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Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide.Aim: To investigate the mechanisms of paclitaxel resistance in hepatocellular carcinoma cells and find promising molecular target for HCC therapy.Materials and Methods: To investigate the effects of FHL1 on chemo resistance in HCC cells, we generated FHL1 knock-down stable cell lines with HepG2 and SMMC7721 cells. Cell viability assay, colony formation and xenograft experiments assay were performed to detect effect of FHL1 on Paclitaxel or Oxaliplatin resistance in vitro and in vivo. Caspase activity assay was performed to explore the activation of caspase-3 and caspase-9 in paclitaxel treated FHL1-knockdown HepG2 cells.Result: In the present study we have investigated that four-and-a-half LIM protein 1 (FHL1), which plays an important role in the development of cancer, is associated with both the chemo resistance of hepatocellular carcinomas cells in vitro and in vivo. Knockdown of FHL1 significantly enhanced the sensitivity of paclitaxel, but had no effects on sensitivity of oxaliplatin. Moreover, knockdown of FHL1 promoted the activation of caspase-3 and caspase-9, which were induced by paclitaxel. Interestingly, FHL1 negatively regulates the chemo resistance of HCC in xenografted nude mice.Conclusion: FHL1 promote paclitaxel resistance in hepatocellular carcinomas cells through regulating apoptosis induced by paclitaxel, suggesting that FHL1 may be a promising molecular target for HCC therapy. [ABSTRACT FROM AUTHOR]

Abstract: Polycrystalline Yb:Gd2GeO5 was prepared by solid state reaction method, and its structure, spectral properties, and energy structure were studied. The Yb:Gd2GeO5 belongs to space group P21/c, and its photoluminescence spectrum includes the range from 975 to 1088nm which is one of the known broader emission of Yb3+. The broad emission spectrum is necessary for ultrashort laser operation and laser tuning. Crystal field parameters and energy levels of Yb3+ at two symmetry sites in Gd2GeO5 were calculated by the simple overlap model, respectively. The calculated energy levels are consistent with the experimental very well. The energy splitting of Yb3+ 2F7/2 ground state in Gd2GeO5 is up to 1065cm−1. According to Boltzmann distribution, the thermal population ratio of the highest terminal laser level is about 0.605% and less than 2.32% of YAG by one order, which is very beneficial to population inversion. All results indicate that Yb:Gd2GeO5 may be a promising laser crystal material for ultrashort and tunable all-solid laser. [Copyright &y& Elsevier]

Abstract: Nd:Lu3Al5O12 (Nd:LuAG) nano-crystalline was synthesized by co-precipitation method. Its phase transformation, structure, absorption and photoluminescence properties were studied. The Nd:LuAG polycrystalline phase is formed above 900°C and its particle sizes are in the range of 18–36nm. The structure of Nd:LuAG was refined by Rietveld method. The lattice parameters and the distortion of Lu3+–O2− polyhedron in Nd:LuAG are larger than that of in pure LuAG. Because the distortion of Lu3+–O2− polyhedron is larger than that of Y3+–O2− polyhedron in YAG and the distance of Lu3+–O2− is smaller than that of Y3+–O2− in YAG, Nd3+ in LuAG experiences a stronger crystal field effect, which is proved by the crystal field strength and the chemical environment parameter. The absorption spectrum shows that Nd:LuAG has a broad absorption band at 808nm with FWHM above 6nm, which is favorable for improving laser efficiency. The fluorescence lifetime from 4 F 3/2 → 4 I 11/2 transition is 320μs and longer than that of Nd:YAG. The longer lifetime is propitious to energy storage. The emission cross section at 1064nm is 2.89×10−19 cm2, taking into account the Boltzmann distribution of the excited state. The emission cross section in Nd:LuAG is also larger than that of Nd:YAG, which is useful for laser operation. All results indicate that Nd:LuAG is a promising crystal material to apply in high energy lasers. [Copyright &y& Elsevier]

