A predictive model for therapy failure in chronic myeloid leukemia patients receiving tyrosine kinase inhibitor therapy.

Although tyrosine kinase inhibitor (TKI) therapy has markedly improved the survival of people with chronic-phase chronic myeloid leukemia (CML), 20-30% of people still experienced therapy failure. Data from 1,955 consecutive subjects with chronic-phase CML diagnosed by the European LeukemiaNet (ELN) recommendations from 1 center receiving initial TKI imatinib or a second-generation (2G-) TKI therapy were interrogated to develop a clinical prediction model for TKI therapy failure. This model was subsequently validated in 3,454 subjects from 76 other centers. Using the predictive clinical co-variates associated with TKI therapy failure, we developed a model that stratified subjects into low-, intermediate- and high-risk subgroups with significantly different cumulative incidences of therapy failure (p < 0.001). There was good discrimination and calibration in the external validation dataset, and the performance was consistent with that of the training dataset. Our model had the better prediction discrimination than the Sokal and ELTS scores did, with the greater time-dependent area under the receiver-operator characteristic curve (AUROC) values and a better ability to re-defined the risk of therapy failure. Our model could help physicians estimate the likelihood of initial imatinib or 2G-TKI therapy failure in people with chronic-phase CML.

Organoids derived from patients provide a new opportunity for research and individualized treatment of malignant peritoneal mesothelioma.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is an extremely rare and highly invasive tumor. Due to the lack of accurate models that reflect the biological characteristics of primary tumors, studying MPM remains challenging and is associated with an exceedingly unfavorable prognosis. This study was aimed to establish a new potential preclinical model for MPM using patient-derived MPM organoids (MPMOs) and to comprehensively evaluate the practicality of this model in medical research and its feasibility in guiding individualized patient treatment. METHODS: MPMOs were constructed using tumor tissue from MPM patients. Histopathological analysis and whole genome sequencing (WGS) were employed to determine the ability of MPMOs to replicate the original tumor's genetic and histological characteristics. The subcutaneous and orthotopic xenograft models were employed to assess the feasibility of establishing an in vivo model of MPM. MPMOs were also used to conduct drug screening and compare the results with retrospective analysis of patients after treatment, in order to evaluate the potential of MPMOs in predicting the effectiveness of drugs in MPM patients. RESULTS: We successfully established a culture method for human MPM organoids using tumor tissue from MPM patients and provided a comprehensive description of the necessary medium components for MPMOs. Pathological examination and WGS revealed that MPMOs accurately represented the histological characteristics and genomic heterogeneity of the original tumors. In terms of application, the success rate of creating subcutaneous and orthotopic xenograft models using MPMOs was 88% and 100% respectively. Drug sensitivity assays demonstrated that MPMOs have different medication responses, and these differences were compatible with the real situation of the patients. CONCLUSION: This study presents a method for generating human MPM organoids, which can serve as a valuable research tool and contribute to the advancement of MPM research. Additionally, these organoids can be utilized as a means to evaluate the effectiveness of drug treatments for MPM patients, offering a model for personalized treatment approaches.

Active Assembly of CsPbBr3 Nanorods into Microcolumns by Electric Field in Nonpolar Solvent.

High-precision, controllable, mass-producible assembly of nanoparticles into complex structures or devices holds immense importance in the application across various fields but it remains challenging. Here a highly controllable and reversible active assembly of colloidal CsPbBr3 nanorods, driven by an external electric field is achieved. This approach enables the nanorods dynamically orient themselves, assemble into chains, aggregate into columns, and eventually form an ordered column array, with the electric field intensity varying from 0 to 50 V µm-1 at 100 kHz. The nanorods inside the columns align parallel to the electric field, leading to a well-ordered structure. With the analysis of the interactions among the nanorods, a quantitative interpretation of the assembly is proposed. Monte Carlo calculation is also introduced to simulate the assembly process and the results prove to be in great agreement with the experimental observations. This electric field-driven assembly presents an exciting opportunity to pave the way for next-generation sensors and photonic devices based on well-developed colloidal nanoparticles.

