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Objective To assess the feasibility and results of tibial cortex transverse distraction (TCTD) followed by open correction with internal fixation (OCIF) for foot and ankle deformity with concurrent ulcers. Methods A retrospective analysis was conducted. Between 2010 and 2019, a two‐stage management of TCTD followed by OCIF was performed in 13 patients (13 feet). There were five males and eight females with a mean age of 33.8 ± 14.6 years. Ten patients had a right‐side lesion, and three patients had a left‐side lesion. The etiology of deformity included seven cases of congenital neurological disease, one case of Charcot–Marie–Tooth disease, one case of trauma sequelae, and three cases of myelomeningocele. Duration of disease, size of ulcers, surgical procedures, healing time, external fixation time, and complications of these patients were recorded. The Texas wound classification and National Pressure Ulcer Advisory Panel (NPUAP) classification were used for assessing the ulcers. The modified Dimeglio score of deformity and American Orthopeadic Foot and Ankle Society (AOFAS) ankle‐hindfoot score were applied to evaluate the status before treatment and the results at final follow‐up. Results The TCTD and wound debridement were performed in all patients, and an additional Ilizarov correction technique was added in two patients. All ulcers were healed in 3 months after first‐stage treatment. The median patient self‐report time of ulcer healing was 2.0 weeks (IQR, 1.8–3.3). The median external fixation time was 138.0 days (IQR, 134.5–141.5) days. After second‐stage operative correction, the patients were followed‐up for an average of 28.0 ± 2.9 months. At the final follow‐up, the modified Dimeglio score of deformity was decreased from 6.7 ± 2.1 to 1 (IQR, 0.0–1.0), and the mean AOFAS score was improved from 42.9 ± 19.1 to 82.6 ± 7.7. Before the treatment, there were eight patients with severe deformity, four patients with moderate deformity, and one patient with mild deformity. Postoperatively, seven patients were classified as mild deformity and six patients had a postural foot. The results of AOFAS ankle‐hindfoot score were defined as excellent in three patients, as good in five, and as fair in five. Complications include one case of mild displacement of the osteotomized cortex and one case of pin‐tract infection. No delayed union, nonunion, relapse of ulcers, or deformity were observed. Conclusions The two‐stage management of TCTD followed by OCIF could be considered as an alternative treatment for foot and ankle deformities combined with chronic ulcers.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Long‐term changes in the microenvironment of the brain contribute to the degeneration of neurological function following TBI. However, current research focuses primarily on short‐term modulation during the early phases of TBI, not on the critical significance of long‐term homeostasis in the brain microenvironment. Notably, dysfunction of the glymphatic‐lymphatic system results in the accumulation of danger/damage‐associated molecular patterns (DAMPs) in the brain, which is regarded as the leading cause of long‐term microenvironmental disturbances following TBI. Here, a nanostructure, Nano‐plumber, that co‐encapsulates the microenvironment regulator pro‐DHA and the lymphatic‐specific growth factor VEGF‐C is developed, allowing for a sustainable and orderly regulation of the microenvironment to promote long‐term neurological recovery. Nano‐plumber reverses the injury microenvironment by suppressing microglia and astrocytes activation and maintaining reduced activation via enhanced glymphatic‐lymphatic drainage, and significantly improves the neurological function of rodents with TBI. This study demonstrates that glymphatic‐lymphatic system reconstruction is essential for enhancing long‐term prognosis following TBI, and that the Nano‐plumber developed here may serve as a clinically translatable treatment option for TBI. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) are the most effective and commonly used drugs for the treatment of systemic lupus erythematosus (SLE). However, a large number of side effects occur after long-term or high-dose glucocorticoid treatment, which severely restricts the use of glucocorticoids. Reconstituted high-density lipoprotein (rHDL), an emerging nanocarrier, is promising for targeted delivery to sites of inflammation and macrophages. Here, we prepared a steroid-loaded recombinant high-density lipoprotein and evaluated its therapeutic efficacy in a murine macrophage cell line (RAW264.7) and a lupus (MRL/lpr mice) mouse model. The obtained corticosteroid-loaded nanomedicine, named PLP-CaP-rHDL, exhibited desirable characteristics. Pharmacodynamics studies revealed that the nanoparticles could significantly reduce the levels of inflammatory cytokines in the macrophages in vitro and also effectively alleviate lupus nephritis in MRL/lpr mice without causing obvious side effects at a dose of 0.25 mg/kg. Thus, our newly developed steroid-loaded rHDL nanocarriers hold a great potential for anti-inflammatory therapy with reduced side effects and may provide a precise targeted therapy for SLE. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction has been recognized as the key pathogenesis of most neurodegenerative diseases including Alzheimer's disease (AD). The dysregulation of mitochondrial calcium ion (Ca2+) homeostasis and the mitochondrial permeability transition pore (mPTP), is a critical upstream signaling pathway that contributes to the mitochondrial dysfunction cascade in AD pathogenesis. Herein, a "two-hit braking" therapeutic strategy to synergistically halt mitochondrial Ca2+ overload and mPTP opening to put the mitochondrial dysfunction cascade on a brake is proposed. To achieve this goal, magnesium ion (Mg2+), a natural Ca2+ antagonist, and siRNAtothe central mPTP regulator cyclophilin D (CypD), are co-encapsulated into the designed nano-brake; A matrix metalloproteinase 9 (MMP9) activatable cell-penetrating peptide (MAP) is anchored on the surface of nano-brake to overcome the blood-brain barrier (BBB) and realize targeted delivery to the mitochondrial dysfunction cells of the brain. Nano-brake treatment efficiently halts the mitochondrial dysfunction cascade in the cerebrovascular endothelial cells, neurons, and microglia and powerfully alleviates AD neuropathology and rescues cognitive deficits. These findings collectively demonstrate the potential of advanced design of nanotherapeutics to halt the key upstream signaling pathways of mitochondrial dysfunction to provide a powerful strategy for AD modifying therapy. [ABSTRACT FROM AUTHOR]

Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α -synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α -mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α -mangostin efficiently delivered α -mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α -mangostin as a potential and universal therapy against neurodegenerative diseases. NP- α -M rejuvenates microglial surveillance of misfolded proteins through metabolic reprogramming, which provides a universal approach to clear multiple misfolded proteins and treat neurodegenerative diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Fiber-distributed optical fiber acoustic sensor (DAS) is generally used in distributed long-distance acoustic/vibration measurement. Recently, DAS is also used in weak airborne sound detection. To improve the sensitivity of DAS, using a state-of-the-art acoustic transducer or a special enhanced scattering fiber, which are uncommon in the industrial site, is often essential, according to the previous research. In this work, the fading of DAS is suppressed by the multi-frequency probes and polarization-diversity-receiver scheme. The self-noise of DAS is further lowered by the phase averaging of multiple acoustic channels wound on the transducer. We found that, supported by this high-performance DAS, even if the transducer is made with an ultra-simple plastic structure in daily life, the system can achieve high-sensitivity airborne sound sensing. The proposed simple acoustic transducer can reach the sensitivity level of −106.5 dB re. 1 rad/μPa at a sensing range of 5.1 km, which can meet many demands on the industrial site. [ABSTRACT FROM AUTHOR]

Objective·To investigate the effects of several key proteins of severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) on macropinocytosis in various cell models. Methods· The interactions between spike protein receptor-binding domain (S-RBD), nucleocapsid protein (N) and non-structural protein-7 (NSP7) of SARS-COV-2 and HEK-293T intracellular proteins were explored by co-immunoprecipitation assay. In vitro, S-RBD, N and NSP7 proteins of SARS-CoV-2 were incubated with HEK-293T/bEnd. 3/Beas-2b cells (normal cell models), respectively, and the changes of macropinocytosis level of cells labeled with fluorescein isothiocyanate (FITC) -70 kDa-dextran were observed. In vitro, S-RBD, N and NSP7 proteins of SARS-CoV-2 were incubated with inflammatory cells induced by lipopolysaccharide (LPS), respectively, and the changes of macropinocytosis level of inflammatory cells were analyzed. In the normal cell models and inflammatory cell model, EIPA or lipoprotein nano-drug carriers loaded with Rab5 small interfering RNA (siRNA) were used to inhibit the macropinocytosis induced by SARS-CoV-2 proteins, respectively, and the uptake of S-RBD, N and NSP7 proteins by cells were further observed. Results· The three proteins of SARSCOV- 2 could bind to Rab small GTPase proteins after being absorbed into cells. It was found that S-RBD, N and NSP7 proteins of SARS-COV-2 could induce the macropinocytosis after entering the HEK-293T/bEnd. 3/Beas-2b cells. Furthermore, the three proteins of SARS-COV-2 could enhance the megapinocytosis of the inflammatory cell. After treatment with EIPA (75 μmol/L) or lipoprotein nano-drug carriers loaded with Rab5 siRNA, the uptake of S-RBD, N and NSP7 proteins were decreased in both types of cells. Conclusion·S-RBD, N and NSP7 proteins of SARS-CoV-2 can up-regulate megapinocytosis levels in various cell models, especially in the case of combined inflammation infection. At the same time, macropinocytosis inhibitor / lipoprotein nano-drug carrier can inhibit the macropinocytosis up-regulated by the above proteins, and then reduce the entry levels of viral proteins. [Key words] macropinocytosis; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); EIPA; Rab5 [ABSTRACT FROM AUTHOR]

