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Circulating tumor cells (CTCs) in cancer patients' peripheral blood have been demonstrated to be a significant biomarker for metastasis detection, disease prognosis, and therapy response. Due to their extremely low concentrations, efficient enrichment and non-destructive release are needed. Herein, an FTO chip modified with multifunctional gelatin nanoparticles (GNPs) was designed for the specific capture and non-destructive release of CTCs. These nanoparticles share a similar dimension with the microvilli and pseudopodium of the cellular surface; thus, they can enhance adhesion to CTCs, and then GNPs can be degraded by the enzyme matrix metalloproteinase (MMP-9), gently releasing the captured cells. In addition, the transparency of the chip makes it possible for fluorescence immunoassay identification in situ under a microscope. Our chip attained a high capture efficiency of 89.27%, a release efficiency of 91.98%, and an excellent cellular viability of 96.91% when the concentration of MMP-9 was 0.2 mg/mL. Moreover, we successfully identified CTCs from cancer patients' blood samples. This simple-to-operate, low-cost chip exhibits great potential for clinical application. [ABSTRACT FROM AUTHOR]

A low cost and easily fabricated 3D micro‐nano biocompatible calcium phosphate (CaP) microstructure platform is developed to efficiently capture and non‐destructively release cancer cells. The thickness of CaP is ≈3 µm after 2.5 min deposition and increased to ≈12 µm after 10 min deposition. The void size between CaP nanosheets is increased when the electro deposition time is increased. This micro‐nano bio‐interface is suitable for cancer cell capturing and culturing. More than 90% for the EpCAM positive cells are captured on the CaP substrates where the specific anti‐EpCAM antibody is modified. On the other hand, the CaP substrates are easily degraded in citric acid (pH 6.0). In this method, 80% of the captured cancer cells can be rapidly released in 2.5 min on the 3 µm thick CaP substrates. The released cancer cells can be well cultured and can keep their viability. This platform is successfully used to capture the CTCs from patients' peripheral blood with different kinds of cancer. This platform can be applied in the controllable single CTC capture and release analysis, including downstream RT‐PCR, gene sequence, and single cell based tumor sphere culture in the future. [ABSTRACT FROM AUTHOR]

Prenatal diagnostics holds great significance for pregnant women desiring healthy babies. Fetal nucleated red blood cells (fNRBCs), bearing the complete genome of the fetus, have been regarded as an important biomarker for noninvasive prenatal diagnostics (NIPD). The high-performance detection and enrichment of fNRBCs from maternal blood, especially during early pregnancy, is urgently needed for NIPD, which, unfortunately, remains a big challenge for early-pregnancy fNRBC isolation. In this study, we developed an innovative platform based on silica microbeads for fNRBC isolation and release in early pregnancy. Microbeads were coated with self-assembled MnO2 nanoparticles (SiO2@MnO2) and then modified with a specific antibody. Benefiting from the three-dimensional nanostructure of the MnO2 nanoparticles, the isolation efficiency of the fNRBCs was enhanced. Subsequently, fNRBCs were released via dissolving the MnO2–nanoparticle coating using oxalic acid. We successfully isolated fNRBCs from the maternal peripheral blood samples of 20 pregnant women in the early pregnancy period, ranging from 41 to 62 gestational days. More importantly, the fetal origin of isolated cells was confirmed via fluorescent in situ hybridization and short tandem repeat analysis. This platform based on SiO2@MnO2 microbeads has verified the existence of fNRBCs in early-pregnancy maternal blood and is a promising approach for NIPD in early pregnancy. [ABSTRACT FROM AUTHOR]

A frequency-modulated continuous-wave (FMCW) coherent lidar with downlink communication capability is proposed based on phase-diversity coherent detection, by which laser ranging, laser velocimetry and free-space optical downlink communications can be simultaneously achieved. In the local transceiver, a linear-frequency modulated (LFM) optical signal is generated and used as the lidar signal. The LFM optical signal is received by the remote transceiver and coded with data via amplitude modulation. Then, the light is transmitted back to the local transceiver, in which a phase-diversity coherent optical receiver is used to simultaneously extract the range, velocity, and communication data. The in-phase and quadrature outputs from the phase-diversity coherent optical receiver are simultaneously recorded to reform a complex signal. The data is extracted from the intensity of the complex signal, while the range and velocity are obtained from the argument of it. A demonstration experiment is carried out. Different digital baseband signals are encoded on the reflected signal via an intensity modulator, while the 80-MHz Doppler frequency shift is simulated by an acousto-optic modulator. The impact of the digital signal on lidar detection is removed. Meanwhile, the communication quality is little affected by the varied frequency of the de-chirped signal. Therefore, the lidar detection and the free-space optical communications are simultaneously implemented. [ABSTRACT FROM AUTHOR]