Brown planthopper infestation on rice reduces plant susceptibility to Meloidogyne graminicola by reducing root sugar allocation.

Plants are simultaneously attacked by different pests that rely on sugars uptake from plants. An understanding of the role of plant sugar allocation in these multipartite interactions is limited. Here, we characterized the expression patterns of sucrose transporter genes and evaluated the impact of targeted transporter gene mutants and brown planthopper (BPH) phloem-feeding and oviposition on root sugar allocation and BPH-reduced rice susceptibility to Meloidogyne graminicola. We found that the sugar transporter genes OsSUT1 and OsSUT2 are induced at BPH oviposition sites. OsSUT2 mutants showed a higher resistance to gravid BPH than to nymph BPH, and this was correlated with callose deposition, as reflected in a different effect on M. graminicola infection. BPH phloem-feeding caused inhibition of callose deposition that was counteracted by BPH oviposition. Meanwhile, this pivotal role of sugar allocation in BPH-reduced rice susceptibility to M. graminicola was validated on rice cultivar RHT harbouring BPH resistance genes Bph3 and Bph17. In conclusion, we demonstrated that rice susceptibility to M. graminicola is regulated by BPH phloem-feeding and oviposition on rice through differences in plant sugar allocation.

Impact of adrenalectomy on hypertension in patients with nonfunctional adrenal tumors: a retrospective study.

OBJECTIVE: To investigate the impact of adrenalectomy on hypertension in patients with nonfunctional adrenal tumors. SUBJECTS AND METHODS: Between January 2020 and October 2022, patients with adrenal lesions were retrospectively screened for nonfunctional adrenal tumors at the Zhongnan Hospital of Wuhan University. All patients underwent detailed endocrinological examination and computed tomography to characterize the lesions. One year after discharge, follow-up blood pressure (BP) was assessed and compared to the blood pressure on admission. Univariate analysis and multivariate regression analysis were performed to determine factors predicting favorable hypertension outcomes after adrenalectomy. RESULTS: A total of 309 patients were found to be eligible, including 123 who underwent adrenalectomy. Patients who underwent adrenalectomy were stratified into two groups: (Bancos I (2022) Adrenal Incidentalomas: Insights Into Prevalence. Ann Intern Med 175:1481-1482. https://doi.org/10.7326/M22-2600 ) those with improved hypertension (n = 71), and (Fassnacht M, Tsagarakis S, Terzolo M, Tabarin A, Sahdev A, Newell-Price J et al. (2023) European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol 189:G1-42. https://doi.org/10.1093/ejendo/lvad066 ) those without improved hypertension (n = 52). In contrast, the blood pressure levels of conservatively treated patients remained relatively stable 1 year after discharge. Univariate analysis and multivariate regression analysis showed that body mass index (BMI) and duration of hypertension were significantly different between the hypertension improvement group and the non-improvement group (p < 0.05). CONCLUSION: Adrenalectomy has been shown to be effective in improving hypertension in certain patients with nonfunctional adrenal tumors. BMI and duration of hypertension were independent factors associated with favorable hypertension outcomes after adrenalectomy.

Anti-inflammatory effects of steroidal alkaloids of Solanum lyratum Thunb.

Solanum lyratum Thunb., a traditional Chinese herbal medicine, has a promising background. However, the anti-inflammatory effects of its component steroid alkaloid have not been explored. In this study, animal and cell experiments were performed to investigate the anti-inflammatory effects and mechanism of action of Solanum lyratum Thunb steroid alkaloid (SLTSA), in order to provide evidence for its potential utilization. SLTSA effectively inhibited ear swelling and acute abdominal inflammation of mice. We observed concentration-dependent inhibition of pro-inflammatory cytokines by SLTSA, as confirmed by the ELISA and RT-qPCR results. Flow cytometry, immunofluorescence and RT-qPCR analyses revealed that SLTSA suppressed TLR4 expression. Western blot results indicated that SLTSA inhibited the activation of the TLR4/MyD88/NF-κB signaling pathway. Our study demonstrated that SLTSA possesses anti-inflammatory properties.

