Temperature-insensitive high-sensitivity refractive index sensor based on a thinned helical fiber grating with an intermediate period.

A temperature-insensitive high-sensitivity refractive index sensor is proposed and experimentally demonstrated, which is based on utilization of a thinned helical fiber grating but with an intermediate period (THFGIP). Attributed to the reduced diameter and an intermediate period of the grating, the proposed sensor has a high surrounding refractive-index (SRI) sensitivity and a low temperature sensitivity. The average SRI sensitivity of the proposed sensor is up to 829.9 nm/RIU in the range of 1.3410-1.4480 RIU. Moreover, unlike the traditional sensitivity-enhancement method by increasing the waveguide dispersion factor, here the waveguide dispersion factor at the resonant wavelength was decreased by reducing the diameter of the fiber grating and as a result, the crosstalk effect due to the temperature change can be further suppressed. The proposed temperature-insensitive SRI sensor has the superiorities of simple structure, ease fabrication, and low cost, which could be found more potential applications in the SRI sensing fields.

Roles of estrogen receptor α in endometrial carcinoma (Review).

Endometrial carcinoma (EC) is a group of endometrial epithelial malignancies, most of which are adenocarcinomas and occur in perimenopausal and postmenopausal women. It is one of the most common carcinomas of the female reproductive system. It has been shown that the occurrence and development of EC is closely associated with the interaction between estrogen (estradiol, E2) and estrogen receptors (ERs), particularly ERα. As a key nuclear transcription factor, ERα is a carcinogenic factor in EC. Its interactions with upstream and downstream effectors and co-regulators have important implications for the proliferation, metastasis, invasion and inhibition of apoptosis of EC. In the present review, the structure of ERα and the regulation of ERα in multiple dimensions are described. In addition, the classical E2/ERα signaling pathway and the crosstalk between ERα and other EC regulators are elucidated, as well as the therapeutic targeting of ERα, which may provide a new direction for clinical applications of ERα in the future.

Programmed release of vascular endothelial growth factor and exosome from injectable chitosan nanofibrous microsphere-based PLGA-PEG-PLGA hydrogel for enhanced bone regeneration.

The healing of large bone defects remains a significant challenge in clinical practice. Accelerating both angiogenesis and osteogenesis can promote effective bone healing. In the natural healing process, angiogenesis precedes osteogenesis, providing a blood supply that supports the subsequent progression of osteogenesis. Developing a biomimetic scaffold that mimics the in vivo environment and promotes the proper sequence of vascularization followed by ossification is crucial for successful bone regeneration. In this study, a novel injectable dual-drug programmed releasing chitosan nanofibrous microsphere-based poly(D, l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(D,l-lactide-co-glycolide) (PLGA-PEG-PLGA) hydrogel is fabricated by incorporating vascular endothelial growth factor (VEGF) and microspheres loaded with dental pulp stem cells-derived exosomes (DPSCs-Exo). Rapid release of VEGF promotes the swift initiation of angiogenesis, while DPSCs-Exo release ensures persistent osteogenesis. Our results demonstrate that chitosan microsphere-based PLGA-PEG-PLGA hydrogel significantly promotes angiogenesis in human umbilical vascular endothelial cells and enhances the osteogenic differentiation of pre-osteoblasts. Furthermore, in vivo transplantation of this injectable chitosan microsphere-based PLGA-PEG-PLGA hydrogel into calvarial bone defects markedly promotes bone formation. Overall, our study provides a promising approach for improving bone regeneration by temporally replicating the behavior of angiogenesis and osteogenesis.

The role of ubiquitination and deubiquitination in PI3K/AKT/mTOR pathway: A potential target for cancer therapy.

The PI3K/AKT/mTOR pathway controls key cellular processes, including proliferation and tumor progression, and abnormally high activation of this pathway is a hallmark in human cancers. The post-translational modification, such as Ubiquitination and deubiquitination, fine-tuning the protein level and the activity of members in this pathway play a pivotal role in maintaining normal physiological process. Emerging evidence show that the unbalanced ubiquitination/deubiquitination modification leads to human diseases via PI3K/AKT/mTOR pathway. Therefore, a comprehensive understanding of the ubiquitination/deubiquitination regulation of PI3K/AKT/mTOR pathway may be helpful to uncover the underlying mechanism and improve the potential treatment of cancer via targeting this pathway. Herein, we summarize the latest research progress of ubiquitination and deubiquitination of PI3K/AKT/mTOR pathway, systematically discuss the associated crosstalk between them, as well as focus the clinical transformation via targeting ubiquitination process.

