Gypenoside A Protects Human Myocardial Cells from Ischemia/Reperfusion Injury via the circ_0010729/miR-370-3p/RUNX1 Axis.

Ischemia/reperfusion (I/R) injury is one of the major causes of cardiovascular disease. Gypenoside A (GP), the main active component of Gynostemma pentaphyllum, alleviates myocardial I/R injury. Circular RNAs (circRNAs) and microRNAs (miRNAs) are involved in the I/R injury. We explored the protective effect of GP on human cardiomyocytes (HCMs) via the circ_0010729/miR-370-3p/RUNX1 axis. Overexpression of circ_0010729 abolished the effects of GP on HMC, such as suppression of apoptosis and increase in cell viability and proliferation. Overexpression of miR-370-3p reversed the effect of circ_0010729 overexpression, resulting in the stimulation of HMC viability and proliferation and inhibition of apoptosis. The knockdown of miR-370-3p suppressed the effects of GP in HCMs. RUNX1 silencing counteracted the effect of miR-370-3p knockdown and maintained GP-induced suppression of apoptosis and stimulation of HMC viability and proliferation. The levels of RUNX1 mRNA and protein were reduced in cells expressing miR-370-3p. In conclusion, this study confirmed that GP alleviated the I/R injury of myocardial cell via the circ_0010729/miR-370-3p/RUNX1 axis.

Study on the Preparation and Process Parameter-Mechanical Property Relationships of Carbon Fiber Fabric Reinforced Poly(Ether Ether Ketone) Thermoplastic Composites.

Carbon fiber fabric-reinforced poly(ether ether ketone) (CFF-PEEK) composites exhibit exceptional mechanical properties, and their flexibility and conformability make them a promising alternative to traditional prepregs. However, the formation of the CFF-PEEK composite is trapped in the high viscosity of PEEK, the smooth surface, and tightly interwoven bundles of CFF. It is more difficult for the resin to flow through the fibers of complex textile structures. Here, a simple film stacking method using the hot-pressing process of plain-woven CFF-PEEK thermoplastic composites is discussed. The uniform distribution of PEEK resin between each layer of CFF reduces the flow distance during the molding process, preventing defects in the composite material effectively. Four process parameters, including molding temperature (370, 385, 400, and 415 °C), molding pressure (1, 2, 4, 8, and 10 MPa), molding time (10, 20, 30, 40, 60, and 90 min), and pre-compaction process, are considered. Interlaminar shear strength (ILSS), tensile strength, and flexural strength of CFF/PEEK composites are evaluated to optimize the process parameters. Moreover, ultrasonic scanning microscopy and scanning electron microscopy are employed to observe the formation quality and microscopic failure modes of CFF/PEEK composites, respectively. The ultimate process parameters are a molding temperature of 410 °C, molding pressure of 10 MPa, molding time of 60 min, and the need for the pre-compaction process. Under the best process parameters, the ILSS is 62.5 MPa, the flexural strength is 754.4 MPa, and the tensile strength is 796.1 MPa. This work provides valuable insight for studying the process parameters of fiber fabric-reinforced thermoplastic polymer composites and revealing their impact on mechanical properties.

Synthesis and Characterization of Phenazine-Based Redox Center for High-Performance Polymer Poly(aryl ether sulfone)-5,10-Diphenyl-dihydrophenazine.

Phenazine-based redox-active centers are capable of averting chemical bond rearrangements by coupling during the reaction process, leading to enhanced stabilization of the material. When introduced into a high-performance polymer with excellent physicochemical properties, they can be endowed with electrochemical properties and related prospective applications while maintaining the capabilities of the materials. In this study, a facile C-N coupling method was chosen for the synthesis of serial poly(aryl ether sulfone) materials containing phenazine-based redox-active centers and to explore their electrochemical properties. As expected, the cyclic voltammetry curves of PAS-DPPZ-60, which basically overlap after thousands of cycles, indicate the stability of the electrochemical properties. As an electrochromic material, the transmittance change in PAS-DPPZ-60 exhibits only a slight attenuation after as long as 600 cycles. Meanwhile, as an organic battery cathode material, PAS-DPPZ has a theoretical specific capacity of 126 mAh g-1, and the capacity retention rate is 82.6% after 100 cycles at a 0.1 C current density. The perfect combination of advantageous features between phenazine and poly(aryl ether sulfone) is considered to be the reason for the favorable electrochemical performance of the material series.

