Helium Ion-Assisted Wet Etching of Silicon Carbide with Extremely Low Roughness for High-Quality Nanofabrication.

Silicon carbide (SiC) is a promising material for a wide range of applications, including mechanical nano-resonators, quantum photonics, and non-linear photonics. However, its chemical inertness poses challenges for etching in terms of resolution and smoothness. Herein, a novel approach known as helium ion-bombardment-enhanced etching (HIBEE) is presented to achieve high-quality SiC etching. The HIBEE technique utilizes a focused helium ion beam with a typical ion energy of 30 keV to disrupt the crystal lattices of SiC, thus enabling wet etching using hydrofluoric acids and hydrogen peroxide. The etching mechanism is verified via simulations and characterization. The use of a sub-nanometer beam spot of focused helium ions ensures fabrication resolution, and the resulting etched surface exhibits an extremely low roughness of ≈0.9 nm. One of the advantages of the HIBEE technique is that it does not require resist spin-coating and development processes, thus enabling the production of nanostructures on irregular SiC surfaces, such as suspended structures and sidewalls. Additionally, the unique interaction volume of helium ions with substrates enables the one-step fabrication of suspended nanobeam structures directly from bulk substrates. The HIBEE technique is expected to facilitate and accelerate the prototyping of high-quality SiC devices.

Identification of a lipid metabolism-related gene for cancer immunotherapy.

Background: Tumors frequently evade immune surveillance through multiple pathways to escape T cell recognition and destruction. Previous studies indicated that lipid metabolism alteration could affect the anti-tumor immunity of cancer cells. Nonetheless, the studies that investigated lipid metabolism-related gene for cancer immunotherapy are still few. Materials and methods: By mining the TCGA database, we screened out carnitine palmitoyltransferase-2 (CPT2), a key enzyme in the fatty acid ß-oxidation (FAO) process associated with anti-tumor immunity. We then analyzed the gene expression and clinicopathological features of CPT2 using open-source platforms and databases. Molecular proteins interacting with CPT2 were also identified using web interaction tools. Subsequently, the relationship between CPT2 and survival was analyzed in cancer patients. Results: Our study revealed that CPT2 played a vital role in tumor microenvironment and immune response signaling pathways. We have also demonstrated that increased CPT2 gene expression could enhance the level of tumor immune cell infiltration. Furthermore, high CPT2 expression positively related with overall survival associated with immunotherapy. CPT2 expression was also associated with the prognosis of human cancers, suggesting that CPT2 may be a potential biomarker for predicting the efficacy of cancer immunotherapy. Conclusion: To the best of our knowledge, the relationship between CPT2 and tumor immune microenvironment was first proposed in this study. Therefore, further studies on CPT2 may provide new insights into the development of effective cancer immunotherapy.

Retro-dihydrochalcones from the resin of Daemonorops draco and their inhibitory activities against renal fibrosis.

Daedracoflavan A-E (1-5), five new flavonoids were isolated from the resin of Daemonorops draco. Their structures including absolute configurations were established by using spectroscopic and computational methods. All the compounds are new chalcones with the same retro-dihydrochalcone skeleton. Compound 1 features the presence of a cyclohexadienone unit originating from a benzene ring, and the ketone group of C-9 reduced to a hydroxyl group. The bioactivity of all isolated compounds was evaluated in kidney fibrosis and found that compound 2 could dose-dependently inhibit the expression of fibronectin, collagen I, and α-SMA in TGF-ß1-induced rat kidney proximal tubular cells (NRK-52E). Interestingly, the replacement of a proton by a hydroxyl group at C-4' seems to play a crucial role in anti-renal fibrosis activity.

NRP1 contributes to stemness and potentiates radioresistance via WTAP-mediated m6A methylation of Bcl-2 mRNA in breast cancer.