The key factors responsible for the single chain magnet (SCM) behavior of the cobalt(II) disphosphonate compound Co([H.sub.2]L)([H.sub.2]O) with a one-dimensional structure are evaluated. The new method used to analyze the SCM properties of 1D chains has emphasized on the qualitative interpretation of the experimental data on the Co([H.sub.2]L)([H.sub.2]O) chain compound.

Cerebrovascular dysfunction characterized by the neurovascular unit (NVU) impairment contributes to the pathogenesis of Alzheimer's disease (AD). In this study, a cerebrovascular‐targeting multifunctional lipoprotein‐biomimetic nanostructure (RAP‐RL) constituted with an antagonist peptide (RAP) of receptor for advanced glycation end‐products (RAGE), monosialotetrahexosyl ganglioside, and apolipoprotein E3 is developed to recover the functional NVU and normalize the cerebral vasculature. RAP‐RL accumulates along the cerebral microvasculature through the specific binding of RAP to RAGE, which is overexpressed on cerebral endothelial cells in AD. It effectively accelerates the clearance of perivascular Aβ, normalizes the morphology and functions of cerebrovasculature, and restores the structural integrity and functions of NVU. RAP‐RL markedly rescues the spatial learning and memory in APP/PS1 mice. Collectively, this study demonstrates the potential of the multifunctional nanostructure RAP‐RL as a disease‐modifying modality for AD treatment and provides the proof of concept that remodeling the functional NVU may represent a promising therapeutic approach toward effective intervention of AD. [ABSTRACT FROM AUTHOR]

Background: Isocitrate dehydrogenase wild-type (WT) glioblastoma (GBM) accounts for 90% of all GBMs, yet only 27% of isocitrate dehydrogenase WT-GBMs have p53 mutations. However, the tumor surveillance function of WT-p53 in GBM is subverted by mechanisms that are not fully understood.Methods: We investigated the proteolytic inactivation of WT-p53 by asparaginyl endopeptidase (AEP) and its effects on GBM progression in cancer cells, murine models, and patients' specimens using biochemical and functional assays. The sera of healthy donors (n = 48) and GBM patients (n = 20) were examined by enzyme-linked immunosorbent assay. Furthermore, effects of AEP inhibitors on GBM progression were evaluated in murine models (n = 6-8 per group). The statistical significance between groups was determined using two-tailed Student t tests.Results: We demonstrate that AEP binds to and directly cleaves WT-p53, resulting in the inhibition of WT-p53-mediated tumor suppressor function in both tumor cells and stromal cells via extracellular vesicle communication. High expression of uncleavable p53-N311A-mutant rescue AEP-induced tumorigenesis, proliferation, and anti-apoptotic abilities. Knock down or pharmacological inhibition of AEP reduced tumorigenesis and prolonged survival in murine models. However, overexpression of AEP promoted tumorigenesis and shortened the survival time. Moreover, high AEP levels in GBM tissues were associated with a poor prognosis of GBM patients (n = 83; hazard ratio = 3.94, 95% confidence interval = 1.87 to 8.28; P < .001). A correlation was found between high plasma AEP levels and a larger tumor size in GBM patients (r = 0.6, P = .03), which decreased dramatically after surgery.Conclusions: Our results indicate that AEP promotes GBM progression via inactivation of WT-p53 and may serve as a prognostic and therapeutic target for GBM. [ABSTRACT FROM AUTHOR]

Glioma initiating cells (GICs) function as the seed for the propagation and relapse of glioma. Designing a smart and efficient strategy to target the GICs and to suppress the multiple signaling pathways associated with stemness and chemoresistance is essential to achieving a cancer cure. Inspired by the metabolic difference in endocytosis between GICs, differentiated glioma cells, and normal cells, a tailored lipoprotein‐like nanostructure is developed to amplify their internalization into GICs through receptor‐stimulated macropinocytosis. As CXCR4 is highly expressed on GICs and glioma tumor sites, meanwhile, the activation of CXCR4 induces the receptor‐stimulated macropinocytosis pathway in GICs, this CXCR4 receptor‐stimulated lipoprotein‐like nanoparticle (SLNP) achieves efficient accumulation in GICs in vitro and in vivo. By carrying microRNA‐34a in the core, this tailored SLNP reduces sex‐determining region Y‐box 2 and Notch1 expression, powerfully inhibits GICs stemness and chemoresistance, and significantly prolongs the survival of GICs‐bearing mice. Taken together, a tailored lipoprotein‐based nanostructure realizes efficient GICs accumulation and therapeutic effect through receptor‐stimulated macropinocytosis, providing a powerful nanoplatform for RNA interference drugs to combat glioma. [ABSTRACT FROM AUTHOR]

