Polyimide Aerogel Fiber Bundles for Extreme Thermal Management Systems in Aerospace Applications.

Aerogel fibers are an emerging class of ultralightweight materials, which, compared to conventional bulk monolithic and aerogel films, provide better flexibility and extensibility. Despite the recent advancements in this field, due to their highly porous structure, their mechanical properties can be deteriorated. Inspired by the textile industry, we report the development of aerogel fiber bundles with twisted structures as a promising strategy to enhance the mechanical performance and practicality of aerogel fibers. Polyimide (PI) aerogel fibers were prepared via the sol-gel confined transition method. The fibers showed a unique nanostructured assembly with high specific surface area, excellent optical transparency, outstanding flexibility at diverse extreme conditions, self-extinguishing behavior, and superior thermal insulation performance. Using PI aerogel fibers as the backbone, aerogel fiber bundles in various configurations were designed and fabricated. A systematic study was performed to analyze the effect of design parameters on the mechanical performance of the bundles. Results revealed an optimal twist level for bundles, leading to a peak in mechanical properties across various bundle configurations. The observed improvement in mechanical properties was attributed to increased fiber-to-fiber binding strength, enhanced friction, and interlocking mechanism of fibers, underscoring the potential of the optimized twist level for enhancing the performance of aerogel fiber bundles. Overall, the development of aerogel fiber bundles holds great promise in revolutionizing the production of high-performance ultralightweight materials for thermal management applications.

Long-Term Prognostic Significance of Three-Dimensional Speckle-Tracking Echocardiography-Derived Left Ventricular Twist in Healthy Adults-Results from the MAGYAR-Healthy Study.

Background: The left ventricular (LV) rotational mechanics are of particular importance in the function of the LV. The rotational movement is the consequence of the arrangement of the subepicardial and subendocardial muscle fibers. These muscle fibers are perpendicular to each other, their contraction creates a characteristic motion. The aim of the present study was to examine the prognostic impact of LV twist assessed by three-dimensional speckle-tracking echocardiography (3D-STE) in healthy circumstances. Methods: 302 healthy adults participated in the study, 181 subjects were excluded due to certain reasons (LV could not be analysed during 3D-STE, subjects were unidentifiable, or lost to follow-up). 121 subjects were involved in the final analysis (mean age of 33.1 ± 12.3 years, 75 males), who were willing to be examined on a voluntary basis. Results: During a mean follow-up of 7.93 ± 4.21 years, 11 healthy adults suffered a cardiovascular event including 2 cardiac deaths. Using receiver operating characteristic analysis, LV twist ≥14.65 degrees as assessed by 3D-STE proved to be significantly predictive regarding the cardiovascular event-free survival (area under the curve 0.70, specificity 70%, sensitivity 65%, p = 0.028). Subjects with LV twist ≥14.65 degrees had higher basal and apical rotations and a significantly higher ratio of these individuals developed cardiovascular events compared to cases with LV twist <14.65 degrees. Subjects with cardiovascular events had lower LV global longitudinal strain, higher basal LV rotation and twist and the ratio of subjects with LV twist ≥14.65 degrees was elevated as compared to cases without events. Conclusions: 3D-STE-derived LV twist independently predicts future cardiovascular events in healthy adults.

A rescue treatment to release the twist of a flow re-direction endoluminal device.

Background: A flow redirection endoluminal device (FRED) is a widely used flow diverter stent. Although high technical success and good treatment results were reported in the SAFE study, cases of technical failure of deployment have also been reported. A case in which a FRED was deployed with the proximal part twisted, but successful deployment was achieved, is presented. Case Description: A woman in her 40s was diagnosed with a left internal carotid artery aneurysm during radiological investigations for headaches. Due to her family's strong history of cerebral aneurysms, she opted for preventive treatment. A 5.5-mm FRED was selected because the proximal vessel diameter was ≥5 mm. However, the stent was deployed with the proximal side twisted. Fortunately, using a Scepter C and a CHIKAI 315 cm, the true lumen could be secure, the wire was guided distally, and the FRED was successfully placed. Later, with the patient's consent, a 3D blood vessel model was created, and whether the stent was difficult to open or whether it was just a technical problem which was verified experimentally. Precisely, the same situation as during the surgery was recreated, and the stent was deployed in the same way. Conclusion: A FRED is an effective device, but there are cases of difficult deployment. The present method may be an option if a FRED is difficult to open.

