Breast cancer is the second cause of cancer mortality in women globally. Early detection, treatment, and metastasis monitoring are of great importance to favorable prognosis. Although conventional ...diagnostic methods, such as breast X-ray mammography and image positioning biopsy, are accurate, they could cause radioactive or invasive damage to patients. Liquid biopsy as a noninvasive method is convenient for repeated sampling in clinical cancer prognostic, metastatic evaluation, and relapse monitoring. MicroRNAs encased in exosomes circulating in biofluids are promising candidate cancer biomarkers because of their cancer-specific expression profiles. Here, we report an in situ detection of microRNA-1246 (miR-1246) in human plasma exosomes as breast cancer biomarker by a nucleic acid functionalized Au nanoflare probe. Needing neither time-consuming and costly isolation of exosomes from the plasma sample nor transfection means, the Au nanoflare probe can directly enter the plasma exosomes to generate fluorescent signal quantitatively by specifically targeting miR-1246. Only 40 μL of plasma is needed to incubate 4 h with the probe, giving signal sensitive enough to distinguish samples of breast cancer to normal control. Using plasma miR-1246 level detected by our assay as a marker, we differentiated 46 breast cancer patients from 28 healthy controls with 100% sensitivity and 92.9% specificity at the best cutoff. This simple, accurate, sensitive, and cost-effective liquid biopsy by the Au nanoflare probe is potent to be developed as a noninvasive breast cancer diagnostic assay for clinical adaption.
Improving plasticity has been an eternal theme of developing metallic materials. It is difficult to increase room‐temperature elongation of metallic materials over 100% without sacrificing strength ...using existing methods. Herein, surface‐roughness‐induced plasticity (SRIP) is discovered in biodegradable Zn–0.4Mn alloy. Surprisingly, in the good surface range that meets the international standard ISO 6892, reducing surface roughness results in significant increase in plasticity without loss of strength. From unground to 5000# sandpaper ground states, the surface roughness Ra of the alloy decreases from 0.63 to 0.05 µm, while its room temperature elongation increases from 74% to 143%. SRIP is the synergistic result of increased microstructure damage tolerance and decreased surface roughness. It provides a new method for improving plasticity.
Surface‐roughness‐induced plasticity (SRIP) solves the dilemma of significantly improving plasticity at the expense of strength. From the unground state to the 5000# sandpaper ground state, room‐temperature elongation of biodegradable Zn–0.4Mn alloy increases from 74% to 143% without loss of strength. SRIP is the synergistic result of increased microstructure damage tolerance and decreased surface roughness.
A specific bone vessel subtype, strongly positive for CD31 and endomucin (CD31
Emcn
), is identified as coupling angiogenesis and osteogenesis. The abundance of type CD31
Emcn
vessels decrease during ...ageing. Here we show that expression of the miR-497∼195 cluster is high in CD31
Emcn
endothelium but gradually decreases during ageing. Mice with depletion of miR-497∼195 in endothelial cells show fewer CD31
Emcn
vessels and lower bone mass. Conversely, transgenic overexpression of miR-497∼195 in murine endothelium alleviates age-related reduction of type CD31
Emcn
vessels and bone loss. miR-497∼195 cluster maintains the endothelial Notch activity and HIF-1α stability via targeting F-box and WD-40 domain protein (Fbxw7) and Prolyl 4-hydroxylase possessing a transmembrane domain (P4HTM) respectively. Notably, endothelialium-specific activation of miR-195 by intravenous injection of aptamer-agomiR-195 stimulates CD31
Emcn
vessel and bone formation in aged mice. Together, our study indicates that miR-497∼195 regulates angiogenesis coupled with osteogenesis and may represent a potential therapeutic target for age-related osteoporosis.
The unique expression pattern makes oncofetal proteins ideal diagnostic biomarkers and therapeutic targets in cancer. However, few oncofetal proteins have been identified and entered clinical ...practice.
Fetal liver, adult liver and hepatocellular carcinoma (HCC) tissues were employed to assess the expression of hepatic leukaemia factor (HLF). The impact of HLF on HCC onset and progression was investigated both in vivo and in vitro. The association between HLF and patient prognosis was determined in patient cohorts. The correlation between HLF expression and sorafenib benefits in HCC was further evaluated in patient cohorts and patient-derived xenografts (PDXs).
