An Injectable Hydrogel Composing Anti-Inflammatory and Osteogenic Therapy toward Bone Erosions Microenvironment Remodeling in Rheumatoid Arthritis.

Healing bone erosions in rheumatoid arthritis (RA) remains greatly challenging via biomaterial strategies. Given the unsuccessful innate bone erosion healing due to an inflammatory disorder, over-activated osteoclasts, and impaired osteoblasts differentiation, RA pathogenesis-guided engineering of an innovative hydrogel platform is needed for remodeling osteoimmune and osteogenic microenvironment of bone erosion healing. Herein, in situ adaptable and injectable interpenetrating polymer network (IPN) hydrogel is developed through an ingenious combination of a bio-orthogonal reaction between hyaluronic acid (HA) and collagen, along with effective electrostatic interactions leveraging bisphosphonate (BP)-functionalized HA macromers (HABP) and nanorod shaped zinc (Zn)-doped biphasic calcium phosphate (ZnBCP). IPN hydrogel exhibits exceptional adaptability to the local shape complexity at bone erosions, and by integrating ZnBCP and HABP, a multi-stage releasing platform is engineered, facilitating controlled cargo delivery for remodeling more anti-inflammatory M2 cells and reducing over-activated osteoclastic activities, thereby reconstructing the bone regeneration microenvironment. Sustainedly co-delivering multiple ions (calcium and phosphate) can display excellent osteogenic properties and be conducive to the bone formation process, by effects of osteogenesis-associated cell differentiation. Overall, the introduced bioactive IPN hydrogel therapy remodels the osteoimmune environment by synergistic pro-inflammation-resolving, osteogenesis, and anti-osteoclastic activities, displaying excellent bone reconstruction in the collagen-induced arthritis rabbit model.

An acoustic method (Spectral Flux) to analyze ECG signals for optimizing timing for defibrillation in a porcine model of ventricular fibrillation.

Aim: Spectral Flux (SF), which is based on common algorithms in the audio processing field, was applied to quantitatively analyze ECG signals to optimize the timing of defibrillation. With the aim of proving the performance in optimizing the timing of defibrillation, SF was compared with Amplitude Spectrum Area (AMSA) in a porcine model of ventricular fibrillation (VF) in a retrospective analysis experiment. Methods: A total of 56 male domestic pigs, weighing 40 ± 5 kg, were induced to undergo VF. Animals were then left untreated for 10 min, and after 6 min of cardiopulmonary resuscitation (CPR) defibrillation was performed. The respective SF and AMSA values were calculated every minute during VF and CPR. Comparisons were made through receiver operating characteristic (ROC) curves, one-way analyses of variance (one-way ANOVA), and scatterplots for the successful initial defibrillation sample (positive samples, Group R) and the failed initial defibrillation sample (negative samples, Group N) to illustrate the performance in optimizing the timing of defibrillation for the AMSA and SF methods. Result: Values of SF and AMSA gradually decreased during the 10 min VF period and increased in during the 6 min CPR period. The scatterplots showed that both metrics had the ability to distinguish positive and negative samples (p < .001). Meanwhile, ROC curves showed that SF (area under the curve, AUC = 0.798, p < .001) had the same ability as AMSA (AUC = 0.737, p < .001) to predict the successful defibrillation (Z = 1.35, p = 0.177). Moreover, when comparing the values for AMSA and SF between the successful initial defibrillation samples (Group R) and the failed initial defibrillation samples (Group N), the results showed that the values of both AMSA and SF in Group R were significantly higher than those in Group N (p < .001). Conclusion: In the present study, SF method had the same ability as AMSA to predict successful defibrillation with significantly higher values in cases of successful defibrillation than the instances in which defibrillation failed. Additionally, SF method might be more stable than AMSA for filtering out the higher frequency interference signals due to the narrower frequency range and had higher specificity and predictive accuracy than AMSA. So SF method had high clinical potential to optimize the timing of defibrillation. Nevertheless, further animal and clinical studies are still needed to confirm the effectiveness and practicality of SF as a predictive module for defibrillators in clinical practice.

Interpenetrating Polymer Network HA/Alg-RGD Hydrogel: An Equilibrium of Macroscopic Stability and Microscopic Adaptability for 3D Cell Growth and Vascularization.