Estrogen receptor GPR30 in the anterior cingulate cortex mediates exacerbated neuropathic pain in ovariectomized mice.

Menopausal women experience neuropathic pain 63% more frequently than men do, which may attribute to the estrogen withdrawal. However, the underlying mechanisms remain unclear. Here, the role of estrogen receptors (ERs) in ovariectomized (OVX) female mice following chronic constriction injury (CCI) was investigated. With 17ß-estradiol (E2) supplemented, aggravated mechanical allodynia in OVX mice could be significantly alleviated, particularly after intra-anterior cingulate cortex (ACC) E2 delivery. Pharmacological interventions further demonstrated that the agonist of G-protein-coupled estrogen receptor 30 (GPR30), rather than ERα or ERß in the ACC, exhibited the similar analgesic effect as E2, whereas antagonist of GPR30 exacerbated allodynia. Furthermore, OVX surgery reduced GPR30 expression in the ACC, which could be restored with estrogen supplementation. Selective downregulation of GPR30 in the ACC of naïve female mice induces mechanical allodynia, whereas GPR30 overexpression in the ACC remarkedly alleviated OVX-exacerbated allodynia. Collectively, estrogen withdrawal could downregulate the ACC GPR30 expression, resulting in exacerbated neuropathic pain. Our findings highlight the importance of GPR30 in the ACC in aggravated neuropathic pain during menopause, and offer a potential therapeutic candidate for neuropathic pain management in menopausal women.

Sexual dimorphic distribution of G protein-coupled receptor 30 in pain-related regions of the mouse brain.

Sex differences in pain sensitivity have contributed to the fact that medications for curing chronic pain are unsatisfactory. However, the underlying mechanism remains to be elucidated. Brain-derived estrogen participates in modulation of sex differences in pain and related emotion. G protein-coupled receptor 30 (GPR30), identified as a novel estrogen receptor with a different distribution than traditional receptors, has been proved to play a vital role in regulating pain affected by estrogen. However, the contribution of its distribution to sexually dimorphic pain-related behaviors has not been fully explored. In the current study, immunofluorescence assays were applied to mark the neurons expressing GPR30 in male and female mice (in metestrus and proestrus phase) in pain-related brain regions. The neurons that express CaMKIIα or VGAT were also labeled to observe overlap with GPR30. We found that females had more GPR30-positive (GPR30+ ) neurons in the primary somatosensory (S1) and insular cortex (IC) than males. In the lateral habenula (LHb) and the nucleus tractus solitarius (NTS), males had more GPR30+ neurons than females. Moreover, within the LHb, the expression of GPR30 varied with estrous cycle phase; females in metestrus had fewer GPR30+ neurons than those in proestrus. In addition, females had more GPR30+ neurons, which co-expressed CaMKIIα in the medial preoptic nucleus (mPOA) than males, while males had more than females in the basolateral complex of the amygdala (BLA). These findings may partly explain the different modulatory effects of GPR30 in pain and related emotional phenotypes between sexes and provide a basis for comprehension of sexual dimorphism in pain related to estrogen and GPR30, and finally provide new targets for exploiting new treatments of sex-specific pain.

InSitu Integrated Fabrication for Multi-Interface Stabilized and Highly Durable Polyaniline@Graphene Oxide/Polyether Ether Ketone Special Separation Membranes.

Special separation membranes are widely employed for separation and purification purposes under challenging operating conditions due to their low energy consumption, excellent solvent, and corrosion resistance. However, the development of membranes is limited by corrosion-resistant polymer substrates and precise interfacial separation layers. Herein, polyaniline (PANI) is employed to achieve insitu anchoring of multiple interfaces, resulting in the fabrication of polyaniline@graphene oxide/polyether ether ketone (PANI@GO/PEEK) membranes. Insitu growth of PANI achieves the adequate bonding of the PEEK substrate and GO separation interface, which solves the problem of solution processing of PEEK and the instability of GO layers. By bottom-up confined polymerization of aniline, it could control the pore size of the separation layer, correct defects, and anchor among polymer, nano-separation layer, and nano-sheet. The mechanism of membrane construction within the confined domain and micro-nano structure modulation is further explored. The membranes demonstrate exceptional stability realizing over 90% rejection in 2 m HCl, NaOH, and high temperatures. Additionally, -membranes exhibit remarkable durability after 240 days immersion and 100 h long-term operation, which display the methanol flux of 50.2 L m-2 h-1 and 92% rejection of AF (585 g mol-1 ). This method substantially contributes to special separation membranes by offering a novel strategy.

