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Casein serves as a protein extract from cow milk and its products; it is an available and cheap natural polymer material. Casein-based hydrogels have been extensively used in drug delivery systems due to their good biocompatibility and fast degradation. Although chemical crosslinking agents have been used for crosslinking of casein hydrogels, it is also associated with adverse effects and potential biotoxicity. In this work, casein was modified with methacrylic anhydride (MA). The functionalized casein (CaseinMA) possessed the ability to form hydrogels under 365 nm UV light in water solution without using toxic agents. Alginate was (0.4%, 0.8%, and 1.2%) found to successfully adjust the mechanical performance of CaseinMA hydrogels. The swelling property and degradation behavior indicated that the composite hydrogels had excellent water holding ability and degradability. MTT assay and hemolytic test demonstrated that CaseinMA/Alg hydrogels containing photoinitiator (Irgacure 2959) had good biocompatibility. At last, CaseinMA/Alg microspheres loaded with metformin hydrochloride (MET) were fabricated by using electrostatic droplet technology. The CaseinMA/Alg microspheres had a pH-sensitive property and slow sustained release as compared to mono-component microspheres in drug releasing test. CaseinMA/Alg hydrogels were confirmed that had good biocompatibility and mechanical properties; it is expected to be applied in many fields such as drug delivery system and wound management. [ABSTRACT FROM AUTHOR]

Abstract The molecular structure of a series of newly developed ultraviolet (UV) curable electrical contact stabilization materials, which contain polyethylene glycol (PEG)-block-polypropylene glycol (PPG)-block-polyethylene glycol (PEG) capped with methacrylate functional groups on both ends as the reactive oligomers and a methacrylated PEG as the reactive diluent was studied in detail. The effects of reactive diluents, including functionalities and compositions were investigated via a combination of dynamic mechanical analysis, differential scanning calorimetry, FT-IR spectroscopy and wide angle X-ray diffraction. All the films exhibit completely amorphous state at room temperature regardless of the composition or thermal history. However, a small amount of PPPDI molecular chains undergo crystallization upon slow cooling. This crystallization is completely inhibited when mixed with di-functional reactive diluents, owing to the high cross-link density. The introduction of mono-functional reactive diluents restricts but not completely prevents the crystallization process, which causes the resulting films to be difficult to crystallize to lower crystallinity levels. On the other hand, adding non-reactive diluents transforms the resulting films to become a fast-crystallizing material, as a result of the low cross-link density and a large portion of unreacted oligomers along with the unreactive component. Additionally, the degree of heterogeneity for the cross-linked networks is generally increased by the addition of reactive diluents. The molecular structures of PEG-b-PPG-b-PEG dimethacrylate cross-linked networks as well as mixed with different types of reactive diluents at both room temperature and crystallizing temperature were proposed. Graphical abstract Image 1 Highlights • UV curable PEG-b-PPG based methacrylate. • Reactive Diluents. • Crystallization and structure development. [ABSTRACT FROM AUTHOR]

The drying behavior of blade casting aqueous chitosan solution was investigated by means of a custom designed real time characterization system that can track the thickness, weight, temperature and in-plane and out-of-plane birefringence. Beyond a critical solvent concentration, initially isotropic cast solution rapidly develops optical anisotropy as detected by out of plane birefringence measurement while it remains isotropic in plane. Increasing drying temperature and air flow speed can both accelerate the drying rate but change the birefringence level in opposite directions. Lower birefringence was obtained at higher drying temperature while, higher birefringence was observed when the air flow speed is increased. This is due to the cumulative effects of the residual stress development in the film and polymer chains relaxation. Using a thermodynamically consistent model developed in the framework of classical irreversible thermodynamics, we quantitatively describe the drying kinetics and evolution of concentration and temperature profiles during the course of drying of the solvent. It was shown that the model can precisely describe the experimental data without using any fitting parameters. [ABSTRACT FROM AUTHOR]

