Tibial cortex transverse transport promotes ischemic diabetic foot ulcer healing via enhanced angiogenesis and inflammation modulation in a novel rat model.

BACKGROUND: Tibial Cortex Transverse Transport (TTT) represents an innovative surgical method for treating lower extremity diabetic foot ulcers (DFUs), yet its underlying mechanisms remain elusive. Establishing an animal model that closely mirrors clinical scenarios is both critical and novel for elucidating the mechanisms of TTT. METHODS: We established a diabetic rat model with induced hindlimb ischemia to mimic the clinical manifestation of DFUs. TTT was applied using an external fixator for regulated bone movement. Treatment efficacy was evaluated through wound healing assessments, histological analyses, and immunohistochemical techniques to elucidate biological processes. RESULTS: The TTT group demonstrated expedited wound healing, improved skin tissue regeneration, and diminished inflammation relative to controls. Marked neovascularization and upregulation of angiogenic factors were observed, with the HIF-1α/SDF-1/CXCR4 pathway and an increase in EPCs being pivotal in these processes. A transition toward anti-inflammatory M2 macrophages indicated TTT's immunomodulatory capacity. CONCLUSION: Our innovative rat model effectively demonstrates the therapeutic potential of TTT in treating DFUs. We identified TTT's roles in promoting angiogenesis and modulating the immune system. This paves the way for further in-depth research and potential clinical applications to improve DFU management strategies.

circNINL facilitates aerobic glycolysis, proliferation, invasion, and migration in lung cancer by sponging miR-3918 to mediate FGFR1 expression.

Previously characterized as an oncogenic player in breast cancer, the function of circular RNA NINL (circNINL) in lung cancer (LC) remained elusive. This study aimed to delineate the biological role of circNINL in LC and to unveil its potential molecular mechanisms. We discovered elevated expression levels of circNINL and Fibroblast Growth Factor Receptor 1 (FGFR1) concomitant with diminished expression of microRNA-3918 (miR-3918) in LC specimens. Knockdown of circNINL led to a marked decrease in cell proliferation, migration, invasion, and aerobic glycolysis, alongside an upsurge in apoptosis in LC cells. Either downregulation of miR-3918 or overexpression of FGFR1 mitigated the suppressive impact of circNINL knockdown on LC pathogenesis. Mechanistic studies validated that circNINL served as a competitive endogenous RNA for miR-3918, thus influencing FGFR1 expression. Further, in vivo experiments using nude mouse xenograft models underscored that silencing circNINL substantially curtailed tumor growth in LC. Collectively, these findings illuminate that circNINL exacerbates LC malignancy via the miR-3918/FGFR1 axis, a process integrally linked with the activation of aerobic glycolysis.

Towards outstanding lubricity performance of proton-type ionic liquids or synergistic effects with friction modifiers used as oil additives at the steel/steel interface.

Anti-wear (AW) additives and friction modifiers (FMs) and their interactions in lubricants are critical to tribological performance. This research investigates the compatibility and synergism of three oil-soluble alkylamine-phosphate ionic liquids with friction modifiers, organomolybdenum compounds. Three proton-based ionic liquids (PILs) were synthesized using a simple, low-cost, and unadulterated procedure as well as the chain lengths of the PILs affected the effectiveness of friction reduction and anti-wear. For example, the effect of a short-chain PIL alone as an additive on friction and wear behavior was not significant, whereas a long-chain PIL was more effective. In addition, PILs appeared to be able to coexist with organic molybdenum compounds and worked synergistically with dialkyl dithiophosphate oxygen molybdenum (MoDDP) to produce a sustained low coefficient of boundary friction (the coefficient of friction approaching 0.042). We proposed a three-stage tribochemical process to explain this interaction of PILs + MoDDP with contact surfaces to form physically adsorbed friction-reducing films and chemically reactive wear-protective films. This study reveals the compatibility and synergistic effects of two common lubricant components, which can be used to guide lubricant development in the future.

Back pressure generated by downwash and crosswind on spatial atomization characteristics during UAV spraying: CFD analysis and verification.