HIV gp120/Tat protein-induced epithelial-mesenchymal transition promotes the progression of cervical lesions.

BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with an elevated incidence of cervical cancer, and accelerated disease progression, but the underlying mechanisms are not well understood. This study aimed to investigate the relationship between HIV infection and epithelial-mesenchymal transition (EMT) in cervical cancer. METHODS: Tissue samples from HIV-positive and negative patients with cervical intraepithelial neoplasia (CIN) and cervical cancer were analyzed for EMT-related proteins. Human cervical cancer SiHa cells were treated with HIV Tat and gp120 proteins to test their effects on EMT, migration, and invasion. RESULTS: HIV-positive patients had lower E-cadherin and cytokeratin, and higher N-cadherin and vimentin levels than HIV-negative patients. HIV Tat and gp120 proteins induced EMT, migration, and invasion in SiHa cells. Transcriptome sequencing analysis revealed that, compared to the control group, the protein-treated group showed upregulation of 22 genes and downregulation of 77 genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed the involvement of the Wnt signaling pathway in EMT. Further analysis of gene expression related to this pathway revealed upregulation of DVL1, TCF7, KRT17, and VMAC, while GSK3ß, SFRP2, and CDH1 were downregulated. Immunofluorescence assay demonstrated that HIVgp120 and Tat proteins treatment induced elevated ß-catenin expression with nuclear accumulation in SiHa cells. CONCLUSIONS: The treatment of SiHa cells with HIV Tat and gp120 proteins induces EMT and activates the Wnt/ß-catenin pathway, suggesting that the Wnt/ß-catenin pathway may play a crucial role in promoting EMT progression in cervical lesion tissues of HIV-infected patients.

MicroRNA-4691-3p inhibits the inflammatory response by targeting STING in human dental pulp cells: A laboratory investigation.

AIM: The regulation of human dental pulp inflammation is not fully understood. This study aims to investigate the effect of miR-4691-3p on the cGAS-STING signalling cascade and its downstream cytokines production in human dental pulp cells (HDPCs). METHODOLOGY: Normal dental pulp tissue and pulp tissue with irreversible pulpitis from third molars were collected. HDPCs were isolated from pulp tissue. The expression of STING mRNA and miR-4691-3p was measured by quantitative real-time PCR. Bioinformatic computation via TargetScanHuman 8.0 and a luciferase reporter assay was used to identify the targets of miR-4691-3p. A miR-4691-3p mimic and inhibitor were used to upregulate or downregulate miR-4691-3p expression in HDPCs. HDPCs were transfected with c-di-AMP, c-di-GMP, cGAMP, interferon stimulatory DNA (ISD) and bacterial genomic DNA. Immunoblot was performed to detect the phosphorylation of TBK1, p65 and IRF3. Enzyme-linked immunoassay was performed to detect the cytokines including IFN-ß, TNF or IL-6 downstream of cGAS-STING. RESULTS: MiR-4691-3p expression was increased in human dental pulp tissue with irreversible pulpitis. Treatment of HDPCs using recombinant human IFN-ß, TNF or IL-6 also upregulated miR-4691-3p. The bioinformatic prediction and luciferase reporter assay confirmed that STING was a direct target of miR-4691-3p. The miR-4691-3p mimic suppressed STING expression, the phosphorylation of TBK1, p65 and IRF3, and the IFN-ß, TNF or IL-6 production. In contrast, the miR-4691-3p inhibitor enhanced the STING expression, the phosphorylation of TBK1, p65 and IRF3 and the IFN-ß, TNF or IL-6 production. CONCLUSIONS: MiR-4691-3p negatively regulates the cGAS-STING pathway by directly targeting STING. This provides insight to utilize miRNA-dependent regulatory effect to treat endodontic disease as well as STING-dependent systemic inflammatory disease.