In this paper, we investigate film drying followed by mechano-optical behavior of PVA films in solid and swollen state, respectively. During drying the real time evolution of thickness, weight, and birefringence (both in and out of plane) are captured using a highly instrumented measurement system. During drying, initially isotropic solution rapidly loses water and beyond a critical stage it develops optical anisotropy in the thickness direction as reflected in rapid development of out of plane birefringence while in-plane isotropy is maintained. Stretching the dried films in the solid state yields three regimes of non-linear stress and strain-optical behavior. The temperature shows a positive effect on the birefringence value at given true strain levels. Swelling the PVA films with water, facilitate room temperature stretchability, hence providing a route of stretching that avoids decomposition and discoloration that occurs at elevated temperatures. The effects of moisture content on mechano-optical properties of PVA films are mapped and opposite dependences of photolelastic and strain optical constants on moisture content are observed. [ABSTRACT FROM AUTHOR]

Selective laser melting (SLM) technology has attracted wide attention because it can produce parts with complex shape or internal characteristics that are difficult to process in traditional ways. SLM process is very easy to produce dross formation and balling defects on the overhanging surface of titanium alloy when forming the overhanging characteristic structural parts, which makes the surface of the formed parts rough. Therefore, how to improve the forming quality of titanium alloy overhanging parts by adding material becomes an urgent problem to be solved. In this paper, the influence factors and mechanism of quality of titanium alloy suspension parts formed by SLM process are experimentally studied. Through analysis and comparison of forming parts under different geometric dimensions and process parameters, appropriate geometric dimensions and process parameters are obtained to improve the quality of forming parts. In terms of scanning strategy, a compound scanning path of "vertical island zoning + contour remelting" is put forward to solve the problems of stress concentration and dross formation on the overhanging surface. This strategy is based on vertical island zoning and improves the heat dissipation at the edge of the part by remelting the contour of the formed layer. The result shows that this method can effectively reduce the residual stress of the overhanging part and improve the dross formation phenomenon. [ABSTRACT FROM AUTHOR]

This paper focuses on the finite-time stabilization issue of a kind of reaction–diffusion memristive neural networks (RDMNNs) with semi-Markov jumping parameters. The boundary control scheme is employed and combined with generalized pinning control strategy to stabilize the considered RDMNNs in finite time while saving communication resources and control costs. A positive constant ϱ is designed in our controller, such that the sharp chattering phenomena in previous similar controllers can be greatly reduced. Moreover, the corresponding finite-time stabilization criterion and related corollaries are obtained by using variable substitution and inequality methods flexibly. Last but not least, an illustrative example is carried out to validate effectiveness and superiority of the developed approach. [ABSTRACT FROM AUTHOR]

Background: Stereotactic radiotherapy (SRT) and hypo-fractionated radiotherapy are feasible treatment options for single glioblastoma multiforme when combined with conventional radiotherapy or delivered alone. HyperArc (HA), a novel linac-based method with 4 noncoplanar arcs, has been introduced into stereotactic radiosurgery (SRS) for single and multiple metastases. In this study, we compared the dosimetric quality of HyperArc with the well-established CyberKnife (CK) and conventional VMAT methods of SRT for a single, large target. Methods: Sixteen patients treated in our center with their clinical CK plans were enrolled, and the linac-based plans were designed in silico. From the aspect of normal tissue protection and treatment efficacy, we compared the conformity index (CI), gradient index (GI), homogeneity index (HI), dose distribution in planning target volume, dose in the normal brain tissue, and mean dose of several organs at risk (OARs). All of the data were evaluated with nonparametric Kruskal‒Wallis tests. We further investigated the relationship of the dose distribution with the tumor volume and its location. Results: The results showed that with a higher CI (0.94 ± 0.03) and lower GI (2.57 ± 0.53), the HA plans generated a lower dose to the OARs and the normal tissue. Meanwhile, the CK plans achieved a higher HI (0.35 ± 0.10) and generated a higher dose inside the tumor. Although manual VMAT showed slight improvement in dose quality and less monitoring units (2083 ± 225), HA can save half of the delivery time of CK (37 minutes) on average. Conclusion: HA plans have higher conformity and spare OARs with lower normal tissue irradiation, while CK plans achieve a higher mean dose in tumors. HA with 4 arcs is sufficient in dosimetric quality for a single tumor with great convenience in planning and treatment processes compared with conventional VMAT. The tumor size and location are factors to be considered when selecting treatment equipment. [ABSTRACT FROM AUTHOR]