BACKGROUND: During unmanned aerial vehicles (UAVs) spraying, downwash and crosswind generate back pressure in comprehensive, which changes in spatial atomization characteristics of spraying droplets. However, the process of such atomization characteristics needs to be clarified. This study focuses on the effect of rotor speed and crosswind speed on spatial atomization characteristics. The computational fluid dynamics (CFD) models of the distributions of airflow, back pressure and atomization characteristics were established, and verification was conducted by developing a validation platform. RESULTS: The CFD results indicated that small droplets of 65-130 µm atomized by negative pressure would be coalesced near the nozzle, while large droplets of 390-520 µm atomized by positive pressure would be aggregated further away. Crosswind caused atomization stratification with droplet sizes of approximately 90 µm, 320 µm and 390 µm. When crosswind speed increased from 3 m/s to 6 m/s, the spraying drifted from 0.5 m to 1 m. When rotor speed increased from 2000 RPM to 3000 RPM, droplet distribution was expanded and droplet particle size was more uniform. Verification results demonstrated that the spraying distribution and the droplet size variation were consistent with the CFD. CONCLUSIONS: Spatial atomization characteristics were highly correlated with airflow and back pressure. Moreover, as crosswind generated droplet drift and atomization stratification and downwash could improve the uniformity of droplet distribution, spraying performance was superior by enhancing downwash to restrain the adverse effect of crosswind in real applications. © 2023 Society of Chemical Industry.

Efficacy and safety of unilateral tibial cortex transverse transport on bilateral diabetic foot ulcers: A propensity score matching study.

Background: Tibial Cortex Transverse Transport (TTT) has been demonstrated to be an effective treatment for unilateral diabetic foot ulcers (UDFUs). However, this retrospective study was designed to compare the efficacy and safety of unilateral TTT on bilateral diabetic foot ulcers (BDFUs). Methods: This retrospective study included a review of patients with TTT treated from January 2017 to August 2019, Propensity Score Matching (PSM) was performed to compare patients with BDFUs to those with UDFUs. Ulcer healing, recurrence, and major amputation rates were evaluated at 1-year follow-up. Changes in foot vessels were assessed in the BDFUs group using computed tomography angiography (CTA). Results: A total of 140 patients with DFUs (106 UDFUs and 34 BDFUs) were included in the study. UDFUs and BDFUs were matched in a 1:1 ratio (34 in each group) using PSM. No significant difference was observed at 1-year-follow-up [91.2% (31/34) vs. 76.5% (26/34), OR 0.315 (95% CI 0.08 to 1.31), P â€‹= â€‹0.10] and 6-month-follow-up [70.6% (24/34) vs. 50.0% (17/34), OR 0.85 (95% CI 0.15 to 1.13), P â€‹= â€‹0.08] in two groups. Significant differences in rates of major amputation and recurrence between the groups (P â€‹> â€‹0.05) were not observed. The BDFUs group appeared more angiogenesis of the foot by CTA after 8 weeks of operation. Conclusion: Results of this study suggest that severe BDFUs can be effectively treated by unilateral TTT. TTT is easy to operate and effective, which may be a good alternative for treating severe BDFUs. The translational potential of this article: In previous retrospective clinical studies, TTT has demonstrated promising clinical outcomes in the management of diabetic foot ulcers. In this current study, we aim to investigate the potential use of TTT in treating distant tissue defects by evaluating the limited availability and safety of TTT for the management of bilateral diabetic foot. While additional basic and clinical research is necessary to fully elucidate the underlying mechanisms, our study offers insight into the potential therapeutic use of TTT for this condition.

In Vitro Anti-Influenza A Virus H1N1 Effect of Sesquiterpene-Rich Extracts of Carpesium abrotanoides.

Due to a high content of sesquiterpenes, Carpesium abrotanoides has been investigated to fully explore its health-promoting properties. Therefore, this work aimed to assess, for the first time, the anti-influenza A virus H1N1 potential of sesquiterpene-targeted fractions of the herb derived from C. abrotanoides. Five compounds, including four sesquiterpenes and one aldehyde, were isolated and identified from the sesquiterpene-rich extracts of C. abrotanoides (SECA), and the contents of three main sesquiterpenes in the SECA were determined. Furthermore, SECA showed a significant protective effect in the MDCK cells infected with influenza A virus (H1N1) in three different conditions: premixed administration, prophylactic administration, and therapeutic administration. SECA can significantly decrease the mRNA expressions of TLR4, MyD88, NF-κB, TNF-α, and IL-6, as well as the protein expressions of TLR4, MyD88, and NF-κB. This result suggests that SECA can resist the influenza A virus H1N1 through the TLR4/MyD88/NF-κB signal pathway.

