Ran-binding protein 3 is associated with human spermatogenesis and male infertility.

Ran-binding protein 3 (RanBP3) is a Ran-interacting protein, which participates in the Ran GTPase system in cancer cell biology. However, the expression pattern and physiological role of RanBP3 remain largely unknown. In this study, we found that RanBP3 was expressed in human testes and localised to spermatogonium and spermatocyte of germ cells. In subcellular structure, its localisation is in the nucleus and cytoplasm. Interestingly, compared with normal groups, RanBP3 expression was lower in groups of patients with Maturation Arrest (MA) and Sertoli cell-only syndrome (SCO) when considered by the Johnson Score. RanBP3 expression in the MA group and SCO groups was dramatically lower than that in the normal control group. Studies have shown that RanBP3, which is one of the helper factors of Ran, is mainly participate in the nucleocytoplasmic transport of cells. RanBP3 helps Ran to achieve some functions such as nucleocytoplasmic transport, spindle assembly during mitosis and nuclear assembly after mitosis. Consequent changes in the expression of RanBP3 may associate with human spermatogenesis disorders and male infertility. The identification and characterisation of RanBP3 enhances our understanding of the molecular mechanisms underpinning its function in human spermatogenesis and male infertility.

The therapeutic effects of qigong in patients with chronic obstructive pulmonary disease in the stable stage: a meta-analysis.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is one global disease. Lung function gradually declines. Medication does not fully reverse the airflow limitation. Qigong's role in COPD rehabilitation has been assessed. We aimed to assess the effects of Qigong practised by COPD patients. METHODS: Eligible articles were obtained through a systematic search. The databased were search on October 8, 2017, and the date range of the searches in the electronic databases had no upper limit. The Cochrane risk-of-bias tool was used to evaluate the quality of the eligible studies. Mean differences with 95% confidence intervals were utilized to analyse the results. RESULTS: Ten included studies contained 993 participants. Statistical improvements occurred in the 6-min walk distance (6MWD) (MD, 30.57 m; 95% CI, 19.61-41.53 m; P < 0.00001); forced expiratory volume in 1 s (FEV1) (MD, 0.32 L; 95% CI, 0.09-0.56 L; P < 0.001); forced vital capacity rate of 1 s (FEV1/FVC) (MD, 2.66%; 95% CI, 1.32-2.26%; P = 0.0001); forced expiratory volume in 1 s/predicted (FEV1/pre) (MD, 6.04; CI, 2.58-9.5; P = 0.006); Monitored Functional Task Evaluation (MD, 0.88; 95% CI, 0.78-0.99; P < 0.00001); COPD Assessment Test for exercise (MD, - 5.54; 95% CI, - 9.49 to - 1.59; P = 0.006); Short Form-36 Health Quality Survey (SF-36)-General Health (MD, 5.22; 95% CI, 3.65-6.80; P < 0.00001); and Short Form-36 Health Quality Survey (SF-36)-Mental Health (MD, - 1.21; 95% CI, - 2.75 to 0.33; P = 0.12). CONCLUSIONS: In this meta-analysis of RCTs between ten included studies, we found that Qigong can improve COPD patients in lung function, exercise capacity and quality of life who were in the stable stage.

Confined co-assembly of AB/BC diblock copolymer blends under 3D soft confinement.

Compared to synthesizing a new block copolymer, blending of two types of block copolymers or a block copolymer and a homopolymer is a simple yet effective approach to create new self-assembled nanostructures. Here, we apply Monte Carlo (MC) simulations to mimic the co-assembly of AB/BC diblock copolymer blends within a three-dimensional (3D) soft confined space, which corresponds to the co-assembly confined in an emulsion droplet in experiment. The confined co-assemblies of four types of block copolymer blends at different block ratios, i.e., A8B8/B8C8, A6B10/B10C6, A12B4/B4C12 and A12B4/B10C6, are investigated by MC simulations. The simulation results reveal that the ratio of different types of blocks and the polymer-solvent interactions between the different blocks and the solvent determine the final self-assembled nanostructures. By tailoring these two controlling parameters, we not only reproduced some classic nanostructures, i.e., pupa-, onion-, and bud-like particles, but also predicted some unconventional nanostructures, such as patch-, Janus-, peanut-, disc- and snowman-like particles via MC simulations.

Disassembly of Multicompartment Polymer Micelles in Spatial Sequence Using an Electrostatic Field and Its Application for Release in Chronological Order.