Background: The most frequently diagnosed primary brain tumor is glioblastoma (GBM). Nearly all patients experience tumor recurrence and up to 90% of which is local recurrence. Thus, increasing the therapeutic ratio of radiotherapy using hypofractionated stereotactic radiotherapy (HSRT) can reduce treatment time and may increase tumor control and improve survival. To evaluate the efficacy and toxicity of the combination of HSRT and intensity-modulated radiotherapy (IMRT) with temozolomide after surgery in GBM patients and provide evidence for further randomized controlled trials.Methods/design: HSCK-010 is an open-label, single-arm phase II trial (NCT04547621) which includes newly diagnosed GBM patients who underwent gross total resection. Patients will receive the combination of 30 Gy/5fx HSRT, and 20 Gy/10fx IMRT adjuvant therapy with concurrent temozolomide and adjuvant chemotherapy. The primary endpoint is overall survival (OS). Secondary outcomes include progression-free survival (PFS) rate, objective-response rate (ORR), quality of life (Qol) before and after the treatment, cognitive function before and after the treatment, and rate of treatment-related adverse events (AE). The combination of HSRT and IMRT with temozolomide can benefit the patients after surgery with good survival, acceptable toxicity, and reduced treatment time.Trial Registration: NCT04547621 . Registered on 14 September 2020. [ABSTRACT FROM AUTHOR]

(1) Background: Hypofractionated stereotactic radiotherapy (HSRT) and anti-vascular endothelial growth factor (VEGF) antibodies have been reported to have a promising survival benefit in recent studies. Anlotinib is a new oral VEGF receptor inhibitor. This report describes our experience using HSRT and anlotinib for recurrent glioblastoma (rGBM). (2) Methods: Between December 2019 and June 2020, rGBM patients were retrospectively analysed. Anlotinib was prescribed at 12 mg daily during HSRT. Adjuvant anlotinib was administered d1-14 every 3 weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS) after salvage treatment, and toxicity. (3) Results: Five patients were enrolled. The prescribed dose was 25.0 Gy in 5 fractions. The median number of cycles of anlotinib was 21 (14–33). The ORR was 100%. Three (60%) patients had the best outcome of a partial response (PR), and 2 (40%) achieved a complete response (CR). One patient died of tumour progression at the last follow-up. Two patients had grade 2 hand-foot syndrome. (4) Conclusions: Salvage HSRT combined with anlotinib showed a favourable outcome and acceptable toxicity for rGBM. A prospective phase II study (NCT04197492) is ongoing to further investigate the regimen. [ABSTRACT FROM AUTHOR]

Management of brainstem metastatic tumor is challenging. This study aimed to evaluate overall survival and quality-of-life in patients with non-small cell lung cancer (NSCLC) brainstem metastases who were treated with the Cyberknife stereotactic radiosurgery. From August 2007 through August 2016, a total of 32 patients with 34 brainstem metastases of NSCLC were consecutively enrolled and treated with the Cyberknife radiosurgery (CKRS) at The Huashan Hospital. The study was limited to patients with NSCLC, which was confirmed by postoperative pathological examination. Patients were treated by CKRS as an initial treatment or a second treatment after whole-brain radiation therapy (WBRT). Quality of life was assessed by the SF-12 score and neurological examination. Four out of the 32 (12.5%) patients received WBRT before or concurrent with CKRS treatment. The mean survival time after CKRS was 10.0 (95%CI: 6.0–14.0) months. Karnofsky performance score was not the independent predictor of survival after radiosurgery as analyzed by log-rank test (p = 0.392). Age, however, was a significant predictor of improved survival as analyzed by multivariate analysis (p = 0.024). SF-12 physical component scores demonstrated no significant change after treatment. The CKSR is a non-invasive, safe, and effective modality in the treatment of patients with brainstem metastases of NSCLC. Better therapeutic outcomes of CKSR for brainstem metastasis might be achieved in the patients older than 65 years old. [ABSTRACT FROM AUTHOR]