Synchronous three-dimensional detection method for multiple parameters of wind fields based on vector principle.

In the area of air-assisted spray, conventional detection of speed and direction of the wind fields for spray are separately conducted, and multiple kinds of sensors have to be laid on each coordinate axis during multidimensional detection. It limits the optimization of operation effect of sprayers based on wind-field distribution characteristics. This paper proposes a novel detection method to achieve synchronous measurement of wind speed and direction in three dimensions. Wind flow was considered as vectors and the sensing structure with a regular triangular pyramid shape supported by cantilever pieces was established. Strain gauges were utilized to detect the deformation in each direction by the wind thrust onto a ball before and after wind flow. Moreover, the calculation models of wind speed and direction were developed respectively based on the relationship of 'strains-force-wind pressure-wind velocity' and the principle of space operation of vectors, so multiple parameters of wind fields could be obtained simultaneously. Calibration was conducted based on a wind tunnel and the Testo 405i anemometers. The results showed that: the minimum relative error of wind-speed values was about 0.06%, while the maximum was about 10%. The average relative error of all the directions was less than 5%. Furthermore, the measurement of the wind among artificial tree canopies demonstrated that the proposed method could effectively measure both speed value and direction of the wind among canopies, and it also helped to find the wind distribution characteristics of the fan, SFG4-2R. The results highlighted both the reliability and the practical meaning of the proposed method, which could be a technical solution for measuring and evaluating wind-field characteristics of sprayers.

Stereoscopic plant-protection system integrating UAVs and autonomous ground sprayers for orchards.

For orchard plant protection, conventional large machines and small sprayers are practically restricted by either narrow planting intervals with dense leaves or their inadequate penetration power, which leads to an unsatisfactory effect of spray. This paper proposes a stereoscopic plant-protection strategy that integrates unmanned air and ground sprayers to spray different parts of canopies to improve uniformity. In order to verify the proposal, a stereoscopic plant-protection system (SPS) was developed, consisting of a small swing-arm sprayer and a T16 plant-protection Unmanned Aerial Vehicle (UAV). Then, optimal operation parameters were determined by Computational Fluid Dynamics (CFD) and orthogonal experiments, and the uniformity was finally quantified by trials. CFD and orthogonal experiments showed that a swing-arm angle of 60° and a forward speed of 0.4 m/s were optimal for the ground sprayer, whilst a height of 2.0 m from the top of canopies and a forward speed of 1.0 m/s were appropriate for the UAV. The trial results showed that the density of vertical droplet deposition varied from 90 to 107 deposits/cm2 in canopies, and the uniformity was 38.3% higher than conventional approaches. The uniformity of top, bottom, inside and outside canopies was significantly improved. Meanwhile, the density of droplet deposition on both sides of leaves in all test points exceeded 25 deposits/cm2, able to meet the standard of spray. This study provides a practical approach for uniform pesticide spray to large-canopy fruit trees. Moreover, the high flexibility of plant-protection UAVs and the significant trafficability of small swing-arm sprayers can solve the problem of large machine entering and leaving orchards.

Wind field and droplet coverage characteristics of air-assisted sprayer in mango-tree canopies.

BACKGROUND: Air-assisted sprayers is one of the primary fruit tree pest control approaches in agricultural production. It is necessary to study the influence of multiple factors on both wind field and droplet coverage of air-assisted sprayers. In this article, foliage area volume density (FAVD) and power gradient were considered factors, and field tests were conducted in an orchard to determine such influence. RESULTS: The results showed that in-canopy wind speed was mainly affected by the air-assisted sprayer. FAVD showed significance to the wind speed and droplet coverage inside canopies (P < 0.001), compared with power gradient (P > 0.05). With the increase of FAVD, the wind speed in the bottom layer of canopies first increased and then decreased, while the wind speed in the middle and top layers first decreased and then increased. Meanwhile, the wind field was mainly concentrated on the surface of canopies and gradually approached the canopy center as the power gradient increased. Furthermore, a Back-Propagation (BP) neural network prediction model was constructed to predict droplet coverage at any canopy location to avoid repeated experiments. The overall correlation coefficient (R) of this model was about 0.731, indicating good fitting performance. CONCLUSION: FAVD has a significant effect on wind speed and droplet deposition inside the canopy, and the air-assisted sprayer parameter setting should consider the effect of FAVD. The prediction model can predict droplet deposition inside the canopy without repeating. The study can provide a reference for selecting operating parameters of air-assisted sprayers and help reduce droplet loss and environmental pollution. © 2022 Society of Chemical Industry.

