Activation of the p62-Keap1-Nrf2 pathway improves pulmonary arterial hypertension in MCT-induced rats by inhibiting autophagy.

Autophagy is implicated in the pathogenesis of pulmonary arterial hypertension (PAH). We aimed to investigate whether the p62-Keap1-Nrf2 pathway affects the development of PAH by mediating autophagy. A PAH rat model was established using monocrotaline (MCT). Pulmonary artery smooth muscle cells (PASMCs) were extracted, and the changes in proliferation, migration, autophagy, and oxidative stress were analyzed following overexpression or knockdown of p62. The impact of p62 on the symptoms of PAH rats was assessed by the injection of an adenovirus overexpressing p62. We found that the knockdown of p62 increased the proliferation and migration of PASMCs, elevating the oxidative stress of PASMCs and upregulating gene expression of NADPH oxidases. Co-IP assay results demonstrated that p62 interacted with Keap1. p62 knockdown enhanced Keap1 protein stability and Nrf2 ubiquitination. LC3II/I and ATG5 were expressed more often when p62 was knocked down. Treating with an inhibitor of autophagy reversed the impact of p62 knockdown on PASMCs. Nrf2 inhibitor treatment reduced the expression of Nrf2 and p62, while increasing the expression of Keap1, LC3II/I, and ATG5 in PASMCs. However, overexpressing p62 diminished mRVP, SPAP, and Fulton index in PAH rats and attenuated pulmonary vascular wall thickening. Overexpression of p62 also decreased the expression of Keap1, LC3II/I, and ATG5 and increased the nuclear expression of Nrf2 in PAH rats. Importantly, overexpression of p62 reduced oxidative stress and the NADPH oxidase expression in PAH rats. Overall, activation of the p62-Keap1-Nrf2 positive feedback signaling axis reduces the proliferation and migration of PASMCs and alleviates PAH by inhibiting autophagy and oxidative stress.

Oceanisphaera pacifica sp. nov., isolated from the intestine of Trichiurus japonicus.

A Gram-stain-negative, strictly aerobic, non-flagellated, oxidase- and catalase-positive, rod-shaped marine bacterium, designated strain DM8T, was isolated from the intestine of Trichiurus japonicus in Weihai, China. The strain optimally grew at 25-35℃, with 1.0-4.0% (w/v) NaCl and at pH 7.0-8.0. Its colonies were circular, slightly yellow, non-transparent, smooth, and approximately 0.8-1.5 mm in diameter, after being cultured for 48 h on marine agar 2216. Based on the result of phylogenetic analysis of 16S rRNA gene sequence, strain DM8T had close relationship with Oceanisphaera profunda SM1222T (96.9%) and the type strain DSM 15406 T of the type species Oceanisphaera litoralis (94.7%), respectively. Genome sequencing revealed a genome size of 3,109,059 bp and a G + C content of 46.9 mol%. It had Q-8 as the sole respiratory quinone and possessed C16:0, summed features 3 (C16:1ω7c/C16:1ω6c) and summed features 8 (C18:1ω7c/C18:1ω6c) as major fatty acids. The major polar lipid profile was composed of phosphatidylglycerol and phosphatidylethanolamine. Based on the phenotypic, chemotaxonomic characterizations, phylogenetic properties and genome analysis, strain DM8T should represent a novel species of the genus Oceanisphaera, for which the name Oceanisphaera pacifica sp. nov. is proposed. The type strain is DM8T (= KCTC 82764 T = MCCC 1K06133T).

Fulvivirga marina sp. nov. and Fulvivirga sediminis sp. nov., two novel Bacteroidetes isolated from the marine sediment.