Multicompartment micelles (MCPs), comprising sequences of repeated elemental discoid parts connected by fasciculus, were formed by self-assembly of polystyrene-block-poly(2-vinyl pyridine)-block-poly(ethylene oxide). Using an electrostatic field, the MCPs can be disassembled through consequent release of small spherical micelles. During this disassembly process, release of loaded species can be achieved from the micelles in chronological order. Two location-selected cargos (mitoxantrone (MTNT) and fluorescein isothiocyanate (FITC)) in the outer and inner compartments of the micelles can be released in chronological order. Under the applied electrostatic field (intensity: 16 kV cm-1 ), the loaded MTNT was rapidly released with more than 80 % release, whereas the loaded FITC was slowly released with less than 20 % release in 12 h. At a later stage (after more than 12 h), the loaded MTNT was slowly released with less than 20 % release, while the loaded FITC was rapidly released with more than 80 % release.

Synthesis and Characterization of PEGylated Trityl Radicals: Effect of PEGylation on Physicochemical Properties.

Tetrathiatriarylmethyl (TAM, trityl) radicals have attracted considerable attention as spin probes for biological electron paramagnetic resonance (EPR) spectroscopy and imaging owing to their sharp EPR singlet signals and high biostability. However, their in vivo applications were limited by the short blood circulation lifetimes and strong binding with albumins. Our previous results showed that PEGylation is a feasible method to overcome the issues facing in vivo applications of TAM radicals. In the present study, we synthesized a series of new PEGylated TAM radicals (TTP1, TPP2, TNP1, TNP2, d-TNP1, and d-TNP3) containing various lengths and numbers of mPEG chains. Our results found that the pattern of PEGylation exerts an important effect on physicochemical properties of the resulting TAM radicals. Dendritic PEGylated TAM radicals, TNP1 and TNP2, have higher water solubility and lower susceptibility for self-aggregation than their linear analogues TPP1 and TPP2. Furthermore, dendritic PEGylated TAM radicals exhibit extremely high stability toward various biological oxidoreductants as well as in rat whole blood, liver homogenate, and following in vivo intravenous administration in mice. Importantly, the deuterated derivatives, especially d-TNP3, exhibit excellent properties including the sharp and O2-sensitive EPR singlet signal, good biocompatibility, and prolonged kinetics with half-life time of ≥10 h in mice. These PEGylated TAM radicals should be suitable for a wide range of applications in in vivo EPR spectroscopy and imaging.

[Erectile dysfunction and psychological status in infertile males].

OBJECTIVE: To investigate the relationship of erectile dysfunction (ED) with psychological factors in male patients with infertility. METHODS: We conducted a questionnaire investigation among 252 male patients with infertility, which involved the general condition, results of semen routine examination, sexual life, and scores in IIEF-5, self-reported 9-item patient health questionnaire (PHQ-9) and 7-item generalized anxiety disorder scale (GAD-7). We analyzed the prevalence of ED, depression, and anxiety and their correlations among the patients in comparison with 100 fertile male controls. RESULTS: In 245 of the infertility patients, the most common symptoms of depression and anxiety were "feeling tired or no vitality" and "easily getting worried or impatient", 20.4% of them with depression disorder and 42.9% with anxiety disorder. The PHQ-9 and GAD-7 scores were significantly higher in the infertile males than in the normal fertile controls (P <0.05), and so was the incidence of ED (28.6% vs 12.4%, P <0.05), while the IIEF-5 scores were markedly lower in the former than in the latter group (P <0.01), and so were sex frequency and sexual satisfaction (P <0.05). The PHQ-9 and GAD-7 scores were remarkably higher in the infertility patients with ED than in those without (P <0.01). Logistic regression analysis showed that the level of libido and results of semen routine examination were the risk factors for depression disorder, while age, education level, disease course and experience of assisted reproduction were those for anxiety disorder. CONCLUSIONS: Male infertility patients have a poorer mental health and a higher incidence of ED than normal fertile men, and there is some interaction between psychological status and ED prevalence.

Complex discharge-affecting networks in juvenile myoclonic epilepsy: A simultaneous EEG-fMRI study.