NRP1 is a transmembrane glycoprotein that is highly expressed in a variety of tumors. There is evidence that NRP1 can enhance the stem cell properties of tumor cells, which are thought to be resistant to radiotherapy. This study aims to elucidate the potential mechanism of NRP1 in radiation resistance. We transfected NRP1 siRNA and plasmid in breast cancer cells to detect the expression of cancer stem cell markers by western blot and qRT-PCR. The effect of NRP1 on radiotherapy resistance was assesses by immunofluorescence and flow cytometry. In vivo, we established xenograft tumor model treating with shRNA-NRP1 to assess radiotherapy sensitivity. We found that NRP1 could enhance the stem cell properties and confer radioresistance of breast cancer cells. Mechanistically, we proved that NRP1 reduced IR-induced apoptosis by downregulation of Bcl-2 via methyltransferase WTAP in m6A-depentent way. It is suggested that these molecules may be the therapeutic targets for improving the efficacy of radiotherapy for breast cancer.

Versatile Approach of Silicon Nanofabrication without Resists: Helium Ion-Bombardment Enhanced Etching.

Herein, we report a helium ion-bombardment enhanced etching method for silicon nanofabrication without the use of resists; furthermore, we demonstrate its unique advantages for straightforward fabrication on irregular surfaces and prototyping nano-electro-mechanical system devices, such as self-enclosed Si nanofluidic channels and mechanical nano-resonators. This method employs focused helium ions to selectively irradiate single-crystal Si to disrupt the crystal lattice and transform it into an amorphous phase that can be etched at a rate 200 times higher than that of the non-irradiated Si. Due to the unique raindrop shape of the interaction volumes between helium ions and Si, buried Si nanofluidic channels can be constructed using only one dosing step, followed by one step of conventional chemical etching. Moreover, suspended Si nanobeams can be fabricated without an additional undercut step for release owing to the unique raindrop shape. In addition, we demonstrate nanofabrication directly on 3D micro/nano surfaces, such as an atomic force microscopic probe, which is challenging for conventional nanofabrication due to the requirement of photoresist spin coating. Finally, this approach can also be extended to assist in the etching of other materials that are difficult to etch, such as silicon carbide (SiC).

A wear-resistant silicon nano-spherical AFM probe for robust nanotribological studies.

Nanoscale wear can severely limit the performance of tips used in atomic force microscopy, especially in contact and lateral mode operations. Hence, we investigated the mechanical and tribological properties of a newly invented nano-spherical silicon tip produced via swelling of single-crystal silicon using helium ion dosing to ascertain its reliability for AFM operations. The nanoindentation test proved that the modulus of elasticity of the nano-spheres tends to increase with the diameter of the spheres at 0.5 mN contact force. However, at 10 mN higher contact force, the elastic modulus was stable at ∼160 GPa irrespective of the sphere diameter. The SEM images confirmed the durability of the tip after 10 000 cycles of sliding on a silicon wafer and quartz surfaces. There was no damage on the tip and the wear debris was suggested to be from the localized wear on the counter wafer surface. Also, the in situ AFM pull-off force test indicated that the geometry of the tip remained unaltered during the wear test. The Si/SiO2 tribology study showed a decrease in coefficient of friction as velocity and sliding cycles increased which was attributed to the tribochemical reactions occurring at the Si/SiO2 interfaces. These results indicate that the new nano-spherical AFM tip has advantages in nanoscale tribology measurement.

The measurement of NRF2 and TP53 in blood expects radiotherapeutic sensitivity in patients with esophageal cancer.

OBJECTIVE: This study investigates the relationship between the mRNA expression of nuclear factor erythroid 2-related factor 2 (NRF2) and Tumor protein p53 (TP53) in circulating tumor cells (CTC) and sensitivity to radiotherapy in patients with esophageal cancer. To investigate the relationship between cytokines IL-6, CD8+, and NRF2 during patient treatment and their predictive role for treatment. METHODS: Radiosensitivity was assessed by measuring a morphological or functional change in the tumor in response to ionizing radiation. Fasting venous anticoagulated blood (EDTA anticoagulation) was drawn from patients, and the Trizol-chloroform two-step method was used for RNA extraction. Data were collected from 45 patients admitted with radiotherapy alone from January 2018 to December 2021. The expression levels of NRF2mRNA (Messenger Ribose Nucleic Acid) and TP53mRNA in CTCs were detected by reverse transcription-polymerase chain reaction (RT-PCR). Pre- and post-treatment changes in IL-6 and CD8+ were recorded. The correlation between their expression level and the clinical stage, radiotherapy sensitivity, and efficacy of patients was analyzed. RESULTS: Twenty-six cases were sensitive to radiotherapy, and 19 were resistant, for a radiotherapy sensitivity rate of 58.8%. NRF2mRNA and TP53mRNA values increased in 19 radiotherapy-resistant patients and decreased in 26 radiotherapy-sensitive patients compared with those before radiotherapy (P = 0.001, P＜0.05). The ΔCT values of NRF2mRNA and TP53mRNA before treatment were moderately correlated with prognosis (P < 0.002). Inflammatory cytokine IL-6 was elevated in 22 of 45 patients after radiation, P = 0.04. NRF2 mRNA level was consistently elevated with CD8+ in 10 patients, P = 0.02. CONCLUSIONS: The expression of NRF2mRNA and TP53mRNA in the CTCs found in the peripheral blood of patients with esophageal squamous carcinoma was significantly associated with the sensitivity to radiotherapy. NRF2 mRNA level was consistently elevated with CD8+ and IL-6 in patients.

