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Diabetes is closely connected with skeletal muscle dysfunction. Ellagic acid (EA) possesses a variety of bio-effects and is applied to the improvement of diabetes. The purpose of this study was to explore the potential improvement effect and mechanisms of EA in streptozotocin (STZ)-induced diabetic muscle atrophy. The model of diabetic mice was established by intra-peritoneal STZ to evaluate treatment effect of EA (100 mg/kg/d for 8 weeks) on muscle atrophy. Our data exhibited that EA enhanced fiber size and weight of gastrocnemius, and promoted grip strength to relieve STZ-induced muscle lesions. In serum, the levels of Creatine kinase (CK), lactate dehydrogenase (LDH), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL) were inhibited, while high-density lipoprotein cholesterol (HDL) level was enhanced by EA treatment in diabetic mice. In gastrocnemius, EA decreased Atrogin-1 and MuRF-1 expressions to relieve STZ-induced muscle atrophy. Moreover, EA increased NRF-1 and PGC-1α expressions to alleviate mitochondrial disorder. Meanwhile, EA suppressed CHOP and GRP-87 levels to relieve ER stress. Lastly, EA inhibited BAX expressions and enhanced Bcl-2 expressions to mitigate apoptosis. In conclusion, EA is preventing the event of STZ-induced gastrocnemia by amelioration of mitochondrial dysfunction, ER stress and apoptosis, and could be used in the protection and therapeutic of muscle atrophy in diabetes.

Background: With an increasing number of patients experiencing infertility due to chronic salpingitis after Chlamydia trachomatis (CT) infection, there is an unmet need for tissue repair or regeneration therapies. Treatment with human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EV) provides an attractive cell-free therapeutic approach.Methods: In this study, we investigated the alleviating effect of hucMSC-EV on tubal inflammatory infertility caused by CT using in vivo animal experiments. Furthermore, we examined the effect of hucMSC-EV on inducing macrophage polarization to explore the molecular mechanism.Results: Our results showed that tubal inflammatory infertility caused by Chlamydia infection was significantly alleviated in the hucMSC-EV treatment group compared with the control group. Further mechanistic experiments showed that the application of hucMSC-EV induced macrophage polarization from the M1 to the M2 type via the NF-κB signaling pathway, improved the local inflammatory microenvironment of fallopian tubes and inhibited tube inflammation.Conclusion: We conclude that this approach represents a promising cell-free avenue to ameliorate infertility due to chronic salpingitis.

This paper presents the design and test results of a Gigabit Cable Receiver ASIC called GBCR for the HL-LHC upgrade of the ATLAS Inner Tracker (ITk) pixel detector. Three prototypes (GBCR1, GBCR2, and GBCR3) have been designed in the CERN-identified 65 nm CMOS technology. GBCR receives seven (GBCR2) or six (GBCR3) channels (RX) each at 1.28 Gbps from the front-end readout chip RD53B via flex cables up to 1 meter and Twinax cables up to 5 meters and sends the equalized and retimed signals to lpGBT. Both GBCR2 and GBCR3 ASICs have two transmitting channels (TX) that pre-emphasize the signals from lpGBT before sending them to RD53B through the same cables. No Single-Event Upset (SEU) is observed in any tested channels of GBCR2 in a 400 MeV proton beam. The extrapolated bit error rate for the future HL-LHC application is below 8*10^(-16), significantly below the specified BER criterion. GBCR3 is designed to improve the immunity to single-event-upset by applying the Triple Modular Redundancy (TMR) technology to all RX channels. The retimed signals from GBCR3 have less total jitter than those from GBCR2 (35 ps versus 79 ps). Each receiver channel of GBCR3 consumes 75% more power than that of GBCR2., 7 pages, 5 figures

We present a pluggable radiation-tolerant 4-level Pulse-Amplitude-Modulation (PAM4) optical transmitter module called GBT20 (Giga-Bit Transmitter at 20 Gbps) for particle-physics experiments. GBT20 has an OSFP or firefly connector to input 16-bit data each at 1.28 Gbps. The GBT20 drives a VCSEL die with an LC lens or a VCSEL TOSA and interfaces an optical fiber with a standard LC connector. The minimum module, including the host connector, occupies 41 mm x 13 mm x 6 mm. At 20.48 Gbps, the minimum Transmitter Dispersion Eye Closure Quaternary (TDECQ) is around 0.7 dB. The power consumption is around 164 mW in the low-power mode. The SEE cross-section is below 7.5x10^(-14) cm^2. No significant performance degrades after a TID of 5.4 kGy., Comment: 7 pages, 7 figures

