Cancer nutritional-immunotherapy with NIR-II laser-controlled ATP release based on material repurposing strategy.

Enlightened by the great success of the drug repurposing strategy in the pharmaceutical industry, in the current study, material repurposing is proposed where the performance of carbonyl iron powder (CIP), a nutritional intervention agent of iron supplement approved by the US FDA for iron deficiency anemia in clinic, was explored in anti-cancer treatment. Besides the abnormal iron metabolic characteristics of tumors, serving as potential targets for CIP-based cancer therapy under the repurposing paradigm, the efficacy of CIP as a catalyst in the Fenton reaction, activator for dihydroartemisinin (DHA), thus increasing the chemo-sensitivity of tumors, as well as a potent agent for NIR-II photothermal therapy (PTT) was fully evaluated in an injectable alginate hydrogel form. The CIP-ALG gel caused a rapid temperature rise in the tumor site under NIR-II laser irradiation, leading to complete ablation in the primary tumor. Further, this photothermal-ablation led to the significant release of ATP, and in the bilateral tumor model, both primary tumor ablation and inhibition of secondary tumor were observed simultaneously under the synergistic tumor treatment of nutritional-photothermal therapy (NT/PTT). Thus, material repurposing was confirmed by our pioneering trial and CIP-ALG-meditated NT/PTT/immunotherapy provides a new choice for safe and efficient tumor therapy.

Wormwood-infused porous-CaCO3 for synthesizing antibacterial natural rubber latex.

Wormwood leaf is a traditional Chinese herbal medicine with a high medicinal value and long application history and its essential oil is a high-purity plant oil extracted from Wormwood leaf. Pharmacological research reveals that Wormwood leaf and Wormwood essential oil are a broad-spectrum antibacterial and antiviral drug, which can inhibit and kill many bacteria and viruses. We loaded wormwood extract on porous calcium carbonate (Porous-CaCO3) and introduced it and Wormwood essential oil into Natural rubber latex (NRL), thus synthesizing NRL composites with excellent vitro and in vivo antibacterial effect, cell compatibility and mechanical properties. This NRL material can delay the light aging and thermal oxidation of some mechanical properties, which provides a broader avenue for its commercialization.

Novel one-pot strategy for fabrication of a pH-Responsive bone-targeted drug self-frame delivery system for treatment of osteoporosis.

Osteoporosis (OP) is a systemic metabolic orthopedic disorder prevalent in elderly people, that is characterized by a decrease in bone mass. Although many therapeutics have been adopted for OP treatment, many of them are still not well satisfied clinical requirements and therefore development of novel therapeutics is of great significance. In this work, a novel bone-targeting drug self-frame delivery system (DSFDS) with high drug loading efficiency and pH responsive drug release was fabricated by condensation of curcumin (Cur), amino group terminated polyethylene glycol (NH2-PEG), and alendronate (ALN) using hexachlorocyclotriphosphonitrile (HCCP) as the linker. The final product named as HCCP-Cur-PEG-ALN (HCPA NPs) displayed excellent water dispersity with small size (181.9 â€‹± â€‹25.9 â€‹nm). Furthermore, the drug loading capacity of Cur can reach 25.8%, and Cur can be released from HCPA NPs under acidic environment. Owing to the introduction of ALN, HCPA NPs exhibited strong binding to HAp in vitro and excellent bone-targeting effect in vivo. Results from cellular and biochemical analyses revealed that HCPA NPs could effectively inhibit the formation and differentiation function of osteoclasts. More importantly, we also demonstrated that HCPA NPs could effectively reduce bone loss in OVX mice with low toxicity to major organs. The above results clearly demonstrated that HCPA NPs are promising for OP treatment. Given the simplicity and well designability of fabrication strategy, explicit therapy efficacy and low toxicity of HCPA NPs, we believe that this work should be of great interest for fabrication of various DSFDS to deal with many diseases.

Acidity-Triggered Charge-Convertible Conjugated Polymer for Dihydroartemisinin Delivery and Tumor-Specific Chemo-Photothermal Therapy.