Juvenile myoclonic epilepsy (JME) is a common subtype of idiopathic generalized epilepsies (IGEs) and is characterized by myoclonic jerks, tonic-clonic seizures and infrequent absence seizures. The network notion has been proposed to better characterize epilepsy. However, many issues remain not fully understood in JME, such as the associations between discharge-affecting networks and the relationships among resting-state networks. In this project, eigenspace maximal information canonical correlation analysis (emiCCA) and functional network connectivity (FNC) analysis were applied to simultaneous EEG-fMRI data from JME patients. The main findings of our study are as follows: discharge-affecting networks comprising the default model (DMN), self-reference (SRN), basal ganglia (BGN) and frontal networks have linear and nonlinear relationships with epileptic discharge information in JME patients; the DMN, SRN and BGN have dense/specific associations with discharge-affecting networks as well as resting-state networks; and compared with controls, significantly increased FNCs between the salience network (SN) and resting-state networks are found in JME patients. These findings suggest that the BGN, DMN and SRN may play intermediary roles in the modulation and propagation of epileptic discharges. These roles further tend to disturb the switching function of the SN in JME patients. We also postulate that emiCCA and FNC analysis may provide a potential analysis platform to provide insights into our understanding of the pathophysiological mechanism of epilepsy subtypes such as JME. Hum Brain Mapp 37:3515-3529, 2016. © 2016 Wiley Periodicals, Inc.

Self-assembly of ABC triblock copolymers under 3D soft confinement: a Monte Carlo study.

Under three-dimensional (3D) soft confinement, block copolymers can self-assemble into unique nanostructures that cannot be fabricated in an un-confined space. Linear ABC triblock copolymers containing three chemically distinct polymer blocks possess relatively complex chain architecture, which can be a promising candidate for the 3D confined self-assembly. In the current study, the Monte Carlo technique was applied in a lattice model to study the self-assembly of ABC triblock copolymers under 3D soft confinement, which corresponds to the self-assembly of block copolymers confined in emulsion droplets. We demonstrated how to create various nanostructures by tuning the symmetry of ABC triblock copolymers, the incompatibilities between different block types, and solvent properties. Besides common pupa-like and bud-like nanostructures, our simulations predicted various unique self-assembled nanostructures, including a striped-pattern nanoparticle with intertwined A-cages and C-cages, a pyramid-like nanoparticle with four Janus B-C lamellae adhered onto its four surfaces, an ellipsoidal nanoparticle with a dumbbell-like A-core and two Janus B-C lamellae and a Janus B-C ring surrounding the A-core, a spherical nanoparticle with a A-core and a helical Janus B-C stripe around the A-core, a cubic nanoparticle with a cube-shape A-core and six Janus B-C lamellae adhered onto the surfaces of the A-cube, and a spherical nanoparticle with helical A, B and C structures, from the 3D confined self-assembly of ABC triblock copolymers. Moreover, the formation mechanisms of some typical nanostructures were also examined by the variations of the contact numbers with time and a series of snapshots at different Monte Carlo times. It is found that ABC triblock copolymers usually aggregate into a loose aggregate at first, and then the microphase separation between A, B and C blocks occurs, resulting in the formation of various nanostructures.

Templated self-assembly of block copolymers and morphology transformation driven by the Rayleigh instability.

In the current study, we investigate the self-assembly of polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) confined in the nanopores of the anodic aluminum oxide (AAO) template and the subsequent morphology transformation induced by the Rayleigh instability. PS-b-P4VP nanotubes and nanorods with various internal nanostructures are fabricated by wetting the AAO template with PS-b-P4VP/chloroform solution, and then followed by solvent evaporation. After the removal of AAO template by potassium hydroxide solution, several different solvents (chloroform, toluene, and N,N-dimethylformamide) with different qualities are used to swell and anneal those nanotubes and nanorods suspended in aqueous media. Morphology transformation from nanostructured PS-b-P4VP nanotubes or nanorods to ordered nanospheres is observed by annealing upon chloroform and toluene while the morphology remains unchanged upon N,N-dimethylformamide annealing, indicating that solvent quality is a key factor in tuning the morphology and internal structures. Kinetics study and theoretical analysis for the morphology transition from two-dimensional (2D) block copolymer (BCP) nanotubes and nanorods to three-dimensional (3D) BCP nanospheres are further performed. From the morphological evolution and the quantitative calculation, it is confirmed that this transition is induced by the Rayleigh instability. This study provides a simple but promising method, that is, solvent annealing method, for the fabrication of BCP nanospheres with ordered internal nanostructures, which may have great application in drug delivery and other nanotechnology.

Online rheological investigation on ion-induced micelle transition for amphiphilic polystyrene-block-poly(acrylic acid) diblock copolymer in dilute solution.