The disadvantages of cell-adaptive microenvironments and cellular diffusion out of the lesion have limited hydrogel-based scaffold transplantation treatment for neural connectivity, leading to permanent neurological disability from spinal cord injury. Herein, porous GelMA scaffold was prepared, in which the inner porous structure was optimized. The average pore size was 168 ± 71 μm with a porosity of 77.1%. The modulus of porous hydrogel was 593 ± 4 Pa compared to 1535 ± 85 Pa of bulk GelMA. The inner connected porous structure provided a cell-infiltrative matrix for neural stem cell migration and differentiation in vitro and eventually enhanced neuron differentiation and hindlimb strength and movement of animals in in vivo experiments. Furthermore, inflammation response and apoptosis were also alleviated after implantation. This work demonstrated that the porous hydrogel with appropriately connected micropores exhibit favorable cellular responses compared with traditional non-porous GelMA hydrogel. Taken together, our findings suggest that porous hydrogel is a promising scaffold for future delivery of stem cells and has prospects in material design for the treatment of spinal cord injury.

Insulating joint is an essential component for pipeline cathodic protection system. During the safety confirmation before the excavation of the station foundation pit, a pipeline company found that the insulating joint was failed due to leakage. In order to determine the causes of leakage, data verification, tests and failure component analysis were carried out. The results show that: (1) the leakage point cannot be detected by NDT, hydraulic pressure test, and hydraulic pressure + bending test, and the gas leak test in the water container demonstrates two leakage points on the fixing sleeve of the insulating joint; (2) the insulating joint has an unfilled cavity, and the mechanical holes on the fixing sleeve are blocked by bolts, which are inconsistent with the assembly drawing; and (3) the leakage of the insulating joint was caused by the sealing failure during assembly or service, which allowed some gas to gather in the cavity between the flange and the fixing sleeve and then leak through the gap between the mechanical hole and the bolt. Accordingly, it is suggested that (1) manufacturers should strictly follow the process when producing insulating joints, the product structure be consistent with the assembly drawing, the product inspection be done according to requirements, and NDT be done on all welding areas; and (2) the insulating joint be leak-tested in the water container where possible.

Porcine circovirus type 2 (PCV2) is an economically important swine pathogen and, although small, it has the highest evolution rate among DNA viruses. Commercial PCV2 commercial vaccines are inactivated PCV2 isolates or a subunit vaccine based on the Cap protein of PCV2. Currently, PCV2 VLPs of individual subtype vaccines are available. Although the main prevalent genotype worldwide is PCV2b, the emerging subtype PCV2d subtype is also increasingly associated with PCV disease. The aim of the study was to evaluate the protective efficacy of VLP based on the PCV2b and 2d subtypes against the mixed challenge of two hypotype PCV2 in mice. Thirty-six female SPV Kunming mice were immunized twice with PCV2b and 2d VLPs, then challenged with PCV2b and PCV2d, to assess the immunogenicity and effectiveness of the VLPs. Vaccination of the mice with PCV2b and 2d VLPs elicited a robust antibody response specific for the PCV2. The virus load detected in the 2b and 2d spleen vaccine group was the lowest compared to other groups. Furthermore, there was no pathological damage in the HE stained sections of the 2b and 2d spleen vaccine, and no virus was detected in the immunohistochemical sections. Our data suggest that the mixed PCV2b and 2d VLP vaccine could protect mice from challenge with the mixed infection of PCV2b and PCV2d..