Label-reconstruction-based pseudo-subscore learning for action quality assessment in sporting events.

Most existing action quality assessment (AQA) methods provide only an overall quality score for the input video and lack an evaluation of each substage of the movement process; thus, these methods cannot provide detailed feedback for users. Moreover, the existing datasets do not provide labels for substage quality assessment. To address these problems, in this work, a new label-reconstruction-based pseudo-subscore learning (PSL) method is proposed for AQA in sporting events. In the proposed method, the overall score of an action is not only regarded as a quality label but also used as a feature of the training set. A label-reconstruction-based learning algorithm is built to generate pseudo-subscore labels for the training set. Moreover, based on the pseudo-subscore labels and overall score labels, a multi-substage AQA model is fine-tuned from the PSL model to predict the action quality score of each substage and the overall score for an athlete. Several ablation experiments are performed to verify the effectiveness of each module. The experimental results show that our approach achieves state-of-the-art performance.

Bean Pod-Like SbSn/N-Doped Carbon Fibers toward a Binder Free, Free-Standing, and High-Performance Anode for Sodium-Ion Batteries.

Bimetallic SbSn alloy stands out among the anode materials for sodium-ion batteries (SIBs) because of its high theoretical specific capacity (752 mAh g-1 ) and good electrical conductivity. However, the major challenge is the large volume change during cycling processes, bringing about rapid capacity decay. Herein, to cope with this issue, through electrostatic spinning and high temperature calcination reduction, the unique bean pod-like free-standing membrane is designed initially, filling SbSn dots into integrated carbon matrix including hollow carbon spheres and nitrogen-doped carbon fibers (B-SbSn/NCFs). Significantly, the synergistic carbon matrix not only improves the conductivity and flexibility, but provides enough buffer space to alleviate the large volume change of metal particles. More importantly, the B-SbSn/NCFs free-standing membrane can be directly used as the anode without polymer binder and conductive agent, which improves the energy density and reaction kinetics. Satisfyingly, the free-standing BSbSn/NCFs membrane anode shows excellent electrochemical performance in SIB. The specific capacity of the membrane electrode can maintain 486.9 mAh g-1 and the coulombic efficiency is close to 100% after 400 cycles at 100 mA g-1 . Furthermore, the full cell based on B-SbSn/NCFs anode also exhibits the good electrochemical performance.

Free Amino Acid-Enriched Diets Containing Rapidly but Not Slowly Digested Carbohydrate Promote Amino Acid Absorption from Intestine and Net Fluxes across Skeletal Muscle of Pigs.

BACKGROUND: The approach to matching appropriate carbohydrates alongside free amino acids to achieve optimal muscle growth remains unclear. OBJECTIVES: We investigated whether the consumption of a diet containing rapidly digested carbohydrate and free amino acids can enhance intestinal absorption and muscular uptake of amino acids in pigs. METHOD: Twelve barrows (28 kg; 11 wk old) with catheters installed in the portal vein, mesenteric vein, femoral artery, and femoral vein were randomly assigned to consume 1 of 2 free amino acid-enriched diets (3.34%) containing rapidly [waxy corn starch (WCS)] or slowly [pea starch (PS)] digested carbohydrate for 27 d. Blood was collected to determine the fluxes of plasma glucose and amino acids across the portal vein and the hindlimb muscle. Dietary in vitro carbohydrate digestive rates were also determined. Data were analyzed using repeated-measures (time × group) ANOVA. RESULTS: Carbohydrate in vitro cumulative digestibility at 30 and 240 min was 69.00% and 95.25% for WCS and 23.25% and 81.15% for PS, respectively. The animal experiment presented WCS increased individual amino acids (lysine, 0.67 compared with 0.53 mmol/min; threonine, 0.40 compared with 0.29 mmol/min; isoleucine, 0.33 compared with 0.22 mmol/min; glutamate, 0.51 compared with 0.35 mmol/min; and proline, 0.51 compared with 0.27 mmol/min), essential amino acid (EAA; 3.26 compared with 2.65 mmol/min), and branched-chain amino acid (BCAA; 0.86 compared with 0.65 mmol/min) fluxes across the portal vein during 8 h postprandial, as well as individual amino acids (isoleucine, 0.08 compared with 0.02 mmol/min; leucine, 0.06 compared with 0.02 mmol/min; and glutamine, 0.44 compared with 0.25 mmol/min), EAA (0.50 compared with 0.21 mmol/min), and BCAA (0.17 compared with 0.06 mmol/min) net fluxes across the hindlimb muscle during 8 h postprandial compared with PS (P < 0.05). CONCLUSIONS: A diet containing rapidly digested carbohydrate and free amino acids can promote intestinal absorption and net fluxes across hindlimb muscle of amino acids in pigs.