The underlying mechanism of the myocardial protective effect of fisetin was studied in a rat ischemia/reperfusion injury model. Sprague-Dawley rats were randomly assigned to seven groups and pretreated with different solutions by gavage administration. A rat model of cardiac ischemia/reperfusion injury was established. Plasma levels of Von Willebrand factor (vWF) were determined by ELISA, flow cytometry was used to determine the level of cardiomyocyte apoptosis and 2,3,5-triphenyltetrazolium staining was used to determine the size of myocardial infarcts. Hematoxylin and eosin-stained sections of myocardial tissues were examined for pathological changes. Expressions of nuclear factor (NF)-κB and matrix metallopeptidase 9 (MMP-9) were measured by immunohistochemistry. Compared with the model group, rats pretreated with fisetin, quercetin and aspirin showed significant prolongation of clotting time, prothrombin time, thrombin time and activated partial thromboplastin time. Fisetin treatment better maintained the integrity of myocardial fibers and nuclear integrity, reduced the percentage of apoptotic myocardial cells, inhibited expression of NF-κB, decreased the loss of MMP-9 and reduced nuclear translocation of NF-kB. Rats pretreated with fisetin also demonstrated a significant decrease in plasma levels of vWF. In addition, the protective effect of fisetin on myocardial cells was found to be dose dependent. [ABSTRACT FROM AUTHOR]

Background: Long noncoding RNAs (lncRNAs) are reported to play important roles in tumorigenesis of various malignant tumors. However, the clinical significance of aberrant lncRNA expression in hepatocellular carcinoma (HCC) is still elusive. Methods: Firstly, a differentially expressed lncRNA CTC‐297N7.9 in HCC was detected by analyzing the data from The Cancer Genome Atlas (TCGA). Secondly, the expression level of CTC‐297N7.9 was examined in four HCC cell lines and 60 pairs of HCC tissues by polymerase chain reaction (PCR) assay at our center. Thirdly, receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic value of CTC‐297N7.9 for HCC. Correlation and survival analysis of HCC patients from the TCGA and our center were also carried out to assess the predictive value of CTC‐297N7.9. Finally, survival prognostic models were established combining lncRNA expression and other clinical parameters. Results: The expression of CTC‐297N7.9 was downregulated in HCC cell lines and HCC tissues. ROC curve revealed its significant diagnostic value in HCC. CTC‐297N7.9 expression correlated with serum alpha‐fetal protein (AFP), tumor stage, and tumor differentiation. Survival analysis indicated that overall survival (OS) and disease‐free survival (DFS) are all positively associated with CTC‐297N7.9 expression, especially in patients without viral hepatitis or cirrhosis. Cox regression analysis showed that CTC‐297N7.9 expression level is an independent prognostic factor for both OS and DFS in HCC patients. Based on the model, CTC‐297N7.9 was observed to be negatively correlated to risk score, indicating its role as a protective factor for HCC. Conclusion: Our study demonstrated that the low expression of CTC‐297N7.9 is associated with poor prognosis in HCC patients, suggesting its possible role as a potential prognostic marker for HCC. [ABSTRACT FROM AUTHOR]