The ion-induced micellar transition is online-investigated by the time dependence of the viscosity of the solution under shear flow for the first time. During the morphological transition, the change in the micellar structure can be tracked by the change in viscosity. Adding HCl or CaCl2 into pre-prepared spherical micelle solution from the self-assembly of polystyrene-block-poly(acrylic acid) (PS144-b-PAA22) in the N,N-dimethylformamide (DMF)/water mixture, the micellar structures change into short cylinders, long, entangled cylinders, and then lamellae or vesicles, corresponding to the viscosity increasing first and then declining. When HCl or CaCl2 is added to the pre-prepared spherical micelle solution formed by PS144-b-PAA50 in the dioxane/water mixture, the micellar structures are quickly transformed into cylinders or lamellae before carrying out the rheological measurement and then are turned to vesicles or spheres under the shearing, corresponding to a gradual decline in viscosity. This study shows that the rheology can be a very simple and effective online method on the investigation of the micellization, which plays an important role in understanding the micellization mechanism and micellar transition pathway of block copolymers in dilute solution.

Highly sensitive and wide-range iontronic pressure sensors with a wheat awn-like hierarchical structure.

Flexible pressure sensors with high sensitivity and wide sensing range are highly desired in e-skins and wearable electronics. However, there is always a trade-off between high sensitivity and broad sensing range for most flexible pressure sensors. Herein, an artificial wheat awn-like hierarchical structure is designed onto the dielectric layer of the iontronic pressure sensor, realizing both high sensitivity and broad working range. The sensor is constructed by sandwiching a wheat awn-like polyvinyl alcohol/H3PO4 dielectric layer between two transparent electrodes of silver nanowires/thermoplastic polyurethane/ionic liquid. The obtained sensor exhibits a high precision of 1 Pa, a high sensitivity of 47.65 kPa-1 (1-200 Pa), a wide measurement range from 1 Pa to 238 kPa, short response/recovery time of 13 ms/12 ms, outstanding stability over 6000 cycles, as well as good transparency. Considering these excellent properties, the sensor shows promising potential in health monitoring, human-computer interaction, wearable electronics, etc.

Causal associations of male infertility with stroke: a two-sample Mendelian randomization study.

Background: Stroke is a devastating global health issue, with high mortality and disability rates. The increasing prevalence of male infertility among reproductive-aged men has become a growing concern worldwide. However, the relationship between male infertility and stroke incidence remains uncertain. This study aimed to address this knowledge gap by employing a Mendelian randomization (MR) approach. Method: Utilizing genetic instrumental variables derived from a genome-wide association study (GWAS) on male infertility and stroke, a two-sample MR design was implemented. Five different analysis methods, with inverse-variance weighted as the primary approach, were used to examine the genetic causal associations between male infertility and various stroke subtypes. Heterogeneity analysis, pleiotropy tests, and leave-one-out validation were conducted to assess heterogeneity, evaluate pleiotropy, and ensure the robustness of the findings. Result: The results indicate a potential lower risk of small vessel stroke associated with male infertility (odds ratio, 95% confidence interval: 0.82, 0.68 to 0.99, p=0.044), although no significant impact on other stroke subtypes was observed. The study exhibited low heterogeneity and no apparent pleiotropy; however, the stability of the results was not optimal. Conclusion: Male infertility might potentially confer a protective effect against small vessel stroke risk. Caution is warranted due to potential confounding factors. Additional studies are necessary to confirm these findings and provide further validation.

Application of mesenchymal stem cell therapy for premature ovarian insufficiency: Recent advances from mechanisms to therapeutics.

The incidence of premature ovarian insufficiency (POI) is increasing worldwide, particularly among younger women, posing a significant challenge to fertility. In addition to menopausal symptoms, POI leads to several complications that profoundly affect female reproductive function and overall health. Unfortunately, current clinical treatment strategies for this condition are limited and often yield unsatisfactory outcomes. These approaches typically involve hormone replacement therapy combined with psychological support. Recently, mesenchymal stem cell (MSC) therapies for POI have garnered considerable attention in global research. MSCs can restore ovarian reproductive and endocrine functions through diverse mechanisms, including controlling differentiation, promoting angiogenesis, regulating ovarian fibrosis, inhibiting apoptosis, enhancing autocrine and paracrine effects, suppressing inflammation, modulating the immune system, and genetic regulation. This editorial offers a succinct summary of the application of MSC therapy in the context of POI, providing evidence for groundbreaking medical approaches that have potential to enhance reproductive health and overall well-being for women.

Bioinspired Mechanically Robust and Recyclable Hydrogel Microfibers Based on Hydrogen-Bond Nanoclusters.