The heterogeneous copper(II)-catalyzed oxidative cyclization of 2-pyridine ketone hydrazones was achieved in ethyl acetate at room temperature in the presence of an MCM-41-anchored bidentate 2-aminoethylamino copper(II) catalyst [MCM-41-2N-Cu(OAc)2 ], in the presence of air as the oxidant, yielding a wide variety of [1,2,3]triazolo[1,5- a ]pyridines in mostly good to high yields. The present method was also applied to the direct one-pot synthesis of [1,2,3]triazolo[1,5- a ]pyridines from 2-acylpyridine derivatives and hydrazine monohydrate. Importantly, this supported copper(II) catalyst could be conveniently obtained via a simple procedure from easily available and inexpensive reagents, recovered by filtration of the reaction mixture, and reused at least seven times without a significant loss of catalytic activity. [ABSTRACT FROM AUTHOR]

Objective: Bacterial canker of kiwifruit caused by Pseudomonas syringae pv. actinidiae (Psa) is a major threat to the kiwifruit industry throughout the world and accounts for substantial economic losses in China. The aim of the present study was to test and explore the possibility of using MaxEnt (maximum entropy models) to predict and analyze the future large-scale distribution of Psa in China. Method: Based on the current environmental factors, three future climate scenarios, which were suggested by the fifth IPCC report, and the current distribution sites of Psa, MaxEnt combined with ArcGIS was applied to predict the potential suitable areas and the changing trend of Psa in China. The jackknife test and correlation analysis were used to choose dominant climatic factors. The receiver operating characteristic curve (ROC) drawn by MaxEnt was used to evaluate the accuracy of the simulation. Result: The results showed that under current climatic conditions, the area from latitude 25° to 36°N and from longitude 101° to 122°E is the primary potential suitable area of Psa in China. The highly suitable area (with suitability between 66 and 100) was mainly concentrated in Northeast Sichuan, South Shaanxi, most of Chongqing, West Hubei and Southwest Gansu and occupied 4.94% of land in China. Under different future emission scenarios, both the areas and the centers of the suitable areas all showed differences compared with the current situation. Four climatic variables, i.e., maximum April temperature (19%), mean temperature of the coldest quarter (14%), precipitation in May (11.5%) and minimum temperature in October (10.8%), had the largest impact on the distribution of Psa. Conclusion: The MaxEnt model is potentially useful for forecasting the future adaptive distribution of Psa under climate change, and it provides important guidance for comprehensive management. [ABSTRACT FROM AUTHOR]

Molten nitrate salt is usually employed as heat transfer or energy storage medium in concentrating solar power systems to improve the overall efficiency of thermoelectric conversion. In the present work, the liquidus curves of the $$\hbox {LiNO}_{3}$$ - $$\hbox {NaNO}_{3}$$ - $$\hbox {KNO}_{3}$$ - $$\hbox {Ca}(\hbox {NO}_{3})_{2}$$ system is determined by conformal ionic solution theory according to the solid-liquid equilibrium state of the binary mixture. The calculated eutectic temperature of the mixture is $$93.17\,{^{\circ }}\hbox {C}$$ , which is close to the experimental value of $$93.22\,{^{\circ }}\hbox {C}$$ obtained from differential scanning calorimetry (DSC). Visualization observation experiments reveal that the quaternary eutectic mixture begins to partially melt when the temperature reaches $$50\,{^{\circ }}\hbox {C}$$ , and the degree of melting increases with temperature. The mixture is completely melted at $$\hbox {130}\,{^{\circ }}\hbox {C}$$ . The observed changes in the dissolved state at different temperatures correlate well with the DSC heat flow curve fluctuations. [ABSTRACT FROM AUTHOR]