Knowledge Domains and Emerging Trends of Osteoblasts-Osteoclasts in Bone Disease From 2002 to 2021: A Bibliometrics Analysis and Visualization Study.

Background: Osteoblasts-Osteoclasts has been a major area in bone disease research for a long time. However, there are few systematic studies in this field using bibliometric analysis. We aimed to perform a bibliometric analysis and visualization study to determine hotspots and trends of osteoblasts-osteoclasts in bone diseases, identify collaboration and influence among authors, countries, institutions, and journals, and assess the knowledge base to develop basic and clinical research in the future. Methods: We collected articles and reviews for osteoblasts-osteoclasts in bone diseases from the Web of Science Core Collection. In addition, we utilized scientometrics software (CiteSpace5.8 and VOSviewer1.6.18) for visual analysis of countries/regions, institutions, authors, references, and keywords in the field. Results: In total, 16,832 authors from 579 institutions in 73 countries/regions have published 3,490 papers in 928 academic journals. The literature in this field is rapidly increasing, with Bone publishing the most articles, whereas Journal of Bone and Mineral Research had the most co-cited journals. These two journals mainly focused on molecular biology and the clinical medicine domain. The countries with the highest number of publications were the US and China, and the University of Arkansas for Medical Sciences was the most active institution. Regarding authors, Stavros C. Manolagas published the most articles, and Hiroshi Takayanagi had the most co-cited papers. Research in this field mainly includes molecular expression and regulatory mechanisms, differentiation, osteoprotection, inflammation, and tumors. The latest research hotspots are oxidative stress, mutation, osteocyte formation and absorption, bone metabolism, tumor therapy, and in-depth mechanisms. Conclusion: We identified the research hotspots and development process of osteoblasts-osteoclasts in bone disease using bibliometric and visual methods. Osteoblasts-osteoclasts have attracted increasing attention in bone disease. This study will provide a valuable reference for researchers concerned with osteoblasts-osteoclasts in bone diseases.

Reading Ability in Patients With Tuberous Sclerosis Complex: Results of Chinese Character Reading and Reading Comprehension Tests.

Background: Most tuberous sclerosis complex (TSC) patients have neurological disorders and are at high risk of academic difficulties. Among academic skills, reading ability is the most important academic skill. The study applied the Chinese character fluency test to measure the word recognition and reading comprehension of TSC children to observe whether they have the characteristics of reading disability, as an indicator of the spectrum of reading ability in TSC patients. Methods: The patients were assessed using the Chinese character fluency test and reading comprehension test to explore the differences in reading ability in terms of gender, age, epilepsy history, genotype, and intelligence level. Results: Of the 27 patients, the assessment of reading accuracy showed statistical differences between intellectual level > 80, PR (p = 0.024), and pass numbers (p = 0.018). For the fluency assessment, there was a difference between different intellectual level (p = 0.050). In the reading comprehension test, there was differences for intellectual level in positivity (p = 0.07) and pass numbers (p = 0.06). Conclusion: The Chinese character fluency and reading comprehension test measure the word recognition and reading comprehension and the spectrum of reading ability in TSC patients. All individuals with TSC, especially those with below average of intellectual ability, should be considered for potential academic difficulties.

A 24-to-30 GHz Ultra-High-Linearity Down-Conversion Mixer for 5G Applications Using a New Linearization Method.