Emerging biological functions of Twist1 in cell differentiation.

Twist1 is required for embryonic development and expresses after birth in mesenchymal stem cells derived from mesoderm, where it governs mesenchymal cell development. As a well-known regulator of epithelial-mesenchymal transition or embryonic organogenesis, Twist1 is important in a variety of developmental systems, including mesoderm formation, neurogenesis, myogenesis, cranial neural crest cell migration, and differentiation. In this review, we first highlight the physiological significance of Twist1 in cell differentiation, including osteogenic, chondrogenic, and myogenic differentiation, and then detail its probable molecular processes and signaling pathways. On this premise, we summarize the significance of Twist1 in distinct developmental disorders and diseases to provide a reference for studies on cell differentiation/development-related diseases.

DNA hypermethylation of tumor suppressor genes TWIST1, GATA4, MUS81 and NTRK1 in endometrial hyperplasia.

OBJECTIVE: To investigate DNA methylation of specific tumor suppressor genes in endometrial hyperplasia compared to normal endometrial tissue. File and methodology: To search for epigenetic events, methylation-specific multiplex ligation-dependent probe amplification was employed to compare the methylation status of 40 tissue samples with atypical endometrial hyperplasia, 40 tissue samples with endometrial hyperplasia without atypia, and 40 control tissue samples with a normal endometrium. RESULTS AND CONCLUSION: Differences in DNA methylation among the groups were found in TWIST1, GATA4, MUS81, and NTRK1 genes (TWIST1: atypical hyperplasia 67.5%, benign hyperplasia 2.5%, normal endometrium 22.5%; P < 0.00001; GATA4: atypical hyperplasia 95%, benign hyperplasia 65%, normal endometrium 22.5%; P < 0.00001; MUS81: atypical hyperplasia 57.5%, benign hyperplasia 22.5%, normal endometrium 5%; P < 0.00001; NTRK1: atypical hyperplasia 65%, benign hyperplasia 27.5%, normal endometrium 10%; P < 0.00001). Higher methylation rates were observed for the tumor suppressor genes of TWIST1, GATA4, MUS81, and NTRK1 in samples with atypical endometrial hyperplasia compared to samples with normal endometrial tissue, and higher methylation rates were found in samples with atypical endometrial hyperplasia compared to samples of benign endometrial hyperplasia. DNA methylation of TWIST1, GATA4, MUS81, and NTRK1 is involved in the pathogenesis of atypical endometrial hyperplasia.

Twist elastic constant of chiral nematic cellulose nanocrystals determined by tactoid reconfiguration in electric field.

Lyotropic chiral nematic cellulose nanocrystals (CNCs) have attracted significant attention and great progress has been made. Investigating their physical parameters, especially the twist elastic constant (K22), is pivotal for advancing our comprehension of fundamental viscoelastic property of chiral nematic phase. In this study, we demonstrate a straightforward method to simultaneously estimate K22 and helical twisting power (Kt) of chiral nematic CNCs. This method involves analyzing rheology properties and electro-response of CNCs, focusing on the rotational dynamics and structural reconfiguration of CNC tactoids under an electric field. By examining the rotation dynamics of CNC tactoids under an electric field, together with the viscosity characterization, the anisotropic dielectric susceptibility (∆χ) of chiral nematic CNC along the helix axis was determined. Subsequently, K22/∆χn was extracted by analyzing CNC tactoid pitch evolution under an electric field, employing the de Gennes model. The K22 for different concentrated CNCs is finally estimated by integrating experimental results and theory. It is shown that the chiral nematic CNCs present concentration-dependent K22, ranging from 0.05 to 0.14 pN, while Kt spans from 0.06 to 0.14 pN/µm. This study offers a comprehensive understanding of the CNC fundamental viscoelastic property and opens up new avenues for K22 measurement in other lyotropic liquid crystals.