Since the nonspecificity and nonselectivity of traditional treatment models lead to the difficulty of cancer treatment, nanobased strategies are needed to fill in the gaps of current approaches. Herein, a tumor microenvironment (TME)-responsive chemo-photothermal treatment model was developed based on dihydroartemisinin (DHA)-loaded conjugated polymers (DHA@PLGA-PANI). The synthesized DHA@PLGA-PANI exhibited enhanced photothermal properties under mild-acidic conditions and thus triggered local heat at the tumor site. Meanwhile, these iron-doped conjugated polymers of PLGA-PANI were used as the source of Fe, and benefiting from the Fe-dependent cytotoxicity of DHA, the burst of free radicals could be generated in tumors. Therefore, the combination of TME-responsive chemo-photothermal therapy could achieve effective tumor efficacy.

Facile synthesis of curcumin-containing poly(amidoamine) dendrimers as pH-responsive delivery system for osteoporosis treatment.

Osteoporosis is an age-related metabolic disease of bone, resulting in bone pain and even bone fragility and brittle fracture. Inhibiting overactive osteoclasts while promoting osteoblast activity is an ideal way to treat osteoporosis. Previous studies have demonstrated that natural compounds, such as curcumin (Cur) have dual roles both in promoting bone formation and inhibiting bone resorption, making them promising candidates for osteoporosis treatment. However, their poor water solubility, high dosage of curative effect and significant toxicity to other organs have largely limited their clinical translations. In this study, a novel method was reported to conjugate Cur and poly(amidoamine) dendrimers (PAD) using hexachlorocyclotriphosphazene (HCCP) as the linkage through a one-pot reaction, forming stable and uniform Cur loaded nanospheres (HCCP-Cur-PAD, HCP NPs). Owing to the hydrophilicity of PAD and hydrophobicity of Cur, HCP NPs can self-assemble into nanoparticles with particle size of 138.8 ± 78.7 nm and display excellent water dispersity. The loading capacity of Cur can reach 27.2% and it can be released from HCP NPs with pH-responsiveness. In vitro experimental results demonstrated that the HCP NPs entered lysosomes by endocytosis and proved dual anti-osteoporosis effects of inhibiting osteoclasts and promoting osteoblasts.

Antimicrobial Lignin-Based Polyurethane/Ag Composite Foams for Improving Wound Healing.

Antimicrobial materials are an urgent need for modern wound care in the clinic. Although traditional polyurethane foams have proven to be clinically valuable for wound treatment, their petroleum-originated preparation and bioinert nature have restricted their efficacy in biomedical applications. Here, we propose a simple one-step foaming method to prepare lignin-based polyurethane foams (LPUFs) in which fully biobased polyether polyols partially replace traditional petroleum-based raw materials. The trace amount of phenolic hydroxyl groups (about 4 mmol) in liquefied lignin acts as a direct reducing agent and capping agent to silver ions (less than 0.3 mmol), in situ forming silver nanoparticles (Ag NPs) within the LPUF skeleton. This newly proposed lignin polyurethane/Ag composite foam (named as Ag NP-LPUF) shows improved mechanical, thermal, and antibacterial properties. It is worth mentioning that the Ag NP-LPUF exhibits more than 99% antibacterial rate against Escherichia coli within 1 h and Staphylococcus aureus within 4 h. Evaluations in mice indicate that the antimicrobial composite foams can effectively promote wound healing of full-thickness skin defects. As a proof of concept, this antibacterial and biodegradable foam exhibits significant potential for clinical translation in wound care dressings.

Demystifying Case Management in Aotearoa New Zealand: A Scoping and Mapping Review.

BACKGROUND: Community-based case managers in health have been compared to glue which holds the dynamic needs of clients to a disjointed range of health and social services. However, case manager roles are difficult to understand due to poorly defined roles, confusing terminology, and low visibility in New Zealand. AIM: This review aims to map the landscape of case management work to advance workforce planning by clarifying the jobs, roles, and relationships of case managers in Aotearoa New Zealand (NZ). METHODS: Our scoping and mapping review includes peer-reviewed articles, grey literature sources, and interview data from 15 case managers. Data was charted iteratively until convergent patterns emerged and distinctive roles identified. RESULTS: A rich and diverse body of literature describing and evaluating case management work in NZ (n = 148) is uncovered with at least 38 different job titles recorded. 18 distinctive roles are further analyzed with sufficient data to explore the research question. Social ecology maps highlight diverse interprofessional and intersectoral relationships. CONCLUSIONS: Significant innovation and adaptations are evident in this field, particularly in the last five years. Case managers also known as health navigators, play a pivotal but often undervalued role in NZ health care, through their interprofessional and intersectoral relationships. Their work is often unrecognised which impedes workforce development and the promotion of person-centered and integrated health care.

