Poly(phenylalanine) and poly(3,4-dihydroxy-L-phenylalanine): Promising biomedical materials for building stimuli-responsive nanocarriers.

Cancer is a serious threat to human health because of its high annual mortality rate. It has attracted significant attention in healthcare, and identifying effective strategies for the treatment and relief of cancer pain requires urgency. Drug delivery systems (DDSs) offer the advantages of excellent efficacy, low cost, and low toxicity for targeting drugs to tumor sites. In recent decades, copolymer carriers based on poly(phenylalanine) (PPhe) and poly(3,4-dihydroxy-L-phenylalanine) (PDopa) have been extensively investigated owing to their good biocompatibility, biodegradability, and controllable stimulus responsiveness, which have resulted in DDSs with loading and targeted delivery capabilities. In this review, we introduce the synthesis of PPhe and PDopa, highlighting the latest proposed synthetic routes and comparing the differences in drug delivery between PPhe and PDopa. Subsequently, we summarize the various applications of PPhe and PDopa in nanoscale-targeted DDSs, providing a comprehensive analysis of the drug release behavior based on different stimulus-responsive carriers using these two materials. In the end, we discuss the challenges and prospects of polypeptide-based DDSs in the field of cancer therapy, aiming to promote their further development to meet the growing demands for treatment.

Repeated high­intensity focused ultrasound combined with iodine­125 seed interstitial brachytherapy offers improved quality of life and pain control for patients with advanced pancreatic cancer: A 52­patient retrospective study.

Patients diagnosed with pancreatic cancer who have 5-year survival rates of ~5% are typically in the advanced stage. Pancreatic cancer has become the third leading cause of cancer-related death in the United States and there is still a lack of effective treatments to improve patient survival rate. Hence, the purpose of the present retrospective study was to assess the potential clinical impact of repeated high-intensity focused ultrasound (HIFU) combined with iodine-125 (125I) interstitial brachytherapy for the treatment of patients with advanced pancreatic cancer who were ineligible for or declined surgery and chemotherapy. A total of 52 patients diagnosed with advanced pancreatic cancer were included in the study. At least one course of HIFU therapy combined with percutaneous ultrasound-guided 125I seed implantation was administered to each patient. The clinical assessment included an evaluation of Karnofsky Performance Scale (KPS) score at baseline, and at 1 and 2 months after combined therapy. Pain intensity was additionally evaluated with the numerical rating score (NRS). Overall survival (OS) times and survival rates at 3, 6, 9 and 12 months after combined treatment were evaluated. Adverse events commonly associated with HIFU and 125I seed implantation were recorded, and the severity of adverse events was graded according to the Common Terminology Criteria for Adverse Events, version 4. All 52 patients received successful repeated HIFU treatment combined with 125I seed implantation and were included in the analysis of efficacy and safety. The median OS time of patients was estimated to be 13.1 months (95% CI, 11.3-14.8). The survival rates at 3, 6, 9 and 12 months were 100.0, 86.5, 61.5 and 53.8%, respectively. The mean KPS score was 62.7±6.3 at baseline, 73.7±7.9 at 1 month and 68.8±6.5 at 2 months after combined treatment. KPS score increased significantly after combined therapy. The mean NRS score was 6.7±1.6 at baseline, and 4.7±1.7 and 5.4±1.5 at 1 and 2 months after combined treatment, respectively. The number of patients with severe pain and the NRS score were both significantly lower at 1 and 2 months after 125I seed implantation compared with those at baseline. No serious complications were detected during the follow-up period. In conclusion, the present study demonstrated the survival benefit and improvement in quality of life of patients with advanced pancreatic cancer receiving repeated HIFU treatment combined with 125I interstitial brachytherapy, which may provide new ideas and methods for the treatment of pancreatic cancer.

Silver oxide decorated urchin-like microporous organic polymer composites as versatile antibacterial organic coating materials.

Microporous organic polymers (MOPs) and metal oxide hybrid composites are considered valuable coating materials because of their versatility derived from the synergistic combination of MOPs' inherent dispersibility and the distinctive properties of metal oxides. In this study, we present the synthesis of sea-urchin-like MOPs hybridised with silver oxide nanoparticles (Ag2O NPs) to fabricate antibacterial composites suitable for potential antibacterial coating applications. Ag2O NP-decorated urchin-like MOPs (Ag2O@UMOPs) were synthesised by employing a combination of two methods: a one-pot Lewis acid-base interaction-mediated self-assembly and a straightforward impregnation process. The as-prepared Ag2O@UMOPs demonstrated high antibacterial efficacy against both E. coli (G-) and S. aureus (G+). The antibacterial mechanism of Ag2O@UMOPs mainly involved the synergistic effects of accumulation of Ag2O@UMOPs, the release of Ag+ ions, and the generation of reactive oxygen species. The exceptional processability and biosafety of Ag2O@UMOPs make them ideal organic coating materials for convenient application on various substrates. These remarkable features of Ag2O@UMOPs provide an effective platform for potential antibacterial applications in biological sciences.

