein IGF2BP2 downregulates NT5DC2, which suppresses cell proliferation, and induces cell cycle arrest and apoptosis in diffuse large B­cell lymphoma cells by regulating the p53 signaling pathway.

Diffuse large B­cell lymphoma (DLBCL) remains difficult to treat clinically due to its highly aggressive characteristics. Insulin­like growth factor 2 mRNA­binding protein 2 (IGF2BP2) and 5'­nucleotidase domain­containing 2 (NT5DC2) have been suggested as potential regulators in numerous types of cancer. The present study aimed to determine whether downregulation of IGF2BP2 and NT5DC2 suppresses cell proliferation, and induces cell cycle arrest and apoptosis in DLBCL cells by regulating the p53 signaling pathway. The expression levels of IGF2BP2 and NT5DC2 in DLBCL cells were determined by reverse transcription­quantitative PCR (RT­qPCR) and western blot analysis. Transfection of cells with IGF2BP2 overexpressing plasmids and NT5DC2 interference plasmids was performed, and the efficacy of transfection was confirmed by RT­qPCR and western blot analysis. The viability, proliferation, cell cycle progression and apoptosis of DLBCL cells were analyzed by Cell Counting Kit­8 assay, 5­bromo­2­deoxyuridine staining and flow cytometry. RNA pull­down and immunoprecipitation assays were used to verify the binding of IGF2BP2 and NT5DC2. The expression levels of apoptosis, cell cycle and p53 pathway­associated proteins were determined by western blotting. The results revealed that NT5DC2 expression was increased in DLBCL cell lines and was the highest in OCI­Ly7 cells. IGF2BP2 expression was also increased in OCI­Ly7 cells and IGF2BP2 bound to NT5DC2. Knockdown of NT5DC2 suppressed cell viability and proliferation, induced cell cycle arrest and promoted apoptosis in DLBCL cells, which was reversed by upregulation of IGF2BP2. In addition, knockdown of NT5DC2 increased the expression of p53 and p21, but suppressed the expression of proliferating cell nuclear antigen, CDK4 and cyclin D1; these effects were reversed by upregulation of IGF2BP2. In conclusion, knockdown of NT5DC2 suppressed cell viability and proliferation, induced cell cycle arrest and promoted apoptosis in DLBCL cells by regulating the p53 signaling pathway and these effects were reversed by upregulation of IGF2BP2.