Background Residual dried blood spots (rDBS) from newborn screening programmes represent a valuable resource for medical research, from basic sciences, through clinical to public health. In Hong Kong, there is no legislation for biobanking. Parents’ view on the retention and use of residual newborn blood samples could be cultural-specific and is important to consider for biobanking of rDBS. Objective To study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese parents. Methods A mixed-method approach was used to study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese parents of children 0–3 years or expecting parents through focus groups (8 groups; 33 participants) and a survey (n = 1012, 85% mothers) designed with insights obtained from the focus groups. We used framework analysis to summarise the themes as supportive factors, concerns and critical arguments for retention and secondary use of rDBS from focus group discussion. We used multiple logistic regression to assess factors associated with support for retention and secondary use of rDBS in the survey. Results Both in focus groups and survey, majority of parents were not aware of the potential secondary use of rDBS. Overall secondary use of rDBS in medical research was well accepted by a large proportion of Hong Kong parents, even if all potential future research could not be specified in a broad consent. However parents were concerned about potential risks of biobanking rDBS including leaking of data and mis-use of genetic information. Parents wanted to be asked for permission before rDBS are stored and mainly did not accept an “opt-out” approach. The survey showed that parents born in mainland China, compared to Hong Kong born parents, had lower awareness of newborn screening but higher support in biobanking rDBS. Higher education was associated with support in rDBS biobanking only among fathers. Conclusion Long-term storage and secondary use of rDBS from newborn screening for biomedical research and a broad consent for biobanking of rDBS are generally acceptable to Hong Kong parents given their autonomy is respected and their privacy is protected, highlighting the importance of an accountable governance and a transparent access policy for rDBS biobanks.

Tea polysaccharides exhibit multiple important bioactivities, but very few of them can be absorbed through the small intestine. To enhance the absorption efficacy of tea polysaccharides, a cationic vitamin B12-conjugated glycogen derivative bearing the diethylenetriamine residues (VB12-DETA-Gly) was synthesized and characterized using FTIR, 1H NMR, and UV-vis spectroscopy. An acidic tea polysaccharide (TPSA) was isolated from green tea. The TPSA/VB12-DETA-Gly complexed nanoparticles were prepared, which showed positive zeta potentials and were irregular spherical nanoparticles in the sizes of 50–100 nm. To enable the fluorescence and UV-vis absorption properties of TPSA, a Congo red residue-conjugated TPSA derivative (CR-TPSA) was synthesized. The interactions and complexation mechanism between the CR-TPSA and the VB12-DETA-Gly derivatives were investigated using fluorescence spectroscopy, resonance light scattering spectroscopy, and UV-vis spectroscopy. The results indicated that the electrostatic interaction could play a major role during the CR-TPSA and VB12-DETA-Gly-II complexation processes. The TPSA/VB12-DETA-Gly nanoparticles were nontoxic and exhibited targeted endocytosis for the Caco-2 cells, and showed high permeation through intestinal enterocytes using the Caco-2 cell model. Therefore, they exhibit potential for enhancing the absorption efficacy of tea polysaccharides through the small intestinal mucosa.

A prototype optical-link board has been developed for the ATLAS Liquid Argon Calorimeter Phase-2 upgrade. The board consists of 24 lpGBT chips and 8 VTRx+ modules and demonstrates the full optical link design of the future front-end board. The board has 22 simplex optical links to transmit detector data, which are emulated in FPGAs and injected through 6 FMC connectors, to the off-detector electronics. The board implements 2 duplex optical links for clocks, control, and monitoring with redundant design to improve the system reliability. Data transmission and all redundant designs have been verified. A fiber routing scheme, in which 2 or 3 VTRx+ modules are re-connected to the front panel with an MPO connector, has been prototyped., 7 pages, 5 figures