Semi-crystalline sulfonated poly(ether ketone) proton exchange membranes: The trade-off of facile synthesis and performance.

Improving the performance of proton exchange membranes (PEMs) through the synthesis of sulfonated polymers with elaborate molecular structures has received extensive approval. However, the tedious synthetic process and consequently high costs restrain their possible substitution for Nafion, a classic PEM material. Herein, a series of semi-crystalline sulfonated poly(ether ketone)s with fluorene-based units were prepared via direct copolymerization of commercially available monomers and followed post-sulfonation, namely SPEK-FD-x, where × represents the molar ratio of the fluorene-containing monomer to the employed bisphenol monomers. The entire synthetic pathway was facile without involving hardly accessible materials. Subsequently, various properties of SPEK-FD-x membranes were investigated and further compared with Nafion 117. Due to the formation of the well-defined hydrophilic-hydrophobic microphase separation morphology and the reinforcement of the PEK crystalline regions, the SPEK-FD-x membranes exhibited outstanding proton conductivity, resistance for methanol permeation, as well as dimensional, thermal, oxidative, and mechanical stability. Among them, the overall behavior of the SPEK-FD-25 membrane was comparable to or even greater than that of Nafion 117, most importantly, it also performed decently in both H2/air fuel cells and direct methanol fuel cells. Therefore, with the straightforward synthesis and superior performance, the SPEK-FD-x membranes may serve as a promising alternative to Nafion.

Foreign body granuloma in the tongue differentiated from tongue cancer: A case report.

BACKGROUND: Embedded foreign bodies in the tongue are rarely seen in clinical settings. An untreated foreign body can cause a granuloma which often presents as an enlarged tongue mass. However, if foreign body ingestion status is unknown, physical examination and magnetic resonance imaging (MRI) tend to lead to suspicion of tongue cancer, especially in older patients. Thus, differential diagnosis of an enlarged tongue mass is important, especially because it is closely related to the choice of treatment method. CASE SUMMARY: A 61-year-old woman was admitted to the hospital with pain and noticeable swelling in the tongue that had persisted for over 1 mo. She had no previous medical history. MRI revealed abnormal signal intensities that were indicative of a neoplasm. Thus, the oral surgeon and radiologist arrived at a primary diagnosis of tongue cancer. The patient visited the Ear Nose and Throat Department for further consultation and underwent an ultrasound examination of the tongue. The ultrasonography was consistent with a linear hyperechoic foreign body which was indicative of an embedded foreign body (bone) in the tongue, even though the patient denied any history of foreign body ingestion. Complete surgical enucleation of the lesion was conducted. The mass which included a fish bone was completely removed. The post-operative pathological examination confirmed that the mass was a granuloma containing collagen fibers, macrophages and chronic inflammatory cells. The patient recovered without complications over a 2 mo follow-up period. CONCLUSION: We report a rare case of foreign body granuloma in the tongue that was primarily diagnosed as tongue cancer. The MRI and ultrasound examinations revealed a piece of bone in the left lateral aspect of the tongue. The granuloma, which contained a fish bone, was completely removed via surgery and confirmed via biopsy. Differential diagnosis of the enlarged tongue mass was critical to the selection of treatment method.

Preparation and Properties of Novel Crosslinked Polyphosphazene-Aromatic Ethers Organic-Inorganic Hybrid Microspheres.