Long non‐coding RNAs (lncRNAs) have been indicated for the regulatory roles in cardiovascular diseases. This study determined the expression of lncRNA TNK2 antisense RNA 1 (TNK2‐AS1) in oxidized low‐density lipoprotein (ox‐LDL)‐stimulated human aortic smooth muscle cells (HASMCs) and examined the mechanistic role of TNK2‐AS1 in the proliferation and migration of HASMCs. Our results demonstrated that ox‐LDL promoted HASMC proliferation and migration, and the enhanced proliferation and migration in ox‐LDL‐treated HASMCs were accompanied by the up‐regulation of TNK2‐AS1. In vitro functional studies showed that TNK2‐AS1 knockdown suppressed cell proliferation and migration of ox‐LDL‐stimulated HASMCs, while TNK2‐AS1 overexpression enhanced HASMC proliferation and migration. Additionally, TNK2‐AS1 inversely regulated miR‐150‐5p expression via acting as a competing endogenous RNA (ceRNA), and the enhanced effects of TNK2‐AS1 overexpression on HASMC proliferation and migration were attenuated by miR‐150‐5p overexpression. Moreover, miR‐150‐5p could target the 3' untranslated regions of vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 1 (FGF1) to regulate FGF1 and VEGFA expression in HASMCs, and the inhibitory effects of miR‐150‐5p overexpression in ox‐LDL‐stimulated HASMCs were attenuated by enforced expression of VEGFA and FGF1. Enforced expression of VEGFA and FGF1 also partially restored the suppressed cell proliferation and migration induced by TNK2‐AS1 knockdown in ox‐LDL‐stimulated HASMCs, while the enhanced effects of TNK2‐AS1 overexpression on HASMC proliferation and migration were attenuated by the knockdown of VEGFA and FGF1. Collectively, our findings showed that TNK2‐AS1 exerted its action in ox‐LDL‐stimulated HASMCs via regulating VEGFA and FGF1 expression by acting as a ceRNA for miR‐150‐5p. [ABSTRACT FROM AUTHOR]

This brief presents an external capacitor-less nMOS low-dropout (LDO) voltage regulator integrated with a standard CSMC 0.6- ${\mu }\text{m}$ BiCMOS technology. Over a −55 °C to +125 °C temperature range, the fabricated LDO provides a stable and considerable amount of 3 A output current over wide ranges of output capacitance $C_{\mathrm {OUT}}$ (from zero to hundreds of ${\mu }\text{F}$) and effective-series-resistance (ESR) (from tens of milliohms to several ohms). A LDO voltage of 200 mV has been realized by accurate modeling. Operating with an input voltage ranging from 2.2 to 5.5 V provides a scalable output voltage from 0.8 to 3.6 V. When the load current jumps from 100 mA to 3 A within 3 ${\mu }\text{s}$ , the output voltage overshoot remains as low as 50 mV without output capacitance, $C_{\mathrm {OUT}}$. The system bandwidth is about 2 MHz, and hardly changes with load altering to ensure system stability. To improve the load transient response and driving capacity of the nMOS power transistor, a buffer with high input impedance and low output impedance is applied between the transconductance amplifier and the nMOS power transistor. The total area of fabricated LDO voltage regulator chip including pads is 2.1 mm $\times $ 2.2 mm. [ABSTRACT FROM AUTHOR]

Chemotherapy resistance is one of the major challenges for the treatment of osteosarcoma (OS). The potential roles of oestrogenic signals in the chemoresistance of OS cells were investigated. As compare to the parental cells, the doxorubicin and cisplatin (CDDP) resistant OS cells had greater levels of oestrogen‐related receptors alpha (ERRα). Targeted inhibition of ERRα by its specific siRNAs or inverse agonist XCT‐790 can restore the sensitivity of OS resistant cells to chemotherapy. This might be due to that si‐ERRα can decrease the expression of P‐glycoprotein (P‐gp, encoded by ABCB1), one important ABC membrane transporter for drug efflux. XCT‐790 can decrease the transcription and mRNA stability of ABCB1, while had no effect on protein stability of P‐gp. ERRα can bind to the transcription factor of SP3 to increase the transcription of ABCB1. Furthermore, XCT‐790 treatment decreased the expression of miR‐9, which can bind to the 3′UTR of ABCB1 and trigger its decay. Collectively, we found that ERRα can regulate the chemoresistance of OS cells via regulating the transcription and mRNA stability of ABCB1. Targeted inhibition of ERRα might be a potential approach for OS therapy. [ABSTRACT FROM AUTHOR]

