Injectable, self-healing hyaluronic acid-based hydrogels for spinal cord injury repair.

The cystic cavity that develops following spinal cord injury is a major obstacle for repairing spinal cord injury (SCI). The injectable self-healing biomaterials treatment is a promising strategy to enhance tissue repair after traumatic spinal cord injury. Herein, a natural extracellular matrix (ECM) biopolymer hyaluronic acid-based hydrogel was developed based on multiple dynamic covalent bonds. The hydrogels exhibited excellent injectable and self-healing properties, could be effectively injected into the injury site, and filled the lesion cavity to accelerate the tissue repair of traumatic SCI. Moreover, the hydrogels were compatible with cells and various tissues and possessed proper stiffness matched with nervous tissue. Additionally, when implanted into the injured spinal cord site, the hyaluronic acid-based hydrogel promoted axonal regeneration and functional recovery by accelerating remyelination, axon regeneration, and angiogenesis. Overall, the injectable self-healing hyaluronic acid-based hydrogels are ideal biomaterials for treating traumatic SCI.

Ppb-level NH3 photoacoustic sensor combining a hammer-shaped tuning fork and a 9.55 µm quantum cascade laser.

We present a quartz enhanced photoacoustic spectroscopy (QEPAS) gas sensor designed for precise monitoring of ammonia (NH3) at ppb-level concentrations. The sensor is based on a novel custom quartz tuning fork (QTF) with a mid-infrared quantum cascade laser emitting at 9.55 µm. The custom QTF with a hammer-shaped prong geometry which is also modified by surface grooves is designed as the acoustic transducer, providing a low resonance frequency of 9.5 kHz and a high-quality factor of 10263 at atmospheric pressure. In addition, a temperature of 50 °C and a large gas flow rate of 260 standard cubic centimeters per minute (sccm) are applied to mitigate the adsorption and desorption effect arising from the polarized molecular of NH3. With 80-mW optical power and 300-ms lock-in integration time, the detection limit is achieved to be 2.2 ppb which is the best value reported in the literature so far for NH3 QEPAS sensors, corresponding to a normalized noise equivalent absorption coefficient of 1.4 × 10-8 W cm-1 Hz-1/2. A five-day continuous monitoring for atmospheric NH3 is performed, verifying the stability and robustness of the presented QEPAS-based NH3 sensor.

Circulating MicroRNAs as Potential Biomarkers for Ischemic Stroke in Patients with Asymptomatic Intracranial Artery Stenosis.

Circulating microRNAs have been shown to be biomarkers of various diseases. We aimed to investigate whether circulating microRNA can serve as a biomarker to predict ischemic stroke risk in asymptomatic intracranial artery stenosis. A total of 716 participants from the Asymptomatic Polyvascular Abnormalities Community study who had asymptomatic intracranial artery stenosis at baseline were enrolled (2010-11). Patients who suffered incident ischemic stroke were classified into the case group, and age- and sex-matched individuals without stroke were used as controls. MicroRNA microarrays were used to distinguish baseline circulating serum microRNA levels between the case and the control groups (GEO accession number GSE201860). The differentially expressed microRNAs were validated by real-time PCR. MicroRNA microarrays were performed in baseline serum samples from12 subjects who developed ischemic stroke and 12 age- and sex-matched subjects without stroke during the 2014-15 follow-up period. Twenty microRNAs were differentially expressed between the two groups (fold change > 1.3 and p < 0.05 for all). Hsa-miR-486-5p, hsa-miR-92a-3p, hsa-miR-6089 from them were selected and validated in the baseline serum samples of ten subjects with incident ischemic stroke and another ten age- and sex-matched subjects without stroke during the 2016-17 follow-up period. Hsa-miR-1225-5p, with a large fold change value and a reported relationship with cardiovascular or cerebrovascular diseases, was also validated. Ultimately, only hsa-miR-6089 was differentially downregulated among patients with intracranial artery stenosis who developed ischemic stroke (p < 0.05). In patients with asymptomatic intracranial artery stenosis, downregulated serum hsa-miR-6089 may be associated with the risk of ischemic stroke.