Two novel, designated strains 29W222T and 2943T, were isolated from the marine sediment from Aoshan Bay, Jimo, PR China. Growth was observed at pH 6.0-8.5 (optimum, pH 7.5) for strain 29W222T, and pH 5.5-8.5 (pH 7.0) for strain 2943T. Both strains displayed growth in 0.5-6 % NaCl with an optimum at 1 % for 29W222T; 0.5 % for 2943T. Both strains grew optimally at 33 °C. The results of phylogenetic analyses based on 16S rRNA gene sequences indicated that 29W222T and 2943T represented members of the genus Fulvivirga and strain 29W222T was most closely related to Fulvivirga kasyanovii KMM 6220T (97.9 % sequence similarity) and Fulvivirga imtechensis AK7T (95.0 %), and 2943T to Fulvivirga imtechensis AK7T (95.7 %) and Fulvivirga kasyanovii KMM 6220T (94.8 %). The genomic DNA G+C contents of 29W222T and 2943T were 39.9 and 37.7 mol%, respectively. The results of chemotaxonomic analysis indicated that the sole respiratory quinone was menaquinone 7 (MK-7), and the major fatty acid was iso-C15 : 0 for both strains. Average nucleotide identity and average amino acid identity values between strain 29W222T and Fulvivirga kasyanovii KMM 6220T were 78.9 and 83.6 %, respectively; the corresponding values between 2943T and Fulvivirga imtechensis AK7T were 69.8 and 63.6 %, respectively. Therefore, strains 29W222T and 2943T represent to two novel species of the genus Fulvivirga, for which the names Fulvivirga marina sp. nov. (29W222T=KCTC 62848T=MCCC 1K05194T) and Fulvivirga sediminis sp. nov. (2943T=KCTC 62847T= MCCC 1K05144T) are proposed, respectively.

A Retrospective Study of 98 Elderly Patients with High-Risk Lateral Femoral Wall Intertrochanteric Hip Fractures to Compare Outcomes Following Surgery with Proximal Femoral Nail Antirotation (PFNA) Versus Dynamic Hip Screw (DHS).

BACKGROUND The aim of this study was to evaluate the efficacy of dynamic hip screw (DHS) and femoral nail antirotation (PFNA) in the treatment of lateral-wall high-risk type of intertrochanteric fractures. MATERIAL AND METHODS A total of 98 patients with high-risk intertrochanteric fractures of the lateral wall who underwent surgery from January 2019 to December 2020 were selected as the study subjects. Of these, 52 were treated surgically with PFNA (mean age 73.45±5.95 years) and 46 with DHS (71.37±6.22 years). We followed up these patients and compared the occurrence of the 2 surgical methods in terms of perioperative period, complication rate, and functional recovery. RESULTS In terms of lateral wall fracture, there were 2 cases of PFNA and 10 cases of DHS, and the difference between groups was statistically significant (P<0.05). Operative time (mean 54.94±7.29 vs 61.17±6.45) and intraoperative blood loss (72.80±9.18 vs 96.12±8.22) was significantly lower in the PFNA group compared to the DHS group (all P<0.05). Efficacy in the PFNA group was significantly better than in the DHS group. The HHS at follow-up was significantly higher in the PFNA group (mean 80.73±9.20 vs 64.19±8.12) than in the DHS group (P<0.001). The VAS score at follow-up was significantly lower in the PFNA group (1.78±0.34 vs 2.65±0.23) than in the DHS group (P<0.001). CONCLUSIONS PFNA is more effective than DHS in the treatment of high-risk lateral wall fractures in the elderly, with the advantages of lower incidence of complications and better recovery of hip joint function. PFNA warrants clinical application.

Detection of epidermal growth factor receptor mutations in non-small cell lung cancer by immunohistochemistry. / å ç–«ç»„ç»‡åŒ–å­¦æ³•æ£€æµ‹éžå°ç»†èƒžè‚ºç™Œè¡¨çš®ç”Ÿé•¿å› å­å—ä½“çªå˜.

OBJECTIVES: To evaluate the sensitivity and specificity of immunohistochemistry (IHC) for detecting common epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) and to estimate the cost-effectiveness of IHC testing. METHODS: A total of 208 NSCLC patients were included in the trial, and the EGFR mutation status in the patients were detected by PCR and IHC. Two mutation-specific antibodies against the most common exon 19 deletion (clone SP111) and exon 21 L858R mutation (clone SP125) were tested by using automated immunostainer. A cost-effectiveness analysis model was built for the analysis of optimal detection scheme. RESULTS: With a cutoff value of IHC 1+, the overall sensitivity and specificity of the IHC-based method compared with the PCR-based method were 81.7% (95% CI 72.4% to 89.0%) and 94.7% (95% CI 92.6% to 99.5%), respectively. EGFR 19del mutation was detected by SP111 antibody with a sensitivity of 65.9% (95% CI 49.4% to 79.9%) and specificity of 98.8% (95% CI 95.7% to 99.9%). EGFR L858R mutation was detected by SP125 antibody with a sensitivity of 94.2% (95% CI 84.1% to 98.8%) and specificity of 99.4% (95% CI 96.5% to 100%). The IHC and PCR cost ratio needed to be 1-to-3 or more in our patients to economically justify before the use of IHC. CONCLUSIONS: The study confirms an excellent specificity with fairly good sensitivity of IHC and mutation-specific antibodies for common EGFR mutations. It is cost-effective to use IHC method to detect EGFR mutation first when the IHC and PCR cost ratio is 1-to-3 or more in Chinese populations.