Two-dimensional (2D) cell culture methods dominate the current research. However, the inherent responsiveness of cells to their native three-dimensional (3D) microenvironment necessitates a paradigm shift toward the development of advanced hydrogels that faithfully mimic the intricacies of the extracellular matrix (ECM) and enable continuous cell-ECM interactions. To address the constraints of traditional static hydrogel networks that impede effective cell-matrix and cell-cell interactions, and to tackle the inherent stability issues associated with dynamically cross-linked hydrogels, which have become a pressing concern. Herein, we present an interpenetrating polymer network (IPN) hydrogel (HA/Alg-RGD hydrogel) that combines a physically cross-linked network between alginate and calcium ions (Alg-Ca2+) for the enhanced cell growth adaptability with a chemically cross-linked hyaluronic acid (HA) network to ensure macroscopic stability during cell culture. The incorporation of arginine-glycine-aspartic peptide modified alginate (Alg-RGD) further facilitates cell adhesion and improves the cell-hydrogel interaction. Notably, this IPN hydrogel demonstrates mechanical stability and enables cell spreading and growth within its structural framework. Leveraging the reversible characteristics of the ionically cross-linked Alg-Ca2+ network within IPN hydrogels, we demonstrate the feasibility of the gelatin sacrificial solution for 3D printing purposes within the hydrogel matrix. Subsequent UV-induced covalent cross-linking enables the fabrication of vascularized microfluidic channels within the resulting construct. Our results demonstrate endothelial cell spreading and spontaneous cell sprouting within the hydrogel matrix, thus highlighting the efficacy of this IPN hydrogel system in facilitating 3D cell growth. Additionally, our study emphasizes the potential of 3D printed constructs as a promising approach for vascularization in tissue engineering. The importance of RGD peptides in promoting favorable cell-hydrogel scaffold interactions is also highlighted, emphasizing their critical role in optimizing biomaterial-cell interfaces.

MMP-Responsive Nanoparticle-Loaded, Injectable, Adhesive, Self-Healing Hydrogel Wound Dressing Based on Dynamic Covalent Bonds.

Developing a multifunctional hydrogel wound dressing with good injectability, self-healing, tissue adhesion, biocompatibility, and fast skin wound healing efficiency remains challenging. In this work, an injectable adhesive dopamine-functionalized oxidized hyaluronic acid/carboxymethyl chitosan/collagen (AHADA/CCS/Col) hydrogel was constructed. The Schiff dynamic bond between AHADA and CCS, the N-Ag-N bond between CCS and Ag ions, and the S-Ag-S dynamic bond between sulfhydryl-modified collagen (ColSH) and Ag ions allowed the hydrogel to be both injectable and self-healing. Moreover, the aldehyde groups and catechol groups presented in the hydrogel could generate force with several groups on the tissue interface; therefore, the hydrogel also had good tissue adhesion. In vitro experiments proved that this hydrogel exhibited good biocompatibility and could promote cell proliferation. Additionally, curcumin (Cur)-loaded gelatin nanoparticles (Cur@Gel NPs) were prepared, which could respond to matrix metalloproteinases (MMPs) and controllably release Cur to hasten wound healing efficiency. Animal experiment results showed that this AHADA/CCS/Col hydrogel loaded with Cur@Gel NPs promoted wound repairing better, indicating its potential as a wound dressing.

Mussel bioinspired, silver-coated and insulin-loaded mesoporous polydopamine nanoparticles reinforced hyaluronate-based fibrous hydrogel for potential diabetic wound healing.