Injectable and fast gelling hyaluronate hydrogels with rapid self-healing ability for spinal cord injury repair.

Self-healing natural hydrogels still suffer from some issues such as unfit stiffness, poor healing efficiency, and lack of biocompatibility and hydrolytic stability, although they have been used to treat spinal cord injury (SCI). Herein, we develop the injectable, self-healing hyaluronate hydrogels based on multiple dynamic covalent bonds. The hydrogels exhibit fast gelation and excellent self-healing capability as well as injectability, favoring in situ formation for the hydrogels in target sites and maintaining their structural stability. Furthermore, the hydrogels are compatible with neural stem cells and various tissues and possess proper stiffness similar to nervous tissue. Interestingly, the hydrogel can induce neural differentiation of neural stem cells. In vivo experiment further illustrates that the hydrogels promote angiogenesis and remyelination as well as neuron regeneration, leading to the significant locomotor recovery of the SCI model rats. This injectable self-healing hyaluronic acid-based hydrogel is a potential candidate for nerve repair.

Self-Healing Hyaluronic Acid Nanocomposite Hydrogels with Platelet-Rich Plasma Impregnated for Skin Regeneration.

The development of natural hydrogels with sufficient strength and self-healing capacity to accelerate skin wound healing is still challenging. Herein, a hyaluronic acid nanocomposite hydrogel was developed based on aldehyde-modified sodium hyaluronate (AHA), hydrazide-modified sodium hyaluronate (ADA), and aldehyde-modified cellulose nanocrystals (oxi-CNC). This hydrogel was formed in situ using dynamic acylhydrazone bonds via a double-barreled syringe. This hydrogel exhibited improved strength and excellent self-healing ability. Furthermore, platelet-rich plasma (PRP) can be loaded in the hyaluronic acid nanocomposite hydrogels (ADAC) via imine bonds formed between amino groups on PRP (e.g., fibrinogen) and aldehyde groups on AHA or oxi-CNC to promote skin wound healing synergistically. As expected, ADAC hydrogel could protect and release PRP sustainably. In animal experiments, ADAC@PRP hydrogel significantly promoted full-thickness skin wound healing through enhancing the formation of granulation tissue, facilitating collagen deposition, and accelerating re-epithelialization and neovascularization. This self-healing nanocomposite hydrogel with PRP loading appears to be a promising candidate for wound therapy.

Quartz-enhanced photoacoustic NH3 sensor exploiting a large-prong-spacing quartz tuning fork and an optical fiber amplifier for biomedical applications.

A sensor system for exhaled ammonia (NH3) monitoring exploiting quartz-enhanced photoacoustic spectroscopy (QEPAS) was demonstrated. An erbium-doped fiber amplifier (EDFA) with an operating frequency band targeting an NH3 absorption line falling at 1531.68 nm and capable to emit up to 3 W of optical power was employed. A custom T-shaped grooved QTF with prong spacing of 1 mm was designed and realized to allow a proper focusing of the high-power optical beam exiting the EDFA between the prongs. The performance of the realized sensor system was optimized in terms of spectrophone parameters, laser power and modulation current, resulting in a NH3 minimum detectable concentration of 14 ppb at 1 s averaging time, corresponding to a normalized noise equivalent absorption coefficient (NNEA) of 8.15 × 10-9 cm-1 W/√Hz. Continuous measurements of the NH3 level exhaled by 3 healthy volunteers was carried out to demonstrate the potentiality of the developed sensor for breath analysis applications.

Compact quartz-enhanced photoacoustic sensor for ppb-level ambient NO2 detection by use of a high-power laser diode and a grooved tuning fork.

A compact quartz-enhanced photoacoustic sensor for ppb-level ambient NO2 detection is demonstrated, in which a high-power blue laser diode module with a small divergence angle was employed to take advantages of the directly proportional relationship between sensitivity and power, hence improving the detection sensitivity. In order to extend the stability time, a custom grooved quartz tuning fork with 800-µm prong spacing is employed to avoid complex signal balance and/or optical spatial filter components. The sensor performance is optimized and assessed in terms of optical coupling, power, gas flow rate, pressure, signal linearity and stability. A minimum detectable concentration (1σ) of 7.3 ppb with an averaging time of 1 s is achieved, which can be further improved to be 0.31 ppb with an averaging time of 590 s. Continuous measurements covering a five-day period are performed to demonstrate the stability and robustness of the reported NO2 sensor system.