Error tracking-control-reduction algorithm for designing diffractive optical element with high image reconstruction quality.

The use of the diffractive optical element (DOE) can often significantly reduce the size and enhance the performance of the optical system, but it is mostly prevented by low diffraction efficiency and serious speckle noise due to the quantization error. In this paper, an error tracking-control-reduction (ETCR) algorithm is proposed to suppress the quantization error, which adjusts the accumulative action, controls the current state and predicts the trend of the error. The simulation and experiment results verify that the ETCR algorithm has high diffraction efficiency which can be comparable with the Gerchberg-Saxton (GS) and Modified GS algorithms. Furthermore, the root-mean-square error (RMSE) of the proposed algorithm is significantly lower than that of the GS and MGS algorithms. Based on the proposed method, a 2-level DOE has been designed and fabricated to generate several grey images with only 0.05 RMSE.

Compact Open-Path Sensor for Fast Measurements of CO2 and H2O using Scanned-Wavelength Modulation Spectroscopy with 1f-Phase Method.

We report here the development of a compact, open-path CO2 and H2O sensor based on the newly introduced scanned-wavelength modulation spectroscopy with the first harmonic phase angle (scanned-WMS-θ1f) method for high-sensitivity, high temporal resolution, ground-based measurements. The considerable advantage of the sensor, compared with existing commercial ones, lies in its fast response of 500 Hz that makes this instrument ideal for resolving details of high-frequency turbulent motion in exceptionally dynamic coastal regions. The good agreement with a commercial nondispersive infrared analyzer supports the utility and accuracy of the sensor. Allan variance analysis shows that the concentration measurement sensitivities can reach 62 ppb CO2 in 0.06 s and 0.89 ppm H2O vapor in 0.26 s averaging time. Autonomous field operation for 15-day continuous measurements of greenhouse gases (CO2/H2O) was performed on a shore-based monitoring tower in Daya Bay, demonstrating the sensor's long-term performance. The capability for high-quality fast turbulent atmospheric gas observations allow the potential for better characterization of oceanographic processes.

Effective method for further magnifying the image in holographic projection under divergent light illumination.

Divergent light illumination can effectively increase the diffraction angle of holographic projection. However, the achieved maximum image size is limited to the geometric enlargement of the hologram size with the existing double-sampling Fresnel diffraction algorithm. In this paper, an effective method for further magnifying the image is proposed. The theoretical maximum size under divergent illumination is first analyzed. On this basis, a virtual intermediate plane is introduced between the source plane and the image plane. Then three-step diffraction calculation is performed to evaluate the Fresnel diffraction between the hologram plane and the image plane so that the sampling interval on the image plane is related to the position of the virtual plane and can be flexibly tuned. Consequently, the achieved image size can be further enlarged. The feasibility of the proposed method is demonstrated by simulations and experiments.

Anterior versus posterior approach for the therapy of multilevel cervical spondylotic myelopathy: a meta-analysis and systematic review.

BACKGROUND: The goal of this meta-analysis is to explore the overall efficacy as well as the safety of anterior versus posterior approach for the therapy of patients with multilevel cervical spondylotic myelopathy based on qualified studies. METHODS: Three electronic databases, PubMed, Cochrane, Embase were searched updated to January 2018 to identify all relevant and qualified studies using the index words. The qualified studies were including prospective or retrospective comparative studies. Relative risk (RR) and mean difference (MD) along with 95% confidence interval (95% CI) were used to analyze the main outcomes. RESULTS: In this meta-analysis, there were a total of 24 studies with 959 patients in the anterior approach group and 1072 patients in the posterior approach group. The final results showed, in comparison of the posterior approach group, the anterior approach group significantly increased the JOA score (SMD: 0.36, 95% CI 0.10-0.62), the operation time (WMD: 49.87, 95% CI 17.67-82.08), and the neurological recovery rate (WMD: 10.55, 95% CI 3.99-17.11) with higher complication rate (RR: 1.53, 95% CI 1.24-1.89). Besides, there was no significant difference of the blood loss (SMD: - 0.40, 95% CI - 1.12 to 0.32) and ROM (SMD: - 0.28, 95% CI - 0.78 to - 0.22) between posterior approach group and anterior approach group. CONCLUSIONS: Studies found a significant increase of JOA score as well as neurological recovery rate by the anterior approach treatment when compared with posterior approach treatment. However, increased operation time and complications could also occur through the anterior approach treatment. More high-quality randomized controlled trials with larger sample size, multi-centric and longer follow-ups are needed to support our current conclusions.