A series of novel crosslinked polyphosphazene-aromatic ether organic-inorganic hybrid microspheres with different structures were prepared via precipitation polycondensation between hexachlorocyclotriphosphazene (HCCP) and bisphenol monomers. The bisphenol monomers have different numbers of -CF3 in the side group, which correspond to distinct oligomeric species-absorbing mechanisms. The wetting behavior of the microsphere surface was evaluated using a water contact angle (CA) measurement, which increased with the increase in the content of -CF3 in polyphosphazene. We also investigated the effects of HCCP concentration and ultrasonic power on the morphology of the microspheres.

The surface modification of long carbon fiber reinforced polyether ether ketone with bioactive composite hydrogel for effective osteogenicity.

Long carbon fiber reinforced polyether ether ketone (LCFRPEEK) is fabricated using a three-dimensional (3D) needle-punched method in our previous work, which is considered as a potential orthopedic implant due to its high mechanical strength and isotropic properties, as well as having an elastic modulus similar to human cortical bone. However, the LCFRPEEK has inferior integration with bone tissue, limiting its clinical application. Thus, a facile surface modification method, using gelatin methacrylate/polyacrylamide composite hydrogel coating (GelMA/PAAM) loading with dexamethasone (Dex) on our newly-developed LCFRPEEK composite via concentrated sulfuric acid sulfonating and ultraviolet (UV) irradiation grafting methods, has been developed to tackle the problem. The results demonstrate that the GelMA/PAAM/Dex coating modified sulfonated LCFRPEEK (SCP/GP/Dex) has a hydrophilicity surface, a long-term Dex release capability and forms more bone-like apatite nodules in SBF. The SCP/GP/Dex also displays enhanced cytocompatibility and osteogenic differentiation in terms of rat bone marrow mesenchymal stem cells (rBMSCs) responses in vitro assay. The in vivo rat cranial defect assay confirms that SCP/GP/Dex boosts bone regeneration/osseointegration, which significantly improves osteogenic fixation between the implant and bone tissue. Therefore, the newly-developed LCFRPEEK modified via GelMA/PAAM/Dex bioactive coating exhibits improved biocompatibility and osteogenic integration capability, which has the basis for an orthopedic implant for clinical application.

[Progress in PiggyBac transposition system research and its application in the gene modified T cell in tumor immunotherapy].

The tumor immunotherapy with gene modified T cells has made inspiring progress in recent years. Foreign gene transduction is the key link before the adoptive transfer of T cells. Advances in this field enhance T cells vitality and achieve precise targeted killing of tumor cells. T cell gene modification technology needs to strike a balance between transduction efficiency, safety, and cost. Transposons are with low immunogenicity, easy to manufacture, and cost-effective. They integrate the gene of interest into the target cell genome and allow stable and durable expression. Active transposons in mammalian cells include PiggyBac (PB), Sleeping Beauty (SB) and Tol2. Among them, the PB transposition system enables seamless genome editing with large gene load, high transposition activity, and strong structural plasticity. This article summarizes the structure, mechanism, characteristics, and transduction efficiency of PB transposition system, as well as its application and prospect in chimeric antigen receptor-engineered T cell therapy.

STROBE-clinical characteristics and prognosis factors of gastric cancer in young patients aged ≤30 years.

ABSTRACT: We aimed to determine the clinical characteristics and prognosis factors of young patients with gastric cancer (GC).A total of 101 young patients with GC referred to Zhengzhou University People's Hospital, Henan province, China between January 1st, 2003 and June 1st, 2015 were retrospectively reviewed. The medical records included ages, genders, marital status, family history of tumors, comorbidity, Helicobacter pylori (H.pylori) infection, fibrinogen, prealbumin, alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), tumor location, tumor size, TNM stage, differentiation of the tumor, WHO type, treatment method and prognostic factors effect were further assessed.The mean age of GC patients in our group was 26.0 years. The incidence was slightly higher in females (female: male = 1.1:1). Some patients had the family history of tumor and H.pylori infection (2.0%, 6.9%). The tumor sizes were mainly under 5 cm (52.4%) and the most locations were in the antrum (43.5%) and body (42.5%). A large number of patients were diagnosed as adenocarcinomas (66.3%) and the main histological of GC was poor differentiated (72.3%). Moreover, a high proportion of patients were diagnosed at the stages III-IV (61.4%), and most patients received surgery combined chemotherapy (63.4%), however, the survival outcome was poor. In univariate Cox analysis, tumor sizes, TNM stage were significantly associated with overall survival (OS) and the multivariate Cox analysis demonstrated that TNM stage was significantly associated with OS.GC in young patients has its unique biological and clinical features. A large majority of young patients were diagnosed at their advanced stages with poor prognostic. TNM stage was an independent prognostic factor for young patients with GC, early GC screening in young people should be actively promoted.