Fabrication and Characterization of π-π Stacking Peptide-Contained Double Network Hydrogels.

Since the physical properties are similar to native extracellular matrices, double network (DN) hydrogels have been studied extensively in the tissue engineering. However, the double chemical crosslinked DN hydrogel is limited by poor fatigue resistance. π-π stacking is a non-covalent bonding interaction, which is essential to maintain and self-assemble the three-dimensional structure of biological proteins and nucleic acids. In this study, a robust polyethylene glycol diacrylate (PEGDA)/FFK hybrid DN hydrogel was prepared by Michael addition and π-π stacking. The hybrid DN hydrogels with π-π stacking interactions have excellent mechanical strength and fatigue resistance. The DN FFK/PEGDA hydrogels reveal great biocompatibility and hemocompatibility. The DN hydrogels containing π-π stacking have the potential to fabricate robust hybrid DN hydrogels in drug release and tissue engineering.

Recent progress and applications of poly(beta amino esters)-based biomaterials.

Poly(beta-amino esters, PBAEs) are a promising class of cationic polymers synthesized from diacrylates and amines via Michael addition. Recently, PBAEs have been widely developed for drug delivery, immunotherapy, gene therapy, antibacterial, tissue engineering and other applications due to their convenient synthesis, good bio-compatibility and degradation properties. Herein, we mainly summarize the recent progress in the PBAEs synthesis and their applications. The amine groups of PBAEs could be protonated in low pH environment, exhibiting proton sponge and pH-sensitive abilities. Furthermore, the positive PBAEs can interact with negative genes via electrostatic interactions for efficient delivery of nucleic acids. Moreover, positive PBAEs could also directly kill bacteria by disrupting their membranes at high doses. Finally, PBAEs can augment the immune responses, and improve the bioactivity of hydrogels in tissue engineering.

A bio-orthogonally functionalized chitosan scaffold with esterase-activatable release for nerve regeneration.

Developing nerve conduits with biological cues is a promising approach for repairing peripheral nerve injuries. Although most biological cues incorporated into conduits generally exert their biological functions at the surface, they could not be released into the on-demand regeneration sites under physiological conditions. Herein, we firstly report a bio-orthogonally functionalized chitosan scaffold with esterase-activatable release for peripheral nerve regeneration. In this study, biological cues are not only selectively conjugated into nerve conduits by bio-orthogonal reaction, but also precisely released in on-demand regeneration sites via esterase-activatable cleavage for peripheral nerve repair. Moreover, this nerve scaffold with esterase-activatable release could promote Schwann cells proliferation. In a rat sciatic nerve defect model, the bio-orthogonally functionalized scaffold with esterase-activatable release significantly increased sciatic nerve function recovery and improved target muscles weight. This strategy of incorporating esterase-activatable bioactive cues into peripheral nerve conduits offers great potential in preclinical studies.

Strict mathematical model of mechanical stress birefringence for optical plates.

The mechanical stress birefringence (SBR) has received attention due to its effect on polarization in immersion lithography. In this paper, we present a strict mathematical model to obtain the correct SBR and slow-axis distributions of optical plates. First, the linear conditions of the model are solved to ensure the reasonable assembly of optical plates. Then we strictly define the plane principal stresses and slow-axis angle, and we give the correct expressions. Utilizing this model, we simulate a transmissivity variable plate, which is divided into 11 layers to obtain the effective SBR experienced by incident light crossing the plate. In this case, the simulation results achieve convergence. The validity of the model is verified by comparing the SBR and slow-axis distributions obtained by different expressions of the plate. This model is of great significance for polarization analysis in lithography systems and the reasonable assembly of optical elements.

High-Intensity Focused Ultrasound Ablation for Unresectable Primary and Metastatic Liver Cancer: Real-World Research in a Chinese Tertiary Center With 275 Cases.

