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Background: Arterial stiffness was cross-sectionally associated with the prevalence of chronic kidney disease (CKD). Whether arterial stiffness was prospectively associated with incident CKD is not well characterized. Methods: Among 3,777 participants (mean age 75 years old, 42.7% female, 21.3% Blacks) without prevalent CKD in ARIC study at visit 5 (2011 to 2013), we examined the association of six measures for arterial stiffness measurements, carotid-femoral pulse wave velocity (cfPWV), heart-ankle PWV (haPWV), brachial-ankle PWV (baPWV), heart-femoral PWV (hfPWV), femoral-ankle PWV (faPWV), heart-carotid PWV (hcPWV) with the risk of incident CKD (defined by >25% decline to estimated glomerular filtration rate 2 or hospitalization with CKD diagnosis) using Cox regression models to estimate hazard ratios (HRs). Each arterial stiffness parameter was stratified by quartiles. Results: During follow-up (median 6.6 years) through 2019, 590 had incident CKD (incidence rate 23.2 per 1000 person-years). In the demographically adjusted model, the highest quartile (Q4) of cfPWV, haPWV, baPWV, and hfPWV were significantly associated with an increased risk of incident CKD compared to the lowest (Q1) (HR, 1.70 [95%CI 1.31 to 2.22], 1.29 [95% CI 1.01 to 1.64], 1.51 [95% CI 1.16 to 1.97], and 1.36 [95% CI 1.05 to 1.76], respectively). Once the model was further adjusted for major clinical risk factors for CKD, the associations were modestly attenuated but remained significant for cfPWV and haPWV (HR in Q4 vs. Q1, 1.34 [95% CI 1.02 to 1.76] and 1.38 [95% CI 1.04 to 1.82]), but not for baPWV and hfPWV. Subgroup analyses showed the associations were consistent in subgroups by gender, race, age, hypertension, and diabetes. Conclusion: Arterial stiffness as measured by PWV was associated with a higher risk of incident CKD in older adults, especially cfPWV and haPWV. Our findings support the temporal relationship of subclinical arterial stiffness predating incident CKD in older adults.

Metastatic microsatellite-stable (MSS) colorectal cancer rarely responds to immune checkpoint inhibitors (ICI). Metabolism heterogeneity in the tumor microenvironment (TME) presents obstacles to antitumor immune response. Combining transcriptome (The Cancer Genome Atlas MSS colorectal cancer, n = 383) and digital pathology (n = 96) analysis, we demonstrated a stroma metabolism–immune excluded subtype with poor prognosis in MSS colorectal cancer, which could be attributed to interaction between chondroitin-6-sulfate (C-6-S) metabolites and M2 macrophages, forming the “exclusion barrier” in the invasive margin. Furthermore, C-6-S derived from cancer-associated fibroblasts promoted co–nuclear translocation of pSTAT3 and GLI1, activating the JAK/STAT3 and Hedgehog pathways. In vivo experiments with C-6-S–targeted strategies decreased M2 macrophages and reprogrammed the immunosuppressive TME, leading to enhanced response to anti–PD-1 in MSS colorectal cancer. Therefore, C-6-S–induced immune exclusion represents an “immunometabolic checkpoint” that can be exploited for the application of combination strategies in MSS colorectal cancer ICI treatment.

Dysregulations in transcription factors (TFs) and their genetic products play important roles in tumorigenesis, tumor progression and metastasis. However, prognostic value of the transcriptional regulatory networks in different cancers has not been investigated in depth. The purpose of our study was to identify and validate a potential predictive signature that combines TFs and their regulatory products in eight solid tumors. We used bioinformatics analysis to identify MET Transcriptional Regulator (MACC1) and Serine Peptidase Inhibitor Kunitz Type 1 (SPINT1) as candidate TFs with the respective downstream regulatory proteins for patient prognosis in pan‐cancer. Subsequent molecular analysis of clinical gastric cancer tissue samples further verified the negative correlation between MACC1 and SPINT1. Further, we showed that mechanistically, MACC1/SPINT1 mediated the pro‐HGF proteolysis and c‐Met phosphorylation in HGF/c‐MET signaling pathway. Kaplan‐Meier plots and receiver operating characteristics analysis revealed that the two‐gene signature combining MACC1 with SPINT1 was effective in predicting survival in all eight cancer cohorts tested. In conclusion, our study clarified the regulatory relationship between MACC1 and SPINT1 in the context of the HGF/c‐MET signaling pathway and determined MACC1/SPINT1 panel as a valuable signature for the prediction of prognosis in patients for multiple solid cancer types., The manuscript addressed on the regulatory relationship and tumor prognostic value of transcription factors (TFs) MACC1 and transmembrane protein SPINT1. Through bioinformatics analysis and molecular experiments, we verified the transcriptional regulatory relationship and biological functions of MACC1 and SPINT1 in HGF/c‐Met signaling axis. Besides, MACC1/SPINT1 panel was established to effectively predict survival in eight cancers.