MiR-330-5p inhibits intervertebral disk degeneration via targeting CILP.

BACKGROUND: Intervertebral disk degeneration (IDD) is caused by nucleus pulposus (NP) degeneration and extracellular matrix (ECM) remodeling and cartilage intermediate layer protein (CILP) expression has been confirmed to be increased in IDD. This study is mainly conducted to clarify the mechanism of CILP in the NP cell degeneration and ECM remodeling in IDD. METHODS: CILP expression in the degenerated NP tissues and cells is quantified by quantitative real-time PCR and western blot. CILP function is assessed by cell cycle assay, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry, ß-galactosidase staining, and the detection of ECM-related molecules aggrecan, collagen type I, collagen type II, MMP-3, and MMP-9 expression is accomplished by qRT-PCR. The potential mechanism is authenticated by dual-luciferase reporter gene assay. RESULTS: CILP was increased in the degenerated NP tissues and cells, and the knockdown of CILP promoted the NP cell cycle, increased cell activity, and repressed cell apoptosis and repressed cell senescence and ECM production. Moreover, miR-330-5p targeted the CILP 3'-untranslated region, and miR-330-5p negatively regulated CILP expression. Moreover, the overexpression of miR-330-5p repressed NP cell degeneration and ECM remodeling to relieve IDD by downregulating CILP. CONCLUSION: MiR-330-5p represses NP cell degeneration and ECM remodeling to ameliorate IDD by downregulating CILP.

Self-healing hyaluronic acid hydrogels based on dynamic Schiff base linkages as biomaterials.

Natural hydrogels are widely investigated for biomedical applications because of their structures similar to extracellular matrix of native tissues, possessing excellent biocompatibility and biodegradability. However, they are often susceptible to mechanical disruption. In this study, self-healing hyaluronic acid (HA) hydrogels are fabricated through a facile dynamic covalent Schiff base reaction. Dialdehyde-modified HA (AHA) precursor was synthesized, and then the AHA/cystamine dihydrochloride (AHA/Cys) hydrogels were formed by blending AHA and Cys at acidic pH levels. By varying Cys to AHA ratio, the hydrogel morphology, swelling and kinetics of gelation could be controlled. Gelation occurred fast, which was predominantly attributed to Schiff base reaction between the dialdehyde groups on AHA and amimo groups on Cys. The hydrogel exhibited improved mechanical properties with increase in Cys content. Furthermore, due to dynamic imine bonds, this hydrogel demonstrated excellent self-healing ability based on the stress after mechanical disruption. Also, it was found to be pH-responsive and injectable. Taken together, this kind of hyaluronic acid hydrogel can provide promising future for various biomedical applications in drug delivery, bioprinting, smart robots and tissue regeneration.

Mid-Infrared Quartz-Enhanced Photoacoustic Sensor for ppb-Level CO Detection in a SF6 Gas Matrix Exploiting a T-Grooved Quartz Tuning Fork.

An optical sensor for highly sensitive detection of carbon monoxide (CO) in sulfur hexafluoride (SF6) was demonstrated by using the quartz-enhanced photoacoustic spectroscopy technique. A spectrophone composed of a custom 8 kHz T-shaped quartz tuning fork with grooved prongs and a pair of resonator tubes, to amplify the laser-induced acoustic waves, was designed aiming to maximize the CO photoacoustic response in SF6. A theoretical analysis and an experimental investigation of the influence of SF6 gas matrix on spectrophone resonance properties for CO detection have been provided, and the performances were compared with the standard air matrix. A mid-infrared quantum cascade laser with a central wavelength at 4.61 µm, resonant with the fundamental band of CO, and an optical power of 20 mW was employed as the light excitation source. A minimum detection limit of 10 ppb at 10 s of integration time was achieved, and a sensor response time of ∼3 min was measured.