Background: The optimal treatment for recurrent high-grade gliomas (rHGGs) remains uncertain. This study aimed to investigate the efficacy and safety of hypofractionated stereotactic radiosurgery (HSRS) as a first-line salvage treatment for in-field recurrence of high-grade gliomas.Methods: Between January 2016 and October 2019, 70 patients with rHGG who underwent HSRS were retrospectively analysed. The primary endpoint was overall survival (OS), and secondary endpoints included both progression-free survival (PFS) and adverse events, which were assessed according to Common Toxicity Criteria Adverse Events (CTCAE) version 5. The prognostic value of key clinical features (age, performance status, planning target volume, dose, use of bevacizumab) was evaluated.Results: A total of 70 patients were included in the study. Forty patients were male and 30 were female. Forty-nine had an initial diagnosis of glioblastoma (GBM), and the rest (21) were confirmed to be WHO grade 3 gliomas. The median planning target volume (PTV) was 16.68 cm3 (0.81-121.96 cm3). The median prescribed dose was 24 Gy (12-30 Gy) in 4 fractions (2-6 fractions). The median baseline of Karnofsky Performance Status (KPS) was 70 (40-90). With a median follow-up of 12.1 months, the median overall survival after salvage treatment was 17.6 months (19.5 and 14.6 months for grade 3 and 4 gliomas, respectively; p = .039). No grade 3 or higher toxicities was recorded. Multivariate analysis showed that concurrent bevacizumab with radiosurgery and KPS > 70 were favourable prognostic factors for grade 4 patients with HGG.Conclusions: Salvage HSRS showed a favourable outcome and acceptable toxicity for rHGG. A prospective phase II study (NCT04197492) is ongoing to further investigate the value of hypofractionated stereotactic radiosurgery (HSRS) in rHGG. [ABSTRACT FROM AUTHOR]

Transcranial focused ultrasound is a novel noninvasive therapeutic modality for glioblastoma and other disorders of the brain. However, because the phase aberrations caused by the skull need to be corrected with computed tomography (CT) images, the transcranial transducer is tightly fixed on the patient’s head to avoid any variation in the relative position, and the focus shifting relies mainly on the capacity for electronic beam steering. Due to the presence of grating lobes and the rapid degradation of the focus quality with increasing focus-shifting distance, transcranial focus-shifting sonication may damage healthy brain tissue unintentionally. To reduce the risks associated with transcranial focused ultrasound therapy, linear frequency-modulated (FM) excitation is proposed. The k-space corrected pseudospectral time domain (PSTD) and acoustic holography approach based on the Rayleigh integral are combined to calculate the distribution of the deposited acoustic power. The corresponding simulation was performed with axial/lateral focus shifting at different distances. The distributions of the deposited acoustic power show that linear FM excitation can effectively suppress undesired prefocal grating lobes without compromising focus quality. [ABSTRACT FROM AUTHOR]

