Pancreatic cancer (PC) is one of the most lethal malignancies. Recent studies indicate that patients with incidentally diagnosed PC have better prognosis than those with symptoms and that there is a ...sufficient window for early detection. However, effective early diagnosis remains difficult and depends mainly on imaging modalities and the development of screening methodologies with highly sensitive and specific biomarkers. This review summarizes recent advances in effective screening for early diagnosis of PC using imaging modalities and novel molecular biomarkers discovered from various “omics” studies including genomics, epigenomics, non‐coding RNA, metabonomics, liquid biopsy (CTC, ctDNA and exosomes) and microbiomes, and their use in body fluids (feces, urine and saliva). Although many biomarkers for early detection of PC have been discovered through various methods, larger scale and rigorous validation is required before their application in the clinic. In addition, more effective and specific biomarkers of PC are urgently needed.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Hepatocellular carcinoma (HCC) is one of the most lethal tumours worldwide. However, the effects of first-line sorafenib treatment in advanced HCC fail to prolong patients' survival due to the highly ...heterogeneous characteristics of HCC etiology. Cyclin-dependent kinase 9 (CDK9) is an important target in the continuous development of cancer therapy. Here, we demonstrate that CDK9 is closely associated with the progression of HCC and can serve as an HCC therapeutic target by modulating the recovery of wild-type p53 (wt-p53) function. We prove that mouse double minute 2 homologue (MDM2) and Sirtuin 1 (SIRT1) are phosphorylated by CDK9 at Ser166 and Ser47, respectively. Inhibition of CDK9 not only reduces the MDM2-mediated ubiquitination and degradation of wt-p53 but also increases wt-p53 stability by suppressing deacetylase activity of SIRT1. Thus, inhibition of CDK9 promotes the wt-p53 stabilization and prevents HCC progression. However, excessive inhibition by high concentrations of specific CDK9 inhibitors counteracts the promotion of p53 stability and reduces their anti-HCC activity because of extreme general transcription repression. The effects of a novel CDK9 inhibitor named oroxylin A (OA) from Scutellaria baicalensis are explored, with the results indicating that OA shows moderate and controlled inhibition of CDK9 activity and expression, and stabilizes wt-p53 by inhibiting CDK9-regulated MDM2 and SIRT1 signaling. These outcomes indicate the high therapeutic potential of OA against HCC and its low toxicity in normal tissue. This study demonstrates a novel mechanism for the regulation of wt-p53 by CDK9 and indicates that OA is a potential candidate for HCC therapy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•Structural characterization of two polysaccharides from Dendrobium officinale were described.•DOP performed the hypoglycemic activity via stimulating GLP-1 secretion in STZ-induced diabetic rats and ...STC-1 cells.•Ca2+/CaM/CaMKII and MAPK pathways might involve in the intracellular DOP-induced GLP-1 secretion.•The repeated unit of backbone of DOP-1 and DOP-2 might be the effective unit of DOP-induced GLP-1 secretion.
Two polysaccharides, named DOP-1 and DOP-2, with molecular weights of 6.8 kDa and 14.3 kDa, respectively, were isolated and purified from the stems of Dendrobium officinale. Monosaccharide composition, Fourier-transform infrared spectroscopy, methylation, and nuclear magnetic resonance analyses indicated that DOP-1 and DOP-2 may have a backbone consisted of →4)-β-d-Glcp-(1→, →4)-β-d-Manp-(1→, →4)-2-O-acetyl-β-d-Manp-(1→ and →4)-3-O-acetyl-β-d-Manp-(1→. In vivo assays showed that D. officinale polysaccharides (DOPs) exerted significant hypoglycemic effects accompanying increased serum insulin and glucagon-like peptide-1 (GLP-1) levels in streptozotocin-induced diabetic rats. Further in vitro experiments showed that DOP-induced GLP-1 secretion was inhibited by an intracellular calcium chelator, a Ca2+/calmodulin-dependent protein kinase (CaMK) II inhibitor, a specific calcium-sensing receptor antagonist, and a p38-mitogen-activated protein kinases (MAPK) inhibitor. These results indicated that DOPs may decrease fasting blood sugar levels by stimulating GLP-1 secretion and that intracellular DOP-induced GLP-1 secretion involved the Ca2+/calmodulin/CaMKII and MAPK pathways.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Zinc oxide (ZnO) nanowires have attracted extensive interests in ultraviolet photodetection fields owing to their outstanding optoelectronic properties. The detectivity of ZnO nanowire photodetectors ...is often limited by large dark current due to a number of defect‐induced carriers. Herein, a thin layer of poly(2‐vinyl naphthalene) (PVN) is introduced between the ZnO nanowire and gate dielectric to deplete defect‐induced carriers with the help of the electrostatic field generated by trapped electrons in the PVN layer. The dark current is successfully reduced from 2.2 × 10−9 to 1.6 × 10−14 A. Particularly, ZnO nanowire photodetectors with a large Ilight/Idark ratio (>107), high photoresponsivity (>106 A W−1), and ultrahigh detectivity (>1018 Jones) are achieved, which are among the best performance in reported ZnO‐based photodetectors. The present simple scheme offers a new strategy to suppress dark current in semiconducting nanomaterials for ultrasensitive photodetection applications.