Chronic restraint stress increases social interaction in C57BL/6J mice monitoring through MiceProfiler analysis.

The social deficit is a prevailing symptom in stress-induced depression. Although social interaction behavior has been widely studied in humans and rodents, it is imprecise to record the social behavior between two free-moving mice via perusal. In the present study, we applied an approach to analyze the social behavior in mice using a software named "MiceProfiler." C57BL/6J mice were stressed via chronic restraint stress (CRS) and housed in three populations of different sizes as follows: single, three in a cage, and six in a cage. The MiceProfiler was used to analyze the video of behavioral repertoire and, the result showed that stressed and single housed mice exhibited more social interaction both in the contact time and contact activities. Furthermore, we investigated the effect of CRS on social behavior when the mice were housed in larger populations size (three or six in a cage) and found that, the CRS procedure promoted social interaction. However, the larger population size resulted in the less total contact time, less time of head-tail, and moving in an opposite way. Besides, the CRS mice showed less social avoidance while the mice from a larger population presented less active contact. And the CRS mice also exhibited a higher social hierarchy compared with the control. Our data indicated that mild restraint stress might increase the intercommunication between mice. Collectively, our findings provided a new evidence for social behavior study and the MiceProfiler could be a new tool to measure the social behaviors of rodents.

Dopamine-Modified Hyaluronic Acid Hydrogel Adhesives with Fast-Forming and High Tissue Adhesion.

Commercial or clinical tissue adhesives are currently limited due to their weak bonding strength on wet biological tissue surface, low biological compatibility, and slow adhesion formation. Although catechol-modified hyaluronic acid (HA) adhesives are developed, they suffer from limitations: insufficient adhesiveness and overfast degradation, attributed to low substitution of catechol groups. In this study, we demonstrate a simple and efficient strategy to prepare mussel-inspired HA hydrogel adhesives with improved degree of substitution of catechol groups. Because of the significantly increased grafting ratio of catechol groups, dopamine-conjugated dialdehyde-HA (DAHA) hydrogels exhibit excellent tissue adhesion performance (i.e., adhesive strength of 90.0 ± 6.7 kPa), which are significantly higher than those found in dopamine-conjugated HA hydrogels (∼10 kPa), photo-cross-linkable HA hydrogels (∼13 kPa), or commercially available fibrin glues (2-40 kPa). At the same time, their maximum adhesion energy is 384.6 ± 26.0 J m-2, which also is 40-400-fold, 2-40-fold, and ∼8-fold higher than those of the mussel-based adhesive, cyanoacrylate, and fibrin glues, respectively. Moreover, the hydrogels can gel rapidly within 60 s and have a tunable degradation suitable for tissue regeneration. Together with their cytocompatibility and good cell adhesion, they are promising materials as new biological adhesives.

Piezo-enhanced acoustic detection module for mid-infrared trace gas sensing using a grooved quartz tuning fork.

A grooved quartz tuning fork (QTF) with a prong spacing of 800 µm for QEPAS application is reported. The prongs spacing is large enough to facilitate optical alignments when a degraded laser beam is used for QEPAS-based trace gas sensors. The grooved QTF has a resonance frequency of 15.2 kHz at atmospheric pressure and is characterized by four rectangular grooves carved on the QTF prong surfaces. With a grooved-prong, the electrical resistance R of the QTF is reduced resulting in an enhanced piezoelectric signal, while the Q factor is not affected, remaining as high as 15000 at atmospheric pressure. The geometric parameters of the acoustic micro resonators (AmRs) for on-beam QEPAS were optimized to match the grooved QTF, and a signal-to-noise gain factor of ∼ 30 was obtained with an optimum configuration. The performance of the QEPAS-based sensor was demonstrated exploiting an interband cascade laser (ICL) for CH4 detection and a 1σ normalized noise equivalent absorption (NNEA) coefficient of 4.1×10-9 cm-1 W/√Hz was obtained at atmospheric pressure.

Ppb-Level Quartz-Enhanced Photoacoustic Detection of Carbon Monoxide Exploiting a Surface Grooved Tuning Fork.