The linearity of active mixers is usually determined by the input transistors, and many works have been proposed to improve it by modified input stages at the cost of a more complex structure or more power consumption. A new linearization method of active mixers is proposed in this paper; the input 1 dB compression point (IP1dB) and output 1 dB compression point (OP1dB) are greatly improved by exploiting the "reverse uplift" phenomenon. Compared with other linearization methods, the proposed one is simpler, more efficient, and sacrifices less conversion gain. Using this method, an ultra-high-linearity double-balanced down-conversion mixer with wide IF bandwidth is designed and fabricated in a 130 nm SiGe BiCMOS process. The proposed mixer includes a Gilbert-cell, a pair of phase-adjusting inductors, and a Marchand-balun-based output network. Under a 1.6 V supply voltage, the measurement results show that the mixer exhibits an excellent IP1dB of +7.2~+10.1 dBm, an average OP1dB of +5.4 dBm, which is the state-of-the-art linearity performance in mixers under a silicon-based process, whether active or passive. Moreover, a wide IF bandwidth of 8 GHz from 3 GHz to 11 GHz was achieved. The circuit consumes 19.8 mW and occupies 0.48 mm2, including all pads. The use of the "reverse uplift" allows us to implement high-linearity circuits more efficiently, which is helpful for the design of 5G high-speed communication transceivers.

Somatic nuclear auto-antigenic sperm protein sensitizes human breast cancer cells to 5-Fluorouracil.

PURPOSE: To assess the potential role of nuclear auto-antigenic sperm protein (NASP) in the cellular sensitivity to 5-Fluorouracil (5-FU) in breast cancer cells. METHODS: The expression of two NASP isotypes, namely somatic NASP (sNASP) and testis NASP (tNASP) in breast cancer lines were detected under 5-FU treatment using real-time polymerase chain reaction and western blot assays. NASP effect on cellular viability and apoptosis under 5-FU treatment were evaluated. The interaction between NASP and its downstream proteins were evaluated using the co-immunoprecipitation (Co-IP) assays. RESULTS: 5-FU significantly decreased the mRNA and protein expression levels of sNASP. Inhibition of sNASP increased cellular viability, colony formation ability, but reduced apoptosis in tested cell lines in response to 5-FU, which were reversed by sNASP over-expression. Further study reveals 5-FU disrupts sNASP/TNF receptor-associated factor 6 (TRAF6) complex, potentiates cellular sensitivity to 5-FU via NK-kB. CONCLUSION: Our findings suggest sNASP is a novel molecular target having potential to overcome the resistance to 5-FU in breast cancer cells.

Downwash characteristics and analysis from a six-rotor unmanned aerial vehicle configured for plant protection.

BACKGROUND: One theoretical advantage of using unmanned aerial vehicles (UAVs) to spray pesticides for maturing corn is that the strong downwash penetrates canopies. However, only few studies have been conducted to examine in-canopy downwash characteristics. This paper investigated the downwash by a six-rotor UAV in mature cornfields. 3D wind speeds in corn canopies and an open area were measured, and comparisons conducted. RESULTS: The downwash by the UAV resulted in in-canopy maximum wind speeds. Z-dimensional downwash was sensitive to all factors, whereas the X- and Y-dimensional downwashes were related to layers and crop positions. Meanwhile, when comparing with the downwash between a 2 m hovering position and the optimal flight parameters, the X-dimensional and Y-dimensional motion time of top-layer downwash generally advanced by 3.8 s and 1.6 s, whereas both motion time and the strength of the Z-dimensional downwash were impeded by ≈2.2-s hysteresis at middle layers and ≈4.5-s time reduction, respectively. Thus, combined with distributions, the corn on the left or right might not be sprayed sufficiently. Furthermore, under the convergence requirement error of 0.01, the overall correlation of the model was ≈0.846 in terms of the Z-dimensional downwash and ≈0.55 and 0.61 for the X- and Y-dimensions, respectively. CONCLUSION: The selection of operation parameters should mainly consider the Z-dimensional downwash. The optimal operation parameters were a height of 2 m with a speed of 4 m s-1 . Meanwhile, the canopy effect could influence the uniformity, motion and strength of downwash. Predictions could be achieved before operation. © 2022 Society of Chemical Industry.

Adjustable Acoustic Field Controlled by "Ultrasonic Projector" on Ultrasound Application.