This retrospective analysis was conducted to evaluate the feasibility and safety of high-intensity focused ultrasound ablation for primary liver cancer and metastatic liver cancer. Patients with liver cancer who received high-intensity focused ultrasound were included in this analysis, including a primary liver cancer cohort (n=80) and a metastatic liver cancer cohort (n=195). The primary endpoint of our research was tumor response. The secondary endpoints included survival outcomes, visual analog scale pain scores, alpha-fetoprotein relief, and complications. Objective response rate and disease control rate were observed to be 71.8% and 81.2%, respectively, in patients with primary liver cancer and were 63.7% and 83.2% in cases with metastatic liver cancer. Alpha-fetoprotein levels and visual analogue scale levels significantly decreased after treatment compared with the baseline levels in patients with primary liver cancer (p<0.05). Median overall survival was estimated to be 13.0 and 12.0 months in the primary liver cancer and metastatic liver cancer cohorts. The 1-year survival rate was 70.69% and 48.00%, respectively. Multivariate regression analysis showed that visual analogue scale ≥ 5, longest diameter ≥ 5 cm, and portal vein invasion were the independent risk factors for poor survival in primary liver cancer. For patients with metastatic liver cancer, independent risk factors were identified as visual analogue scale ≥ 5, longest diameter ≥ 5 cm, existence of extrahepatic metastases, existence of portal vein invasion, and time to high-intensity focused ultrasound treatment from diagnosis < 3 months. Severe adverse events were rarely reported. In conclusion, high-intensity focused ultrasound might be an effective and safe option for patients with liver cancer regardless of primary and metastatic lesions.

Mechanical stress birefringence of optical plates.

Modeling the mechanical stress birefringence and slow-axis distributions of optical plates is critical for optical lithography systems. In this paper, the distributions of mechanical stress birefringence and the slow axes of optical plates were modeled by the finite element (FE) model, stress optic relations, and the ray-traced Jones matrices method. To validate this model, the load incremental approach was utilized to reduce the disturbance of residual birefringence in mechanical stress birefringence measurement. The measured distributions of birefringence and the slow axis of the optical plate show a good agreement with our numerical simulation results. This model provides a better understanding of simulation of mechanical stress birefringence and provides a reference for optical design and polarization analysis of other optical elements.

ß­elemene inhibits the generation of peritoneum effusion in pancreatic cancer via suppression of the HIF1A­VEGFA pathway based on network pharmacology.

Pancreatic cancer remains one of the most lethal types of cancer. Late­stage pancreatic cancer patients usually suffer peritoneum effusion, which severely compromises quality of life. Great efforts have been made concerning the treatment of peritoneum effusion, including treatment with ß­elemene. Although peritoneal perfusion of ß­elemene attenuates the progression of malignant effusion without severe adverse effects in the clinic, the underlying molecular mechanism underlying the activity of ß­elemene against peritoneum effusion remains unclear. In the present study, a network pharmacology approach was undertaken to explore the mechanism of ß­elemene against peritoneum effusion. Particularly, the networks of ß­elemene and pancreatic cancer target genes were constructed based on the BATMAN­TCM and DigSee databases, respectively. Thirty­three genes, including hypoxia inducible factor 1 subunit α (HIF1A), were discovered in both networks. A potential interaction of ß­elemene with HIF1A was revealed by molecular docking simulation and co­expression analysis of pancreatic cancer datasets from The Cancer Genome Atlas (TCGA) database. Additionally, experimental validation by MTT assay demonstrated that ß­elemene suppressed proliferation of PANC­1 and BxPC3 cells and cells from peritoneum effusion in patients with pancreatic cancer. Furthermore, the protein expression levels of HIF1A and vascular endothelial growth factor A (VEGFA), as detected by western blotting, were reduced by ß­elemene. Overall, this study proposes a potential molecular mechanism illustrating that ß­elemene can block the HIF1A/VEGFA pathway, thereby inhibiting the generation of peritoneum effusion in pancreatic cancer based on network pharmacology analysis, and further highlights the importance of targeting the HIF1A/VEGF pathway as a therapeutic approach to treat peritoneum effusion in patients with pancreatic cancer.

Polarization simulation and analysis of residual birefringence in optical materials for a hyper-NA lithography illumination system.

A polarization simulation and analysis method was carried out for a hyper numerical apertures (NA) lithography illumination system which is affected by residual birefringence in optical materials. The lens is divided into multiple small annuli according to the finite element method, and the retardation distribution is obtained by setting the residual birefringence of each annulus. Finally, the polarized ray tracing is cleverly changed to geometric ray tracing. A hyper-NA lithography illumination system is modeled, and the residual birefringence is set between 0.1 nm/cm and 1 nm/cm. The simulation result shows that the degree of polarization performance degradation is proportional to the magnitude of residual birefringence, and the tolerance of residual birefringence in lens materials is below 1 nm/cm for the system. The polarization simulation and analysis method provides a powerful tool to calculate the polarized parameters of the system, which is helpful for selecting lens material of the hyper-NA illumination system.

Response of patients with locally advanced pancreatic adenocarcinoma to high-intensity focused ultrasound treatment: a single-center, prospective, case series in China.