Background The effects of bone marrow mesenchymal stem cells (BMSCs) during the treatment of cartilage damage have been proven to be attributed to paracrine mechanisms, particularly the effect of exosomes. Exosomes from different batches are inhomogeneous, and different treatment effects are observed between samples. The purpose of this research was to find more effective and homogeneous exosomes for the repair of chondrocytes in osteoarthritis (OA). We observed the potential effects and possible mechanisms of exosomes derived from parathyroid hormone (PTH) (1-34)-preconditioned BMSCs (ExoPTH) in the alleviation of OA. Materials and methods Exosomes derived from BMSCs (ExoBMSC) and ExoPTH were isolated by differential centrifugation. Primary rat chondrocytes were used to establish the OA model by interleukin 1 beta (IL-1β) in vitro. The effects of these two types of exosomes on OA chondrocyte proliferation, migration, apoptosis, and extracellular matrix formation were measured and compared. We observed changes in IL-2, TNF-α, and IL-6 levels via Western blotting (WB), and quantitative real-time PCR (qRT–PCR). Results We successfully extracted ExoBMSC and ExoPTH and established an IL-1β-induced OA model in primary chondrocytes from rats. Our study showed that IL-2, TNF-α, and IL-6 levels increased significantly in OA chondrocytes; however, both ExoBMSC and ExoPTH reduced the levels of IL-2, TNF-α, and IL-6. In addition, ExoPTH exhibited stronger anti-inflammatory effects. ExoPTH had a more marked effect on proliferation, migration, and production of the extracellular matrix (Col-II) in OA chondrocytes than ExoBMSC at 24 h. Conclusion ExoPTH increased the migration, proliferation, and chondral matrix formation of OA chondrocytes in vitro. In OA chondrocyte therapy, the potential mechanism of ExoPTH might involve the inhibition of production of proinflammatory cytokines. Although the two types of exosomes had some similar effects, most effects of ExoPTH were better than those of ExoBMSC, so ExoPTH may have a better ability to alleviate OA.

We propose a line code that has fast resynchronization capability and low latency. Both the encoder and decoder have been implemented in FPGAs. The encoder has also been implemented in an ASIC. The latency of the whole optical link (not including the optical fiber) is estimated to be less than 73.9 ns. In the case of radiation-induced link synchronization loss, the decoder can recover the synchronization in 25 ns. The line code will be used in the ATLAS liquid argon calorimeter Phase-I trigger upgrade and can also be potentially used in other LHC experiments., 10 pages, 7 figures

This paper presents several component prototypes towards a low-latency, small-form-factor optical link designed for the ATLAS Liquid Argon Calorimeter Phase-I trigger upgrade. A prototype of the custom-made dual-channel optical transmitter module, the Miniature optical Transmitter (MTx), with separate transmitter optical sub-assemblies (TOSAs) has been demonstrated at data rates up to 8 Gbps per channel. A Vertical-Cavity Surface-Emitting Laser (VCSEL) driver ASIC has been developed and is used in the current MTx prototypes. A serializer ASIC prototype, operating at up to 8 Gbps per channel, has been designed and tested. A low-latency, low-overhead encoder ASIC prototype has been designed and tested. The latency of the whole link, including the transmitter latency and the receiver latency but not the latency of the fiber, is estimated to be less than 57.9 ns. The size of the MTx is 45 mm x 15 mm x 6 mm., 12 pages, 13 figures

The Phase-I trigger readout electronics upgrade of the ATLAS Liquid Argon calorimeters enhances the physics reach of the experiment during the upcoming operation at increasing Large Hadron Collider luminosities. The new system, installed during the second Large Hadron Collider Long Shutdown, increases the trigger readout granularity by up to a factor of ten as well as its precision and range. Consequently, the background rejection at trigger level is improved through enhanced filtering algorithms utilizing the additional information for topological discrimination of electromagnetic and hadronic shower shapes. This paper presents the final designs of the new electronic elements, their custom electronic devices, the procedures used to validate their proper functioning, and the performance achieved during the commissioning of this system., Comment: 56 pages, 41 figures, 6 tables

In this work, we have prepared an antiferromagnetic insulated α-Fe2O3 film with a large out-of-plane magnetic component and studied the spin Hall magnetoresistance (SMR) in α-Fe2O3/Pt bilayers. Both angular-dependent magnetoresistance and field-dependent magnetoresistance have featured a sign change characteristic with varying temperature, which is ascribed to the competition between a modulated interface magnetic state and an antiferromagnetic bulk state of the α-Fe2O3 film. According to a generalized theoretical model, which takes the effective spin conductance into consideration, the spin transport can be mathematically expressed as the change of field dependent average spin operators with varying temperature. The critical temperature also depends on the α-Fe2O3 film thickness and the magnetic field, which are ascribed to the magnons transport and long-range order of non-collinear spin textures, respectively. Furthermore, we have given a phenomenological form to fit the SMR curves in the critical temperature interval, which further reveals the origin of SMR with complex magnetic structures.