A compact and sensitive carbon monoxide (CO) sensor was demonstrated by using quartz enhanced photoacoustic spectroscopy (QEPAS) exploiting a novel 15.2 kHz quartz tuning fork (QTF) with grooved surfaces. The custom QTF was designed to provide a quality factor as high as 15 000 at atmospheric pressure, which offers a high detection sensitivity. A large QTF prong spacing of 800 µm was selected, allowing one to avoid the use of any spatial filters when employing a quantum cascade laser as the excitation source. Four rectangular grooves were carved on two prong surfaces of the QTF to decrease the electrical resistance and hence enhance the signal amplitude. With water vapor as the catalyst for vibrational energy transfer, the sensor system using the novel surface grooved QTF achieved a CO minimum detection limit of 7 ppb for a 300 ms averaging time, which corresponds to a normalized noise equivalent absorption coefficient of 8.74 × 10-9 cm-1W /√Hz. Continuous measurements covering a seven-day period for atmospheric CO were implemented to verify the reliability and validity of the developed CO sensor system.

Simultaneous multi-gas detection between 3 and 4µm based on a 2.5-m multipass cell and a tunable Fabry-Pérot filter detector.

We demonstrated a versatile and innovative gas sensing system based on a Fabry-Pérot (FP) filter detector, which operates in the spectral range from 3.1 to 4.4µm (3226-2273cm-1) with a spectral resolution of 20nm. The developed sensor system can be used to record the entire spectrum by means of a one-time scan or, alternatively, to access selected spectral regions by using the tunable FP filter detector. A multipass cell with an effective path length of 2.5m was implemented to improve the detection sensitivity. The spectra of methane, formaldehyde and carbon dioxide were simultaneously measured, with detection limits of 200ppm, 900ppm and 20ppm, respectively. A seven-day continuous measurement for indoor carbon dioxide gas was carried out demonstrating the stability and robustness of the reported sensor system.

Calculation model of dense spot pattern multi-pass cells based on a spherical mirror aberration.

We report a novel calculation model for dense spot pattern multi-pass cells consisting of two common identical spherical mirrors. A modified ABCD matrix without the paraxial approximation was developed to describe the ray propagation between two spherical mirrors and the reflection on the mirror surfaces. The intrinsic aberration from the spherical curvature creates a set of intricate variants with respect to a standard Herriot circle spot pattern. A series of detailed numerical simulations are implemented to verify that the input and output beams remain the same and, hence, retrace the same ray pattern. The set of exotic spot patterns obtained with a high fill factor improves the utilization efficiency of the mirror surfaces and produces a longer total optical path length with a low mirror cost.

Socioeconomic and lifestyle factors associated with HPV infection in pregnant women: a matched case-control study in Beijing, China.

BACKGROUND: Human papillomavirus (HPV) infection plays key role in the development of cervical cancer. The purpose of this study was to investigate socioeconomic and lifestyle factors associated with HPV infection in pregnant women in Beijing, China. METHODS: An age matched case-control study designed with 66 women as the case group (HPV positive) and 132 women as the control group (HPV negative) was carried out in two hospitals in Beijing. Socioeconomic and lifestyle factors were obtained using a standard questionnaire. Cervical cells from study subjects were collected for HPV detection. An unconditional logistic regression model with backward stepwise selection was performed to predict the odds ratio (OR) and 95% confidence interval (CI) for the significant factors associated with HPV infection. RESULTS: The analyses of present data show that alcohol consumption during pregnancy was the strongest significant factor (OR = 3.35, 95% CI = 1.40-8.03, p = 0.007) when comparing the case (HPV positive) group with the control (HPV negative) group. There were no statistical differences observed in any of the socioeconomic factors when comparing the case and control groups. CONCLUSION: The results of this study may help to prevent HPV infection in China by providing evidence to support improving the national policy on alcohol restriction and introducing public health interventions, especially for pregnant women in Beijing.

Highly sensitive and selective CO sensor using a 2.33 µm diode laser and wavelength modulation spectroscopy.