Abstract: Four and a half LIM domains 1 (FHL1) belongs to a family of LIM-only proteins that regulate gene transcription, cell proliferation, differentiation and apoptosis. However, the biological function of FHL1 remains largely unknown. We used a yeast two-hybrid system and identified receptor interacting protein of 140kDa (RIP140) as a novel FHL1-binding protein. RIP140 interacted with FHL1 both in vitro and in mammalian cells and estrogen enhanced this interaction. All domains of FHL1 are required to interact with RIP140. Overexpression of FHL1 enhanced RIP140 repression of estrogen signaling in breast cancer cells in a reporter assay, whereas reduction of endogenous FHL1 with FHL1 small interfering RNA abolished this effect. Furthermore, overexpression of the FHL1 deletion mutant that lacks the RIP140-binding sites had no effect on RIP140 repression of estrogen signaling. Consistent with the results of the reporter assays, FHL1 and RIP140 synergistically inhibited the transcription of the estrogen-responsive gene pS2. The results presented here suggested the cooperative transcriptional regulation of estrogen signaling by FHL1 and RIP140, and might provide a new regulation mechanism by which estrogen signaling-related diseases such as breast cancer develop. [Copyright &y& Elsevier]

Abstract: Nano-polycrystalline Cr3+:Lu3Ga5O12 (Cr:LGG) has been obtained by sintering its precursor, which was synthesized via coprecipitation method. The obtained nanopowders were charactered by X-ray diffraction (XRD), scanning electron microscopy (SEM), excitation and emission spectra and fluorescence decay curve measurements. XRD result shows that Cr:LGG precursor has translated into polycrystalline Cr:LGG after being sintered at 1000°C for 3h. Three broad excitation bands locate around 462, 608 and below 300nm, respectively. The emission spectrum shows a broadband from 600 to 840nm with maximum at 708nm. The fluorescence decay time is determined as 890μs. [Copyright &y& Elsevier]

Herein, a direct-contact photocurrent-direction-switching photoelectrochemical (PEC) biosensing platform for the ultrasensitive and selective detection of soluble CD146 (sCD146) is reported for the first time via in situ formation of carbon nitride quantum dots (CN QDs)/titanium dioxide (TiO 2 ) nanodiscs with the double-supported 3D DNA walking amplification. In this platform, metal organic frameworks (MOFs)-derived porous TiO 2 nanodiscs exhibit excellent anodic photocurrent, whereas a single-stranded auxiliary DNA (ssDNA) as biogate is absorbed onto the TiO 2 nanodiscs to block active sites. Subsequently, with the help of intermediate DNAs from target sCD146-induced double-supported 3D DNA walking signal amplification, the ssDNA can leave away from the surface of TiO 2 nanodiscs due to the specific hybridization with intermediate DNAs. Afterward, the successful direct contact of CN QDs on TiO 2 nanodiscs by porosity and electrostatic adsorption, leads to the effective photocurrent-direction switching from anodic to cathodic photocurrent. Based on direct-contact photocurrent-direction-switching CN QDs/TiO 2 nanodiscs system and double-supported 3D DNA walking signal amplification, sCD146 is detected sensitively with a wide linear range (10 fg mL -1 to 5 ng mL -1 ) and a low limit of detection (2.1 fg mL -1 ). Also, the environmentally friendly and direct-contact photocurrent-direction-switching PEC biosensor has an application prospect for cancer biomarker detection., (© 2023 Wiley-VCH GmbH.)

MicroRNAs (miRNAs) encapsulated in tumor-derived exosomes are becoming ideal biomarkers for the early diagnosis and prognosis of lung cancer. However, the accuracy and sensitivity are often hampered by the extraction process of exosomal miRNA using traditional methods. Herein, this study developed a fluorogenic quantitative detection method for exosomal miRNA using the fluorescence quenching properties of molybdenum disulfide (MoS 2 ) nanosheets and the enzyme-assisted signal amplification properties of duplex-specific nuclease (DSN). First, a fluorescently-labeled nucleic acid probe was used to hybridize the target miRNA to form a DNA/RNA hybrid structure. Under the action of the DSN, the DNA single strand in the DNA/RNA hybrid strand was selectively digested into smaller oligonucleotide fragments. At the same time, the released miRNA target triggers the next reaction cycle, so as to achieve signal amplification. Then, MoS 2 was used to selectively quench the fluorescence of the undigested probe leaving the fluorescent signal of the fluorescently-labeled probe fragments. The fluorometric signals for miRNA-21 had a maximum excitation/emission wavelength of 488/518 nm. Most importantly, the biosensor was then applied for the accurate quantitative detection of miRNA-21 in exosome lysates extracted from human plasma and this method was able to successfully distinguish lung cancer patients from healthy people. This biosensor provides a simple, rapid, and a highly specific quantitative method for exosomal miRNA and has promising potential to be used in the early diagnosis of lung cancer.