Combined Plate and Long Screw Fixation of Transverse Condylar Head Fractures.

We describe a method of fixing transverse condylar head fractures using a combination of a plate and long screw fixation. In the technical procedure, a 4-hole mini-plate was placed on the lateral side of the condylar head and the condylar stump after the fracture reduction. The first hole was drilled in the lateral side of the condylar head, and one 9 mm mini-screw was inserted, a second hole drilled from the lateral side of the condyle stump through the medial pole of the condylar head and a 16 mm screw was inserted in an oblique direction from inferior to superior, then 2 more 9 mm mini-screws were inserted just below the long one to complete the procedure. This technique showed excellent results in both short and long-term stability of and healing of the fracture. Furthermore, it is more standardized, reproducible, and less technically demanding.

Applications of Stimuli-Responsive Hydrogels in Bone and Cartilage Regeneration.

Bone and cartilage regeneration is an area of tremendous interest and need in health care. Tissue engineering is a potential strategy for repairing and regenerating bone and cartilage defects. Hydrogels are among the most attractive biomaterials in bone and cartilage tissue engineering, mainly due to their moderate biocompatibility, hydrophilicity, and 3D network structure. Stimuli-responsive hydrogels have been a hot topic in recent decades. They can respond to external or internal stimulation and are used in the controlled delivery of drugs and tissue engineering. This review summarizes current progress in the use of stimuli-responsive hydrogels in bone and cartilage regeneration. The challenges, disadvantages, and future applications of stimuli-responsive hydrogels are briefly described.

Implementation of an interactive virtual microscope laboratory system in teaching oral histopathology.

Laboratory course acts as a key component of histopathology education. Recent trends of incorporating visual and interactive technology in active and inquiry-based learning pedagogical methods have led to significant improvement of histopathology laboratory courses. The present work aimed to describe interactive virtual microscope laboratory system (IVMLS) as a virtual platform for teaching histopathology in order to improve the quality and efficiency of teaching. The system is based on interactive technology and consists of interactive software, slide-reading software, teaching resources and integrated auxiliary equipment. It allows real-time interaction between teachers and students and provides students with a wealth of learning and review materials. In order to evaluate the effectiveness of the system, we conducted a comparative study with the use of light microscope (LM) as a method. Specifically, we compared the results of six assignments and one laboratory final exam between IVMLS group and LM group to analyse the impact of IVMLS on students' academic performance. A questionnaire survey was also conducted to obtain students' attitudes and views on this system. There was no overall difference in assignment performance between IVMLS group and LM group. But laboratory final test grades increased from a mean of 62% (43.8-80.0, 95% CI) before to 83% (71.0-94.2, 95% CI) after implement IVMLS, suggesting highly significant (p < 0.001) improvement on students' histopathology laboratory performance. Feedback of the questionnaire was positive, indicating that students were satisfied with the system, which they believed improved student communication and teacher-student interaction, increased learning resources, increased their focus on learning, and facilitated their independent thinking process. This study proves that IVMLS is an efficient and feasible teaching technology and improves students' academic performance.

Interference-free SERS nanoprobes for labeling and imaging of MT1-MMP in breast cancer cells.

The expression of membrane type-1 matrix metalloproteinase (MT1-MMP) in cancer cells is critical for understanding the development, invasion and metastasis of cancers. In this study, we devised an interference-free surface-enhanced Raman scattering (SERS) nanoprobe with high selectivity and specificity for MT1-MMP. The nanoprobe was comprised of silver core-silica shell nanoparticle with a Raman reporter tag (4-mercaptobenzonitrile) embedded in the interface. Moreover, the nitrile group in 4-mercaptobenzonitrile shows a unique characteristic peak in the Raman-silent region (1800-2800 cm-1), which eliminates spectral overlapping or background interference in the Raman fingerprint region (500-1800 cm-1). After surface modification with a targeting peptide, the nanoprobe allowed visualization and evaluation of MT1-MMP in breast cancer cells via SERS spectrometry. This interference-free, peptide-functionalized SERS nanoprobe is supposed to be conducive to early diagnosis and invasive assessment of cancer in clinical settings.

Mussel-inspired functionalization of electrospun scaffolds with polydopamine-assisted immobilization of mesenchymal stem cells-derived small extracellular vesicles for enhanced bone regeneration.