Aim Laparoscopic hepatectomy (LH), microwave ablation (MWA), and open hepatectomy (OH) are three widely used methods to treat small hepatocellular carcinoma (HCC). However, few studies have compared the short- and long-term outcomes of these three treatments. The aim of this study was to investigate their effectiveness. Methods The data were reviewed from 280 patients with HCCs measuring ≤3 cm (Barcelona Clinic Liver Cancer stage 0 or A) who received LH ( n = 133), OH ( n = 87), or MWA ( n = 60) in our research center from 2005 to 2010. Short-term outcomes included intraoperative blood loss, operation time, and length of hospital stay. The disease-free survival and overall survival rates were analyzed as long-term outcomes. Results The patients in the MWA and LH groups showed better short-term outcomes compared with those in the OH group. There were no significant differences in overall survival rates among the three treatments. The LH group showed significantly lower recurrence rates than the MWA group ( P = 0.0146). Conclusions Laparoscopic hepatectomy may be a better option for patients with small HCC located on the liver surface and left lateral lobe. The short-term outcome of MWA is promising, although the high risk of local recurrence after the operation should be considered when planning treatment. [ABSTRACT FROM AUTHOR]

The authors report a feasible simple method to fabricate two kinds of micellar nanocarriers (MPEG-SS-CPT/DOX) with polyethylene glycol (PEG) based on the self-assembly of glutathione (GSH)-responsive amphiphilic PEGylated polymers (MPEG-SS-CPT) in free doxorubicin (DOX) solution, which could carry two anticancer drugs of camptothecin (CPT) and DOX toward cancer cells together. In in vitro release studies, the micelles of MPEG-SS-CPT/DOX could undergo the triggered disassembly to release CPT and DOX under GSH stimulus much faster than without GSH. Furthermore, the MPEG-SS-CPT nanocarriers could release CPT with no change of its original structure after degradation. From the experiments of loading and release of drugs, the cell viability assay, cellular uptake, and flow cytometry studies, it was found that the fibrous micelles modified by PEG with a molecular weight of 350 had greater potential in the field of drug delivery than the other with a molecular weight of 1900. [ABSTRACT FROM PUBLISHER]

Background: The molecular pathways along with the clinical significance of long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) remain uncertain. Our study sought to identify and characterize lncRNAs associated with HCC. Methods: LncRNA TMCO1-AS1 was identified by differential expression analysis, receiver operating characteristic (ROC) analysis, and univariate analysis using RNA sequencing and clinical information of HCC from the public database. Then clinical correlations and survival analysis were conducted to further appraise the prognostic significance of lncRNA TMCO1-AS1 in HCC. Hepatoma and adjoining normal tissues from 66 patients who received surgical operation at our center were used to verify the results of the bioinformatics analysis. A survival prognostic model was established combining TMCO1-AS1 expression and other clinical characteristics. Results: Bioinformatics analysis showed the aberrant high expression of TMCO1-AS1 in HCC tissue. TMCO1-AS1 expression was positively correlated with alpha-fetoprotein (AFP) level, vascular invasion, tumor stage, as well as tumor differentiation. Moreover, survival analysis found a significant inverse association between the expression of TMCO1-AS1 and the survival of patients with HCC. Cox analysis indicated that TMCO1-AS1 was an independent factor for HCC prognosis. Analysis of the HCC tissues from patients at our center provided results similar to those of the bioinformatics analysis. Risk models for overall survival (OS) and recurrence-free survival (RFS) incorporating TMCO1-AS1 exhibited better sensitivity and specificity than using clinical characteristics alone. Conclusion: High TMCO1-AS1 expression is significantly correlated with the unfavorable poor prognosis of HCC, indicating its potential of being a novel prognostic marker for HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Zhu, Zhang, Tan, Chen and Shang.)

We report here a novel doxorubicin (DOX) prodrug that reduces the proportion of inactive materials and minimizes drug leak. In aqueous solutions, the resulting DOX prodrug could spontaneously form stable micelles with diameters of ∼80 nm with a DOX loading content as high as ∼40 wt%. The subsequent cytotoxicity and cell internalization behavior indicated that the resulting prodrug could show a high in vitro anticancer efficacy. We believe that this strategy could be developed to design prodrugs of various anticancer drugs and thus offer new prodrugs for cancer therapy.