Spinal cord injury (SCI) is a complex pathological process. Based on the encouraging results of preclinical experiments, some stem cell therapies have been translated into clinical practice. Mesenchymal stem cells (MSCs) have become one of the most important seed cells in the treatment of SCI due to their abundant sources, strong proliferation ability and low immunogenicity. However, the survival rate of MSCs transplanted to spinal cord injury is rather low, which hinders its further clinical application. In recent years, hydrogel materials have been widely used in tissue engineering because of their good biocompatibility and biodegradability. The treatment strategy of hydrogel combined with MSCs has made some progress in SCI repair. This review discusses the significance and the existing problems of MSCs in the repair of SCI. It also describes the research progress of hydrogel combined with MSCs in repairing SCI, and prospects its application in clinical research, aiming at providing reference and new ideas for future SCI treatment.脊髓损伤是一个复杂的病理过程。基于临床前实验令人鼓舞的结果，部分干细胞治疗已转化为临床实践。间充质干细胞因其来源丰富、增殖能力强、低免疫原性，现已成为干细胞移植治疗脊髓损伤策略中重要的种子细胞之一。然而，将间充质干细胞移植到脊髓损伤处后的存活率较低，阻碍了其在临床上的进一步应用。近年来，水凝胶材料因其良好的生物相容性、生物降解性被广泛应用于组织工程，水凝胶联合间充质干细胞的治疗策略在脊髓损伤修复中已取得一定进展。本综述讨论了间充质干细胞修复脊髓损伤的意义以及目前存在的问题，阐述了水凝胶联合间充质干细胞修复脊髓损伤的研究进展并对其在临床研究中的应用进行了展望，旨在为该技术今后在脊髓损伤治疗中的应用提供借鉴和新思路。.

We report the development of a new interferometer with two stable, high-power, 320 GHz solid-state sources in Heliotron J. A heterodyne Michelson interferometer optical scheme is employed. Two solid-state oscillators are utilized as sources with a fixed frequency at 320 GHz and frequency tunable of 312–324 GHz. Quasi-optical techniques are used for beam transmission. The beam is elongated in the vertical direction with two off-axis parabolic mirrors and injected into the plasma as a sheet beam for the multi-channel measurement (>5 ch.). Passing through the plasma, the beam is reflected at a retroreflector-array installed at the vacuum chamber wall. The retroreflector-array is a bunch of retroreflector structures, which can suppress the beam refraction caused by plasma without much space inside a vacuum chamber unlike a single retroreflector and can facilitate the system design. The source, detectors, and the retroreflector-array are tested to evaluate their basic performance on a tabletop experiment.

Purpose Peptide drugs have been used in therapy various diseases. However, the poor bioavailability of peptide drugs for oral administration has limited their clinical applications, on account of the acidic environment and digestive enzymes inside the human gastrointestinal tract. To enhance stability in the human gastrointestinal tract, bioavailability, and targeted drug delivery of peptide drugs through oral administration, a vitamin B12-modified amphiphilic sodium alginate derivative (CSAD-VB12) was synthesized. Materials and methods A vitamin B12-modified amphiphilic sodium alginate derivative (CSAD-VB12) was synthesized via the N,N'-dicyclohexylcarbodiimide active method at room temperature, and then characterized using FTIR and 1H NMR spectroscopy. Insulin was used as a model peptide drug and the insulin-loaded CSAD-VB12 (CSAD-VB12/insulin) nanoparticles with negative zeta potentials were prepared in PBS (pH=7.4). Scanning electron microscopy was used to observe CSAD-VB12/insulin as spherical nanoparticles. The CSAD-VB12 derivatives and CSAD-VB12/insulin nanoparticles displayed nontoxicity towards the human colon adenocarcinoma (Caco-2) cells by CCK-8 test. Caco-2 cell model was used to measure the apparent permeability (Papp) of insulin, CSAD/insulin and CSAD-VB12/insulin. Furthermore, confocal was used to confirm the endocytosis of intestinal enterocytes. Type 1 diabetes mice were used to evaluate the intestinal absorption and retention effect of test nanoparticles. Results They were observed as spherical nanoparticles in the size of 30-50 nm. The CSAD-VB12 derivatives and CSAD-VB12/insulin nanoparticles displayed nontoxicity towards the human colon adenocarcinoma (Caco-2) cells. Comparing with insulin and the CSAD/insulin nanoparticles, the CSAD-VB12/insulin nanoparticles exhibited higher permeation ability through intestinal enterocytes in the Caco-2 cell model. Oral administration of the CSAD-VB12/insulin nanoparticles to Type 1 diabetic mice yields higher intestinal retention effect, targeted absorption, and outstanding efficacy. Conclusion CSAD-VB12 derivatives enhance the small intestinal absorption efficacy and retention of peptide by oral administration, which indicated that it could be a promising candidate for oral peptide delivery in the prospective clinical application.