Efficient point-of-care diagnosis of severe acute respiratory syndrome-corovavirus-2 (SARS-CoV-2) is crucial for the early control of novel coronavirus infections. At present, polymerase chain reaction (PCR) is primarily used to detect SARS-CoV-2. Despite the high sensitivity, the PCR process is time-consuming and complex which limits its applicability for rapid testing of large-scale outbreaks. Here, we propose a rapid and easy-to-implement approach for SARS-CoV-2 detection based on surface enhanced infrared absorption (SEIRA) spectroscopy. The evaporated gold nano-island films are used as SEIRA substrates which are functionalized with the single-stranded DNA probes for specific binding to selected SARS-CoV-2 genomic sequences. The infrared absorption spectra are analyzed using the principal component analysis method to identify the key characteristic differences between infected and control samples. The SEIRA-based biosensor demonstrates rapid detection of SARS-CoV-2, completing the detection of 1 μM viral nucleic acids within less than 5 min without any amplification. When combined with the recombinase polymerase amplification treatment, the detection capability of 2.98 copies per μL (5 aM) can be completed within 30 min. This approach provides a simple and economical alternative for COVID-19 diagnosis, which can be potentially useful in monitoring and controlling future pandemics in a timely manner.

Chemotherapy is the preferred treatment for advanced stage gastric cancer (GC) patients and chemotherapy resistance is the major obstacle to effective cancer therapy. Increasing evidence suggests that mesenchymal stem cells (MSCs) make important contributions to development of drug resistance. However, the underlying mechanism remains elusive. In this study, we discovered that abundant MSCs in tumor tissues predicted a poor prognosis in GC patients. MSCs promoted stemness and chemoresistance in GC cells through fatty acid oxidation (FAO) in vitro and in vivo. Mechanically, transforming growth factor β1 (TGF-β1) secretion by MSCs activated SMAD2/3 through TGF-β receptors and induced long non-coding RNA (lncRNA) MACC1-AS1 expression in GC cells, which promoted FAO-dependent stemness and chemoresistance through antagonizing miR-145-5p. Moreover, pharmacologic inhibition of FAO with etomoxir (ETX) attenuated MSC-induced FOLFOX regiment resistance in vivo. These results suggest that FAO plays an important role in MSC-mediated stemness and chemotherapy resistance in GC and FAO inhibitors in combination with chemotherapeutic drugs present as a promising strategy to overcome chemoresistance.

Photonic synapses provide fast response, high bandwidth, and less crosstalk in neuromorphic computation as well as simulation of visual perception systems. Herein, phototransistor-based photonic synapses that can be triggered by near-infrared light are reported. The artificial synapse is based on organic heterojunction phototransistors comprising the organic polymer semiconductor PDPPBTT and inorganic SnO2. The organic semiconducting polymer PDPPBTT serves as the near-infrared light absorbing materials and transistor channel, whereas SnO2 serves as the charge trapping materials. By adopting the heterojunction architecture, generation, separation, and transport of charge carriers are optimized under near-infrared illumination and electrical gating to yield photonic synaptic properties that can be readily modulated, including the excitatory postsynaptic current and paired-pulse facilitation. The results reveal a simple and effective concept for photonic synapses in the near-infrared region and provide insights into the development of advanced visual processing, neuromorphic computation, and biological nervous systems.