Twists through turbidity: propagation of light carrying orbital angular momentum through a complex scattering medium.

We explore the propagation of structured vortex laser beams-shaped light carrying orbital angular momentum (OAM)-through complex multiple scattering medium. These structured vortex beams consist of a spin component, determined by the polarization of electromagnetic fields, and an orbital component, arising from their spatial structure. Although both spin and orbital angular momenta are conserved when shaped light propagates through a homogeneous, low-scattering medium, we investigate the conservation of these angular momenta during the propagation of Laguerre-Gaussian (LG) beams with varying topological charges through a turbid multiple scattering environment. Our findings demonstrate that the OAM of the LG beam is preserved, exhibiting a distinct phase shift indicative of the 'twist of light' through the turbid medium. This preservation of OAM within such environments is confirmed by in-house developed Monte Carlo simulations, showing strong agreement with experimental studies. Our results suggest exciting prospects for leveraging OAM in sensing applications, opening avenues for groundbreaking fundamental research and practical applications in optical communications and remote sensing.

Miscibility Studies of Bismesogen CBnCB Forming Nematic Twist-Bend Phase with Cyanobiphenyls nCB.

This work aims to determine how the nematic twist-bend phase (NTB) of bismesogens containing two rigid parts of cyanobiphenyls connected with a linking chain containing n = 7, 9, and 11 methylene groups behaves in mixtures with structurally similar cyanobiphenyls nCB, n = 4-12, 14. The whole phase diagrams are presented for the CB7CB-nCB system. For the other systems, CB9CB-nCB and CB11CB-nCB, only curves corresponding to NTB-N phase transition are presented. Based on the temperature-concentration range of the existence of NTB phase, it was established that an increase in the alkyl chain length of CBnCB causes an increase in the stability of the NTB phase. But surprisingly, an increase in the alkyl chain length of nCB compounds does not change the slope of the NTB-N equilibrium line on phase diagrams. It is slightly bigger when the nCB compound has the same length of alkyl chain as the length of the linking group of a bismesogen. XRD studies were carried out for two mixtures.

δ-catenin promotes Twist1 stabilization in prostate cancer through ubiquitination modification.

Prostate cancer generally has a high long-term survival rate; however, metastatic prostate cancer remains largely incurable despite intensive multimodal therapy. Recent research has identified δ-catenin, a member of the catenin family, as playing a crucial role in the progression of prostate cancer. Nonetheless, the extent to which δ-catenin influences transcription factors associated with epithelial-mesenchymal transition (EMT) has not been thoroughly explored. This study aims to investigate the hypothesis that δ-catenin enhances the stability of Twist1, thereby promoting the migratory and invasive capabilities of prostate cancer cells. Clinical data indicate a strong correlation between δ-catenin and Twist1 expression levels. Western blot analysis confirmed that δ-catenin stabilizes Twist1 and induces ectopic expression. Additionally, δ-catenin was found to reduce Twist1 phosphorylation by inhibiting GSK-3ß activity. Immunoprecipitation analysis suggested that δ-catenin exerts its effect by competing with Twist1 for binding to ubiquitin (Ub). These results highlight the role of δ-catenin in the ubiquitination modification of Twist1, suggesting that the combined presence of δ-catenin and Twist1 could serve as a biomarker for tumor progression in prostate cancer.

Control of Subband Energies via Interlayer Twisting in an Artificially Stacked WSe2 Bilayer.

Tuning the electronic structure of artificially stacked bilayer crystals using their twist angle has attracted a significant amount of interest. In this study, resonant tunneling spectroscopy was performed on trilayer WSe2/h-BN/twisted bilayer (tBL) WSe2 devices with a wide range of twist angles (θBL) of tBL WSe2, from 0° to 34°. We observed two resonant tunneling peaks, identified as the first and second lowest hole subbands at the valence band Γ point of tBL WSe2. The subband separation, which directly measured the interlayer coupling strength, was tuned by ∼0.1 eV as θBL increased toward 6° and remained nearly constant for larger θBL values. The θBL dependence was attributed to the emergence of a stable W/Se (Se/W) stacking domain in the small θBL region, owing to the atomic reconstruction of the moiré lattice in tBL WSe2. Our findings demonstrate that the twist-controlled subband energies in tBL WSe2 are predominantly determined by local atomic reconstruction.