The narrow absorption and emission bands, long fluorescence lifetime, and excellent stability of rare earth nanoparticles (referred to as RE NPs) make them very attractive for multimodal imaging and therapy of cancer. Their narrow absorption requires the careful selection of laser wavelength to achieve the best performance, particularly for RE NPs simultaneously having photothermal and photoluminescent properties (e.g., Nd-based nanoparticles), which has not been investigated. Herein, we prepared a series of different-sized NaNdF 4 nanoparticles (referred to as NNF NPs) (i.e., 4.7, 5.9, 12.8, and 15.6 nm) from ultrasmall nanoclusters and investigated their in vitro and in vivo size-dependent photothermal conversion and photoluminescence under irradiation by a 793 nm laser and an 808 nm laser, respectively. We find that all nanoparticles exhibited the better photothermal conversion performance under the irradiation of the 808 nm laser than under the 793 nm laser, of which 12.8 nm NNF NPs showed the best performance, and the temperature of their solution can be quickly increased from 30 °C to around 60 °C within 10 min under the irradiation of the 808 nm laser with a power intensity of 0.75 W/cm 2 . When we used the 793 nm laser to excite these NNF NPs, we found that all nanoparticles exhibited the stronger photoluminescence in the second near-infrared window (NIR-II) than under the excitation by the 808 nm laser, of which 15.6 nm NNF NPs possessed the strongest NIR-II luminescence. We then modified 12.8 nm NNF NPs with phospholipid carboxyl PEG and functionalized with RGD for actively targeted imaging of cancer. The NaNdF 4 @PEG@RGD nanoparticles (referred to as NNF-P-R NPs) have good biocompatibility, stability, and excellent targeting capability. The in vivo result show that 12.8 nm NNF NPs exhibited better photothermal conversion performance under the irradiation of the 808 nm laser, and stronger NIR-II fluorescence under irradiation of the 793 nm laser, which are consistent with the in vitro result. This work demonstrates the significance of selection of the proper laser wavelength for maximally taking advantage of RE nanoparticles for the diagnosis and treatment of cancer.

The estrogen receptor (ER) is a member of a large superfamily of nuclear receptors that regulates the transcription of estrogen-responsive genes. Several recent studies have demonstrated that XBP-1 mRNA expression is associated with ERalpha status in breast tumors. However, the role of XBP-1 in ERalpha signaling remains to be elucidated. More recently, two forms of XBP-1 were identified due to its unconventional splicing. We refer to the spliced and unspliced forms of XBP-1 as XBP-1S and XBP-1U, respectively. Here, we report that XBP-1S and XBP-1U enhanced ERalpha-dependent transcriptional activity in a ligand-independent manner. XBP-1S had stronger activity than XBP-1U. The maximal effects of XBP-1S and XBP-1U on ERalpha transactivation were observed when they were co-expressed with full-length ERalpha. SRC-1, the p160 steroid receptor coactivator family member, synergized with XBP-1S or XBP-1U to potentiate ERalpha activity. XBP-1S and XBP-1U bound to the ERalpha both in vitro and in vivo in a ligand-independent fashion. XBP-1S and XBP-1U interacted with the ERalpha region containing the DNA-binding domain. The ERalpha-interacting regions on XBP-1S and XBP-1U have been mapped to two regions, including the N-terminal basic region leucine zipper domain (bZIP) and the C-terminal activation domain. The bZIP-deleted mutants of XBP-1S and XBP-1U completely abolished ERalpha transactivation by XBP-1S and XBP-1U. These findings suggest that XBP-1S and XBP-1U may directly modulate ERalpha signaling in both the absence and presence of estrogen and, therefore, may play important roles in the proliferation of normal and malignant estrogen-regulated tissues.