Forkhead transcription factor FoxO3a has been reported to have ambiguous functions and distinct mechanisms in various solid tumors, including glioblastoma (GBM). Although a preliminary analysis of a small sample of patients indicated that FoxO3a aberrations in glioma might be related to aggressive clinical behavior, the clinical significance of FoxO3a in glioblastoma remains unclear. We investigated the expression of FoxO3a in a cohort of 91 glioblastoma specimens and analyzed the correlations of protein expression with patient prognosis. Furthermore, the functional impact of FoxO3a on GBM progression and the underlying mechanisms of FoxO3a regulation were explored in a series of in vitro and in vivo assays. FoxO3a expression was elevated in glioblastoma tissues, and high nuclear FoxO3a expression in human GBM tissues was associated with poor prognosis. Moreover, knockdown of FoxO3a significantly reduced the colony formation and invasion ability of GBM cells, whereas overexpression of FoxO3a promoted the colony formation and invasion ability. The results of in vivo GBM models further confirmed that FoxO3a knockdown inhibited GBM progression. More, the pro-oncogenic effects of FoxO3a in GBM were mediated by the activation of c-Myc, microtubule-associated protein 1 light chain 3 beta (LC3B) and Beclin1 in a mixed-lineage leukemia 2 (MLL2)-dependent manner. These findings suggest that high FoxO3a expression is associated with glioblastoma progression and that FoxO3a independently indicates poor prognosis in patients. FoxO3a might be a novel prognostic biomarker or a potential therapeutic target in glioblastoma. [ABSTRACT FROM AUTHOR]

Solar salt is current commercial molten salt product, and that is usually used for thermal energy storage in solar thermal power plants. In order to obtain the release properties of nitrogen oxides of this salt mixture in the actual application, the effects of container materials (SS316, SS304, SS201 and quartz), cover gases and heating temperature on thermal decomposition of solar salt in atmospheric pressure are researched in this paper. The results indicate SS316 has the most significant effect, and quartz has the minor influence on the decomposition of solar salt in nitrogen, so SS304 may be selected for container material of molten salt system. Besides, the formation rate of NO in nitrogen is higher than the rate in air, but the formation laws of NO 2 is very complex in two atmospheres which may be attributed to the reaction of the metal elements in stainless steel with solar salt, so sealing system is suggested for using in molten salt system. Finally, it is also observed that the changes in volume of nitrogen oxide are very small in nitrogen when the temperature is lower than 550 o C, so solar salt is thermally stable at temperatures up to 550 o C, and may be used up to 600 o C for short periods. [ABSTRACT FROM AUTHOR]

To enable us better understand the performance of molten salt energy storage in a solar thermal power system, thermodynamic properties of the solid $$\hbox {KNO}_{2}$$ system at ambient pressure and temperatures between 0 K and 711 K are determined by first-principles simulation based on density functional perturbation theory calculations with plane waves and pseudopotentials. Thermodynamic parameters of the Debye temperature, specific heat capacity at constant volume, phonon transfer speed, phonon mean free path, and phonon thermal conductivity as a function of temperature are estimated. The results show that the calculated phonon thermal conductivity is in good agreement with experimental values, but the calculated specific heat capacity at constant volume is lower than measured values. The isometric specific heat capacity of $$\hbox {KNO}_{2}$$ is $$75.03\,\hbox {J}{\cdot }\hbox {mol}^{-1}{\cdot }\hbox {K}^{-1}$$ , and the phonon thermal conductivity is $$2.37\,\hbox {W}{\cdot }\hbox {m}^{-1}{\cdot }\hbox {K}^{-1}$$ at ambient temperature. [ABSTRACT FROM AUTHOR]

Hyperactivated Ras regulates many oncogenic pathways in several malignant human cancers including glioblastoma and it is an attractive target for cancer therapies. Ras activation in cancer cells drives protein internalization via macropinocytosis as a key nutrient-gaining process. By utilizing this unique endocytosis pathway, here we create a biologically inspired nanostructure that can induce cancer cells to 'drink drugs' for targeting activating transcription factor-5 (ATF5), an overexpressed anti-apoptotic transcription factor in glioblastoma. Apolipoprotein E3-reconstituted high-density lipoprotein is used to encapsulate the siRNA-loaded calcium phosphate core and facilitate it to penetrate the blood-brain barrier, thus targeting the glioblastoma cells in a macropinocytosis-dependent manner. The nanostructure carrying ATF5 siRNA exerts remarkable RNA-interfering efficiency, increases glioblastoma cell apoptosis and inhibits tumour cell growth both in vitro and in xenograft tumour models. This strategy of targeting the macropinocytosis caused by Ras activation provides a nanoparticle-based approach for precision therapy in glioblastoma and other Ras-activated cancers. [ABSTRACT FROM AUTHOR]