Gasless transaxillary endoscopic thyroidectomy for unilateral low-risk thyroid cancer: Li's six-step method.

The past decade has witnessed rapid advances in gasless transaxillary endoscopic thyroidectomy (GTET) for thyroid cancer, which has become a reliable procedure with good therapeutic effectiveness, aesthetic benefits, and safety. This procedure has been widely promoted in some Asian countries; however, few studies have described the specific surgical steps for unilateral low-risk thyroid cancer. Based on a review of the literature and our own clinical experience, we introduce in detail the surgical procedure of GTET for the unilateral low-risk thyroid cancer, briefly summarized into Li's 6 steps: surgical position and incision design; creation of surgical cavities; dissection of the superior pole of the thyroid and its vessels, and identification and protection of superior laryngeal nerve; identification and protection of the superior parathyroid gland, and identification of the inferior parathyroid gland; identification and protection of the recurrent laryngeal nerve and the inferior parathyroid gland, and central neck dissection; and processing of the suspensory ligaments of thyroid gland and en bloc resection of the tumor. The six-step approach is simple to learn. The lymph nodes are dissected first, followed by resection of the primary lesion and protect important structures, which meets the principles of radical tumor treatment. It is hoped that the proposed Li's six-step method can promote the standardized, safe, and wide application in treating early thyroid cancer.

An MD2-perturbing peptide has therapeutic effects in rodent and rhesus monkey models of stroke.

Studies have failed to translate more than 1000 experimental treatments from bench to bedside, leaving stroke as the second leading cause of death in the world. Thrombolysis within 4.5 hours is the recommended therapy for stroke and cannot be performed until neuroimaging is used to distinguish ischemic stroke from hemorrhagic stroke. Therefore, finding a common and critical therapeutic target for both ischemic and hemorrhagic stroke is appealing. Here, we report that the expression of myeloid differentiation protein 2 (MD2), which is traditionally regarded to be expressed only in microglia in the normal brain, was markedly increased in cortical neurons after stroke. We synthesized a small peptide, Trans-trans-activating (Tat)-cold-inducible RNA binding protein (Tat-CIRP), which perturbed the function of MD2 and strongly protected neurons against excitotoxic injury in vitro. In addition, systemic administration of Tat-CIRP or genetic deletion of MD2 induced robust neuroprotection against ischemic and hemorrhagic stroke in mice. Tat-CIRP reduced the brain infarct volume and preserved neurological function in rhesus monkeys 30 days after ischemic stroke. Tat-CIRP efficiently crossed the blood-brain barrier and showed a wide therapeutic index for stroke because no toxicity was detected when high doses were administered to the mice. Furthermore, we demonstrated that MD2 elicited neuronal apoptosis and necroptosis via a TLR4-independent, Sam68-related cascade. In summary, Tat-CIRP provides robust neuroprotection against stroke in rodents and gyrencephalic nonhuman primates. Further efforts should be made to translate these findings to treat both ischemic and hemorrhagic stroke in patients.

Side-Chain-Type Anion Exchange Membranes Based on Poly(arylene ether sulfone)s Containing High-Density Quaternary Ammonium Groups.

To obtain anion exchange membranes with both high ionic conductivity and good dimensional stability, a series of side-chain-type poly(arylene ether sulfone)s (PAES-QDTPM-x) were designed and synthesized. Quaternary ammonium (QA) groups were densely aggregated and grafted onto the main chain via flexible hydrophobic spacers. Well-defined microphase separation was confirmed by small-angle X-ray scattering. PAES-QDTPM-0.30 exhibited reasonably high conductivity (39.4 mS cm-1 at 20 °C and 76.1 mS cm-1 at 80 °C) and excellent dimensional stability at 80 °C (11.9% in length, 11.2% in thickness) due to the concentration of ion clusters and the side-chain-type structure. All membranes maintained over 82% of the conductivity after alkali treatment for 14 days. In the H2/O2 fuel cell performance test, the maximum power density of PAES-QDTPM-0.30 at 60 °C was 225.8 mW cm-2.