For minimizing the dark current of ZnO nanowire photodetectors, a thin layer of polymer electret, poly(2‐vinyl naphthalene), is inserted between the ZnO nanowire and gate dielectric to deplete defect‐induced carriers in the channel. Through this strategy, the dark current of the ZnO nanowire photodetectors can be significantly reduced (<10−13 A) and ultrahigh detectivity (>1018 Jones) is achieved.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Diabetic foot wound healing is a major clinical problem due to impaired angiogenesis and bacterial infection. Therefore, an effective regenerative dressing is desiderated with the function of ...promoting revascularization and anti-bacteria. Herein, a multifunctional injectable composite hydrogel was prepared by incorporation of the cerium-containing bioactive glass (Ce-BG) into Gelatin methacryloyl (GelMA) hydrogel. The Ce-BG was synthesized by combining sol-gel method with template method, which maintained spherical shape, chemical structure and phase constitution of bioactive glass (BG). The Ce-BG/GelMA hydrogels had good cytocompatibility, promoted endothelial cells migration and tube formation by releasing Si ion. In vitro antibacterial tests showed that 5 mol % CeO
-containing bioactive glass/GelMA (5/G) composite hydrogel exhibited excellent antibacterial properties. In vivo study demonstrated that the 5/G hydrogel could significantly improve wound healing in diabetic rats by accelerating the formation of granulation tissue, collagen deposition and angiogenesis. All in all, these results indicate that the 5/G hydrogel could enhance diabetic wound healing. Therefore, the development of multifunctional materials with antibacterial and angiogenic functions is of great significance to promote the repair of diabetic wound healing.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PbS colloidal quantum dots passivated by the thiocyanate anion (SCN–) are developed to combine with perovskite (CH3NH3PbI3) as building blocks for UV–vis–NIR broadband photodetectors. Both high ...electrical conductivity and appropriate energy-level alignment are obtained by the in situ ligand exchange with SCN–. The PbS-SCN/CH3NH3PbI3 composite photodetectors are sensitive to a broad wavelength range covering the UV–vis–NIR region (365–1550 nm), possessing an excellent responsivity of 255 A W–1 at 365 nm and 1.58 A W–1 at 940 nm, remarkably high detectivity of 4.9 × 1013 Jones at 365 nm and 3.0 × 1011 Jones at 940 nm, and fast response time of ≤42 ms. Furthermore, a 10 × 10 photodetector array is fabricated and integrated, which constitutes a high-performance broadband image sensor. Our approach paves a way for the development of highly sensitive broadband photodetectors/imagers that can be easily integrated.