A ppm-level CO sensor based on a 2f wavelength modulation spectroscopy (2f-WMS) technique was developed for the application of SF6 decomposition analysis in an electric power system. A detailed investigation of the optimum target line selection was carried out to avoid spectral interference from high purity SF6 in a wide wavelength range. A diode laser emitting at 2.33 µm and a 14.5-m multipass gas cell (MGC) was employed to target the R(6) line of the CO first overtone band and increase the optical path, respectively, thus resulting in a minimum detection sensitivity of 1 ppm. A Levenberg-Marquardt nonlinear least-squares fit algorithm makes full use of the information from all data points of the 2f spectrum and as a result, a measurement precision of ~40 ppb was achieved with a data update rate of 0.6 s. The sensor performance was also evaluated in terms of the gas flow rate, stability, and linearity. The results showed that the best operating condition with a precision of 6 ppb can be achieved by increasing the gas flow rate to the value that matches the optimum averaging time of 48 s.

Biological Silicon Stimulates Collagen Type 1 and Osteocalcin Synthesis in Human Osteoblast-Like Cells Through the BMP-2/Smad/RUNX2 Signaling Pathway.

Silicon is essential for bone formation. A low-silicon diet leads to bone defects, and numerous animal models have demonstrated that silicon supplementation increases bone mineral density (BMD) and reduces bone fragility. However, the exact mechanism of this action has not been characterized. In this study, we aimed to determine the role of biological silicon in the induction of osteoblast differentiation and the possible underlying mechanism. We examined whether orthosilicic acid promotes collagen type 1 (COL-1) and osteocalcin synthesis through the bone morphogenetic protein-2 (BMP-2)/Smad1/5/runt-related transcription factor 2 (RUNX2) signaling pathway by investigating its effect in vitro at several concentrations on COL-1 and osteocalcin synthesis in human osteosarcoma cell lines (MG-63 and U2-OS). The expression of relevant proteins was detected by Western blotting following exposure to noggin, an inhibitor of BMP-2. In MG-63 cells, immunofluorescence methods were applied to detect changes in the expression of BMP-2, phosphorylated Smad1/5 (P-Smad1/5), and RUNX2. Furthermore, rat bone mesenchymal stem cells (BMSCs) were used to determine the effect of orthosilicic acid on osteogenic differentiation. Exposure to 10 µM orthosilicic acid markedly increased the expression of BMP-2, P-Smad1/5, RUNX2, COL-1, and osteocalcin in osteosarcoma cell lines. Enhanced ALP activity and the formation of mineralized nodules were also observed under these conditions. Furthermore, preconditioning with noggin inhibited the silicon-induced upregulation of P-Smad1/5, RUNX2, and COL-1 expression. In conclusion, the BMP-2/Smad1/5/RUNX2 signaling pathway participates in the silicon-mediated induction of COL-1 and osteocalcin synthesis, and orthosilicic acid promotes the osteogenic differentiation of rat BMSCs.

Striatal extracts promote the dopaminergic differentiation of GFP-bone mesenchymal stem cells.

Bone mesenchymal stem cells (BMSCs) are an attractive donor graft source because of the potential of self-renewal and multi-direction differentiation. However, it is a great challenge to induce BMSCs to specifically differentiate to dopamine (DA) neurons for the treatment of Parkinson's disease. Because the striatum is the target tissue for the projection of DA neurons in the midbrain, we investigated whether its extracts could promote the dopaminergic differentiation of BMSCs. BMSCs were isolated from green fluorescent protein (GFP) transgenic mice. Flow cytometry was used to identify the expression of CD29 and CD11b in cultured BMSCs; and immunochemical staining was employed to determine the differentiation of BMSCs. Our results showed that striatal extracts could induce differentiation of BMSCs into both neurons and glia, especially the DA neurons. When transplanted to the rat striatum, GFP-BMSCs could differentiate into tyrosine hydroxylase positive neurons and demonstrate potential migration in the brain. Taking together, our results suggest that striatal extracts can specifically promote the dopaminergic differentiation of GFP-BMSCs, thereby providing a feasible strategy for the treatment of Parkinson's disease.