Diabetes wounds take longer to heal due to extended inflammation, decreased angiogenesis, bacterial infection, and oxidative stress. These factors underscore the need for biocompatible and multifunctional dressings with appropriate physicochemical and swelling properties to accelerate wound healing. Herein, insulin (Ins)-loaded, and silver (Ag) coated mesoporous polydopamine (mPD) nanoparticles were synthesized (Ag@Ins-mPD). The nanoparticles were dispersed into polycaprolactone/methacrylated hyaluronate aldehyde dispersion, electrospun to form nanofibers, and then photochemically crosslinked to form a fibrous hydrogel. The nanoparticle, fibrous hydrogel, and nanoparticle-reinforced fibrous hydrogel were characterized for their morphological, mechanical, physicochemical, swelling, drug-release, antibacterial, antioxidant, and cytocompatibility properties. The diabetic wound reconstruction potential of nanoparticle-reinforced fibrous hydrogel was studied using BALB/c mice. The results indicated that Ins-mPD acted as a reductant to synthesize Ag nanoparticles on their surface, held antibacterial and antioxidant potential, and their mesoporous properties are crucial for insulin loading and sustained release. The nanoparticle-reinforced scaffolds were uniform in architecture, porous, mechanically stable, showed good swelling, and possessed superior antibacterial, and cell-responsive properties. Furthermore, the designed fibrous hydrogel scaffold demonstrated good angiogenic, anti-inflammatory, increased collagen deposition, and faster wound repair capabilities, therefore, it could be used as a potential candidate for diabetic wound treatment.

OH planar laser-induced fluorescence imaging system using a kilohertz-rate 283 nm UV Ti:sapphire laser.

A narrow linewidth Ti:sapphire laser is developed and characterized for the generation of an ultraviolet nanosecond laser pulses for the planar laser-induced fluorescence (PLIF) imaging of hydroxyl (OH). With a pump power of 11.4 W at 1 kHz, the Ti:sapphire laser produces 3.5 mJ at 849 nm with pulse duration of 17 ns and achieves a conversion efficiency of 28.2%. Accordingly, its third-harmonic generation outputs 0.56 mJ at 283 nm in BBO with type I phase match. An OH PLIF imaging system has been built; a 1 to 4 kHz fluorescent image of OH of a propane Bunsen burner has been captured based on this laser system.

Nonlinear Absorption Response of Zirconium Carbide Films.

Zirconium carbide (ZrC), a novel representative of the MXene family, has attracted considerable interest because of its outstanding physicochemical properties and potential applications in optoelectronic devices. For improving its performance as an optical modulator for ultrashort lasers, there is a call to continue studying the nonlinear optical behavior of MXene ZrC. Herein, for the first time, MXene ZrC films were fabricated on fused silica by magnetron sputtering deposition technology and used as a saturable absorber (SA) optical modulator in a passive Q-switched Nd:YAG laser. The saturation absorption behaviors of the prepared ZrC films were characterized by the Z-scan method. Their morphology, band structure, damage threshold, carrier recovery time, and saturation absorption properties were analyzed. The experimental results show that the MXene ZrC SA films exhibit excellent nonlinear optical characteristics, with a saturation intensity of 48.4 MW/cm2, a large modulation depth of 6.9%, and an ultrashort recovery time of 2.72 ps. In addition, the damage threshold of MXene ZrC SA films was estimated to be greater than 0.2516 J/cm2. By integrating the ZrC SA film optical modulator into the oscillator of the Nd:YAG laser, we achieved stable operation of the Q-switched laser with a central wavelength at 1.06 µm, with the shortest pulse width of 78 ns. The results of this study demonstrate the potential use of MXene ZrC SA films as optical modulators in ultrashort lasers.

Construction of adhesive and bioactive silk fibroin hydrogel for treatment of spinal cord injury.

Spinal cord injury (SCI) often causes severe and permanent disabilities due to the complexity of injury progression. The promising methods are generally based on tissue engineering technology using biocompatible hydrogels to achieve SCI repair. However, hydrogels are commonly incapable of close contact with the damaged spinal cord stumps and fail to support neural regeneration in SCI. Therefore, it is still a challenge to achieve stable contact with the transected nerve stumps and accelerate neural regeneration in the lesion microenvironment. Here, an in situ forming glycidyl methacrylated silk fibroin/ laminin-acrylate (SF-GMA/LM-AC) hydrogel was fabricated for SCI repair. The polymer chains formed a network quickly after ultraviolet (UV)-light trigger, in topological entanglement with the spinal cord, stitching the hydrogel and wet tissues together like a suture at the molecular scale. The SF-GMA/LM-AC hydrogel also provided a favorable environment for the growth of cells due to the incorporation of LM-AC. Compared with physical entrapment of LM, LM-AC immobilized in the hydrogel by covalent technology provided better microenvironments for neural stem cells (NSCs) growth. The repair of complete transection SCI in rats demonstrated that this hydrogel guided and promoted neural regeneration over 8 weeks, leading to hind limb locomotion recovery. This adhesive and bioactive SF-GMA/LM-AC hydrogel may open many opportunities in various therapeutic indications, including SCI. STATEMENT OF SIGNIFICANCE: Many materials have been developed for building transplanted scaffolds, but it is still a challenge to fabricate bioactive scaffolds and adhesion to wet tissues. In this study, we successfully developed an in situ forming SF-GMA/LM-AC hydrogel for SCI repair. This in situ forming hydrogel formed significant adhesion to the native spinal cord, stitching hydrogel and tissue together like a suture at the molecular scale. In addition, covalent immobilized LM-AC was used as the contact guidance biochemical cues for axonal outgrowth and had much better bioactive effects than physically entangled LM. Moreover, this universal strategy would open an avenue to fabricate adhesive and bioactive hydrogel for various disease treatments including SCI.