Relationship of Signaling Pathways between RKIP Expression and the Inhibition of EMT-Inducing Transcription Factors SNAIL1/2, TWIST1/2 and ZEB1/2.

Untreated primary carcinomas often lead to progression, invasion and metastasis, a process that involves the epithelial-to-mesenchymal transition (EMT). Several transcription factors (TFs) mediate the development of EMT, including SNAIL1/SNAIL2, TWIST1/TWIST2 and ZEB1/ZEB2, which are overexpressed in various carcinomas along with the under expression of the metastasis suppressor Raf Kinase Inhibitor Protein (RKIP). Overexpression of RKIP inhibits EMT and the above associated TFs. We, therefore, hypothesized that there are inhibitory cross-talk signaling pathways between RKIP and these TFs. Accordingly, we analyzed the various properties and biomarkers associated with the epithelial and mesenchymal tissues and the various molecular signaling pathways that trigger the EMT phenotype such as the TGF-ß, the RTK and the Wnt pathways. We also presented the various functions and the transcriptional, post-transcriptional and epigenetic regulations for the expression of each of the EMT TFs. Likewise, we describe the transcriptional, post-transcriptional and epigenetic regulations of RKIP expression. Various signaling pathways mediated by RKIP, including the Raf/MEK/ERK pathway, inhibit the TFs associated with EMT and the stabilization of epithelial E-Cadherin expression. The inverse relationship between RKIP and the TF expressions and the cross-talks were further analyzed by bioinformatic analysis. High mRNA levels of RKIP correlated negatively with those of SNAIL1, SNAIL2, TWIST1, TWIST2, ZEB1, and ZEB2 in several but not all carcinomas. However, in these carcinomas, high levels of RKIP were associated with good prognosis, whereas high levels of the above transcription factors were associated with poor prognosis. Based on the inverse relationship between RKIP and EMT TFs, it is postulated that the expression level of RKIP in various carcinomas is clinically relevant as both a prognostic and diagnostic biomarker. In addition, targeting RKIP induction by agonists, gene therapy and immunotherapy will result not only in the inhibition of EMT and metastases in carcinomas, but also in the inhibition of tumor growth and reversal of resistance to various therapeutic strategies. However, such targeting strategies must be better investigated as a result of tumor heterogeneities and inherent resistance and should be better adapted as personalized medicine.

Twist-Controlled Ferroelectricity and Emergent Multiferroicity in WSe2 Bilayers.

Recently, researchers have been investigating artificial ferroelectricity, which arises when inversion symmetry is broken in certain R-stacked, i.e., zero-degree twisted, van der Waals (vdW) bilayers. Here, the study reports the twist-controlled ferroelectricity in tungsten diselenide (WSe2) bilayers. The findings show noticeable room temperature ferroelectricity that decreases with twist angle within the range 0° < θ < 3°, and disappears completely for θ ≥ 4°. This variation aligns with moiré length scale-controlled ferroelectric dynamics (0° < θ < 3°), while loss beyond 4° may relate to twist-controlled commensurate to non-commensurate transitions. This twist-controlled ferroelectricity serves as a spectroscopic tool for detecting transitions between commensurate and incommensurate moiré patterns. At 5.5 K, 3° twisted WSe2 exhibits ferroelectric and correlation-driven ferromagnetic ordering, indicating twist-controlled multiferroic behavior. The study offers insights into twist-controlled coexisting ferro-ordering and serves as valuable spectroscopic tools.

NSC-38270 Exhibits Anti-invasive and Pro-apoptotic Effects on Hepatocellular Carcinoma Huh7 Cells.

BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is a main type of liver cancer with high metastatic potential, and its incidence is steadily increasing worldwide. However, the development of new drugs for the treatment of HCC is still insufficient. This study aimed to determine the anticancer effect of NSC-38270, a natural product, on HCC. MATERIALS AND METHODS: After treating HCC Huh7 cells with NSC-38270, cell growth, wound healing, migration, and invasion assays were conducted. We investigated the effects of NSC-38270 on Twist1, a crucial epithelial-mesenchymal transition (EMT)-related transcription factor. In addition, apoptosis, histone H2A.X activation, and cell morphology assays were performed in Huh7 and immortalized normal liver cells following treatment with NSC-38270. RESULTS: NSC-38270 reduced the migration and invasion ability of Huh7 cells, accompanied by a decrease in Twist1. Furthermore, NSC-38270 induced apoptosis in Huh7 cells, whereas apoptosis was not observed in immortalized normal liver cells (THLE-2 cells and Chang liver cells). CONCLUSION: NSC-38270 exhibited significant inhibitory effects on the migration and invasion of Huh7 cells by repressing Twist1. Importantly, it induced cancer cell-specific apoptotic effects. These findings suggest that NSC-38270 holds promising potential as a therapeutic candidate for cancer treatment.

Clinical Implications of Circulating Tumor Cells in Patients with Esophageal Squamous Cell Carcinoma: Cancer-Draining Blood Versus Peripheral Blood.

Circulating tumor cells (CTCs) in cancer-draining veins have diagnostic and prognostic value. However, studies on esophageal squamous cell carcinoma (ESCC) are limited. This study aimed to compare CTCs obtained from different sampling sites (peripheral vein vs. cancer-draining azygos vein) and to investigate their association with the clinicopathological characteristics of ESCC patients. Blood samples were collected preoperatively from both veins in 40 ESCC patients at Pusan National University Hospital from June 2020 to April 2022. CTCs were detected using a centrifugal microfluidic method with fluid-assisted separation. CTCs and TWIST (+) CTCs were detected more frequently in the azygos vein blood than in the peripheral vein blood; however, the difference was not statistically significant (85.0% [34/40] vs. 77.5% [31/40], p = 0.250 and 82.5% [33/40] vs. 75.0% [30/40], p = 0.586, respectively). CTC and TWIST (+) CTC counts were significantly higher in the azygos vein blood than in the peripheral vein blood (7 vs. 3, p < 0.001, and 6 vs. 2, p < 0.001, respectively). CTCs and TWIST (+) CTCs from peripheral and azygos veins showed no association with clinicopathological characteristics. Further large-scale studies are needed to clarify their role as predictive biomarkers for prognosis and chemotherapy responses in ESCC patients.

MFN2-dependent mitochondrial dysfunction contributes to Relm-ß-induced pulmonary arterial hypertension via USP18/Twist1/miR-214 pathway.

Induction of resistin-like molecule ß (Relm-ß) and mitofusin 2 (MFN2) mediated aberrant mitochondrial fission have been found to be involved in the pathogenesis of pulmonary arterial hypertension (PAH). However, the molecular mechanisms underlying Relm-ß regulation of MFN2 therefore mitochondrial fission remain unclear. This study aims to address these issues. Primary cultured PASMCs and monocrotaline (MCT)-induced PAH rats were applied in this study. The results showed that Relm-ß promoted cells proliferation in PASMCs, this was accompanied with the upregulation of USP18, Twist1 and miR-214, and downregulation of MFN2. We found that Relm-ß increased USP18 expression which in turn raised Twist1 by suppressing its proteasome degradation. Elevation of Twist1 increased miR-214 expression and then reduced MFN2 expression and mitochondrial fragmentation leading to PASMCs proliferation. In vivo study, we confirmed that Relm-ß was elevated in MCT-induced PAH rat model, and USP18/Twist1/miR-214/MFN2 axis was altered similar as in vitro. Targeting this cascade by Relm-ß receptor inhibitor Calhex231, proteasome inhibitor MG-132, Twist1 inhibitor Harmine or miR-214 antagomiR prevented the development of pulmonary vascular remodeling and therefore PAH in MCT-treated rats. In conclusion, we demonstrate that Relm-ß promotes PASMCs proliferation and vascular remodeling by activating USP18/Twist1/miR-214 dependent MFN2 reduction and mitochondrial fission, suggesting that this signaling pathway might be a promising target for management of PAH.

