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In the last two decades, the application of surface enhanced Raman scattering (SERS) nanoparticles for preclinical cancer imaging has attracted increasing attention. Raman imaging with SERS nanoparticles offers unparalleled sensitivity, providing a platform for molecular targeting, and granting multiplexed and multimodal imaging capabilities. Recent progress has been facilitated not only by the optimization of the SERS contrast agents themselves, but also by the developments in Raman imaging approaches and instrumentation. In this article, we review the principles of Raman scattering and SERS, present advances in Raman instrumentation specific to cancer imaging, and discuss the biological means of ensuring selective in vivo uptake of SERS contrast agents for targeted, multiplexed, and multimodal imaging applications. We offer our perspective on areas that must be addressed in order to facilitate the clinical translation of SERS contrast agents for in vivo imaging in oncology.

Stapled peptides have been widely applied in many fields, including pharmaceutical chemistry, diagnostic reagents, and materials science. However, most traditional stapled peptide preparation methods rely on prefunctionalizations, which limit the diversity of stapled peptides. Recently, the emergence of late-stage transition metal-catalyzed C-H activation in amino acids and peptides has attracted wide interest due to its robustness and applicability for peptide stapling. In this review, we summarize the methods for late-stage construction of stapled peptides via transition metal-catalyzed C-H activation.

El presente trabajo de investigación analizas el desempeño energético de una instalación industrial utilizando la Norma Internacional ISO 50001. Los usos energéticos significativos, utilizando los criterios establecidos por la Norma Internacional ISO 50001, resultan ser la iluminación, uso motores eléctricos, compresores de aire, bombas de agua, equipos de refrigeración y aire acondicionado, así como calderas de vapor. Los costos unitarios determinados para la instalación industrial resultan en 16.10 USD/GJ para el caso de la energía térmica y en 26.0 USD/GJ para el caso de energía eléctrica (monómico). La determinación de la línea base energética en la instalación industrial establece un consumo total de 96124 GJ/año incluyendo energía térmica y eléctrica. Con relación a las áreas de consumo de energía eléctrica, se establece una demanda de potencia de 12860 kW, así como un consumo de energía anual de 7592862 kW.h. Los ahorros obtenidos en términos de reducción del consumo de energía y de la demanda de potencia se reflejan en el análisis comparativo entre la línea base energética preliminar y la línea base energética actualizada. En total se obtiene una reducción de 4,0% del consumo de energía en la instalación industrial, de la cual las reducciones más significativas son: el consumo de energía de las calderas (35,2%) y de las bombas (25,7%). Debido a la reducción del consumo de energía, tanto térmica como eléctrica, se considera también una reducción en emisiones de carbono. La reducción de emisiones de carbono debido a la reducción del consumo de energía térmica es 304.9 tCO2/año, mientras que la reducción de emisiones de carbono debido a la reducción del consumo de energía eléctrica es 487.6 tCO2/año. Tesis

Isomerization is an essential chemical process that often evokes dramatic change of chemical, physical, or biological properties. For a long time, isomerization has been known as a transformation that is induced by certain external energy such as light, heat, or mechanical force. Herein, a new isomerization phenomenon is described, which does not require external energy but simply occurs during molecular packing. The proposed isomerization is demonstrated by a series of symmetric donor-acceptor-donor (D-A-D) molecules, the donor of which may adopt two different stereoisomeric forms. Based on the evidence of the asymmetric isomers in crystals, the occurrence of isomerization during molecular packing is proved. Moreover, the unique asymmetric geometry in the solid state favors the restriction of intramolecular motion, resulting in highly efficient organic solids with quantum yields approaching unity.

Polymeric nanoparticles play important roles in the delivery of a multitude of therapeutic and imaging contrast agents. Although these nanomaterials have shown tremendous potential in disease diagnosis and therapy, there have been many reports on the failure of these nanoparticles in realizing their intended objectives due to an individual or a combination of factors, which have collectively challenged the merit of nanomedicine for disease theranostics. Herein, we investigate the interactions of polymeric nanoparticles with biological entities from molecular to organism levels. Specifically, the protein corona formation, in vitro endothelial uptake, and in vivo circulation time of these nanoparticles are systematically probed. We identify the crucial role of nanocarrier lipophilicity, zeta-potential, and size in controlling the interactions between nanoparticles and biological systems and propose a two-step framework in formulating a single nanoparticle system to regulate multiple biological effects. This study provides insight into the rational design and optimization of the performance of polymeric nanoparticles to advance their theranostic and nanomedicine applications.