Non-iterative phase-only Fourier hologram generation with high image quality.

We report a novel and non-iterative method for the generation of phase-only Fourier hologram for image projection. Briefly, target image is first added with a special quadratic phase and then padded with zeros. A complex Fourier hologram is generated via the simple fast Fourier transform. Subsequently, the error diffusion algorithm is applied to convert the complex hologram into a phase-only hologram. The numerical, as well as the optical reconstructed images with the proposed method are of higher visual quality and contain less speckle noise compared to the original random phase method, which add the random phase to the target image and then preserve the phase component of the complex hologram. The influences of quadratic phase and zero-padding on the image quality are also discussed in detail.

Vector optical field generation based on birefringent phase plate.

Vector optical field has recently gained interest in a variety of application fields due to its novel characteristics. Conventional approaches of generating vector optical fields have difficulties in forming highly continuous polarization and suffer from the issue of high energy utilization rates. In order to address these issues, in this study a single optical path was proposed to generate vector optical fields where the birefringent phase plate modulated a linear polarized light into a vector optical field, which was then demodulated to a non-uniform linear polarization distribution of the vector optical field by the polarization demodulation module. Both a theoretical model and numerical simulations of the vector optical field generator were developed, illustrating the relationship between the polarization distribution of the target vector optical field and the depth distribution of the birefringent phase plate. Furthermore, the birefringent phase plate with predefined surface distributions was fabricated by grayscale exposure and ion etching. The generated vector optical field was experimentally characterized, capable of producing continuous polarization with high light energy utilization ratio, consistent with simulations. This new approach may have the potential of being widely used in future studies of generating well-controlled vector optical fields.

One exposure processing to fabricate spiral phase plate with continuous surface.

An economical method for fabricating spiral phase plate (SPP) with continuous surface is proposed in this paper. We use an interval to quantize a three dimensional surface of an SPP into two dimensional bars to form a binary mask. The exposure dose can be precisely distributed through this mask in the exposure process. We discuss the select criterion of the quantization interval and the fabricating processes of SPP in detail. In the results, we present the fabrication of four kinds of high quality SPPs with different topological charges. The morphology analysis and the corresponding optical measurements verify the reliability of our fabrication method.

Hollow Nanospheres Array Fabrication via Nano-Conglutination Technology.

Hollow nanospheres array is a special nanostructure with great applications in photonics, electronics and biochemistry. The nanofabrication technique with high resolution is crucial to nanosciences and nano-technology. This paper presents a novel nonconventional nano-conglutination technology combining polystyrenes spheres (PSs) self-assembly, conglutination and a lift-off process to fabricate the hollow nanospheres array with nanoholes. A self-assembly monolayer of PSs was stuck off from the quartz wafer by the thiol-ene adhesive material, and then the PSs was removed via a lift-off process and the hollow nanospheres embedded into the thiol-ene substrate was obtained. Thiolene polymer is a UV-curable material via "click chemistry" reaction at ambient conditions without the oxygen inhibition, which has excellent chemical and physical properties to be attractive as the adhesive material in nano-conglutination technology. Using the technique, a hollow nanospheres array with the nanoholes at the diameter of 200 nm embedded into the rigid thiol-ene substrate was fabricated, which has great potential to serve as a reaction container, catalyst and surface enhanced Raman scattering substrate.

[Expressions of TUBB3 and γ-synuclein in colorectal adenocarcinoma and their clinical significance].