Mesenchymal stem cells-derived small extracellular vesicles (MSCs-sEV) have shown promising prospects as a cell-free strategy for bone tissue regeneration. Here, a bioactive MSCs-sEV-loaded electrospun silk fibroin/poly(ε-caprolactone) (SF/PCL) scaffold was synthesized via a mussel-inspired immobilization strategy assisted by polydopamine (pDA). This pDA modification endowed the as-prepared scaffold with high loading efficiency and sustained release profile of sEV. In addition, the fabricated composite scaffold exhibited good physiochemical, mechanical, and biocompatible properties. In vitro cellular experiments indicated that the MSCs-sEV-loaded composite scaffold promoted the adhesion and spreading of preosteoblast and endothelial cells, as well as enhanced osteogenic differentiation and angiogenic activity. In vivo experiments showed that the functionalized electrospun scaffolds promoted bone regeneration in a rat calvarial bone defect model. Results suggest that the developed MSCs-sEV-anchored pDA-modified SF/PCL electrospun scaffolds possess high application potential in bone tissue engineering owing to their powerful pro-angiogenic and -osteogenic capacities, cell-free bioactivity, and cost effectiveness.

SPOP suppresses testicular germ cell tumors progression through ubiquitination and degradation of DPPA2.

Dysregulation of the ubiquitin-proteasome pathway is strongly associated with cancer initiation and progression. Speckle-type POZ(pox virus and zinc finger protein) protein(SPOP) is an adapter protein of CUL3-based E3 ubiquitin ligase complexes. Gene expression profiling from the Cancer Genome Atlas (TCGA) suggests that SPOP is downregulated in testicular germ cell tumors (TGCTs), but the specific contribution of this protein remains to be explored. In this study, we show that the germ line-specific factor DPPA2 was identified as a proteolytic substrate for the SPOP-CUL3-RBX1 E3 ubiquitin-ligase complex. SPOP specifically binds to a SPOP-binding consensus (SBC) degron located in DPPA2 and targets DPPA2 for degradation via the ubiquitin-proteasome pathway. SPOP downregulation increases the expression of pluripotency markers OCT4 and Nanog but decreases that of early differentiation marker gene Fst. This effect is partly dependent on its activity toward DPPA2. In addition, the dysregulation of SPOP-DPPA2 axis contributes to the malignant transformation phenotypes of TGCT cells.

Note: Simultaneous measurement of in-plane and out-of-plane displacement by using orthogonally polarized self-mixing grating interferometer.

In this paper, we present an orthogonally polarized self-mixing grating interferometer (SMGI) for simultaneous measurement of in-plane and out-of-plane displacements. The measurement ranges in both directions are limited only by the length of grating. The orthogonally polarized lights emitted from a birefringent He-Ne laser are separated and enter the grating at ±1st-order Littrow angles. The diffraction beams re-enter the laser cavity and cause self-mixing interference. To differentiate the orthogonally polarized lights and obtain high resolution, phase modulation technique is introduced to extract phases from the orthogonally polarized SMGI signals. The measurement results show that the proposed system can reach a submicron accuracy in the experiment. This work provides a good way to achieve high precision two-dimensional displacement measurement with a robust system configuration.

Design of a multiple self-mixing interferometer for a fiber ring laser.

In this Letter, a novel multiple self-mixing interferometer for a fiber ring laser (FRL) is designed by introducing a circular feedback cavity. A system model is established based on an injection-seeded erbium-doped FRL proposed by Dragic. Owing to the reflection of the collimating lens, the multiplied fringes have different depths, which shows two Doppler frequencies in the spectrum of the self-mixing signal. A double-peak frequency identification algorithm is proposed to extract the Doppler frequency from the unique signal. This technique has the potential to improve the accuracy of fiber self-mixing measurement systems, particularly in Doppler velocimeters.

High-accuracy vibration sensor based on a Fabry-Perot interferometer with active phase-tracking technology.

A novel position-sensitive Fabry-Perot interferometer was constructed with direct phase modulation by a built-in electro-optic modulator. Pure sinusoidal phase modulation of the light was produced, and the first harmonic of the interference signal was extracted to dynamically maintain the interferometer phase to the most sensitive point of the interferogram. Therefore, the minute vibration of the object was coded on the variation of the interference signal and could be directly retrieved by the output voltage of a photodetector. The operating principle and the signal processing method for active feedback control of the interference phase have been demonstrated in detail. The developed vibration sensor was calibrated through a high-precision piezo-electric transducer and tested by a nano-positioning stage under a vibration magnitude of 60 nm and a frequency of 300 Hz. The active phase-tracking method of the system provides high immunity against environmental disturbances. Experimental results show that the proposed interferometer can effectively reconstruct tiny vibration waveforms with subnanometer resolution, paving the way for high-accuracy vibration sensing, especially for micro-electro-mechanical systems/nano-electro-mechanical systems and ultrasonic devices.