Accuracy of Physiotherapist Predictions for Independent Walking After Stroke.

BACKGROUND: The use of prediction tools in stroke rehabilitation research and clinical practice is increasing, but it is not clear whether these prediction tools out-perform clinician predictions. OBJECTIVE: This study aimed to compare physiotherapist predictions for independent walking with the Time to Walking Independently after STroke (TWIST) prediction tool. METHODS: Adults with new lower limb weakness and unable to walk independently (Functional Ambulation Category [FAC] < 4) were recruited. At 1 week post-stroke, the treating physiotherapist was asked to predict whether their patient would achieve independent walking by 4, 6, 9, 12, 16, or 26 weeks, or remain dependent. Predictions were also made using the TWIST prediction tool, but not shared. Binary logistic regressions were conducted with the time independent walking was achieved as the dependent variable and independent variables were the physiotherapist and TWIST predictions. RESULTS: Ninety-one participants were included (median age 71 years, 36 [40%] female). Most participants (67 [74%]) were non-ambulatory (FAC = 0) at 1-week post-stroke. Thirty-seven physiotherapists were recruited. Physiotherapists made accurate predictions for time taken to achieve independent walking for 39 participants (43%). Prediction accuracy was not related to physiotherapist confidence or years of stroke-specific experience. TWIST out-performed physiotherapist predictions (Physiotherapists 76%-77%, TWIST 86%-88% accurate) for participants who achieved independent walking by 4, 6, and 9 weeks post-stroke. Accuracy of physiotherapist and TWIST predictions was similar for 16 and 26 weeks post-stroke. CONCLUSIONS: The TWIST prediction tool is more accurate than physiotherapists at predicting whether a patient will achieve independent walking by 4, 6, or 9 weeks post-stroke, but not for 16 or 26 weeks post-stroke. TWIST may be useful to inform early rehabilitation and discharge planning. Clinical Trial Registration-URL: www.anzctr.org.au Unique Identifier: ACTRN12617001434381.

ROR2 promotes cell cycle progression and cell proliferation through the PI3K/AKT signaling pathway in gastric cancer.

Proliferation is a critical characteristic of the progression of gastric cancer (GC). Receptor tyrosine kinase-like orphan receptor 2 (ROR2), the orphan receptor tyrosine kinase-like receptor, exhibits effects on tumor growth due to its abnormal expression in cancer. The goal of our study was to assess the potential regulatory role exerted by the ROR2 on GC cells. Through previous bioinformatics analysis, we discovered an association between ROR2 and the G2/M phase of the GC cell cycle. However, little is known about the link between ROR2 and the G2/M phase cell cycle in GC. Here, the findings of our study indicate that ROR2, after transcribed expression by Twist1, activates the PI3K/AKT/mTOR/S6K signal transduction pathway, thus leading to the acceleration of the G2/M phase and subsequent promotion of cell proliferation in GC. Furthermore, the functional link among ROR2, Twist1, and G2/M phase of cell cycle was also confirmed in mouse xenograft tissues and human tissues. ROR2 expression was correlated with Twist expression and lower survival in vivo. Notably, our suggestion is that focusing on ROR2 as a potential therapeutic approach could show potential for the management of GC.

Arsenic-induced transition of thymic inflammation-to-fibrosis involves Stat3-Twist1 interaction: Melatonin to the rescue.

Groundwater arsenic is a notorious toxicant and exposure to environmentally relevant concentrations persists as a healthcare burden across the world. Arsenic has been reported to jeopardize the normal functioning of the immune system, but there are still gaps in the understanding of thymic T cell biology. Immunotoxic influence of arsenic in thymic integrity demands a potent restorative molecule. The objectives of this study were to examine key signaling cross-talks associated with arsenic-induced immune alterations in the thymus and propose melatonin as a potential candidate against immunological complications arising from arsenic exposure. Swiss albino mice were exposed to sodium arsenite (0.05 mg/L; in drinking water) and melatonin (IP:10 mg/kg BW) for 28 days. Melatonin successfully protected thymus from arsenic-mediated tissue degeneration and maintained immune homeostasis including T cell maturation and proliferation by mitigating oxidative stress through Nrf2 upregulation. Additionally, melatonin exerted ameliorative effect against arsenic-induced apoptosis and inflammation by inhibiting p53-mediated mitochondrial cell death pathway and NF-κB-p65/STAT3-mediated proinflammatory pathway, respectively. For the first time, we showed that arsenic-induced profibrotic changes were inhibited by melatonin through targeting of inflammation-associated EMT. Our findings clearly demonstrate that melatonin can be a viable and promising candidate in combating arsenic-induced immune toxicity with no collateral damage, making it an important research target.