Multifaceted tannin crosslinked bioinspired dECM decorated nanofibers modulating cell-scaffold biointerface for tympanic membrane perforation bioengineering.

Tympanic membrane (TM) perforation leads to persistent otitis media, conductive deafness, and affects life quality. Ointment medication may not be sufficient to treat TM perforation (TMP) due to the lack of an underlying tissue matrix and thus requiring a scaffold-based application. The engineering of scaffold biointerface close to the matrix via tissue-specific decellularized extracellular matrix (dECM) is crucial in instructing cell behaviour and regulating cell-material interaction in the bioengineering domain. Herein, polycaprolactone (PCL) and TM-dECM (from Sprague-Dawley rats) were combined in a different ratio in nanofibrous form using an electrospinning process and crosslinked via tannic acid. The histological and biochemical assays demonstrated that chemical and enzymatic decellularization steps removed cellular/immunogenic contents while retaining collagen and glycosaminoglycan. The morphological, physicochemical, thermomechanical, contact angle, and surface chemical studies demonstrated that the tannin crosslinked PCL/dECM nanofibers fine-tune biophysical and biochemical properties. The multifaceted crosslinked nanofibers hold the tunable distribution of dECM moieties, assembled into a spool-shaped membrane, and could easily insert into perforated sites. The dECM decorated fibers provide a preferable biomimetic matrix for L929 fibroblast adhesion, proliferation, matrix adsorption, and f-actin saturation, which could be crucial for bioengineering. Overall, dECM patterning, surface hydrophilicity, interconnected microporosities, and multifaceted nanofibrous biosystem modulate cell-scaffold performance and could open opportunities to reconstruct TMP in a biomimetic fashion.

Injectable thioketal-containing hydrogel dressing accelerates skin wound healing with the incorporation of reactive oxygen species scavenging and growth factor release.

Wound healing is a complex dynamic process. During the occurrence of skin injury, the excessive reactive oxygen species (ROS) level is associated with sustained inflammatory response, which limits efficient wound repair. Although multifunctional hydrogels are considered ideal wound dressings due to their unique advantages, the development of hydrogel dressings with rapid gelling rates, shape adaptation, and antioxidant function is still a vital challenge. In this work, a ROS-responsive injectable polyethylene glycol hydrogel containing thioketal bonds (PEG-TK hydrogel) was synthesized and utilized to deliver epidermal growth factor (EGF). We adopted bio-orthogonal click chemistry for crosslinking the polymer chains to obtain the EGF@PEG-TK hydrogel with fast gelation time, injectability and shape-adaptability. More interestingly, the thioketal bonds in the PEG-TK hydrogel not only scavenged excessive ROS in the wound sites but also achieved responsive and controlled EGF release to facilitate regeneration. The EGF@PEG-TK hydrogel treatment offered the benefits of protecting cells from oxidative stress, accelerating wound closure, and reducing scar formation in the full-thickness skin defect model. This work provides a promising strategy for developing antioxidant hydrogel dressing for facilitating the repair of wounds.

In Situ Forming Cellulose Nanofibril-Reinforced Hyaluronic Acid Hydrogel for Cartilage Regeneration.