Demodulation of an optical fiber MEMS pressure sensor based on single bandpass microwave photonic filter.

In this paper, a demodulation method for optic fiber micro-electromechanical systems (MEMS) extrinsic Fabry-Perot interferometer (EFPI) pressure sensor exploiting microwave photonics filter technique is firstly proposed and experimentally demonstrated. A single bandpass microwave photonic filter (MPF) which mainly consists of a spectrum-sliced light source, a pressurized optical fiber MEMS EFPI, a phase modulator (PM) and a length of dispersion compensating fiber (DCF) is demonstrated. The frequency response of the filter with respect to the pressure is studied. By detecting the resonance frequency shifts of the MPF, the pressure can be determined. The theoretical and experimental results show that the proposed EFPI pressure demodulation method has a higher resolution and higher speed than traditional methods based on optical spectrum analysis. The sensitivity of the sensor is measured to be as high as 86 MHz/MPa in the range of 0-4Mpa. Moreover, the sensitivity can be easily adjusted.

High-resolution fiber Bragg grating based transverse load sensor using microwave photonics filtering technique.

In this paper, a new fiber Bragg grating (FBG) sensor exploiting microwave photonics filter technique for transverse load sensing is firstly proposed and experimentally demonstrated. A two-tap incoherent notch microwave photonics filter (MPF) based on a transverse loaded FBG, a polarization beam splitter (PBS), a tunable delay line (TDL) and a length of dispersion compensating fiber (DCF) is demonstrated. The frequency response of the filter with respect to the transverse load is studied. By detecting the resonance frequency shifts of the notch MPF, the transverse load can be determined. The theoretical and experimental results show that the proposed FBG sensor has a higher resolution than traditional methods based on optical spectrum analysis. The sensitivity of the sensor is measured to be as high as 2.5 MHz/N for a sensing fiber with a length of 18mm. Moreover, the sensitivity can be easily adjusted.

Ferrocene-functionalized SWCNT for electrochemical detection of T4 polynucleotide kinase activity.

A novel electrochemical strategy for monitoring the activity and inhibition of T4 polynucleotide kinase (PNK) is developed by use of titanium ion (Ti(4+)) mediated signal transition coupled with signal amplification of single wall carbon nanotubes (SWCNTs). In this method, a DNA containing 5'-hydroxyl group is self-assembled onto the gold electrode and used as substrate for PNK. The biofunctionalized SWCNTs with anchor DNA and ferrocene are chosen as the signal indicator by virtue of the intrinsic 5'-phosphate end of anchor DNA and the high loading of ferrocene for electrochemical signal generation and amplification. The 5'-hydroxyl group of the substrate DNA on the electrode is phosphorylated by T4 PNK in the presence of ATP, and the resulting 5'-phosphoryl end product can be linked with the signal indicator by Ti(4+). The redox ferrocene group on the SWCNTs is grafted to the electrode and generates the electrochemical signal, the intensity of which is proportional to the activity of T4 PNK. This assay can measure activity of T4 PNK down to 0.01 UmL(-1). The developed method is a potentially useful tool in researching the interactions between proteins and nucleic acids and provides a diversified platform for a kinase activity assay.

A sensitive signal-on electrochemical assay for MTase activity using AuNPs amplification.

A sensitive and simple signal-on electrochemical assay for detection of Dam methyltransferase (MTase) activity based on DNA-functionalized gold nanoparticles (AuNPs) amplification coupled with enzyme-linkage reactions is presented. This new assay takes advantage of the steric hindrance of AuNPs and the electrostatic repulsion between the negative-charge phosphate backbones of DNA modified on the AuNPs and redox probe [Fe(CN)(6)](3-/4-). In this method, the self-assembled ssDNA on the electrode is hybridized with its complement ssDNA modified on AuNPs to form dsDNA AuNPs bioconjugates containing specific recognition sequence of Dam MTase and methylation-sensitive restriction endonuclease Dpn I. Then, the AuNPs approach to the electrode and result in blockage of electronic transmission. It is eT OFF state. In the presence of Dam MTase and Dpn I, the specific sequence is methylated and cleavaged, which in turn release the DNA modified AuNPs from the electrode surface allowing free exchange of electrons. It generates a measurable electrochemical signal (eT ON). Differential pulse voltammetry (DPV) is employed to detect the recover current, which is related to the concentration of the Dam MTase. This method is simple, sensitive, nonradioactive and without use of gel-electrophoresis, PCR or chromatographic separation. Under optimized conditions, a linear response to concentration of Dam MTase range from 0.2U/mL to 10 U/mL and a detection limit of 0.12 U/mL are obtained. Furthermore, our new assay is a promising method to detect Dam MTase in the Luria-Bertani (LB) medium, as well as to screen inhibitors or drugs for Dam MTase.