Status of medication literacy and its related factors among undergraduate students in Shanxi Province, China: A cross-sectional study.

WHAT IS KNOWN AND OBJECTIVE: Medication safety problem has always been the focus of healthcare providers and public health community scholars. As the backbone of the future society, the mastery of college students' knowledge to use medicine will directly affect the level of medication literacy (ML) of the public in the future. The purpose of this study was to investigate the current ML of college students in Shanxi Province and to identify its related factors. METHODS: A cluster random sampling method was utilized to select 800 college students from 10 universities in Shanxi province as participants from 21 March to 10 April 2020. After quality control, 763 valid questionnaires were collected (effective rate 95.4%). This study applied the ML scale adapted from the 14-item health literacy scale (HLS-14) to estimate ML, which contains functional ML, communicative ML and critical ML dimensions to estimate the ML situation. Then, we used structural equation modelling (SEM) to test the hypothesized relationship among three dimensions of ML, self-evaluated health status and safety medication science popularization activities on campus. RESULTS AND DISCUSSION: The results showed that the reliability and validity of the ML scale were good. The average score of ML level of college students in Shanxi Province was 44 points, and the interquartile range was 40-48 points (full score is 65 points). The proportion of high ML level was estimated at as low as 26.7%. 73.1% participants had an average level, and only 1 participant (0.1%) had a low level of ML. Univariate analysis showed that the ML level was significantly influenced by gender, universities, field of study, academic performance and ethnic group (p < 0.05). SEM showed that functional ML (λ = 0.01) and communicative ML (λ = 0.75) had a direct positive association with critical ML. Meanwhile, the model also had a mediating effect. Functional ML had an indirect positive association with critical ML through the mediating effect of communicative ML (λ = 0.11). In addition, both self-evaluated health status and safety medication science popularization activities on campus had an indirect positive association with critical ML through the mediating effect of functional ML and communicative ML. WHAT IS NEW AND CONCLUSION: The study revealed that the ML of most college students in Shanxi Province was at the average level. Among them, medical college student (including pharmacy, nursing, public health, preventive medicine, basic medicine and clinical medicine students), the Han nationality students (the students of China's majority ethnic group), students of good self-evaluated health status, and students who were more exposed to safety medication science popularization activities had a relatively higher ML level. Moreover, it highlighted the importance of self-evaluated health status and safety medication science popularization activities on campus to ML.

A Novel Pathway of Chlorimuron-Ethyl Biodegradation by Chenggangzhangella methanolivorans Strain CHL1 and Its Molecular Mechanisms.