Neural stem cells (NSCs) transplantation represents a promising strategy for the repair of injured neurons, since NSCs not only produce multiple neurotrophic growth factors but also differentiate into mature cells to replace damaged cells. Previous studies have shown that Notch signaling pathway had negative effects on neuronal differentiation; however, the precise mechanism remained inadequately understood. This research aimed to investigate whether inhibition of Notch1 signaling promotes neuronal differentiation and improves functional recovery in rat spinal cord injury through suppressing the activation of Ras homolog family member A (RhoA). QPCR, western blot, and immunofluorescence experiments were used to analyze Notch1 signaling pathways, RhoA, Ras homologous -associated coiled-coil containing protein kinase 1 (ROCK1), cleaved caspased-3, and neuronal/astrocytic differentiation markers. The expression of RhoA and ROCK1 was inhibited by lentivirus or specific biochemical inhibitors. In spinal cord injury (SCI), motor function was assessed by hind limbs movements and electrophysiology. Tissue repairing was measured by immunofluorescence, Nissl staining, Fluorogold, HE staining, QPCR, western blot, and magnetic resonance imaging (MRI) experiments. Our results demonstrate that inhibition of Notch1 in NSCs can promote the differentiation of NSCs to neurons. Knockdown of RhoA and inhibition of ROCK1 both can promote neuronal differentiation through inhibiting the activation of Notch1 signaling pathway in NSCs. In SCI, silencing RhoA enhanced neuronal differentiation and improved tissue repairing/functional recovery by inhibiting the activation of Notch1 signaling pathway. Since Notch1 inhibits neuronal differentiation through activating the RhoA/ROCK1 signaling pathway in NSCs, our data suggest that the Notch1/RhoA/ROCK1/Hes1/Hes5 signaling pathway may serve as a novel target for the treatment of SCI.

We present a 3.2-Gb/s serial link transmitter for MAPS application in future subatomic physics experiments. The transmitter features the inclusion of Reed–Solomon codes to achieve low transmission error rate. A CML driver with pre-emphasis in the transmitter allows serial transmission over low mass cables. The critical digital circuits are triplicated to resist SEU. The transmitter is fabricated in a 0 . 18 μ m CMOS Technology. A power consumption of 135 mW was measured at a typical setting. A frame data rate of 3 ⋅ 1 0 − 12 with confidence level of 94.5% was obtained through a FPGA based receiver, corresponding to a payload BER of 1 . 2 ⋅ 1 0 − 14 with confidence level of 94.9%. The transmitter functions well after being irradiated with 4.5 Mrad TID.

Spinal cord injury (SCI) is one of the most challenging clinical issues. It is characterized by the disruption of neural circuitry and connectivity, resulting in neurological disability. Adipose-derived stem cells (ADSCs) serve as a promising source of therapeutic cells for SCI treatment. However, the therapeutic outcomes of direct ADSCs transplantation are limited in the presence of an inflammatory microenvironment. Herein, a cell-adaptable neurogenic (CaNeu) hydrogel was developed as a delivery vehicle for ADSCs to promote neuronal regeneration after SCI. The dynamic network of CaNeu hydrogel loaded with ADSCs provides a cell-infiltratable matrix that enhances axonal growth and eventually leads to improved motor evoked potential, hindlimb strength, and coordination of complete spinal cord transection in rats. Furthermore, the CaNeu hydrogel also establishes an anti-inflammatory microenvironment by inducing a shift in the polarization of the recruited macrophages toward the pro-regeneration (M2) phenotype. Our study showed that the CaNeu-hydrogel‒mediated ADSCs delivery resulted in significantly suppressed neuroinflammation and apoptosis, and that this phenomenon involved the PI3K/Akt signaling pathway. Our findings indicate that the CaNeu hydrogel is a valuable delivery vehicle to assist stem cell therapy for SCI, providing a promising strategy for central nervous system diseases.