Exploring the mechanical properties of nanometer-thick elastic films through micro-drop impinging on large-area suspended graphene.

In this work, the dependence of effective Young's modulus on the thickness of suspended graphene was confirmed through a drop impingement method. Large area suspended graphene (LSG) layers with a diameter of up to 400 µm and a nanometer thickness were prepared through transferring chemical vapor deposition grown graphene from copper substrates. 4, 8, and 12-layer LSG samples were found to be crumpled yet defect-free. The mechanical properties of LSG were first studied by observing its interaction with impinging droplets from an ink-jet nozzle. First, the effective Young's modulus was calculated by fitting the instant deformation captured by high speed photography within microseconds. Next, droplets deposited on LSG caused deformation and generated wrinkles and the effective Young's modulus was calculated from the number of wrinkles. The above methods yielded effective Young's modulus values ranging from 0.3 to 3.4 TPa. The results from these methods all indicated that the effective Young's modulus increases with the decreasing thickness or size of suspended graphene layers. Moreover, the crumpled LSG yields higher effective Young's modulus than ideal flat graphene. These comprehensive results from complementary methodologies with precise LSG thickness control down to the nanometer scale provide good evidence to resolve the debate on the thickness dependence of mechanical strength for LSG.

Red aggregation-induced emission luminogen and Gd3+ codoped mesoporous silica nanoparticles as dual-mode probes for fluorescent and magnetic resonance imaging.

Fluorescence imaging and magnetic resonance imaging have been research hotspots for adjuvant therapy and diagnosis. However, traditional fluorescent probes or contrast agents possess insurmountable weaknesses. In this work, we reported the preparation of dual-mode probes based on mesoporous silica nanomaterials (MSNs), which were doped with an aggregation-induced emission (AIE) dye and Gd3+ through a direct sol-gel method. In this system, the obtained materials emitted strong red fluorescence, in which the maximum emission wavelength was located at 669 nm, and could be applied as effective fluorescence probes for fluorescence microscopy imaging. Furthermore, the introduction of Gd3+ made the nanoparticles effective contrast agents when applied in contrast-enhanced magnetic resonance (MR) imaging because they could improve the contrast of MR imaging. The excellent biocompatibility of these nanoparticles, as demonstrated via a typical CCK-8 assay, and their performance in fluorescence cell imaging and MR imaging shows their potential for applications in biomedical imaging.

Cryogenic 3D printing of porous scaffolds for in situ delivery of 2D black phosphorus nanosheets, doxorubicin hydrochloride and osteogenic peptide for treating tumor resection-induced bone defects.

Tumor resection is widely used to prevent tumor growth. However, the defected tissue at the original tumor site also causes tissue or organ dysfunction which lowers the patient's life quality. Therefore, regenerating the tissue and preventing tumor recurrence are highly important. Herein, according to the concept of 'first kill and then regenerate', a versatile scaffold-based tissue engineering strategy based on cryogenic 3D printing of water-in-oil polyester emulsion inks, containing multiple functional agents, was developed, in order to realize the elimination of tumor cells with recurrence suppression and improved tissue regeneration sequentially. To illustrate our strategy, water/poly(lactic-co-glycolic acid)/dichloromethane emulsions containing ß-tricalcium phosphate (ß-TCP), 2D black phosphorus (BP) nanosheets, low-dose doxorubicin hydrochloride (DOX) and high-dose osteogenic peptide were cryogenically 3D printed into hierarchically porous and mechanically strong nanocomposite scaffolds, with multiple functions to treat bone tumor, resection-induced tissue defects. Prompt tumor ablation and long-term suppression of tumor recurrence could be achieved due to the synergistic effects of photothermotherapy and chemotherapy, and improved bone regeneration was obtained eventually due to the presence of bony environment and sustained peptide release. Notably, BP nanosheets in scaffolds significantly reduced the long-term toxicity phenomenon of released DOX during in vivo bone regeneration. Our study also provides insights for the design of multi-functional tissue engineering scaffolds for treating other tumor resection-induced tissue defects.

Recent development and prospects of surface modification and biomedical applications of MXenes.