Vascular tubulogenesis is tightly linked with physiological and pathological events in the living body. Endothelial cells (ECs), which are constantly exposed to hemodynamic forces, play a key role in tubulogenesis. Hydrostatic pressure in particular has been shown to elicit biophysical and biochemical responses leading to EC-mediated tubulogenesis. However, the relationship between tubulogenesis and hydrostatic pressure remains to be elucidated. Here, we propose a specific mechanism through which hydrostatic pressure promotes tubulogenesis. We show that pressure exposure transiently activates the Ras/extracellular signal-regulated kinase (ERK) pathway in ECs, inducing endothelial tubulogenic responses. Water efflux through aquaporin 1 and activation of protein kinase C via specific G protein–coupled receptors are essential to the pressure-induced transient activation of the Ras/ERK pathway. Our approach could provide a basis for elucidating the mechanopathology of tubulogenesis-related diseases and the development of mechanotherapies for improving human health., Yoshino et al. investigate the mechanism by which exposure to pressure promotes endothelial cells to form tubes and find that Aquaporin-mediated water efflux activates the Ras-ERK pathway via PKC and GPCR activation. These findings may be relevant to understand how blood pressure affects vascular tubulogenesis.

Integration of AIEgens with upconversion nanoparticles inhibits tumor recurrence and metastasis., Reactive oxygen species (ROS) are essential for the regulation of antitumor immune responses, where they could induce immunogenic cell death, promote antigen presentation, and activate immune cells. Here, we report the development of near-infrared (NIR)–driven immunostimulants, based on coupling upconversion nanoparticles with aggregation-induced emission luminogens (AIEgens), to integrate the immunological effects of ROS for enhanced adaptive antitumor immune responses. Intratumorally injected AIEgen-upconversion nanoparticles produce high-dose ROS under high-power NIR irradiation, which induces immunogenic cell death and antigen release. These nanoparticles can also capture the released antigens and deliver them to lymph nodes. Upon subsequent low-power NIR treatment of lymph nodes, low-dose ROS are generated to further trigger efficient T cell immune responses through activation of dendritic cells, preventing both local tumor recurrence and distant tumor growth. The utility of dual-mode pumping power on AIEgen-coupled upconversion nanoparticles offers a powerful and controllable platform to activate adaptive immune systems for tumor immunotherapy.

Summary Effective photosensitizers are highly desirable in many applications, such as photodynamic therapy, photocatalytic organic waste decomposition, and synthetic chemistry. Herein, we demonstrate polymerization-enhanced photosensitization, in which conjugated-polymer-based photosensitizers show much higher efficiency in singlet oxygen (1O2) production than their small-molecule analogs. Based on small-molecule photosensitizers SM1–SM4 with long wavelength emission, four conjugated polymer photosensitizers, CP1–CP4, were prepared. Interestingly, the conjugated polymer photosensitizers CP1–CP4 showed 5.06-, 5.07-, 1.73-, and 3.42-fold higher 1O2 generation efficiency than SM1–SM4, respectively. The improved intersystem crossing process from the singlet excitation states to the triplet excitation states and improved light-harvesting ability are essential to the enhancement of 1O2 generation efficiency. To illustrate the advantages of conjugated polymer photosensitizers on various applications, we demonstrate the superior performance of CP1 by using photoinduced organic waste decomposition, photoinduced organic oxidation reaction, and photodynamic cancer therapy as examples.