METTL3 potentiates progression of cervical cancer by suppressing ER stress via regulating m6A modification of TXNDC5 mRNA.

N6-methyladenosine (m6A) is the most abundant chemical modification on mRNA and plays significant roles in many bioprocesses. However, the functions of m6A on cervical cancer (CC) tumorigenesis remain unclear. Here we found methyltransferase-like 3 (METTL3), a core member of the m6A methyltransferase family, was greatly upregulated as an independent prognostic factor in CC. Mechanistically, the transcription factor ETS1 recruited P300 and WDR5 which separately mediated H3K27ac and H3K4me3 histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. Functionally, we verified that METTL3 promoted proliferation and metastasis of CC cells by regulating of TXNDC5 expression through in vitro and in vivo experiments. In addition, our study verified the effect of METTL3/TXNDC5 axis on ER stress. Taken together, METTL3 facilitates the malignant progression of CC, suggesting that METTL3 might be a potential prognostic biomarker and therapeutic target for CC.

Bio-Inspired Hierarchical Micro-/Nanostructures for Anti-Icing Solely Fabricated by Metal-Assisted Chemical Etching.

We report a cost-effective and scalable methodology for producing a hierarchical micro-/nanostructured silicon surface solely by metal-assisted chemical etching. It involves two major processing steps of fabricating micropillars and nanowires separately. The process of producing micro-scale structures by masked metal-assisted chemical etching was optimized. Silicon nanowires were created on the micropillar's surface via maskless metal-assisted chemical etching. The hierarchical micro-/nanostructured surface exhibits superhydrophobic properties with a high contact angle of ~156° and a low sliding angle of <2.5° for deionized water. Furthermore, due to the existence of microscale and nanoscale air trapped at the liquid/solid interface, it exhibits a long ice delay time of 2876 s at −5 °C, more than 5 times longer than that of smooth surfaces. Compared to conventional dry etching methods, the metal-assisted chemical etching approach excludes vacuum environments and high-temperature processes and can be applied for applications requiring hierarchical micro-/nanostructured surfaces or structures.

Bio-Inspired Hierarchical Micro/Nanostructured Surfaces for Superhydrophobic and Anti-Ice Applications.

We report a scalable and cost-effective fabrication approach for constructing bio-inspired micro/nanostructured surfaces. It involves silicon microstructure etching using a deep reactive ion etch (DRIE) method, nanowires deposition via glancing angle deposition (GLAD) process, and fluorocarbon thin film deposition. Compared with the smooth, microstructured, and nanostructured surfaces, the hierarchical micro/nanostructured surfaces obtained via this method showed the highest water contact angle of ∼161° and a low sliding angle of <10°. It also offered long ice delay times of 2313 s and 1658 s at -5°C and -10°C respectively, more than 10 times longer than smooth surfaces indicating excellent anti-icing properties and offering promising applications in low-temperature environments. These analyses further proved that the surface structures have a significant influence on surface wettability and anti-icing behavior. Hence, the GLAD process which is versatile and cost-effective offers the freedom of constructing nanostructures on top of microstructures to achieve the required objective in the fabrication of micro/nanostructured surfaces when compared to other fabrication techniques.

Long noncoding RNA RP11-70C1.3 confers chemoresistance of breast cancer cells through miR-6736-3p/NRP-1 axis.