Electrochemical detection of thrombin based on aptamer and ferrocenylhexanethiol loaded silica nanocapsules.

A sensitive and specific electrochemical assay for detection of thrombin based on aptamer and ferrocenylhexanethiol loaded silica nanocapsules (FcSH/SiNCs) amplification is described. In the protocol, a double aptamer sandwich structure was formed in the presence of thrombin, in which an aptamer-labeled FcSH/SiNCs for electrochemical detection, and a streptavidin-coated magnetic bead immobilized aptamer for rapid and specific separation of target protein. After separated from the sample mixture under a magnetic field, the sandwich complex was treated with NaOH to release the loaded ferrocenylhexanethiol (FcSH) from the silica nanocapsules (SiNCs). Differential pulse voltammetry (DPV) was employed to detect the released FcSH, which was related to the concentration of the thrombin. The method took advantage of sandwich binding of two affinity aptamers for increased specificity, high payload of FcSH in SiNCs for signal amplification, magnetic beads for fast magnetic separation. The peak current of released FcSH had a good linear relationship with the thrombin concentration in the range of 0.1-5 nmol/L, and the detection limit of thrombin in the method was 0.06 nmol/L. The detection was also specific for thrombin without being affected by other proteins, such as immunoglobulin G, bovine serum albumin, lysozyme and human serum albumin. The method has been used to detect thrombin in human serum albumin with minimum background interference.

Electrochemical detection of nicotinamide adenine dinucleotide based on molecular beacon-like DNA and E. coli DNA ligase.

An electrochemical method for nicotinamide adenine dinucleotide (NAD(+)) detection with high sensitivity and selectivity has been developed by using molecular beacon (MB)-like DNA and Escherichia coli DNA ligase. In this method, MB-like DNA labeled with 5'-SH and 3'-biotin was self-assembled onto a gold electrode in its duplex form by means of facile gold-thiol chemistry, which resulted in blockage of electronic transmission. It was eT OFF state. In the presence of NAD(+), E. coli DNA ligase was activated, and the two nucleotide fragments which were complementary to the loop of the MB-like DNA could be ligated by the NAD(+)-dependent E. coli DNA ligase. Hybridization of the ligated DNA with the MB-like DNA induced a large conformational change in this surface-confined DNA structure, which in turn pushed the biotin away from the electrode surface and made the electrons exchange freely with the electrode. Then the generated electrochemical signals can be measured by differential pulse voltammetry (DPV). Under optimized conditions, a linear response to logarithmic concentration of NAD(+) range from 3 nM to 5 µM and a detection limit of 1.8 nM were obtained. Furthermore, the proposed strategy had sufficient selectivity to discriminate NAD(+) from its analogues.

A sensitive ligase-based ATP electrochemical assay using molecular beacon-like DNA.

A sensitive and selective ligase-based signal-on electrochemical sensing method for adenosine-5'-triphosphate (ATP) detection had been developed using molecular beacon (MB)-like DNA. In this method, the biotin-tagged MB-like DNA was self-assembled onto a gold electrode to form a stem-loop structure by means of facile gold-thiol chemistry, which resulted in blockage of electronic transmission. It was eT OFF state. In the presence of ATP, two nucleotide fragments which were complementary to the loop of the MB-like DNA could be ligated by the ATP-dependent T4 DNA ligase. Hybridization of the ligated DNA with the MB-like DNA induced a significant conformational change in this surface-confined DNA structure, which in turn released the biotin from the surface allowing free exchange of electrons with the electrode generating a measurable electrochemical signal (eT ON). The resulting change in electron transfer efficiency was readily measured by differential pulse voltammetry at target ATP concentrations as low as 0.05 nM and with linear response range from 0.1 to 1000 nM. Moreover, it was also able to discriminate ATP from its analogues. The proposed method had been successfully applied to the determination of ATP in the Escherichia coli O157:H7 extracts of water samples, and the linear response was found between the concentrations of 10(3) and 10(7) cfu/mL.