Recent advances in stem cell research and nanotechnology have significantly influenced the landscape of tissue engineering and regenerative medicine. Precise and reproducible control of the fate of stem cells and their lineage specification have, therefore, become more crucial than ever for the success of stem cell-based technologies. Extensive research has been geared towards developing materials that are capable of mimicking the physiological microenvironment of stem cells and at the same time, controlling their eventual fate. An interesting example of these materials is two-dimensional graphene and its related derivatives. A high specific surface area coupled with superior chemical stability, biocompatibility, and flexibility in functionalization render graphene-based nanomaterials one of the most exciting platforms for tissue engineering and regenerative medicine applications, especially for stem cell growth, proliferation, and differentiation. In this review, we discuss the love-hate relationship between stem cells and graphene-based nanomaterials in tissue engineering and regenerative medicine. We first discuss the role and importance of stem cells in tissue engineering and regenerative medicine. We then highlight the use of nanomaterials for stem cell control, the interaction between stem cells and graphene nanomaterials as well as their biocompatibility, biodistribution, and biodegradability considerations. We also offer our perspectives on the various challenges and opportunities facing the use of graphene and its derivatives for stem cell growth and differentiation.

Multiplexed cellular organelle imaging using single wavelength excitation is highly desirable for unravelling cellular functions but remains challenging. This requires the design of organelle specific fluorophores with distinct emission but similar absorption. Herein, we present two unique aggregation-induced emission (AIE) probes to track mitochondria and lysosomes simultaneously with emission colors that can be distinguished from that of the nucleus stain Hoechst 33342 upon single wavelength excitation. Compared to conventional organelle stains, the two AIE probes have larger Stokes shifts and higher photostability, which endow them with the capability to monitor bioprocesses, such as mitophagy with strong and sustained fluorescent signals. Moreover, both probes can also stain intracellular organelles in zebrafish larvae with good cell-penetrating capabilities, showing their great potential to monitor bioprocesses in vivo.

Phospholipid nanoparticles have been actively explored for biological and biomedical applications. These nanoparticles display excellent cargo encapsulation efficiency, high water dispersibility, and outstanding biocompatibility, rendering them highly attractive for cancer nanomedicine applications. While the promising utilizations of phospholipid nanoparticles for cancer theranostic have been widely documented, the cellular biophysical responses elicited by phospholipid nanoparticles have been less investigated. Notably, the effects of phospholipid nanoparticles on collective cancer cell behaviors have not been well delineated. In fact, most of the studies examining nanoparticle-cancer interactions have focused largely on the nanoparticle toxicity on individual cells, but paid little attention to other nanoparticle effects on multicellular systems and their collective behaviors. A better appreciation of the effects of nanoparticles on multicellular system dynamics is necessary as collective cancer cell behaviors are central to the regulation of various processes, particularly cancer invasion and metastasis. Motivated by this, we sought to interrogate the effects of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG) nanoparticles, which are some of the most commonly used phospholipid nanoparticles for cancer nanomedicine, on the collective behaviors of healthy and cancerous breast epithelial cell monolayers. DSPE-PEG nanoparticles with two sizes (i.e., 20 and 60 nm) and three surface functional groups (i.e., COOH, OCH3, and NH2) as well as three types of breast epithelial cell sheets with varying malignancy potential (i.e., MCF-10A, MCF-7, and MDA-MB-231) were used in this work. Utilizing a series of microscopy and molecular biology techniques and quantitative image analysis, we comprehensively examined the collective cell migratory dynamics in the absence and presence of DSPE-PEG nanoparticles. We noted that DSPE-PEG nanoparticles retarded the migration of the healthy MCF-10A epithelial cell sheets. In contrast, the cancerous MCF-7 and MDA-MB-231 cell sheets experienced accelerated collective migration in the presence of the nanoparticles. Moreover, these nanoparticles altered the migration directionality of the cancerous breast cell sheets. We ascribed the differential nanoparticle-modulated collective cell migratory behaviors to changes in the stiffness of the cell nuclei, cytoplasm, and cell-cell junctions, as well as the reorganization of the cellular actin filament networks after the nanoparticle-cell interactions. We anticipate that this study will provide a deeper insight into the nanomaterial-cancer interactions and aid the formulation of phospholipid nanoparticles for more effective and safer cancer theranostic and nanomedicine applications. Citation Format: Kenry, Bin Liu. Differential collective cell migratory behaviors modulated by phospholipid nanoparticles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 266.