Studies have shown that the use of proangiogenic genes can improve the prognosis of ischemic stroke by promoting angiogenesis at the injury site. For example, within this study, hypoxia-inducible factor 1-α (HIF-1α) has exhibited an angiogenic effect. Our previous study reported a more stable HIF-1α mutant form (HIF-1α-AA), which was transfected into mesenchymal stem cells to provide neuroprotective effects against ischemic stroke. The safety of nonviral gene vectors has attracted researchers' attention. This study encapsulated the HIF-1α-AA plasmid DNA into a newly synthesized effective nonviral gene vector, a hyperbranched cationic amylopectin derivative (DMAPA-Amyp) nanocarrier. In addition, a targeting strategy was applied to select the RGD peptides and bind to the designed nanocarrier as a molecule targeting endothelial cells. The targeting strategy is used to directly deliver the nanocarriers to the vascular endothelial cells of the brain peri-infarct site. This study emphasizes the targeting ability of nanocarrier and its therapeutic effect on cerebral ischemia. The results showed that RGD-DMAPA-Amyp had good biocompatibility and a high cell uptake rate, indicating that it is a safe nonviral gene vector that can be endocytosed by human cells. In rat models of ischemic stroke, compared with the nontargeted nanocarrier group, more RGD-DMAPA-Amyp nanoparticles aggregated in vascular endothelial cells of the peri-infarct region and significantly improved the recovery of neurological function. It is indicated that the RGD-modified nanomedicine promotes the recovery of nerve function more efficiently. Further study on the mechanism of RGD-DMAPA-Amyp/HIF-1α-AA in the treatment of cerebral ischemia displayed potential to significantly promote the formation of new blood vessels in vivo. Our findings suggest that the RGD-modified nonviral gene vector containing HIF-1α-AA appears to be a safe and promising therapeutic strategy for ischemic stroke gene therapy.

Identifying severe acute pancreatitis (SAP) as soon as possible is critical for achieving optimal outcomes and saving lives. In this study, a novel P-selectin-targeted, NIR fluorescent dye (Cy 5.5)-labeled dual-modal nanoprobe based on diethylenetriaminepentaacetic chelates (Gd-DTPA-Cy5.5-PsLmAb) was constructed for the bimodal imaging of SAP at the early stage. Gd-DTPA-Cy5.5-PsLmAb was prepared, and its structure was characterized by Fourier transform infrared spectroscopy, UV-vis spectroscopy, and fluorescence spectroscopy, and its stability was evaluated. Biocompatibility was evaluated by the hemolysis and cytotoxicity assays. The enzyme-linked immunosorbent assay was used to detect and evaluate the expression of P-selectin in the peripheral blood of 11 patients with acute pancreatitis (AP) and 5 healthy volunteers. The bimodal imaging ability of Gd-DTPA-Cy5.5-PsLmAb nanoprobes was evaluated via near-infrared fluorescence (NIRF) and magnetic resonance imaging (MRI) in AP animal models in vivo. Gd-DTPA-Cy5.5-PsLmAb showed low toxicity to human embryonic kidney cells (293T cells) and good blood compatibility. The P-selectin levels of humans and rats in the mild acute pancreatitis (MAP)/SAP stage were significantly higher than those in the control group and reached the highest level at the SAP stage. Furthermore, Gd-DTPA-Cy5.5-PsLmAb nanoprobes showed clear NIRF imaging of mouse pancreas at the MAP stage and SAP stage by a fluorescence signal at 6.09 × 108 and 1.95 × 109, respectively. Meanwhile, Gd-DTPA-Cy5.5-PsLmAb nanoprobes also successfully showed the T1-weighted MR signal of rat pancreas at the MAP stage, but Gd-DTPA seldom showed any signal increase at the MAP stage; Gd-DTPA-Cy5.5-PsLmAb and Gd-DTPA could show an increasing MR signal of rat pancreas at the SAP stage. Gd-DTPA-Cy5.5-PsLmAb proved to offer a stronger signal than Gd-DTPA.Our findings indicate that Gd-DTPA-Cy5.5-PsLmAb is an effective and specific MR/NIRF dual nanoprobe for bimodal imaging, providing a promising diagnostic approach for early SAP in clinic.