HLF is a novel oncofetal protein which is reactivated in HCC by SOX2 and OCT4. Functional studies revealed that HLF transactivates c-Jun to promote tumour initiating cell (TIC) generation and enhances TIC-like properties of hepatoma cells, thus driving HCC initiation and progression. Consistently, our clinical investigations elucidated the association between HLF and patient prognosis and unravelled the close correlation between HLF levels and c-Jun expression in patient HCCs. Importantly, HLF/c-Jun axis determines the responses of hepatoma cells to sorafenib treatment, and interference of HLF abrogated c-Jun activation and enhanced sorafenib response. Analysis of patient cohorts and PDXs further suggests that HLF/c-Jun axis might serve as a biomarker for sorafenib benefits in HCC patients.
Our findings uncovered HLF as a novel oncofetal protein and revealed the crucial role of the HLF/c-Jun axis in HCC development and sorafenib response, rendering HLF as an optimal target for the prevention and intervention of HCC.
Van der Waals (vdWs) heterostructures based on 2D metals and semiconductors have attracted considerable attention due to their excellent properties and great application potential in next‐generation ...electronic and optoelectronic devices. To obtain such vdWs heterostructures, the conventional approach with artificial exfoliation and stacking of 2D metals onto 2D semiconductors in the vertical direction is still far from satisfactory, because of the low yield and impurity‐involved transfer process. Here, two‐step vapor deposition growth of 2D TaSe2‐MoSe2 metal–semiconductor heterostructures is reported. Raman maps confirm the precise spatial modulation of the as‐grown 2D TaSe2‐MoSe2 heterostructures. Structural analysis reveals that the upper 1T‐TaSe2 is formed heteroepitaxially on/around the presynthesized 2H‐MoSe2 monolayers with an epitaxial relationship of (10‐10)TaSe2//(10‐10)MoSe2 and 0001TaSe2//0001MoSe2. Based on the detailed characterizations of morphology, structure, and composition, an edge‐induced growth mechanism is proposed to illustrate the formation process of the 2D heterostructures, confirmed by first‐principle calculations. In addition, Kelvin probe force microscope characterizations and electrical transport measurements confirm that the 2D metal–semiconductor heterostructures exhibit typical rectification characteristics with a contact potential height of ≈431 mV. The direct growth of high‐quality 2D metal–semiconductor heterostructures marks an important step toward high‐performance integrated optoelectronic devices.
2D TaSe2‐MoSe2 metal–semiconductor heterostructures are successfully achieved usin an edge‐induced epitaxial growth mode. The unique contact potential and strong current rectification behavior will facilitate the development high‐performance transition metal dichalcogenide‐based electronic devices.
Physical and mental health and hormonal imbalance are associated with the problems related to infertility and reproductive disorders. The rate of infertility has increased globally over the years, ...due to various reasons. Given the psychosocial implications of infertility and its effects on the life of the affected people, there has been an increased focus on its treatment over the last several years. Assisted reproductive technology can only solve about 50% of the cases. Moreover, it contains significant risks and does not solve the fundamental problem of infertility. As pluripotent stem cells have the potential to differentiate into almost any type of cell, they have been widely regarded as a promising option in the development of stem cell-based fertility treatments, which could even correct genetic diseases in offspring. These advancements in reproductive biotechnology present both challenges and possibilities for solving infertility problems caused by various unexplainable factors. This review briefly presents the different types of infertility disorders and the potential applications of stem cells in the treatment of these reproductive diseases.
Sepsis is a life‐threatening organ dysfunction syndrome, and liver is a susceptible target organ in sepsis, because the activation of inflammatory pathways contributes to septic liver injury. ...Oxidative stress has been documented to participate in septic liver injury, because it not only directly induces oxidative genotoxicity, but also exacerbates inflammatory pathways to potentiate damage of liver. Therefore, to ameliorate oxidative stress is promising for protecting liver in sepsis. Wogonin is the compound extracted from the medicinal plant Scutellaria baicalensis Geogi and was found to exert therapeutic effects in multiple inflammatory diseases via alleviation of oxidative stress. However, whether wogonin is able to mitigate septic liver injury remains unknown. Herein, we firstly proved that wogonin treatment could improve survival of mice with lipopolysaccharide (LPS)‐ or caecal ligation and puncture (CLP)‐induced sepsis, together with restoration of reduced body temperature and respiratory rate, and suppression of several pro‐inflammatory cytokines in circulation. Then, we found that wogonin effectively alleviated liver injury via potentiation of the anti‐oxidative capacity. To be specific, wogonin activated Nrf2 thereby promoting expressions of anti‐oxidative enzymes including NQO‐1, GST, HO‐1, SOD1 and SOD2 in hepatocytes. Moreover, wogonin‐induced Nrf2 activation could suppress NF‐κB‐regulated up‐regulation of pro‐inflammatory cytokines. Ultimately, we provided in vivo evidence that wogonin activated Nrf2 signalling, potentiated anti‐oxidative enzymes and inhibited NF‐κB‐regulated pro‐inflammatory signalling. Taken together, this study demonstrates that wogonin can be the potential therapeutic agent for alleviating liver injury in sepsis by simultaneously ameliorating oxidative stress and inflammatory response through the activation of Nrf2.