Hyaluronic acid (HA) based hydrogels are one of most functional natural biomaterials in the field of cartilage tissue engineering (CTE). Even with the promising advantages of HA hydrogels, the complicated mechanical properties of the native cartilage have not been realized, and fabricating HA hydrogels with excellent mechanical properties to make them practical in CTE still remains a current challenge. Here, a strategy that integrates hydrogels and nanomaterials is shown to form a HA hydrogel with sufficient mechanical loading for cartilage tissue production and recombination. Cellulose nanofibrils (CNFs) are promising nanomaterial candidates as they possess high mechanical strength and excellent biocompatibility. In this study, we developed methacrylate-functionalized CNFs that are able to photo-crosslink with methacrylated HA to fabricate HA/CNF nanocomposite hydrogels. The present composite hydrogels with a compressive modulus of 0.46 ± 0.05 MPa showed adequate compressive strength (0.198 ± 0.009 MPa) and restorability, which can be expected to employ as a stress-bearing tissue such as articular cartilage. Besides, this nanocomposite hydrogel could provide a good microenvironment for bone marrow mesenchymal stem cell proliferation, as well as chondrogenic differentiation, and exhibit prominent repair effect in the full-thickness cartilage defect model of SD rats. These results suggest that the HA/CNF nanocomposite hydrogel creates a new possibility for fabricating a scaffold in CTE.

Sodium-Glucose Co-Transporter 2 Inhibition With Empagliflozin Improves Cardiac Function After Cardiac Arrest in Rats by Enhancing Mitochondrial Energy Metabolism.

Empagliflozin is a newly developed antidiabetic drug to reduce hyperglycaemia by highly selective inhibition of sodium-glucose co-transporter 2. Hyperglycaemia is commonly seen in patients after cardiac arrest (CA) and is associated with worse outcomes. In this study, we examined the effects of empagliflozin on cardiac function in rats with myocardial dysfunction after CA. Non-diabetic male Sprague-Dawley rats underwent ventricular fibrillation to induce CA, or sham surgery. Rats received 10 mg/kg of empagliflozin or vehicle at 10 min after return of spontaneous circulation by intraperitoneal injection. Cardiac function was assessed by echocardiography, histological analysis, molecular markers of myocardial injury, oxidative stress, mitochondrial ultrastructural integrity and metabolism. We found that empagliflozin did not influence heart rate and blood pressure, but left ventricular function and survival time were significantly higher in the empagliflozin treated group compared to the group treated with vehicle. Empagliflozin also reduced myocardial fibrosis, serum cardiac troponin I levels and myocardial oxidative stress after CA. Moreover, empagliflozin maintained the structural integrity of myocardial mitochondria and increased mitochondrial activity after CA. In addition, empagliflozin increased circulating and myocardial ketone levels as well as heart ß-hydroxy butyrate dehydrogenase 1 protein expression. Together, these metabolic changes were associated with an increase in cardiac energy metabolism. Therefore, empagliflozin favorably affected cardiac function in non-diabetic rats with acute myocardial dysfunction after CA, associated with reducing glucose levels and increasing ketone body oxidized metabolism. Our data suggest that empagliflozin might benefit patients with myocardial dysfunction after CA.

Slide-Ring Structure-Based Double-Network Hydrogel with Enhanced Stretchability and Toughness for 3D-Bio-Printing and Its Potential Application as Artificial Small-Diameter Blood Vessels.

Artificial small-diameter blood vessels (SDBVs) are extremely limited in their thrombosis and still present significant clinical challenges worldwide. In recent years, 3D-bio-printing has offered a powerful technique to fabricate vessel channels in tissue engineering applications. Hydrogels are attractive bio-inks for SDBVs 3D-bio-printing, but they usually present weak mechanical properties. To overcome the weak mechanical properties of hydrogel bio-inks, a printable human umbilical vein endothelial cell (HUVEC)-laden polyrotaxane-alginate (PR-Alg) double-network (DN) hydrogel was fabricated. The PR-Alg DN hydrogel consists of a Ca2+ cross-linked alginate network to form the first network rapidly, and a photo-cross-linked slide-ring network was designed as the second network. By combining special hydrogel structures of slide-ring (SR) and double network (DN), we significantly improved the mechanical properties of hydrogels. The PR-Alg DN hydrogel provides excellent stress (199 ± 20 kPa) and strain (1239 ± 58%), and the fracture energy reaches 668 ± 80 J/m2. Additionally, due to the presence of biocompatible materials and the gentle 3D-bio-printing process, the 3D-bio-printed channels showed outstanding biocompatibility, particularly in HUVECs' survival and proliferation. We anticipate that this work will expand the application of hydrogels with improved mechanical properties in biomedicine, particularly for artificial SDBVs.