Rosmarinic acid protects rats against post-stroke depression after transient focal cerebral ischemic injury through enhancing antioxidant response.

Rosmarinic acid (RA), a natural polyphenol, possesses potent antioxidant and anti-inflammatory activities. To evaluate the ability of RA to cure ischemic stroke and post-stroke depression (PSD), rats were treated with various doses of RA after cerebral ischemia. Neurological deficits and infarct volume of the brain were measured. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) were examined at different time points. In addition, a forced swimming test and sucrose preference test were performed to detect the anti-depressive effects of RA. Our results revealed RA administration significantly alleviated neurological deficits and reduced infarct volumes. RA attenuated the decrease of SOD, CAT activities and GSH levels in the ischemic penumbra of the brain. Most importantly, RA treatment alleviated the depression behaviors. Increased expression of Nrf2 was also induced by RA, while down regulation Nrf2 by Nrf2-short-hairpin RNA sequences reversed the increasing activity of SOD and CAT induced by RA, as well as the protection against PSD. The present study indicates that RA exerts a potent neuroprotective effect against stroke and PSD, which could be a promising therapeutic intervention for stroke.

An algorithm for one-stage malignant oncologic scalp reconstruction.

BACKGROUND: Scalp reconstruction has always been a challenging problem after oncological resection. Advanced surgical techniques can reconstruct any defects, but there are a large number of patients who cannot benefit from surgery for immature strategies. The authors here describe an algorithm for selecting the best reconstructive categories and minimizing complications according to the surgical defect of scalp tumors. METHODS: A single-institution retrospective review was conducted that included 173 patients with scalp tumors treated with surgery followed by reconstruction. Patients were identified by tumor type and nature; the location of scalp defect, size, and depth; the types of reconstructions and surgical. A systematic algorithm was developed according to our findings and current literature. RESULTS: Small defects (≤4 cm2) could be closed by primary closure. Medium defects (4-30 cm2) were reconstructed by local flaps. We routinely used skin graft for significant surgical defects (30-90 cm2). And the tumor's location did not have an impact on reconstructive categories of above three types of defects. Free flaps should reconstruct very large-sized defects (>90 cm2) in frontal, temporal, and vertex locations while pedicle flaps suited for occipital defects due to its anatomic vicinity. The reconstruction algorithm of recurrent disease was like the management in primary tumors except for the medium size defect in the occipital region that was primarily reconstructed by a skin graft. Multiple free flaps reconstruction is the best possibility for total scalp resection. Free flap reconstruction is used mainly for composite resection of the scalp, calvarium, and dura. CONCLUSIONS: Successful scalp reconstruction requires careful preoperative assessment, flexible and precisely intraoperative management. The algorithm based on defect size, depth, and location can supply some degree of guidelines when considering choosing suitable reconstructive procedures.

Enhanced High-Temperature Dielectric Properties of Poly(aryl ether sulfone)/BaTiO3 Nanocomposites via Constructing Chemical Crosslinked Networks.

Heat-resistant and crosslinked polymers/ceramic composites have been prepared and investigated for enhancing high-temperature dielectric properties to adapt the development of advanced electric and electronic systems. Here, a series of crosslinkable heat-resistant poly(arylene ether sulfone)s (DPAES) with large dipole units of -SO2 - are designed and synthesized as matrix, which are blended with BaTiO3 (BT) nanoparticles to fabricate crosslinked polymer composites for boosting high-temperature dielectric properties. The results show that BT/c-DPAES possess great dielectric stability at measured frequency and temperature. Meanwhile, the discharged energy density and efficiency of BT/c-DPAES composites are higher than that of BT/DPAES at high temperatures, e.g., 10 vol% BT/c-DPAES has a discharged energy density of 1.7 J cm-3 and efficiency of 73%, increasing by 42% and 128% in contrast to BT/DPAES, respectively. The enhanced high-temperature energy storage properties can be attributed to the construction of a crosslinked polymer network, reducing leakage current density of composites.