Chlorimuron-ethyl is a widely used herbicide in agriculture. However, uncontrolled chlorimuron-ethyl application causes serious environmental problems. Chlorimuron-ethyl can be effectively degraded by microbes, but the underlying molecular mechanisms are not fully understood. In this study, we identified the possible pathways and key genes involved in chlorimuron-ethyl degradation by the Chenggangzhangella methanolivorans strain CHL1, a Methylocystaceae strain with the ability to degrade sulfonylurea herbicides. Using a metabolomics method, eight intermediate degradation products were identified, and three pathways, including a novel pyrimidine-ring-opening pathway, were found to be involved in chlorimuron-ethyl degradation by strain CHL1. Transcriptome sequencing indicated that three genes (atzF, atzD, and cysJ) are involved in chlorimuron-ethyl degradation by strain CHL1. The gene knock-out and complementation techniques allowed for the functions of the three genes to be identified, and the enzymes involved in the different steps of chlorimuron-ethyl degradation pathways were preliminary predicted. The results reveal a previously unreported pathway and the key genes of chlorimuron-ethyl degradation by strain CHL1, which have implications for attempts to enrich the biodegradation mechanism of sulfonylurea herbicides and to construct engineered bacteria in order to remove sulfonylurea herbicide residues from environmental media.

Molecular characterization of a novel partitivirus isolated from the phytopathogenic fungus Aplosporella javeedii.

Aplosporella javeedii is a pathogenic fungus that causes canker and dieback of jujube in China. In this study, we report a new mycovirus, Aplosporella javeedii partitivirus 1 (AjPV1), isolated from A. javeedii strain NX55-3. The AjPV1 genome contains two double-stranded RNA elements (dsRNA1 and dsRNA2). The size of dsRNA1 is 2,360 bp, and it encodes a putative RNA-dependent RNA polymerase (RdRp), while dsRNA2 is 2,301 bp in length and encodes a putative capsid protein (CP). The sequences of RdRp and CP have significant similarity to those of members of the family Partitiviridae. Sequence alignment and phylogenetic analysis showed that AjPV1 is a new member of the family Partitiviridae that is related to members of the genus Betapartitivirus. To our knowledge, AjPV1 is the first mycovirus reported from A. javeedii.

A Comprehensive Survey of Vision-Based Human Action Recognition Methods.

Although widely used in many applications, accurate and efficient human action recognition remains a challenging area of research in the field of computer vision. Most recent surveys have focused on narrow problems such as human action recognition methods using depth data, 3D-skeleton data, still image data, spatiotemporal interest point-based methods, and human walking motion recognition. However, there has been no systematic survey of human action recognition. To this end, we present a thorough review of human action recognition methods and provide a comprehensive overview of recent approaches in human action recognition research, including progress in hand-designed action features in RGB and depth data, current deep learning-based action feature representation methods, advances in human⁻object interaction recognition methods, and the current prominent research topic of action detection methods. Finally, we present several analysis recommendations for researchers. This survey paper provides an essential reference for those interested in further research on human action recognition.

Ultrasensitive Graphene Optoelectronic Probes for Recording Electrical Activities of Individual Synapses.

The complex neuronal circuitry connected by submicron synapses in our brain calls for technologies that can map neural networks with ultrahigh spatiotemporal resolution to decipher the underlying mechanisms for multiple aspects of neuroscience. Here we show that, through combining graphene transistor arrays with scanning photocurrent microscopy, we can detect the electrical activities of individual synapses of primary hippocampal neurons. Through measuring the local conductance change of graphene optoelectronic probes directly underneath neuronal processes, we are able to estimate millivolt extracellular potential variations of individual synapses during depolarization. The ultrafast nature of graphene photocurrent response allows for decoding of activity patterns of individual synapses with a sub-millisecond temporal resolution. This new neurotechnology provides promising potentials for recording of electrophysiological outcomes of individual synapses in neural networks.

Comparative study of stress response, growth and development of uteri in post-weaning gilts challenged with zearalenone and estradiol benzoate.