Phased-control focused ultrasound transducers provide a new and noninvasive treatment method for brain disease. However, improving the accuracy of phase correction and reducing the calculation time during treatment have always been contradictory constraints. In this paper, a hybrid acoustic signal correction (HASC) method combined with k-Wave stage and holography stage was introduced for phase correction and simulation of transcranial focused ultrasound. The k-Wave stage is mainly used to calculate the sound field in a heterogeneous medium (skull), which divides the sound field calculation process into paths that can be calculated in parallel, and the transcranial correction phase can also be obtained during the calculation. The holography stage is sufficient to simulate the acoustic field in the homogenous intracranial medium after ultrasound transmitting through the skull. The agreement of the k-space corrected pseudospectral time domain method and HASC method was assessed by statistical methods: linear regression between the two methods provided a slope of 0.9735, intercept of 0.0078, and R2 of 0.9982. The Bland–Altman method provided a bias of 0.0015 and 95% limits of agreement 0.065 apart. We demonstrated that the difference in sound intensity at the focal point corrected by HASC and time reversal phase correction method was 0.2% and 0.5% in the results of simulation and experiment, respectively. Not only that, the phase calculation time by the HASC phase correction method can be reduced to 11 min on a multi GPU array, which has clinical potential for ultrasound treatment of brain therapy. [ABSTRACT FROM AUTHOR]

Introduction: About 50% of patients with non‐small cell lung cancers (NSCLC) are diagnosed with brain metastases during treatment, and stereotactic radiosurgery (SRS) is an important treatment for brain oligometastasis. Some patients with brain metastases have cerebral edema before treatment, and radiation therapy may also cause, or aggravate brain edema. Vascular endothelial growth factor (VEGF) promotes angiogenesis and increase vascular permeability, and previous studies have shown that anti‐VEGF treatment can reduce brain edema. We hypothesized that anlotinib hydrochloride can reduce perilesional edema around brain metastases, create conditions for subsequent SRS, increase local control rate and improve patient prognosis. Methods: From one week before stereotactic radiosurgery, patients begin to receive anlotinib once a day (12 mg) from day 1–14 of a 21 day cycle, with two cycles in total. Brain magnetic resonance imaging (MRI) scan is taken before treatment, one week and one month after medication. A total of 50 patients will be included in this study. The primary endpoint is the Edema Index, and the secondary endpoints are intracranial objective response rate (iORR), intracranial progression‐free survival (iPFS), objective response rate (ORR), disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), safety, and the rate of SRS after anlotinib treatment. Discussion: This study is a multicenter, prospective, single‐arm, phase II clinical study, and explores the efficacy and tolerability of SRS with anlotinib in NSCLC patients with limited brain metastases. The aim of the study is to provide new treatment options for NSCLC patients with brain metastases. [ABSTRACT FROM AUTHOR]