Fabrication of an injectable BMSC-laden double network hydrogel based on silk fibroin/PEG for cartilage repair.

An injectable BMSC-encapsulated double network (DN) hydrogel was fabricated via silk fibroin (SF) and poly(ethylene glycol) (PEG), which could efficiently support the survival and proliferation of BMSCs in vitro as well as cartilage repair in vivo, and provides a new strategy for cartilage tissue engineering.

An injectable BMSC-laden enzyme-catalyzed crosslinking collagen-hyaluronic acid hydrogel for cartilage repair and regeneration.

Articular cartilage has limited self-healing ability due to its lack of abundant nutrients and progenitor cells. In this study, an injectable hydrogel system consisting of collagen type I-tyramine (Col-TA) and hyaluronic acid-tyramine (HA-TA) was fabricated as the bone marrow mesenchymal stem cell (BMSC)-laden hydrogel system for cartilage regeneration. Next, the physiochemical properties of this hydrogel system were well characterized and optimized, including gelation time, stiffness, water absorption and degradability. Further, the proliferation and differentiation of BMSCs within the Col-HA hydrogel were evaluated, and the ability of in vivo cartilage repair was also examined in the presence of the transforming growth factor-ß1 (TGF-ß1). These results illustrate that this hydrogel can offer a great microenvironment for BMSC growth and cartilage differentiation both in vitro and in vivo, and the Col-HA hydrogel can serve as an ideal hydrogel for cartilage tissue regeneration.

L-band mode-locked femtosecond fiber laser with gigahertz repetition rate.

We demonstrate an L-band passively mode-locked femtosecond fiber laser with a fundamental repetition rate of 1.013 GHz based on a semiconductor saturable absorber mirror. Compared with other reported L-band fiber lasers that use overlong Er-doped fiber, the laser here consists of 10 cm heavily doped fiber to increase the fundamental pulse repetition rate to gigahertz level. An output ratio as low as 0.2% is used to make the central wavelength up to 1.6 µm. The laser operates at the soliton regime with a 3 dB spectral bandwidth of 13.6 nm and a pulse duration of 229 fs.

Endovascular hypothermia improves post-resuscitation myocardial dysfunction by increasing mitochondrial biogenesis in a pig model of cardiac arrest.

The aim of the study was to investigate the effects of endovascular hypothermia on mitochondrial biogenesis in a pig model of prolonged cardiac arrest (CA). Ventricular fibrillation was electrically induced, and animals were left untreated for 10 min; then after 6min of cardiopulmonary resuscitation (CPR), defibrillation was attempted. 25 animals that were successfully resuscitated were randomized into three groups: Sham group (SG, 5, no CA), normal temperature group (NTG, 5 for 12 h observation and 5 for 24 h observation), and endovascular hypothermia group (EHG, 5 for 12 h observation and 5 for 24 h observation). The core temperatures (Tc) in the EHG were maintained at 34 ±â€¯0.5 °C for 6 h by an endovascular hypothermia device (Coolgard 3000), then actively increased at the speed of 0.5 °C per hour during the next 6 h to achieve a normal body temperature, while Tc were maintained at 37.5 ±â€¯0.5 °C in the NTG. Cardiac and mitochondrial functions, the quantification of myocardial mitochondrial DNA (mtDNA), peroxisome proliferator-activated receptor coactivator-1α (PGC-1α), nuclear respiratory factor (NRF)-1, and NRF-2 were examined. Results showed that myocardial and mitochondrial injury and dysfunction increased significantly at 12 h and 24 h after CA. Endovascular hypothermia offered a method to rapidly achieve the target temperature and provide stable target temperature management (TTM). Cardiac outcomes were improved and myocardial injuries were alleviated with endovascular hypothermia. Compared with NTG, endovascular hypothermia significantly increased mitochondrial activity and biogenesis by amplifying mitochondrial biogenesis factors' expressions, including PGC-1α, NRF-1, and NRF-2. In conclusions, endovascular hypothermia after CA alleviated myocardial and mitochondrial dysfunction, and was associated with increasing mitochondrial biogenesis.