Chemoresistance remains a major obstacle for improving the clinical outcome of patients with breast cancer. Recently, long noncoding RNAs (lncRNAs) have been implicated in breast cancer chemoresistance. However, the function and underlying mechanism are still largely unknown. Using lncRNA microarray, we identified 122 upregulated and 475 downregulated lncRNAs that might be related to the breast cancer chemoresistance. Among them, RP11-70C1.3 was one of the most highly expressed lncRNAs. In breast cancer patients, high RP11-70C1.3 expression predicted poor prognosis. Knockdown of RP11-70C1.3 inhibited the multidrug resistance of breast cancer cells in vitro and in vivo. Further investigations revealed that RP11-70C1.3 functioned as a competing endogenous RNA (ceRNA) for miR-6736-3p to increase NRP-1 expression. Notably, the rescue experiments showed that both miR-6736-3p inhibitor and NRP-1 overexpression could partly reverse the suppressive influence of RP11-70C1.3 knockdown on breast cancer chemoresistance. In conclusion, our study indicated that lncRNA RP11-70C1.3 regulated NRP-1 expression by sponging miR-6736-3p to confer chemoresistance of breast cancer cells. RP11-70C1.3 might be a potential therapeutic target in enhancing the clinical efficacy of chemotherapy in breast cancer.

Complete chloroplast genome of the rare medicinal vegetable Allium hookeri.

Allium hookeri is a rare medicinal plant with unique flavor. In this study, the first complete chloroplast (cp) genome of A. hookeri was sequenced and assembled based on the next generation sequencing. The cp genome is 153,592 bp in length, including a large single-copy (LSC) region of 82,609 bp, a small single-copy (SSC) region of 17,487 bp, and a pair of inverted repeat (IR) regions of 26,748 bp each. The genome encodes 131 genes, including 86 protein-coding genes, 39 tRNA genes, and six rRNA genes. The GC content of whole genome is 36.99%. The phylogenetic analysis based on 24 complete cp sequences revealed that A. hookeri was at the base of the phylogenetic tree, indicating an older species in the Allium genus.

Bio-Inspired Micromachined Volumetric Flow Sensor with a Big Dynamic Range for Intravenous Systems.

Real-time monitoring of drug delivery in an intravenous infusion system can prevent injury caused by improper drug doses. As the medicine must be administered into the vein at different rates and doses in different people, an ideal intravenous infusion system requires both a low flow rate and large dynamic range monitoring. In this study, a bio-inspired and micromachined volumetric flow sensor is presented for the biomedical application of an intravenous system. This was realized by integrating two sensing units with different sensitivities on one silicon die to achieve a large dynamic range of the volumetric flow rate. The sensor was coated with a parylene layer for waterproofing and biocompatibility purposes. A new packaging scheme incorporating a silicon die into a flow channel was employed to demonstrate the working prototype. The test results indicate that the sensor can detect a volumetric flow rate as low as 2 mL/h, and its dynamic range is from 2 mL/h to 200 mL/h. The sensor performed better than the other two commercial sensors for low-flow detection. The high sensitivity, low cost, and small size of this flow sensor make it promising for intravenous applications.

MicroRNA-138-1-3p sensitizes sorafenib to hepatocellular carcinoma by targeting PAK5 mediated ß-catenin/ABCB1 signaling pathway.

BACKGROUND: Sorafenib is a kinase inhibitor that is used as a first-line therapy in advanced hepatocellular carcinoma (HCC) patients. However, the existence of sorafenib resistance has limited its therapeutic effect. Through RNA sequencing, we demonstrated that miR-138-1-3p was downregulated in sorafenib resistant HCC cell lines. This study aimed to investigate the role of miR-138-1-3p in sorafenib resistance of HCC. METHODS: In this study, quantitative real-time PCR (qPCR) and Western Blot were utilized to detect the levels of PAK5 in sorafenib-resistant HCC cells and parental cells. The biological functions of miR-138-1-3p and PAK5 in sorafenib-resistant cells and their parental cells were explored by cell viability assays and flow cytometric analyses. The mechanisms for the involvement of PAK5 were examined via co-immunoprecipitation (co-IP), immunofluorescence, dual luciferase reporter assay and chromatin immunoprecipitation (ChIP). The effects of miR-138-1-3p and PAK5 on HCC sorafenib resistant characteristics were investigated by a xenotransplantation model. RESULTS: We detected significant down-regulation of miR-138-1-3p and up-regulation of PAK5 in sorafenib-resistance HCC cell lines. Mechanistic studies revealed that miR-138-1-3p reduced the protein expression of PAK5 by directly targeting the 3'-UTR of PAK5 mRNA. In addition, we verified that PAK5 enhanced the phosphorylation and nuclear translocation of ß-catenin that increased the transcriptional activity of a multidrug resistance protein ABCB1. CONCLUSIONS: PAK5 contributed to the sorafenib resistant characteristics of HCC via ß-catenin/ABCB1 signaling pathway. Our findings identified the correlation between miR-138-1-3p and PAK5 and the molecular mechanisms of PAK5-mediated sorafenib resistance in HCC, which provided a potential therapeutic target in advanced HCC patients.