Omental metastasis occurs frequently in gastric cancer (GC) and is considered one of the major causes of gastric cancer-related mortality. Recent research indicated that omental adipocytes might mediate this metastatic predilection. Phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1) was identified to have a crucial role in metastasis. However, whether PITPNC1 participates in the interaction between adipocytes and GC omental metastasis is unclear. Methods: We profiled and analyzed the expression of PITPNC1 through analysis of the TCGA database as well as immunohistochemistry staining using matched GC tissues, adjacent normal gastric mucosa tissues (ANTs), and omental metastatic tissues. The regulation of PITPNC1 by adipocytes was explored by co-culture systems. By using both PITPNC1 overexpression and silencing methods, the role of PITPNC1 in anoikis resistance and metastasis was determined through in vitro and in vivo experiments. Results: PITPNC1 was expressed at higher rates in GC tissues than in ANTs; notably, it was higher in omental metastatic lesions. Elevated expression of PITPNC1 predicted higher rates of omental metastasis and a poor prognosis. PITPNC1 promoted anoikis resistance through fatty acid metabolism by upregulating CD36 and CPT1B expression. Further, PITPNC1 was elevated by adipocytes and facilitated GC omental metastasis. Lastly, in vivo studies showed that PITPNC1 was a therapeutic indicator of fatty acid oxidation (FAO) inhibition. Conclusion: Elevated expression of PITPNC1 in GC is correlated with an advanced clinical stage and a poor prognosis. PITPNC1 promotes anoikis resistance through enhanced FAO, which is regulated by omental adipocytes and consequently facilitates GC omental metastasis. Targeting PITPNC1 might present a promising strategy to treat omental metastasis.

In-depth temperature sensing in air plasma sprayed (APS) thermal barrier coatings (TBCs) has been achieved with europium (Eu) and dysprosium (Dy) doped yttria stabilized zirconia (YSZ) sensor coatings. The luminescence properties of YSZ:Eu and YSZ:Dy, including spectrum, intensity and lifetime, were evaluated and their temperature sensing performances were compared using a lifetime-based measurement system. Both sensor TBCs display excellent temperature sensitivity in high temperature environment (400–800 °C for YSZ:Eu, 500–900 °C for YSZ:Dy) with a topcoat thickness up to 300 μm. It was found that the upper limit of temperature sensing was determined by the ratio between luminescence intensity and background thermal radiation (signal-background-ratio). YSZ:Dy showed higher luminescent intensity than YSZ:Eu at elevated temperatures, and therefore displayed better temperature sensing performance with an increased limit. The effect of topcoat thickness on the temperature sensing performance was also evaluated, showing that the attenuation factor of YSZ increased significantly with topcoat thickness. Interestingly, it was found that the topcoat attenuation factor gradually decreased as temperature increased, which improved the temperature sensing performance of sensor TBCs at elevated temperature. The findings in the temperature sensing of APS TBCs provide basis for the future development of on-line APS TBCs temperature monitoring technology.

The microstructural evolution of the Ni-based superalloy CMSX-4 including the change in gamma prime morphology, size, and distribution after high-temperature degradation and subsequent rejuvenation heat treatments has been examined using field emission gun scanning electron microscopy and transmission electron microscopy. In this paper, it is shown that there are significant differences in the size of the ‘channels’ between gamma prime particles, the degree of rafting, and the size of tertiary gamma prime particles in each of the different microstructural conditions studied. Chemical analysis has been carried out to compare rejuvenated and pre-service samples after the same subsequent degradation procedure. The results indicate that although the microstructures of pre-service and rejuvenated samples are similar, chemical differences are more pronounced in the rejuvenated samples, suggesting that chemical segregation from partitioning of the elements was not completely eliminated through the applied rejuvenation heat treatment. A number of modified rejuvenation heat treatment trials were carried out to reduce the chemical segregation prior to creep testing. The creep test results suggest that chemical segregation has an immeasurable influence on the short-term mechanical properties under the test conditions used here, indicating that further work is required to fully understand the suitability of specific rejuvenation heat treatments and their role in the extension of component life in power plant applications.