MXenes, as a novel kind of two-dimensional (2D) materials, were first discovered by Gogotsi et al. in 2011. Owing to their multifarious chemical compositions and outstanding physicochemical properties, the novel types of 2D materials have attracted intensive research interest for potential applications in various fields such as energy storage and conversion, environmental remediation, catalysis, and biomedicine. Although many achievements have been made in recent years, there still remains a lack of reviews to summarize these recent advances of MXenes, especially in biomedical fields. Understanding the current status of surface modification, biomedical applications and toxicity of MXenes and related materials will give some inspiration to the development of novel methods for the preparation of multifunctional MXene-based materials and promote the practical biomedical applications of MXenes and related materials. In this review, we present the recent developments in the surface modification of MXenes and the biomedical applications of MXene-based materials. In the first section, some typical surface modification strategies were introduced and the related issues were also discussed. Then, the potential biomedical applications (such as biosensor, biological imaging, photothermal therapy, drug delivery, theranostic nanoplatforms, and antibacterial agents) of MXenes and related materials were summarized and highlighted in the following sections. In the last section, the toxicity and biocompatibility of MXenes in vitro were mentioned. Finally, the development, future directions and challenges about the surface modification of MXene-based materials for biomedical applications were discussed. We believe that this review article will attract great interest from the scientists in materials, chemistry, biomedicine and related fields and promote the development of MXenes and related materials for biomedical applications.

Small fluorescent albumin nanoparticles for targeted photothermal therapy via albumin-Binding protein pathways.

Targeted delivery of nanotheranostics to tumor site plays critical roles in the diagnosis and treatment of cancers, therefore, fabrication of targeted nanotheranostics has attracted increasing interest these years. Especially, nutrient transporters exhibit great prospect in the targeted delivery of nanotheranostics. However, small albumin nanoparticles which could even demonstrate more outstanding targeting ability via albumin-binding protein pathways than those nanoparticles modified with targeting ligands, have not been reported before. Herein, a facile strategy to construct small albumin nanoparticles of about 30 nm in one pot for better targeted fluorescence imaging and photothermal therapy of U87 tumors through albumin-binding protein pathways is presented. Compared with BSA-PhENH2-PPy-cRGD NPs those with a larger size but less BSA molecules on the surface, more BSA-PhENH2-PPy NPs could target the tumor site of mice in vivo, and BSA-PhENH2-PPy NPs could also demonstrate more outstanding performance in the photothermal therapy of tumors than BSA-PhENH2-PPy-cRGD NPs. This work provides a facile approach to construct small albumin nanoparticles in one pot for targeted fluorescence imaging and photothermal therapy, which also clearly proved the huge prospect of albumin nanoparticles for targeted tumor therapy via albumin-binding protein pathways.

Nonmagnetic Hypertonic Saline-Based Implant for Breast Cancer Postsurgical Recurrence Prevention by Magnetic Field/pH-Driven Thermochemotherapy.

Magnetic-mediated hyperthermia (MMT) is emerging as one of the promising techniques, which could synergistically treat cancer along with current treatment techniques such as chemotherapy and radiotherapy and trigger on-demand release of therapeutic macromolecules. However, the low specific absorption rate and potential in vivo toxicity of magnetic nanomaterials as the MMT mediators restrict the new advancements in MMT treatment. Herein, for the first trial, the unique inductive heating property of hypertonic saline (HTS), a clinically applied solution exhibiting several physiological effects under alternative magnetic field (AMF), was systematically investigated. Though without magnetic property, due to the dipolar polarization under the electromagnetic radiation, HTS can induce enough high and rapid temperature increase upon exposure under AMF. Based on such an observation, PEG-based HTS hydrogel was fabricated for the inhibition of unwanted diffusion of ions so as to ensure the ideal temperature rise at the targeted region for a longer time. Furthermore, an anticancer drug (doxorubicin) was also incorporated into the hydrogel to achieve the magnetic field/pH stimuli-responsive drug-sustainable release as well as synergistic thermochemotherapy. The potential application of the drug-loaded HTS-PEG-injectable hydrogel for breast cancer postsurgical recurrence prevention is demonstrated. Significant in vivo suppression of two kinds of breast cancer models was achieved by the hybrid hydrogel system. This work explores a new biomedical use of clinical HTS and a promising cancer treatment protocol based on HTS-PEG hydrogel for magnetic hyperthermia combined with stimuli-responsive chemotherapy for breast cancer postsurgical recurrence prevention.