Design and Implementation of a Composite Hydrophone of Sound Pressure and Sound Pressure Gradient.

The bionic cilium MEMS vector hydrophone has the characteristics of low power consumption, small volume, and good low-frequency response. Nevertheless, there exists the problem of left-right ambiguity in the azimuth estimation of a single hydrophone. In order to solve the engineering application problem, a sound-pressure sound-pressure-gradient hydrophone is designed in this paper. The new composite hydrophone consists of two channels. The bionic cilium microstructure is optimized and used as the vector channel, to collect the sound pressure gradient information, and a scalar channel, based on a piezoelectric ceramic tube, is added, to receive the sound pressure information. The theoretical analysis, simulation analysis, and test analysis of the composite hydrophone are carried out, respectively. The test results show that the sensitivities of the hydrophone can reach up to -188 dB (vector channel) and -204 dB (scalar channel). The problem of left-right ambiguity is solved by combining the sound pressure and sound pressure gradient in different ways. This is of great significance in the engineering application of single cilium MEMS hydrophone orientation.

Epidermal growth factor-like domain multiple 6 (EGFL6) promotes the migration and invasion of gastric cancer cells by inducing epithelial-mesenchymal transition.

Epidermal growth factor-like domain multiple 6 (EGFL6) is implicated in tumor growth, metastasis and angiogenesis, and its ectopic alteration has been detected in aggressive malignancies. However, the pathophysiologic roles and molecular mechanisms of EGFL6 in gastric cancer (GC) remain to be elucidated. In this study, we investigated EGFL6 expression in GC cell lines and tissues using western blotting and immunohistochemistry. We found that EGFL6 was elevated expression in GC cell lines and tissues. The high expression of EGFL6 significantly was correlated with histological grade, depth of invasion, lymph node involvement, distant metastasis and TNM stage in GC and predicted poorer prognosis, and it could act an independent prognostic factor for GC patients. EGFL6 enhanced the proliferation, migration and invasion of GC cells. In addition, we identified the possible molecular mechanisms of EGFL6-involved epithelial-mesenchymal transition (EMT). EGFL6 regulated EMT process and induced metastasis partly through FAK/PI3K/AKT/mTOR, Notch and MAPK signaling pathways. In conclusion, EGFL6 confers an oncogenic function in GC progression and may be proposed as a potential therapeutic target for GC.

Rhein-8-O-ß-D-glucopyranoside inhibited high glucose-induced apoptosis of human mesangial cells by regulating the lincRNA ANRIL/let-7a/TGF-ß1/Smad signaling pathway.

Diabetic nephropathy is one of most frequent complications of diabetes, and is the major cause of end-stage disease in diabetic patients. The present study investigated the roles and mechanisms of Rhein-8-O-ß-D-glucopyranoside (Rg) protecting human mesangial cells (HMCs) from high glucose (HG)-induced apoptosis. Using a Cell Counting Kit-8 assay the proliferation of HMCs was analyzed, and flow cytometry was applied to detect apoptosis. The apoptosis-associated protein Bcl-2, caspase-3 and members of the transforming growth factor-ß1 (TGF-ß1)/Smad signaling pathway were analyzed using a western blotting assay. HG significantly induced HMC apoptosis, and Rg markedly attenuated the HG-induced apoptosis. HG decreased the Bcl-2 expression and increased the caspase-3 expression, and Rg treatment recovered the expressions of Bcl-2 and caspase-3 affected by HG. The underlying mechanisms were further analyzed, and it was demonstrated that HG significantly upregulated the long intervening non-coding RNA (lincRNA) ANRIL expression level, downregulated let-7a expression and activated the TGF-ß1/Smad signaling pathway; Rg treatment recovered the expressions of lincRNA ANRIL and let-7a, and inhibited the TGF-ß1/Smad signaling pathway in the condition of HG. In conclusion, the present results suggested that Rg attenuated HG-induced apoptosis of HMCs by regulating the lincRNA ANRIL/let-7a/TGF-ß1/Smad signaling pathway.