The control of acoustic field has great potential in many applications such as medical treatment, neuro-modulation, and bio-imaging. Recently, acoustic lenses and phased arrays have become common ways of controlling acoustic fields. However, the shortcomings of the two ways are obvious. Acoustic lenses lack flexibility after design, and phased arrays have complicated structures and need to adjust the parameters of each array element. In this work, we propose an alternative for sound field control using a flexible and adjustable "acoustic projector," and two symmetric mirrors are used to change the direction of propagation of an acoustic wave produced by a piezoelectric element and realize acoustic focusing in the target region. The 2-D "acoustic projector" model was built in finite element simulation, and the feasibility was verified with an actual prototype. The sound intensity produced by the piezoelectric element at different horizontal and vertical positions along the target area can be accurately controlled by two adjustable mirrors. When the angle of the mirror ranges from 30° to 40°, the focal depth can change from 39 to 140 mm. Furthermore, the focus can be controlled in a sector with an angle of 60°. The "acoustic projector" demonstrates simple but precise control of acoustic fields and may broaden their applicability. To show its imaging ability, the three groups of target balls at different positions were imaged and their position information by scanning the mirrors in simulation was given.

LncRNA MSC-AS1 facilitates lung adenocarcinoma through sponging miR-33b-5p to up-regulate GPAM.

Many reports have indicated that long non-coding RNAs (lncRNAs) are closely associated with the occurrence and development of various cancers. Musculin antisense RNA 1 (MSC-AS1) is a an lncRNA known to act as an oncogene in several types of human cancers; however, its specific function in lung adenocarcinoma (LUAD) is still unclear. For this study, we designed and conducted experiments to clarify the function of the lncRNA MSC-AS1 in LUAD and its underlying mechanisms. We found that the expression of MSC-AS1 was significantly higher in LUAD tissues and cells than that in normal ones. Through loss-of function assays, we confirmed that the proliferation of LUAD cells was significantly restrained by down-regulation of MSC-AS1 and the rate of cell apoptosis was accelerated. The results from our mechanistic experiments showed that MSC-AS1 interacts with microRNA-33b-5p (miR-33b-5p). Moreover, glycerol-3-phosphate acyltransferase, mitochondrial (GPAM) was found to be a direct target gene of miR-33b-5p, and it has similar functions to MSC-AS1. Further, inhibition of miR-33b-5p or overexpression GPAM reversed the inhibitory effects of MSC-AS1 silencing on LUAD cell growth. In short, MSC-AS1 facilitates LUAD progression through sponging miR-33b-5p to up-regulate GPAM.

Forkhead box protein O3a promotes glioma cell resistance to temozolomide by regulating matrix metallopeptidase and ß-catenin.

Glioblastoma multiforme (GBM) is the most common type of malignant brain tumor. GBM is currently treated with temozolomide (TMZ), although patients often exhibit resistance to this agent. Although several mechanisms underlying the resistance of GBM to TMZ have been identified, the combination of these mechanisms is not sufficient to fully account for this phenomenon. Our previous study demonstrated that knocking down the Forkhead box protein O3a (FoxO3a) gene, a member of the FoxO subfamily of transcription factors, resulted in glioma cell sensitization to TMZ, accompanied by reduced levels of nuclear ß-catenin. The aim of the present study was to specify how FoxO3a and ß-catenin are implicated in glioma cell TMZ resistance. Using the U87 and U251 parental cell lines (also designated as sensitive cell lines) and corresponding resistant cell lines (U87-TR and U251-TR, generated by repeated TMZ treatments), coupled with a combined knockdown/overexpression strategy, it was revealed that FoxO3a or ß-catenin overexpression in TMZ-treated U87 and U251 cells markedly increased cellular proliferation; co-expression of both FoxO3a and ß-catenin resulted in the highest increase. Knockdown of either FoxO3a or ß-catenin in U87-TR and U251-TR cells led to a significant decrease in cell viability, which was rescued by the re-expression of FoxO3a in FoxO3a-knockdown cells. Subsequent experiments demonstrated that, in U87-TR and U251-TR cells, FoxO3a knockdown significantly reduced the protein levels of matrix metallopeptidase (MMP)9, while overexpression of FoxO3a in U87 and U251 cells enhanced the nuclear accumulation of ß-catenin, concomitantly with an increase in MMP9 levels. Furthermore, MMP9 knockdown markedly reduced the levels of nuclear ß-catenin. Collectively, the findings of the present study suggest that FoxO3a may regulate the nuclear accumulation of ß-catenin by modulating MMP9 expression, thereby rendering glioblastoma cells resistant to TMZ, and may provide unique molecular insights into the mechanisms underlying the development of TMZ resistance in GBM.

lncRNA PVT1 accelerates progression of non-small cell lung cancer via targeting miRNA-526b/EZH2 regulatory loop.