Recent Advances and Progress on Melanin-like Materials and Their Biomedical Applications.

Melanins are well-known biopolymers that are ubiquitous in nature, distributed widely in microorganisms, plants, and animals, and play significant physiological roles. They are mostly biopolymers formed from phenolic compounds by polymerization via quinones. Poly(dopamine) (PDA), a melanin-like material, is similar in structure and properties to eumelanin and has attracted considerable interest for various types of biological applications. This review outlines the recent advances in the structure and synthesis of PDA and discusses applications of PDA in many biological fields, such as biological imaging, photothermal therapy, and drug delivery systems. The purpose of this review is to give a brief overview of the synthesized procedures, structure, biomedical applications, and prospects of melanin-like materials.

Effect of nanoheat stimulation mediated by magnetic nanocomposite hydrogel on the osteogenic differentiation of mesenchymal stem cells.

Hyperthermia has been considered as a promising healing treatment in bone regeneration. We designed a tissue engineering hydrogel based on magnetic nanoparticles to explore the characteristics of hyperthermia for osteogenic regeneration. This nanocomposite hydrogel was successfully fabricated by incorporating magnetic Fe3O4 nanoparticles into chitosan/polyethylene glycol (PEG) hydrogel, which showed excellent biocompatibility and were able to easily achieve increasing temperatures under an alternative magnetic field (AMF). With uniformly dispersed nanoparticles, the composite hydrogel resulted in high viability of mesenchymal stem cells (MSCs), and the elevated temperature contributed to the highest osteogenic differentiation ability compared with direct heat treatment applied under equal temperatures. Therefore, the nanoheat stimulation method using the magnetic nanocomposite hydrogel under an AMF may be considered as an alternative candidate in bone tissue engineering regenerative applications.

A versatile CeO2/Co3O4 coated mesh for food wastewater treatment: Simultaneous oil removal and UV catalysis of food additives.

Food waste water is one of the most urgent environmental problems for the close connection between food and our daily life. Herein, we use a simple hydrothermal method to prepare a highly efficient catalyst-CeO2/Co3O4 compound on the stainless steel mesh, aiming for food waste water treatment. Possessing the superhydrophilic property and catalytic ability under ultraviolet light, CeO2/Co3O4 coated mesh has successfully processed three representative contaminants in food wastewater, which are soybean oil (food oil), AR (food dye) and VA (food flavor) simultaneously with an one-step filtration. Besides, the mesh is stable in a wide pH range and performs well in reusability. Therefore, such a multifunctional material with simple preparation method, high processing efficiency and facile operation shows a promising prospect for practical production and application for food wastewater treatment.

One-pot synthesis of AIE based bismuth sulfide nanotheranostics for fluorescence imaging and photothermal therapy.

Photothermal therapy (PTT) has been widely investigated as a minimally invasive strategy for cancer therapy due to its favorable biosafety. Nevertheless, there is only limited success in the exploration of nanotheranostics composing of both fluorescent dyes and PTT agents since their fluorescence would always be quenched. Herein, a facile one-pot synthesis approach of Aggregation Induced Emission (AIE) based Bi2S3 nanotheranostics is described, and their effectiveness for fluorescence imaging and simultaneous PTT has been demonstrated. AIE incorporated BSA was employed for the biomineralization synthesis of Bi2S3 nanoparticles (NPs), which endowed as-prepared BSA-PhENH2-Bi2S3 NPs with excellent biocompatibility and ultrasmall size. Moreover, the resulted NPs also exhibited remarkable photothermal effect and photostability. Importantly, BSA-PhENH2-Bi2S3 NPs could efficiently get into HepG2 cells, and light their cytoplasm region with bright fluorescence owning to the superb fluorescence property of AIE, which could simultaneously prompt cancer cells death under an 808nm laser irradiation. This work provides a universal approach for the fabrication of AIE based nanotheranostics via albumin-mediated biomineralization method, and the as-prepared BSA-PhENH2-Bi2S3 NPs possess great potential for cancer theranostics.

Thermally Triggered in Situ Assembly of Gold Nanoparticles for Cancer Multimodal Imaging and Photothermal Therapy.