Rynchopeterine F, unique heterodimer of phenethanol-phenylacetyl linking with lactic acid from the medicinal insect Blaps rynchopetera.

A new heterodimer, rynchopeterine F (1), a new natural product, rynchopeterine G (2), and eleven known phenolics were isolated from Blap rynchopetera Fairmaire, a kind of medicinal insect utilized by the Yi and Bai Nationality in Yunnan Province of China. Their structures were established on the basis of extensive spectroscopic analyses (1D and 2D NMR, HR-MS) along with calculated electronic circular dichroism method. Rynchopeterine F was a unusual heterodimer of a 3,4-dihudroxy phenylethanol unit fused to a 3,4-dihudroxy phenylacetyl group through two ester bonds with lactic acid, and rynchopeterine G was a 3,4-dihudroxy phenylethanyl monoester succinate. Attributed to the adjacent dihydroxyl grops, compounds 1 and 2 exhibited significant anti-radical activity with an IC50 value of 3.52 and 7.83 µg/mL for DPPH radical-scavenging, similar with that of the positive controls, vitamin C, 6.92 µg/mL and rutin, 8.28 µg/mL.

Array MEMS Vector Hydrophone Oriented at Different Direction Angles.

A new type of array MEMS (Microelectro Mechanical Systems) vector hydrophone has been proposed to solve the left-right ambiguity problem that is commonly found in current ones. Meanwhile, the advantages of good sensitivity and low fabrication cost are maintained. The array MEMS vector hydrophone is integrated by four units oriented at different direction angles. By the aid of this kind of vector hydrophone, not only the exact direction of the sound source can be measured, but also the position obtained. The working principle of the array microstructure has been analyzed and simulated. The result shows that the position of the sound source can be well determined. The prototype of the hydrophone is fabricated based on standard MEMS technology, and its performance is tested in a standing wave tube and an anechoic tank. The testing results show that the array hydrophone exhibits a good consistency of all the four units and satisfactory performance. More importantly, this array hydrophone exhibits excellent ability of positioning with the relatively small angle error. Thus, a MEMS hydrophone with multiple functions and relatively high performance is realized, which has important theoretical and practical significance in relevant applications such as the small-size underwater vehicles.

MicroRNA-98-5p regulates the proliferation and apoptosis of A549 cells by targeting MAP4K3.

Non-small cell lung cancer (NSCLC) is a primary subtype of lung cancer that is accompanied by a high incidence rate and poor prognosis. The primary treatment for NSCLC is chemotherapy, which has low effectiveness and high toxicity. Thus, novel targeted therapy has drawn much attention in recent years. MicroRNAs (miRs) serve important roles in multiple cancer types. In the current study, a decrease in miR-98-5p and an increase in mitogen-activated protein kinase kinase kinase kinase 3 (MAP4K3) was observed in NSCLC tumor tissues compared with normal tissues. miR-98-5p was predicted to target positions 1,056-1,063 of the MAP4K3 3'-untranslated region (UTR). The binding sites between miR-98-5p and the 3'-UTR of MAP4K3 messenger RNA were supported by the results of a dual-luciferase reporter assay. Compared with the control and miR-negative control (NC) groups, miR-98-5p mimic significantly reduced cell proliferation and increased apoptosis in NSCLC cells. In addition, miR-98-5p mimic reduced the expression of MAP4K3 and mammalian target of rapamycin while increasing the expression of cleaved caspase-3 compared with the control group and miR-NC groups. In conclusion, miR-98-5p may inhibit the progression of NSCLC via targeting of MAP4K3.