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IJS, KILJ, NUK, PNG, UL, UM
A hybrid structure strategy, utilizing a perovskite/MoS2 bulk heterojunction (BHJ) as the photosensitizer and a reduced graphene oxide (rGO) layer as the conducting channel, is developed to realize ...high‐performance photodetectors. All the active layers are prepared by a simple and low‐cost solution process. The perovskite/MoS2 BHJ can significantly suppress the recombination of photogenerated carriers due to the selective electron trapping in the MoS2 nanoflakes, and thus the photoinduced hole transfer from perovskite to rGO is facilitated to largely increase the photocurrent. The hybrid photodetectors show excellent figures of merit, such as high responsivity of 1.08 × 104 A W−1, high detectivity of 4.28 × 1013 Jones, high external quantum efficiency of 2.0 × 106%, and fast photoresponse time less than 45 ms. The demonstration of flexible photodetectors on a flexible substrate finds potential applications in wearable and portable electronics. This work highlights the significance of a hybrid structure, combining an appropriate BHJ film with a graphene channel, as a general and effective way for achieving low‐cost and high‐performance photodetectors.
A hybrid structure strategy, using a perovskite/MoS2 bulk heterojunction (BHJ) as the photosensitizer and a reduced graphene oxide (rGO) layer as the conducting channel, is developed to realize high‐performance photodetectors. The BHJ can significantly suppress the photogenerated carrier recombination due to selective electron trapping in MoS2, and thus photoinduced hole transfer from perovskite to rGO is facilitated for performance enhancement.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Organized flaking techniques to obtain predetermined stone tools have been traced back to the early Acheulean (also known as mode 2) in Africa and are seen as indicative of the emergence of advanced ...technical abilities and in-depth planning skills among early humans. Here, we report one of the earliest known examples of prepared core technology in the archaeological record, at the Cenjiawan (CJW) site in the Nihewan basin of China, dated 1.1 Mya. The operational schemes reconstructed from the CJW refit sets, together with shaping patterns observed in the retouched tools, suggest that Nihewan basin toolmakers had the technical abilities of mode 2 hominins, and developed different survival strategies to adapt to local raw materials and environments. This finding predates the previously earliest known prepared core technology from Eurasia by 0.3 My, and the earliest known mode 2 sites in East Asia by a similar amount of time, thus suggesting that hominins with advanced technologies may have migrated into high latitude East Asia as early as 1.1 Mya.
Five-year survival rate of esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy is <20%. Our study aimed to investigate whether cancer-associated fibroblasts (CAFs), one major ...component of tumor microenvironment, were involved in tumor radioresistance in ESCC. By use of human chemokine/cytokine array, human chemokine CXCL1 was found to be highly expressed in CAFs compared with that in matched normal fibroblasts. Inhibition of CXCL1 expression in CAFs significantly reversed CAF-conferred radioresistance in vitro and in vivo. CAF-secreted CXCL1 inhibited the expression of reactive oxygen species (ROS)-scavenging enzyme superoxide dismutase 1, leading to increased ROS accumulation following radiation, by which DNA damage repair was enhanced and the radioresistance was mediated. CAF-secreted CXCL1 mediated the radioresistance also by activation of Mek/Erk pathway. The cross talk of CAFs and ESCC cells induced CXCL1 expression in an autocrine/paracrine signaling loop, which further enhanced tumor radioresistance. Together, our study highlighted CAF-secreted CXCL1 as an attractive target to reverse tumor radioresistance and can be used as an independent prognostic factor of ESCC patients treated with chemoradiotherapy.
A simple and effective strategy, that is the use of 2-Methoxyethanol rather than anhydrous ethanol as the ZnO precursor solvent, is developed to greatly improve the photoresponsivity in the PbS ...colloidal quantum dot (CQD)/ZnO heterojunction short-wavelength infrared (SWIR) photodiodes. This approach significantly modifies the PbS/ZnO interface through an increase of electron concentration and a reduction of surface defects in the ZnO layer, which is critical to suppressing carrier recombination at the PbS/ZnO interface. The optimized photodiodes show superior figures of merit, including low dark current density of 1.28 <inline-formula> <tex-math notation="LaTeX">\times \,\,10^{-{8}} </tex-math></inline-formula> A/cm 2 at −0.5 V, high photoresponsivity of 0.47 A/W and high specific detectivity of 2.22 <inline-formula> <tex-math notation="LaTeX">\times \,\,10^{{12}} </tex-math></inline-formula> Jones at 1413 nm, and fast response/recovery time of 6.8/8.6 <inline-formula> <tex-math notation="LaTeX">\mu \text{s} </tex-math></inline-formula>.
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