Mechanically robust hydrogel fibers have demonstrated great potential in energy dissipation and shock-absorbing applications. However, developing such materials that are recyclable, energy-efficient, and environmentally friendly remains an enormous challenge. Herein, inspired by spider silk, a continuous and scalable method is introduced for spinning a polyacrylamide hydrogel microfiber with a hierarchical sheath-core structure under ambient conditions. Applying pre-stretch and twist in the as-spun hydrogel microfibers results in a tensile strength of 525 MPa, a toughness of 385 MJ m-3, and a damping capacity of 99%, which is attributed to the reinforcement of hydrogen-bond nanoclusters within the microfiber matrix. Moreover, it maintains both structural and mechanical stability for several days, and can be directly dissolved in water, providing a sustainable spinning dope for re-spinning into new microfibers. This work provides a new strategy for the spinning of robust and recyclable hydrogel-based fibrous materials.

Efficacy of natural products on premature ovarian failure: a systematic review and meta-analysis of preclinical studies.

OBJECTIVE: This study aims to investigate the effects of natural products on animal models of premature ovarian failure (POF). METHODS: We conducted comprehensive literature searches and identified relevant studies that examined the protective effects of natural products on experimental POF. We extracted quantitative data on various aspects such as follicular development, ovarian function, physical indicators, oxidative stress markers, inflammatory factors, and protein changes. The data was analyzed using random-effects meta-analyses, calculating pooled standardized mean differences and 95% confidence intervals. Heterogeneity was assessed using the I2 statistic, and bias was estimated using the SYRCLE tool. RESULTS: Among the 879 reviewed records, 25 articles met our inclusion criteria. These findings demonstrate that treatment with different phytochemicals and marine natural products (flavonoids, phenols, peptides, and alkaloids, etc.) significantly improved various aspects of ovarian function compared to control groups. The treatment led to an increase in follicle count at different stages, elevated levels of key hormones, and a decrease in atretic follicles and hormone levels associated with POF. This therapy also reduced oxidative stress (specifically polyphenols, resveratrol) and apoptotic cell death (particularly flavonoids, chrysin) in ovarian granulosa cells, although it showed no significant impact on inflammatory responses. The certainty of evidence supporting these findings ranged from low to moderate. CONCLUSIONS: Phytochemicals and marine natural product therapy (explicitly flavonoids, phenols, peptides, and alkaloids) has shown potential in enhancing folliculogenesis and improving ovarian function in animal models of POF. These findings provide promising strategies to protect ovarian reserve and reproductive health. Targeting oxidative stress and apoptosis pathways may be the underlying mechanism.

Mechanisms of Bushen Tiaoxue Granules against controlled ovarian hyperstimulation-induced abnormal morphology of endometrium based on network pharmacology.

Bushen Tiaoxue Granules (BTG) is an empirical Chinese herbal formula that has been used for the treatment of subfertility. The protective effect of BTG on controlled ovarian hyperstimulation (COH)-induced impaired endometrial receptivity has been reported in our previous study. This study aims to explore the mechanisms of BTG on ameliorating abnormal morphology of endometrium based on network pharmacology. Active compounds of BTG were identified via the traditional Chinese medicine systems pharmacology and UPLC-MS technology. The SwissTargetPrediction platform and HERB database were used to screen out the putative targets of BTG. Potential targets of endometrial dysfunction caused by COH were obtained from three GEO databases. Through the STRING database, the protein-protein interaction was carried out according to the cross-common targets of diseases and drugs. GO terms and KEGG pathways enrichment analyses were conducted via the Metascape database. AutoDock Vina was used for docking validation of the affinity between active compounds and potential targets. Finally, in vivo experiments were used to verify the potential mechanisms derived from network pharmacology study. A total of 141 effective ingredients were obtained from TCMSP and nine of which were verified in UPLC-MS. Six genes were selected through the intersection of 534 disease related genes and 165 drug potential targets. Enrichment analyses showed that BTG might reverse endometrial dysfunction by regulating adherens junction and arachidonic acid metabolism. Hematoxylin-eosin staining revealed that BTG ameliorated the loose and edematous status of endometrial epithelium caused by COH. The protein expression of FOXO1A, ß-Catenin and COX-2 was decreased in the COH group, and was up-regulated by BTG. BTG significantly alleviates the edema of endometrial epithelium caused by COH. The mechanisms may be related to adheren junctions and activation of arachidonic acid metabolism. The potential active compounds quercetin, taxifolin, kaempferol, eriodictyol, and isorhamnetin identified from the BTG exhibit marginal cytotoxicity. Both high and low concentrations of kaempferol, eriodictyol, and taxifolin are capable of effectively ameliorating impaired hESC cellular activity.