The assembly of gold nanoparticles (AuNPs) to AuNP assemblies is of interest for cancer therapy and imaging. Herein we introduce a new and general paradigm, thermally triggered AuNP assembly, for the development of novel intelligent platforms for cancer photothermal therapy (PTT) and multimodal imaging. Site-specific conjugation of a thermally sensitive elastin-like polypeptide (ELP) to AuNPs yields thermally sensitive ELP-AuNPs. Interestingly, ELP-AuNPs can in situ form AuNP assemblies composed of short necklace-like gold nanostructures at elevated temperatures and thus show strong near-infrared light absorption and high photothermal effect. These thermally responsive properties of ELP-AuNPs enable simultaneous photothermal/photoacoustic/X-ray computed tomographic imaging and PTT of melanoma after single intratumoral injection of ELP-AuNPs. The thermally triggered assembly of a variety of nanoparticles with optical, electronic, and magnetic properties into nanoparticle assemblies may open new ways for the establishment of intelligent platforms for various applications in biomedicine.

Photoinduced Mild Hyperthermia and Synergistic Chemotherapy by One-Pot-Synthesized Docetaxel-Loaded Poly(lactic-co-glycolic acid)/Polypyrrole Nanocomposites.

Mild hyperthermia has shown great advantages when combined with chemotherapy. The development of a multifunctional platform for the integration of mild hyperthermia capability into a drug-loading system is a key issue for cancer multimodality treatment application. Herein, a facile one-pot in situ fabrication protocol of docetaxel (DTX)-loaded poly(lactic-co-glycolic acid) (PLGA)/polypyrrole (PPy) nanocomposites was developed. While the PLGA nanoparticles (NPs) allow efficient drug loading, the PPy nanobulges embedded within the surface of the PLGA NPs, formed by in situ pyrrole polymerization without the introduction of other template agents, can act as ideal mediators for photoinduced mild hyperthermia. Physiochemical characterizations of the as-prepared nanocomposites, including structure, morphology, photothermal effects, and an in vitro drug release profile, were systematically investigated. Further, 2-deoxyglucose-terminated poly(ethylene glycol) (PEG) was anchored onto the surface of the nanocomposites to endow the nanoplatform with targeting ability to tumor cells, which resulted in a 17-fold increase of NP internalization within human breast cancer cells (MCF-7) as competed with PEG-modified nanocomposites. Mild hyperthermia can be successfully mediated by the nanoplatform, and the temperature can be conveniently controlled by careful modulation of the PPy contents within the nanocomposites or the laser power density. Importantly, we have demonstrated that MCF-7 cells, which are markedly resistant to heat treatment of traditional water-bath hyperthermia, became sensitive to the PLGA/PPy nanocomposite-mediated photothermal therapy under the same mild-temperature hyperthermia. Moreover, DTX-loaded PLGA/PPy-nanocomposite-induced mild hyperthermia can strongly enhance drug cytotoxicity to MCF-7 cells. Under the same thermal dose, photoinduced hyperthermia can convert the interaction between hyperthermia and drug treatment from interference to synergism. This is the first report on the one-pot synthesis of PLGA/PPy nanocomposites by in situ pyrrole polymerization, and such a multifunctional nanoplatform is demonstrated as a high-potential agent for photoinduced mild hyperthermia and enhanced chemotherapy.

Salt-induced aggregation of gold nanoparticles for photoacoustic imaging and photothermal therapy of cancer.

The challenge in photothermal therapy (PTT) is to develop biocompatible photothermal transducers that can absorb and convert near-infrared (NIR) light into heat with high efficiency. Herein, we report salt-induced aggregation of gold nanoparticles (GNPs) in biological media to form highly efficient and biocompatible NIR photothermal transducers for PTT and photothermal/photoacoustic (PT/PA) imaging of cancer. The GNP depots in situ formed by salt-induced aggregation of GNPs show strong NIR absorption induced by plasmonic coupling between adjacent GNPs and very high photothermal conversion efficiency (52%), enabling photothermal destruction of tumor cells. More interestingly, GNPs in situ aggregate in tumors to form GNP depots, enabling simultaneous PT/PA imaging and PTT of the tumors. These findings may provide a simple and effective way to develop a new class of intelligent and biocompatible NIR photothermal transducers with high efficiency for PT/PA imaging and PTT.