The objective of this study was to evaluate the effects of zearalenone (ZEA) and estradiol benzoate (EB) on stress injury and uterine development in post-weaning gilts. Thirty healthy post-weaning female gilts (Duroc × Landrace × Large White) aged 28-32 days were randomly allocated to three treatments as follows: (a) basal diet (Control), (b) basal diet plus 1.0 mg/kg purified ZEA (ZEA) and (c) basal diet plus 0.75 ml (1.5 mg) EB per pig at 3-days intervals by intramuscular injection (EB). The serum estradiol (E2 ), the final and the increased vulvar area, uterine index, thickness of the myometrium and endometrium, and protein expression of heat shock protein 70 (HSP70) in ZEA group were higher than those in the control group (p < .05), but lower than those in the EB group (p < .05). The serum luteinizing hormone in ZEA group was lower than that of the control group (p < .05), but higher than that in the EB group (p < .05). Higher serum follicle-stimulating hormone and progesterone were observed in the ZEA and control groups than those in the EB group (p < .05). The serum glutathione peroxidase activity in the ZEA group was lower than that in the control and EB groups (p < .001), and the malondialdehyde in the ZEA group was higher than that in the control and EB groups (p < .001). Moreover, the relative mRNA and protein expression of growth hormone receptor (GHR) and relative mRNA expression of HSP70 in the ZEA and EB groups were higher than those in the control group (p < .05). In conclusion, both ZEA (1.0 mg/kg) and EB (1.5 mg at 3 days intervals by intramuscular injection) stimulated vulvar swelling and uterine hypertrophy by disordering serum hormones and up-regulating GHR expression, and induced stress by different mechanisms in this study. Furthermore, the observed up-regulating HSP70 expression challenged by ZEA or EB may be part of the mechanism to resist stress injury.

Forkhead box p3 controls progression of oral lichen planus by regulating microRNA-146a.

Oral lichen planus (OLP) is a severe T cell-mediated disorder of the mucosa, which causes chronic inflammation. Forkhead box P3 (Foxp3) regulates the immune response and plays an important role in immunological diseases. The current study aimed to determine the role of Foxp3 and microRNA (miR)-146a in OLP. Western blot analysis and a quantitative real-time polymerase chain reaction assay showed that the expression of Foxp3 and miR-146a was upregulated in OLP tissues and in lipopolysaccharide (LPS)-incubated HaCaT cells, compared with controls. Foxp3 inhibition significantly decreased miR-146a expression, ameliorated LPS stimulation by decreased cell proliferation, and apoptosis in LPS-incubated HaCaT cells as compared with the LPS group. Cotransfection of Foxp3 small interfering RNA and miR-146a mimics elevated cell proliferation and apoptosis compared with the Foxp3 small interfering RNA group. In addition, miR-146a overexpression upregulated, whereas miR-146a inhibition downregulated, the proliferation and apoptosis of LPS-incubated HaCaT cells. The target gene of miR--146a, tumor necrosis factor receptor-associated factor 6 (TRAF6), was predicted by bioinformatics software and identified by the luciferase reporter assay. Furthermore, Foxp3/miR-146a elevated T regulatory cells and regulated TRAF6 expression in CD4+ T cells that were isolated from peripheral blood of patients with OLP. In conclusion, our study suggests that Foxp3 and miR-146a regulate the progression of OLP by negatively regulating TRAF6, which may provide a promising therapeutic target for OLP treatment.

Biomechanics of cell reorientation in a three-dimensional matrix under compression.

Although a number of studies have reported that cells cultured on a stretchable substrate align away from or perpendicular to the stretch direction, how cells sense and respond to compression in a three-dimensional (3D) matrix remains an open question. We analyzed the reorientation of human prostatic normal tissue fibroblasts (NAFs) and cancer-associated fibroblasts (CAFs) in response to 3D compression using a Fast Fourier Transform (FFT) method. Results show that NAFs align to specific angles upon compression while CAFs exhibit a random distribution. In addition, NAFs with enhanced contractile force induced by transforming growth factor ß (TGF-ß) behave in a similar way as CAFs. Furthermore, a theoretical model based on the minimum energy principle has been developed to provide insights into these observations. The model prediction is in agreement with the observed cell orientation patterns in several different experimental conditions, disclosing the important role of stress fibers and inherent cell contractility in cell reorientation.