Nanofibers have emerged as exciting one-dimensional nanomaterials for a broad spectrum of research and commercial applications owing to their unique physicochemical properties and characteristics. As a class of nanomaterials with cross-sectional diameters ranging from tens to hundreds of nanometers, nanofibers possess extremely high specific surface area and surface area-to-volume ratio. They are capable of forming networks of highly porous mesh with remarkable interconnectivity between their pores, making them an attractive choice for a host of advanced applications. In fact, the significant impact of nanofiber technology can be traced from the wide range of fundamental materials that can be used for the synthesis of nanofibers. These include natural polymers, synthetic polymers, carbon-based materials, semiconducting materials, and composite materials. Correspondingly, the emerging proof-of-concept applications of nanofibers spanning several important areas have been rapidly reported. This Review explores the current status and up-and-coming development of nanofiber technology, with an emphasis on its syntheses and applications. First, we highlight the current and emerging strategies used in synthesizing nanofibers. We briefly introduce the various established nanofiber synthesis techniques, especially the electrospinning method. We then focus on the emerging nanofiber synthesis strategies, such as solution blow spinning, centrifugal jet spinning, and electrohydrodynamic direct writing. Next, we discuss the emerging applications of nanofiber technology in various fields, specifically in three important areas of energy generation and storage, water treatment and environmental remediation, and healthcare and biomedical engineering. Despite all these advancements, there are still challenges to be addressed and overcome for nanofiber technology to move towards maturation. Nevertheless, we envision that with further progress in the development of nanofiber synthesis strategies and identification of “killer” applications of nanofibers, nanofiber technology will mature and move beyond its current state towards commercial realization and applications.

A new second near-infrared (NIR II) conjugated polymer (CP) was designed and synthesized. The CP nanoparticles have good biocompatibility, excellent photostability and high imaging contrast, and have been successfully used to demonstrate the first example of NIR II photoacoustic imaging of orthotopic brain tumors. In comparison with existing contrast agents for photoacoustic imaging, the NIR II CP nanoparticles showed more efficient skull penetration and a much higher signal/background ratio using a 1064 nm laser.

The interactions between graphene oxide (GO) and various biological entities have been actively investigated in recent years, resulting in numerous potential bioapplications of these nanomaterials. Despite this, the biological interactions between GO and disease-causing protozoan parasites have not been well elucidated and remain relatively unexplored. Here, we investigate the in vitro interactions between GO nanosheets and a particular species of malaria parasites, Plasmodium falciparum (P. falciparum). We hypothesize that GO nanosheets may exhibit antimalarial characteristic via action mechanisms of physical obstruction of P. falciparum parasites as well as nutrient depletion. To ascertain this, we characterize the physical interactions between GO nanosheets, red blood cells (RBCs), and malarial parasites as well as the adsorption of several biomolecules necessary for parasitic survival and growth on GO nanosheets. Subsequent to establishing the origin of this antimalarial behavior of GO nanosheets, their efficiency in inhibiting parasite invasion is evaluated. We observe that GO nanosheets at various tested concentrations significantly inhibit the invasion of malaria parasites into RBCs. Furthermore, GO nanosheets delay parasite progression from the ring to the trophozoite stage. Overall, this study may further shed light on the graphene-parasite interactions and potentially facilitate the development of nanomaterial-based strategies for combating malaria.

Layered two-dimensional (2D) nanomaterials, such as graphene, transition metal dichalcogenides (TMDs), layered metal oxides (LMOs), black phosphorus (BP), and hexagonal boron nitride (hBN), have attracted tremendous interest recently owing to their unique structural morphologies and outstanding physicochemical properties. Consequently, these nanomaterials have been actively explored for different biological and biomedical applications, such as tissue engineering, drug delivery, bioimaging, and biosensing. As increasing efforts have been focused on identifying the potential bioapplications of layered 2D nanomaterials, one of the fundamental aspects that is of considerable interest and ought to be studied in greater depth is their biocompatibility and nanotoxicity. In addition, as the elucidation and understanding of the physicochemical properties of this new class of nanomaterials are still in their infancy, information on both in vitro and in vivo biocompatibility and nanotoxicity is still scarce and remains poorly understood. As such, there is an immediate need to explore and establish the biocompatibility and nanotoxicological profiles of these nanomaterials in order to develop and optimize them for specific bioapplications. Here, in this Focus Review, we will provide a broad overview of recent advances on the biocompatibility and nanotoxicity of layered 2D nanomaterials. First, a wide range of established and emerging layered 2D nanomaterials actively investigated for bioapplications will be introduced. Next, the different physicochemical aspects governing the biocompatibility and nanotoxicity of these nanomaterials, such as lateral size, concentration, exposure time, number of layers, and chemical composition and surface functionalization, will be evaluated. Finally, we will summarize the review and provide our perspectives on the challenges and opportunities facing this important field.