Biological function of plasmacytoma variant translocation 1 (PVT1) in influencing the progression of non-small cell lung cancer (NSCLC) through Micro ribonucleic acid (miRNA)-526b/EZH2 regulatory loop was elucidated. Relative levels of PVT1 and miRNA-526b in NSCLC tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Prognostic potential of PVT1 in NSCLC was assessed by Kaplan-Meier curves. The interaction among PVT1/miRNA-526b/EZH2 regulatory loop was confirmed by dual-luciferase reporter gene assay. Regulatory effects of PVT1/miRNA-526b/EZH2 axis on viability and wound closure of A549 cells were evaluated by cell counting kit-8 (CCK-8) and wound closure assay, respectively. PVT1 was upregulated in NSCLC tissues, while miRNA-526b was downregulated. PVT1 level was negatively related to that of miR-526 in NSCLC tissues. Worse survival was seen in NSCLC patients expressing high level of PVT1 compared to those with low level. Knockdown of PVT1 attenuated viability and wound closure ability in A549 cells, which were partially reversed after miRNA-526b knockdown. miRNA-526b is the downstream target of PVT1 and its level was negatively regulated by PVT1. EZH2 is the target gene of miRNA-526b. Transfection of miRNA-526b mimic remarkably downregulated EZH2 in A549 cells. Importantly, the attenuated viability and wound closure ability in A549 cells overexpressing miRNA-526b were reversed after EZH2 overexpression. PVT1 is upregulated in NSCLC, and predicts a poor prognosis. PVT1 accelerates the progression of NSCLC via targeting miRNA-526b/EZH2 regulatory loop.

Type I IFN expression is stimulated by cytosolic MtDNA released from pneumolysin-damaged mitochondria via the STING signaling pathway in macrophages.

Pneumolysin (Ply), a major virulence factor of Streptococcus pneumoniae (S. pn), affects the immunity of host cells during infection. It has been reported that Ply is involved in S. pn standard strain D39-induced interferon-ß (IFN-ß) expression; however, other findings suggest that recombinant Ply protein is incapable of triggering IFN-ß expression. Here, we demonstrated that purified Ply was capable of initiating oxidative damage to mitochondria, resulting in the subsequent release of mitochondrial deoxyribonucleic acid (mtDNA), which mediated IFN-ß expression in macrophages. Importantly, we determined that IFN-ß expression was regulated by stimulator of interferon genes (STING) signaling in response to Ply. In conclusion, our study identified that IFN-ß production was triggered by Ply in macrophages and mtDNA released from Ply-damaged mitochondria mediated this process, through the STING pathway. This is a novel mechanism by which S. pn modulates type I IFN response in macrophages.

Type I interferon induced by DNA of nontypeable Haemophilus influenza modulates inflammatory cytokine profile to promote susceptibility to this bacterium.

Type I interferon (IFN) is indispensable for antiviral immunity, but its role in bacterial infections is controversial and not fully described. Nontypeable Haemophilus influenzae (NTHi) is one of the most common bacterial pathogens in patients with chronic obstructive pulmonary disease (COPD). NTHi-DNA activates type I IFN production in macrophages, but the function of type I IFN in host-pathogen interactions, in the context of NTHi infection, is still unclear. Here, we showed that type I IFN, induced by NTHi-DNA, restrained bacterial killing in vitro and promoted COPD development in vivo in response to NTHi. Mice deficient for type I IFN receptor (IFNAR) exhibited improved resistance to NTHi infection. Moreover, similar to exogenous IFN-ß, NTHi-DNA-induced type I IFN increased the production of IL-6, IL-1ß, IL-12 and CXCL10 via p38 MAPK activation. Our findings demonstrated that NTHi-DNA-induced type I IFN signaling played a negative role in host defense against NTHi infection and identified potential targets for future therapeutic management of COPD.