Establishing superfine nanofibrils for robust polyelectrolyte artificial spider silk and powerful artificial muscles.

Spider silk exhibits an excellent combination of high strength and toughness, which originates from the hierarchical self-assembled structure of spidroin during fiber spinning. In this work, superfine nanofibrils are established in polyelectrolyte artificial spider silk by optimizing the flexibility of polymer chains, which exhibits combination of breaking strength and toughness ranging from 1.83 GPa and 238 MJ m-3 to 0.53 GPa and 700 MJ m-3, respectively. This is achieved by introducing ions to control the dissociation of polymer chains and evaporation-induced self-assembly under external stress. In addition, the artificial spider silk possesses thermally-driven supercontraction ability. This work provides inspiration for the design of high-performance fiber materials.

Shear flow controlled morphological polydispersity of amphiphilic ABA triblock copolymer vesicles.

Self-assembled polymeric aggregates are generally polydisperse in morphology due to the existence of many metastable states in the system. This shortcoming becomes a bottleneck for preparing high quality self-assembled polymeric materials. An important concern is the possibility of controlling morphological polydispersity through the modulation of the metastable states. In this study, both simulative and experimental results show that the metastable states can be modulated. As a typical example, the morphological polydispersity of amphiphilic ABA triblock copolymer vesicles have been successfully controlled by shear flow. A higher shear rate results in more uniform and smaller vesicles. However, if the shear rate is extremely high, small spheres and short rods can be observed. These findings not only give a deeper insight into the metastable behavior of self-assembled polymeric aggregates but also provide a new strategy for improving the uniformity of vesicles.

Multifunctional Iontronic Sensor Based on Liquid Metal-Filled Ho llow Ionogel Fibers in Detecting Pressure, Temperature, and Proximity.

Fiber-based pressure/temperature sensors are highly desired in wearable electronics because of their natural advantages of good breathability and easy integrability. However, it is still a great challenge to fabricate reliable and highly sensitive fiber-based pressure/temperature sensors via a scalable and facile strategy. Herein, a novel fiber-based iontronic sensor with excellent pressure- and temperature-sensing capabilities is designed by assembling two crossed hollow and porous ionogel fibers filled with liquid metal. Serving as a pressure sensor, a high detection resolution (1.16 Pa), a high sensitivity of 13.30 kPa-1 (0-2 kPa), and a wide detection range (∼207 kPa) are realized owing to its novel hierarchical structure and the selection of deformable liquid electrodes. As a temperature sensor, it exhibits a high temperature sensitivity of 25.99% °C-1 (35-40 °C), high resolution of 0.02 °C, and good repeatability and reliability. On the basis of these excellent sensing capabilities, the as-prepared sensor can detect not only pressure signals varied from weak pulse to large joint movements but also the proximity of different objects. Furthermore, a large-area fiber array can be easily woven for acquiring the pressure mapping to intuitively distinguish the location, magnitude, and shape of the loaded object. This work provides a universal strategy to design fiber-shaped iontronic sensors for wearable electronics.

A modified mouse model of haemorrhagic transformation associated with tPA administration after thromboembolic stroke.

Objective: To establish a new mouse model of haemorrhagic transformation associated with delayed tissue-type plasminogen activator (tPA) treatment to provide a novel tool to study therapeutic strategies for haemorrhagic transformation. Methods: Male C57BL/6 mice were subjected to carotid artery thrombosis stimulated with ferric chloride. The thrombus was then mechanically detached to induce migration toward the intracranial circulation. To induce haemorrhagic transformation, mice were intravenously injected with 10 mg/kg tPA 4.5 h after the onset of ischaemia and were sacrificed 24 h after tPA treatment. Results: In this new model, administration of tPA 4.5 h after stroke exacerbated the risk of intracerebral haemorrhage. Thrombolysis with tPA also exacerbated cerebral infarction, brain oedema, blood-brain barrier breakdown, and neurological deficits. However, cerebral blood flow was not significantly affected. Conclusion: The present model is reproducible, easy to perform, and mimics the clinical situation of haemorrhagic transformation after tPA treatment in humans. This modified model can be used as a new tool to test experimental drugs for haemorrhagic transformation associated with delayed tPA administration after an ischaemic stroke.