OBJECTIVE: To explore the expressions of TUBB3 (ß-tubulin III) and γ-synuclein (SNCG) in colorectal adenocarcinoma and their clinical significance. METHODS: The expressions of TUBB3 and γ-synuclein were detected by SP immunohistochemistry in 180 cases of colorectal adenocarcinoma. RESULTS: TUBB3 protein positive rate was 82.2% and γ-synuclein protein positive rate 73.9% in colorectal adenocarcinoma. And there were insignificant differences of positive expression between TUBB3 and γ-synuclein (P > 0.05). The positive expression of TUBB3 was not correlated with gender, age, histological differentiation, depth of tumor invasion or clinical stage (P > 0.05). The positive expression of γ-synuclein was closely correlated with depth of tumor invasion and clinical stage (P < 0.05), but with gender, age or histological differentiation (P > 0.05). The positive expressions of TUBB3 and γ-synuclein were correlated in colorectal adenocarcinoma (r = 0.154, P < 0.05). CONCLUSIONS: γ-synuclein, detected by immunohistochemistry is better than TUBB3 in colorectal adenocarcinoma. And γ-synuclein may be used as a new prognostic biomarker and therapeutic target.

Association Between Preoperative Long-Term Poor Sleep Quality and Postoperative Delirium in Elderly Patients Undergoing Cardiac Surgery: A Multi-Center Observational Study.

BACKGROUND: Delirium is a common complication in elderly patients after cardiac surgery, and sleep disorders have been suggested as a potential risk factor. However, few studies have explored the link between long-term preoperative poor sleep quality and postoperative delirium (POD) in this population. This study aimed to investigate the association between preoperative sleep quality and POD in elderly cardiac surgery patients. METHODS: The study enrolled 194 patients aged 60 years or older who underwent cardiac surgery. The Pittsburgh Sleep Quality Index (PSQI) objectively assessed preoperative sleep quality, while the Confusion Assessment Method screened for POD. The measurable outcomes encompassed the identification of risk factors associated with POD, while the secondary outcomes focused on factors influencing levels of consciousness. The statistical analysis is logistic regression analysis. RESULTS: Patients with POD had a higher prevalence of preoperative sleep disorders and higher PSQI scores than those without delirium (12.9 ± 5.1 vs 7.8 ± 3.4, P = .007). Logistic regression analysis demonstrated that the number of months with high PSQI scores and age were significantly associated with POD. The predictive ability of the number of months with high PSQI scores for POD was .762 (95% CI: .671-.854). Multivariate linear regression analysis revealed that preoperative sleep disorder was a significant predictor of exacerbation of POD (P < .05). CONCLUSION: This study suggests that long-term poor preoperative sleep quality, as assessed by the PSQI, is associated with an increased risk of POD in elderly patients undergoing cardiac surgery.

The effect of pre-treatments on atrazine removal from source water by microbubble ozonation.

Ozone-based advanced oxidation processes (AOPs) have emerged a promising avenue for water treatment, offering effective removal of micropollutants. Recent research underscores the potential of ozone microbubbles to enhance ozone mass transfer during water treatment, particularly when combined with pre-treatment steps. This study aimed to evaluate the efficacy of three different combined processes (chlorine/KMnO4/PAC pre-treatment followed by ozonation) in removing atrazine, a common micropollutant from natural source water. Results revealed that all combined processes achieved higher atrazine removal rates compared to individual pre-treatment or ozonation methods. Notably, the highest atrazine removal rates were observed under alkaline pH conditions, with treatment outcomes influenced by oxidant dose and pH levels. Among the combined processes, chlorine pre-treatment followed by ozonation emerged as the most effective approach, achieving a removal rate of 59.7% that exceeded the sum of individual treatments. However, this treatment efficacy was affected by water quality parameters, particularly the presence of organic matter and elevated ammonia nitrogen concentration (> 0.5 mg/L). This study highlights the potential for utilizing ozone micro/nanobubbles to enhance ozone mass transfer and offers valuable insights for optimizing the combined application of pre-treatment and ozonation strategies for efficient atrazine removal from natural water sources.

Primary Malignant Peripheral Nerve Sheath Tumor of the Stomach: A Rare Case Report and Review of Literature.