Selection of appropriate treatment for patients with recurrent brain metastasis (BM) remains uncertain. Recent studies have demonstrated a significant response rate and acceptable toxicity using fractionated stereotactic radiosurgery (FSRS) in patients with locally recurrent large BM. The aim of this study was to evaluate efficacy and toxicity of FSRS with bevacizumab as a new salvage treatment for locally recurrent BM with previous high-dose irradiation. Patients with recurrent BM previously irradiated were enrolled. Salvage FSRS dose was 9.5–29 Gy (2–5 fractions) with 62%–75% isodose line by CyberKnife according to the brain tumor volume, site, and previous dose. Bevacizumab was prescribed for 4 cycles (5 mg/kg, every 3 weeks). The primary objective was to identify the overall survival after salvage treatment. Secondary objectives included clinical response (Karnofsky performance scale), imaging response (magnetic resonance imaging) and treatment-related adverse events. From December 2009 to October 2016, 24 patients were enrolled. The 1-year overall survival after salvage stereotactic radiosurgery was 87.5%. Twenty-three (96%) patients had a positive imaging response with a T2 volume reduction range of 6–22 cm3 (median 14 cm3, P = 0.032, paired t test). Significant clinical improvement was achieved (best Karnofsky performance scale score, P < 0.05, paired t test). Grade 1/2 fatigue was observed in 8 (33%) patients. Grade 3 fatigue and headache occurred in 1 patient. FSRS with adjuvant bevacizumab treatment showed favorable clinical and radiologic control as a salvage treatment regimen. The diagnoses of radiation necrosis and local recurrence after salvage FSRS warrant further study. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Chemically neutral silica colloid particles stay at the interface of PS and PMMA. • Solvent evaporation rate induced phase separation transition. • Porous membrane with partially exposed silica colloid particles. Abstract During the solvent evaporation induced phase separation of PS and PMMA blends with silica nanoparticles, the dispersed and bicontinuous morphologies need to be stabilized by the absorption of silica nanoparticles at the interface. In order to accomplish this, the silica nanoparticles need to be chemically neutral to PS and PMMA homopolymers. For this purpose, their surfaces were modified by attaching mono-hydroxyl group terminated polystyrene poly(methyl methacrylate) random (PS-r-PMMA-OH) copolymer via the condensation reaction between the hydroxyl groups of silica particles and copolymer. The resulting morphology was found to be affected by the rate of solvent evaporation, blend compositions, particle loading and size. In the symmetric blend system, the dispersed phase was observed at low evaporation rate and bicontinuous morphology was obtained at high evaporation rate. The silica nanoparticles were found to be densely packed at the interface of PS and PMMA. For asymmetric blend system, only dispersed phase was observed at both low and high evaporation rates. The size of phase separated domains decreases with increasing solvent evaporation rate and particle loading. The silica nanoparticles with smaller size resulted in relatively smaller domain size due to their higher surface area to volume ratio. Porous membranes with partially exposed nanoparticles were fabricated by etching PMMA phase in acetic acid. [ABSTRACT FROM AUTHOR]

A convenient and new copper nanoparticles-catalyzed cross-coupling reaction of imidazo[1,2- a]pyridines with methyl ketones has been developed to synthesize 1,2-diketones that have an imidazo[1,2- a]pyridine core. Highly active magnetic copper nanoparticles [i.e., Cu4O3@Fe3O4_C(II)] were prepared and characterized by standard materials characterization techniques, which included transmission electron microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy (XPS) and X-ray diffraction. These methods were also used to acquire information about the size, oxidation state, and crystallinity of the nanoparticle catalyst. With this method, a variety of pharmaceutically important 1,2-dicarbonyl imidazo[1,2- a]pyridines were readily synthesized in moderate to good yields. The catalyst was easily separated from the reaction mixture by using an external magnetic field and could be recycled 6 times with only a negligible change in the catalytic performance. [ABSTRACT FROM AUTHOR]

Purpose: Cavernous sinus hemangioma is a rare vascular tumor. The direct microsurgical approach usually results in massive hemorrhage. Although radiosurgery plays an important role in managing cavernous sinus hemangiomas as a treatment alternative to microsurgery, the potential for increased toxicity with single-session treatment of large tumors is a concern. The purpose of this study was to assess the efficacy of hypofractionated stereotactic radiotherapy in patients with large cavernous sinus hemangiomas. Methods: Fourteen patients with large (volume >20 cm3) cavernous sinus hemangiomas were enrolled in a prospective Phase II study between December 2007 and December 2010. The hypofractionated stereotactic radiotherapy dose was 21 Gy delivered in 3 fractions. Results: After a mean follow-up of 15 months (range, 6–36 months), the magnetic resonance images showed a mean of 77% tumor volume reduction (range, 44–99%). Among the 6 patients with cranial nerve impairments before hypofractionated stereotactic radiotherapy, 1 achieved symptomatic complete resolution and 5 had improvement. No radiotherapy-related complications were observed during follow-up. Conclusion: Our current experience, though preliminary, substantiates the role of hypofractionated stereotactic radiotherapy for large cavernous sinus hemangiomas. Although a longer and more extensive follow-up is needed, hypofractionated stereotactic radiotherapy of 21 Gy delivered in 3 fractions is effective in reducing the tumor volume without causing any new deficits and can be considered as a treatment modality for large cavernous sinus hemangiomas. [ABSTRACT FROM AUTHOR]