PURPOSE: Patients with unresectable locally advanced pancreatic cancer (LAPC) are still in dire need of effective therapies. We performed this cohort study in order to assess the efficacy and safety of high-intensity focused ultrasound (HIFU) ablation in treating patients with unresectable LAPC. PATIENTS AND METHODS: Eighty-seven cases with unresectable LAPC from January 2014 to December 2016 were finally recruited according to the inclusion criteria. The primary end point of our study was OS of all the cases, and the secondary end points included 6-month and 12-month survival rate, tumor response rate, carbohydrate antigen (CA) 19-9 response rate, VAS, quality of life, and safety. RESULTS: All the 87 patients received HIFU ablation successfully, and were included in the efficacy and safety analysis. With a median follow-up of 16 months, median OS was estimated to be 12.2 months, with 95 % CI of 11.1-12.7 months. The 6-month and 12-month survival rates were 94.25% (95% CI =86.74-97.57) and 50.85% (95% CI =38.17-62.21), respectively. Multivariate analysis revealed that patients with VAS <4, Karnofsky performance status ≥80, and tumor size <3 cm have a significant improvement in their OS (adjusted HR [aHR] =0.26 [95% CI =0.12-0.57], P=0.001; aHR =0.34 [95% CI =0.17-0.68], P=0.02; and aHR =0.39 [95% CI =0.20-0.78], P=0.007; respectively). Tumor responses were observed in 32 (36.8%) of 87 patients and CA 19-9 response rate was 56.2%. Global health status, physical function, emotional function, and cognitive function of patients were significantly improved after HIFU treatment, and symptoms of fatigue and pain were significantly reduced. A total of 28.7% (25/87) of patients reported adverse events (AEs), mainly including fatigue (14/87), abdominal pain (7/87), fever (7/87), nausea (5/87), and rash (4/87). No severe AEs and HIFU-related deaths were reported. CONCLUSION: HIFU ablation might be a potentially effective and safe therapeutic option for the patients with unresectable LAPC.

High-intensity focused ultrasound (HIFU) treatment for uterine fibroids: a meta-analysis.

PURPOSE: High-intensity focused ultrasound (HIFU) is a non-invasive uterine-preserving treatment alternative to hysterectomy for women with fibroids. METHODS: We performed this meta-analysis to evaluate the efficacy of HIFU in the treatment of women with symptomatic fibroids comparing it to other approaches including medical treatment with mifepristone (Mife), traditional surgery with myomectomy or hysterectomy (MYC/HRM), and radiofrequency ablation (RF). 16 studies with 1725 women were included. RESULTS: The pooled data of HIFU comparing it to other methods in terms of complete or partial response rate (CR/PR) was not significantly better, but in subgroup analysis, the response rate was significantly higher than Mife, significantly lower than RF and comparable to MYC/HRM, respectively. For the endpoints of safety, the superiority of HIFU compared to MYC/HMR or Mife was found to be significant in terms of pain/discomfort, fever, transfusion, genital tract, gastrointestinal tract, and anesthesia-related complications, while no superiority was identified for skin burn, urinary tract, and nervous system complications. CONCLUSION: These results suggest that HIFU treatment of uterine leiomyomas leads to clinical improvement with few significant clinical complications and adverse events.

Lateral shearing interferometer with variable shearing for measurement of a small beam.

A lateral shearing interferometer with variable shearing for measurement of a small beam is proposed. The interferometer is composed of a polarization beam splitter, a thick birefringent plate, a quarter-wave plate, a mirror, and an image sensor. The shearing amount can be tiny by using the thick birefringent plate as the shear generator. The shearing amount of the interferometer can be continuously adjusted by rotating the thick birefringent plate, and 2D interferograms can be obtained by rotating the thick birefringent plate along the mutually perpendicular directions. The optical path difference is compensated with a double lateral shearing by using a quarter-wave plate and a mirror. The interferometer is verified by simulation and experiment; the experiment result is well coincident with the simulation result. The usefulness of the interferometer is verified.

Simultaneous measurement of retardance and fast axis angle of a quarter-wave plate using one photoelastic modulator.

A method for simultaneous measurement of the retardance and the fast axis angle of quarter-wave plate using one photoelastic modulator is presented. A laser beam passes through a polarizer, a photoelastic modulator, the quarter-wave plate to be measured, and an analyzer to be detected. Before and after the quarter-wave plate is rotated 45° at any initial fast axis direction, two detection signals are obtained to resolve simultaneously the retardance and the fast axis angle. In experiments, a quarter-wave plate was measured with fast axis angles from -89° to 90°. The average and the standard deviation of the retardances at different fast axis directions are respectively 89.50° and 0.17°. The maximum measurement deviation of the fast axis angle is 0.5°. The usefulness of the method is verified.