Transcription factor Twist1 drives fibroblast activation to promote kidney fibrosis via signaling proteins Prrx1/TNC.

The transcription factor Twist1 plays a vital role in normal development in many tissue systems and continues to be important throughout life. However, inappropriate Twist1 activity has been associated with kidney injury and fibrosis, though the underlying mechanisms involved remain incomplete. Here, we explored the role of Twist1 in regulating fibroblast behaviors and the development kidney fibrosis. Initially Twist1 protein and activity was found to be markedly increased within interstitial myofibroblasts in fibrotic kidneys in both humans and rodents. Treatment of rat kidney interstitial fibroblasts with transforming growth factor-ß1 (a profibrotic factor) also induced Twist1 expression in vitro. Gain- and loss-of-function experiments supported that Twist1 signaling was responsible for transforming growth factor-ß1-induced fibroblast activation and fetal bovine serum-induced fibroblast proliferation. Mechanistically, Twist1 protein promoted kidney fibroblast activation by driving the expression of downstream signaling proteins, Prrx1 and Tnc. Twist1 directly enhanced binding to the promoter of Prrx1 but not TNC, whereas the promoter of TNC was directly bound by Prrx1. Finally, mice with fibroblast-specific deletion of Twist1 exhibited less Prrx1 and TNC protein abundance, interstitial extracellular matrix deposition and kidney inflammation in both the unilateral ureteral obstruction and ischemic-reperfusion injury-induced-kidney fibrotic models. Inhibition of Twist1 signaling with Harmine, a ß-carboline alkaloid, improved extracellular matrix deposition in both injury models. Thus, our results suggest that Twist1 signaling promotes the activation and proliferation of kidney fibroblasts, contributing to the development of interstitial fibrosis, offering a potential therapeutic target for chronic kidney disease.

Hydroquinone impairs trophoblast migration and invasion via AHR-twist-IFITM1 axis.

INTRODUCTION: Embryo implantation is a tightly regulated process, critical for a successful pregnancy. After attachment of the blastocyst to the surface epithelium of the endometrium trophoblast migrate from the trophectoderm and invade into the stromal component of endometrium. Alterations on either process will lead to implantation failure or miscarriage. Volatile organic compounds (VOCs) such as benzene induce pregnancy complications, including preterm birth and miscarriages. The mechanism of this effect is unknown. The objective of this study was to elucidate the impact of benzene metabolite, Hydroquinone, on trophoblast function. We tested the hypothesis that Hydroquinone activates the Aryl hydrocarbon receptor (AhR) pathway modulating trophoblast migration and invasion. METHODS: First-trimester trophoblast cells (Sw.71) were treated with hydroquinone (6 and 25 µM). Trophoblast migration and invasion was evaluated using a 3D invasion/migration model. Gene expression was quantified by q-PCR and Western blot analysis. RESULTS: Hydroquinone impairs trophoblast migration and invasion. This loss is associated with the activation of the AhR pathway which reduced the expression of Twist1and IFITM1. IFITM1 overexpression can rescue impaired trophoblast migration. DISCUSSION: Our study highlights that hydroquinone treatment induces the activation of the AhR pathway in trophoblast cells, which impairs trophoblast invasion and migration. We postulate that activation of the AhR pathway in trophoblast suppress Twist1 and a subsequent IFITM1. Thus, the AhR-Twist1-IFITM1 axis represent a critical pathway involved in the regulation of trophoblast migration and it is sensitive to benzene exposure. These findings provide crucial insights into the molecular mechanisms underlying pregnancy complications induced by air pollution.