e16016 Background: Colorectal cancer (CRC) molecular subtype has been emphasized and links to biological and clinical behavior. However, comprehensive metabolism of CRC has not been characterized. Subtype-specific metabolic differences and immunometabolism phenotypes remain unclear. Therefore, this study performed metabolism clustering and explore its relation with immune phenotypes as well as prognosis predictive value. Methods: Transcriptome of TCGA CRC cohort was utilized to generate 113 KEGG metabolism pathway scores via GSVA algorithm. Consensus clustering were used to identify metabolism subtypes. Bioinformatic algorithms were applied in classification and survival analysis. Results: Energy metabolism-oriented subtype, featured by nitrogen metabolism and immune-inflamed, correlated with good prognosis (log rank P < 0.001). Pyrimidine synthesis activated most in nucleotide metabolism-oriented subtype, which was immune-deserted. Stroma metabolism-oriented subtype, characterized by glycosaminoglycan (GAG) biosynthesis and immune-suppressive phenotype, was an independent risk factor for overall survival (multivariate Cox: HR = 2.30 95% CI 1.23-4.28, P = 0.009). Clinical cohort from Nanfang Hospital composed of RNA-Seq data from 26 pre- and post-treatment samples in mCRC patients receiving mFOLFOX+Bevacizumab were classified. 22 were identified and 8 of them were pre-treatment, 4 of which were nucleotide subtype being 100% PR. The rest were stroma subtype with SD or PD, indicating drug resistance in stroma subtype. Interestingly, GAG chondroitin sulfate featured in stroma subtype outperformed other metabolisms in predicting negative prognosis (HR = 1.42 95% CI 1.18-1.71, P < 0.001). We then tested GAG metabolism in TCGA pan-cancer cohort. Chondroitin sulfate and heparan sulfate metabolism subtype correlated inversely with bladder (HR = 1.23 95% CI 1.06-1.43, P = 0.007) and breast cancer (HR = 1.27 95% CI 1.10-1.47, P = 0.001) patients’ survival, respectively. Keratan sulfate subtype predicted worse survival in glioblastoma, pancreatic and liver cancer (HR = 1.31 95% CI 1.09-1.57, P = 0.003; HR = 1.31 95% CI 1.06-1.61, P = 0.01; HR = 1.23 95% CI 1.04-1.46, P = 0.02). These indicated a pan-cancer relevant role of GAG disorder. Conclusions: CRC metabolism subtypes unraveled metabolism heterogeneity with prognosis value. CRC stroma subtype and other stroma-involved cancers share active GAG metabolism, which may lighten common targeting strategies in multiple stroma-accompanied cancers.

Contact guidance or bidirectional migration along aligned fibers modulates many physiological and pathological processes such as wound healing and cancer invasion. Aligned 2D collagen fibrils epitaxially grown on mica substrates replicate many features of contact guidance seen in aligned 3D collagen fiber networks. However, these 2D collagen self-assembled substrates are difficult to image through, do not have known or tunable mechanical properties and cells degrade and mechanically detach collagen fibrils from the surface, leading to an inability to assess contact guidance over long times. Here, we describe the transfer of aligned collagen fibrils from mica substrates to three different functionalized target substrates: glass, polydimethylsiloxane (PDMS) and polyacrylamide (PA). Aligned collagen fibrils can be efficiently transferred to all three substrates. This transfer resulted in substrates that were to varying degrees resistant to cell-mediated collagen fibril deformation that resulted in detachment of the collagen fibril field, allowing for contact guidance to be observed over longer time periods. On these transferred substrates, cell speed is lowest on softer contact guidance cues for both MDA-MB-231 and MTLn3 cells. Intermediate stiffness resulted in the fastest migration. MTLn3 cell directionality was low on soft contact guidance cues, whereas MDA-MB-231 cell directionality marginally increased. It appears that the stiffness of the contact guidance cue regulates contact guidance differently between cell types. The development of this collagen fibril transfer method allows for the attachment of aligned collagen fibrils on substrates, particularly flexible substrates, that do not normally promote aligned collagen fibril growth, increasing the utility of this collagen self-assembly system for the fundamental examination of mechanical regulation of contact guidance.

This study used electroencephalogram measurements to investigate the effects of aging on oscillatory theta modulation during an audiovisual discrimination task. By a wavelet-based time-frequency analysis, age-related theta oscillation response differences were observed within a relatively restricted time range (0-500 ms) over frontal-central regions. Older adults showed stronger theta spectral power during visual and audiovisual stimuli in the left frontal regions; however, young adults showed stronger theta spectral power during auditory and audiovisual stimuli in the central regions. These findings suggest that multisensory oscillatory theta responses differ according to age, which further proves that the left frontal regions play an important role in audiovisual integration.

DNA origami can be used to create a variety of complex and geometrically unique nanostructures that can be further modified to produce building blocks for applications such as in optical metamaterials. We describe a method for creating metal-coated nanostructures using DNA origami templates and a photochemical metallization technique. Triangular DNA origami forms were fabricated and coated with a thin metal layer by photochemical silver reduction while in solution or supported on a surface. The DNA origami template serves as a localized photosensitizer to facilitate reduction of silver ions directly from solution onto the DNA surface. The metallizing process is shown to result in a conformal metal coating, which grows in height to a self-limiting value with increasing photoreduction steps. Although this coating process results in a slight decrease in the triangle dimensions, the overall template shape is retained. Notably, this coating method exhibits characteristics of self-limiting and defect-filling growth, which results in a metal nanostructure that maps the shape of the original DNA template with a continuous and uniform metal layer and stops growing once all available DNA sites are exhausted.