Undecorated and Pt-decorated SnO2 nanoparticles (NPs) were prepared using sol-gel and hydrothermal methods. The tin dioxide NPs, as sensing materials, were screen printed on alumina substrates with ...Pt test electrode to fabricate the gas sensors. The characteristics of these gas sensors in terms of composition, morphology, and sensing property were investigated by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), high resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), and electrochemical workstation, respectively. The results elucidated that the response time of Pt-decorated SnO2 sensor to 100 ppm H2 is 29 s at 350 °C, which is almost half of that of pure SnO2 gas sensor. Meanwhile, the effect of operating temperature and Pt decorating on the sensing properties and the ‘n’ value is studied. Comparing with many fabricated H2 gas sensors, our as-prepared sensor exhibits not only a high response time but also detects H2 gas down to 0.08 ppm. To the author's best knowledge, the detection limit of 0.08 ppm is the best reported detection limit for the gas sensors based on tin oxide NPs so far. Moreover, there is a significant enhancement in the selectivity of Pt-decorated SnO2 sensor to the H2 gas against other investigated gases such as carbon monoxide (CO), methane (CH4), nitrogen dioxide (NO2), sulfur dioxide (SO2). Overall, the obtained results clearly demonstrate that the Pt-decorated SnO2 is an excellent sensing material for the fabrication of gas sensors and the detection of trace concentration of H2 down to 0.08 ppm. Furthermore, the results of statistical and fractal analysis on 2D microstructures of FESEM images showed a coefficient correlation of about 0.991 for all the samples.
•Pt-SnO2 was synthesized using sol-gel and hydrothermal techniques.•The influence of ‘n’ value on the sensing properties of the fabricated gas sensors is discussed in details.•Pt-SnO2 gas sensors demonstrated excellent sensing properties and can detect H2 down to 0.08 ppm.
Taking the advantage of estimation of distribution algorithms (EDAs) in preserving high diversity, this paper proposes a multimodal EDA. Integrated with clustering strategies for crowding and ...speciation, two versions of this algorithm are developed, which operate at the niche level. Then these two algorithms are equipped with three distinctive techniques: 1) a dynamic cluster sizing strategy; 2) an alternative utilization of Gaussian and Cauchy distributions to generate offspring; and 3) an adaptive local search. The dynamic cluster sizing affords a potential balance between exploration and exploitation and reduces the sensitivity to the cluster size in the niching methods. Taking advantages of Gaussian and Cauchy distributions, we generate the offspring at the niche level through alternatively using these two distributions. Such utilization can also potentially offer a balance between exploration and exploitation. Further, solution accuracy is enhanced through a new local search scheme probabilistically conducted around seeds of niches with probabilities determined self-adaptively according to fitness values of these seeds. Extensive experiments conducted on 20 benchmark multimodal problems confirm that both algorithms can achieve competitive performance compared with several state-of-the-art multimodal algorithms, which is supported by nonparametric tests. Especially, the proposed algorithms are very promising for complex problems with many local optima.
In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2, no specific and effective drugs for treating this disease have been reported until today. ...Angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2, mediates the virus infection by binding to spike protein. Although ACE2 is expressed in the lung, kidney, and intestine, its expressing levels are rather low, especially in the lung. Considering the great infectivity of COVID-19, we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection. Here, we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein. The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody, Meplazumab, inhibits SARS-CoV-2 amplification. Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells, which can be neutralized by CD147 extracellular fragment. Viral loads are detectable in the lungs of human CD147 (hCD147) mice infected with SARS-CoV-2, but not in those of virus-infected wild type mice. Interestingly, virions are observed in lymphocytes of lung tissue from a COVID-19 patient. Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dose-dependent manner, which is specifically inhibited by Meplazumab. Furthermore, CD147 mediates virus entering host cells by endocytosis. Together, our study reveals a novel virus entry route, CD147-spike protein, which provides an important target for developing specific and effective drug against COVID-19.
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