Compact low-noise passively mode-locked Er-doped femtosecond all-fiber laser with 2.68 GHz fundamental repetition rate.

A passively mode-locked Er-doped fiber laser with a fundamental repetition rate of 2.68 GHz is reported. The oscillator operating at a central wavelength of 1558.35 nm has a compact, robust structure and low-noise performance. The timing jitter integrated from 30 MHz down to 300 Hz is 82.5 fs, and the timing jitter performance is analyzed based on the theory model. The amplification and compression of the high repetition rate optical pulses are also investigated. After a three-stage amplifier, the average power is boosted to 430 mW. Meanwhile, based on the nonlinear self-phase modulation effect, the spectral bandwidth is broadened from 7.56 to 19.2 nm, and the corresponding pulse width is compressed to 244 fs.

Activation of Sigma-1 Receptor by Cutamesine Attenuates Neuronal Apoptosis by Inhibiting Endoplasmic Reticulum Stress and Mitochondrial Dysfunction in a Rat Model of Asphyxia Cardiac Arrest.

BACKGROUND: Global cerebral ischemic/reperfusion (I/R) injury after cardiac arrest (CA) is a major cause of mortality and morbidity in survivors of resuscitation. We utilized a rat model of asphyxia CA to explore the functional effects and mechanisms of Sigma-1 receptor (Sig-1R) activation in cerebral protection using the Sig-1R agonist cutamesine (SA-4503). METHODS: After resuscitation, the surviving rats were randomly divided into three groups (n = 18 each): the cardiopulmonary resuscitation (CPR) group (0.9% saline at 1 mL/kg); the SA4503 low-dose group (1 mg/kg SA4503); and the SA4503 high-dose group (2.5 mg/kg SA4503). The neurological deficit scores were recorded, and the cerebral cortex was harvested for western blotting. Mitochondrial transmembrane potential, adenosine triphosphate (ATP) concentrations, calcium homeostasis, and mitochondrial ultrastructure were also studied. RESULTS: The SA4503 treatment groups exhibited improved neurological outcomes compared with the CPR group. The protein levels of caspase-3 and the endoplasmic reticulum stress markers C/EBP homologous protein and caspase-12 were lower in the SA4503 treatment groups compared with the CPR group. SA4503 treatment also normalized mitochondrial membrane potential, tissue ATP concentrations, intracellular Ca overload, and upregulated Sig-1R protein level compared with the CPR group. The SA4503 high dose treatment showed significant cerebral protective effects compared with the SA4503 low dose treatment. The therapeutic effect of SA4503 was dose-dependent. CONCLUSIONS: CA downregulated Sig-1R protein expression. Activating Sig-1R using SA4503 protected against global cerebral I/R injury in a rat model of asphyxia CA by alleviating endoplasmic reticulum stress and mitochondrial dysfunction and eventually inhibiting neuronal apoptosis.

Robust soliton crystals in a thermally controlled microresonator.

We demonstrate robust soliton crystals generation with a fixed frequency pump laser through a thermoelectric-cooler-based thermal-tuning approach in a butterfly-packaged complementary-metal-oxide-semiconductor-compatible microresonator. Varieties of soliton crystal states, exhibiting "palm-like" optical spectra that result from the strong interactions between the dense soliton ensembles and reflect their temporal distribution directly, are experimentally observed by sweeping one cavity resonance across the pump frequency from the blue-detuned side by reducing the operating temperature of the resonator. Benefitting from the tiny intra-cavity energy change, repeatable interconversion between the chaotic modulation instability and stable soliton crystal states can be successfully achieved via simple tuning of the temperature or pump power, showing the easy accessibility and excellent stability of such soliton crystals. This work could facilitate microresonator-based optical frequency combs towards a portable, adjustable, and low-cost system while avoiding the requirements of delicate frequency-sweeping pump techniques.