Malignant peripheral nerve sheath tumor (MPNST) is a spindle cell sarcoma originating from peripheral nerves or showing differentiation of nerve sheath components. Primary MPNST of the stomach is an extremely rare neoplasm with only a few published reports in the literature. We present the case of a 58-year-old male patient with MPNST in the stomach. The patient was admitted due to upper abdomen discomfort. Gastroscopy revealed a huge ulcer lesion in the stomach, and biopsy revealed a spindle cell malignant neoplasm. No other specific findings were found in the whole-body imaging examination. Subtotal gastrectomy was performed. Histologically, an ulcer-type, push-infiltrating mass composed of dense, woven-like spindle cells with frequent mitosis could be seen. In immunohistochemistry, the tumor cells were negative for expression of H3K27 trimethylation (H3K27me3), keratin (AE1/AE3), epithelial membrane antigen (EMA), CD34, KIT, DOG1 (ANO1), S-100, SOX10, smooth muscle actin, desmin, myogenin, MDM2, CDK4, P16 (CDKN2A) and SS18-SSX (SS18::SSX). Primary MPNST of the stomach was diagnosed based on histological and immunohistochemical results. During the 2.5 years follow-up period after surgery, no recurrence was observed.

Transglutaminase 2 regulates terminal erythroid differentiation via cross-linking activity.

Transglutaminase 2 (TGM2) is a versatile enzyme that modulates cell survival and differentiation. However, its role in terminal erythroid differentiation is poorly understood. In this study, we investigated the function of TGM2 in primary fetal liver erythroid differentiation. We predicted TGM2 as an upstream regulator via ingenuity pathway analysis (IPA), and found that its expression was increased at both RNA and protein level during terminal erythroid differentiation. TGM2 cross-linking activity inhibitors GK921 and Z-DON suppressed erythroid maturation and enucleation, while its GTPase inhibitor LDN27219 had no such effect. Z-DON treatment arrested differentiation at basophilic erythroblast stage, and interfered with cell cycle progression. RT-PCR demonstrated decreased GATA-1 and KLF1, and disarranged cyclin, CDKI and E2F family genes expression after Z-DON treatment. In conclusion, TGM2 regulates terminal erythroid differentiation through its cross-linking enzyme activity.

Full-Endoscopic Decompression for Thoracic Ossification of the Ligamentum Flavum Combined with Dural Ossification.

Ossification of the ligamentum flavum (OLF) can result in spinal stenosis. Thoracic spinal cord compression due to spinal stenosis is a common cause of progressive thoracic myelopathy in Asian countries. The incidence of complications is high in open decompression surgeries for thoracic OLF. With dural ossification (DO), the risk of complications is even higher in thoracic OLF. We introduce a full-endoscopic decompression surgery for thoracic OLF combined with DO under local anesthesia. Hemilaminectomy is performed using a high-speed burr under the endoscopy first, and then decompression of the contralateral spinal canal is completed using an "over the top" technique. DO resection uses the eggshell technique; after the base of the DO is cut from the lamina, forceps or lamina rongeurs are typically used for removal. The dural defect left after resection does not need repair. Neurological function was improved, and no complications such as hematoma or neck pain occurred. On imaging, no pseudodural cyst, cerebrospinal fluid leakage, or wound complications were observed after the operation. Endoscopic surgery causes less damage to the posterior ligament complex, so no cases of persistent back pain complaints or secondary internal fixation requirements were found in this study. Full-endoscopic decompression can achieve good imaging and clinical effects in the treatment of thoracic OLF with DO.

Nanostructures of designed geometry and functionality enable regulation of cellular signaling processes.

Extracellular matrices (ECM) triggered cellular signaling processes often begin with the clustering of the cellular receptors such as integrin and FcεRI. The sizes of these initial protein complexes or clusters are tens to 100 nm in dimension; therefore, engineered nanostructures could provide effective mimics of ECM for investigation and control of the initial and downstream specific signaling processes. This current topic discusses recent advances in nanotechnology in the context of design and production of matching chemical functionality and geometry for control of specific cellular signaling processes. Two investigations are reported to demonstrate this concept: (a) how the presentation of antigen at the nanometer scale would influence the aggregation of FcεRI, which would impact the formation of activation complexes, leading to the rearrangement of actin in cytoskeleton and degranulation or activation of mast cells; (b) how the engineered nanostructure could guide the initial integrin clustering, which would impact the formation of focal adhesion and downstream cell signaling cascades, leading to polarization, migration, and morphological changes. Complementary to engineered ECMs using synthetic ligands or peptides, or topographic control at the micrometer scale, nanostructures of designed geometry and chemical functionality provide new and effective biochemical cues for regulation of cellular signaling processes and downstream behaviors.