Recognizing neuro-motor control process of human locomotion is challenging and the progress was limited due to the complex dynamic control progress and the motion artifacts. We applied Adaptive Mixture Independent Component Analysis (AMICA) to explore the voluntary cortical contribution during pedaling process and compared the difference between active and passive pedaling in this preliminary study. We explored the power spectral density, source localization, and event-related spectral perturbations of selected independent components (ICs). The results demonstrated typical IC clusters during pedaling, and various cortical regions contribute differently to the locomotion control process. The active and passive pedaling showed different activation pattern in the cortex, but no significant difference was found, further study is still necessary to confirm the cortical contribution difference for different pedaling conditions.

o-Alkenylation of unprotected phenols has been developed by direct C-H functionalization catalyzed by Pd

Horseradish peroxidase (HRP) and fluorogen-dextran conjugate are tracers extensively used for injection-based lineage tracing. However, HRP is sensitive to proteolytic digestion, whereas the high-molecular-weight dextran may have antigenicity. Small molecular tracers can overcome these problems, but they usually diffuse from labeled cells, causing inaccurate information. Herein, we developed a small-molecular-weight fluorogen with aggregation-induced emission (AIEgen) for embryonic cell tracing with strong signals against tracer dilution caused by cell division. Once injected into the ancestor cells, the AIEgen can be entrapped in the cells without leakage because of the two hydrophilic and neutral arms. Consequently, it can specifically trace the progenies of the treated ancestor cells. More importantly, the operating concentration of AIEgen can be much higher than that of fluorogens with aggregation-caused quenching, which provides bright signals in daughter cells during embryonic cell tracing, thus overcoming the problem of fast signal degradation typically encountered with the use of traditional cell tracers.

Photosensitizer (PS) serves as the central element of photodynamic therapy (PDT). The use of common nanoparticles (NPs) for PDT has typically been rendered less effective by the undesirable aggregation-caused quenching (ACQ) effect, resulting in quenched fluorescence and reduced reactive oxygen species (ROS) generation that diminish the imaging quality and PDT efficacy. To overcome the ACQ effect and to enhance the overall efficacy of PDT, herein, integrin ανβ3-targeted organic nanodots for image-guided PDT were designed and synthesized based on a red emissive aggregation-induced emission (AIE) PS. Methods: The TPETS nanodots were prepared by nano-precipitation method and further conjugated with thiolated cRGD (cRGD-SH) through a click reaction to yield the targeted TPETS nanodots (T-TPETS nanodots). Nanodots were characterized for encapsulation efficiency, conjugation rate, particle size, absorption and emission spectra and ROS production. The targeted fluorescence imaging and antitumor efficacy of T-TPETS nanodot were evaluated both in vitro and in vivo. The mechanism of cell apoptosis induced by T-TPETS nanodot mediated-PDT was explored. The biocompatibility and toxicity of the nanodots was examined using cytotoxicity test, hemolysis assay, blood biochemistry test and histological staining. Results: The obtained nanodots show bright red fluorescence and highly effective 1O2 generation in aggregate state. Both in vitro and in vivo experiments demonstrate that the nanodots exhibit excellent tumor-targeted imaging performance, which facilitates image-guided PDT for tumor ablation in a hepatocellular carcinoma model. Detailed analysis reveals that the nanodot-mediated PDT is able to induce time- and concentration-dependent cell death. The use of PDT at a high PDT intensity leads to direct cell necrosis, while cell apoptosis via the mitochondria-mediated pathway is achieved under low PDT intensity. Conclusion: Our results suggest that well-designed AIE nanodots are promising for image-guided PDT applications.

We demonstrate a highly selective and sensitive aptamer-based “capture-release” fluorescence detection of a malarial biomarker, i.e., Plasmodium lactose dehydrogenase (pLDH) protein, using single-layer two-dimensional MoS2 nanosheets. The detection of the target pLDH protein utilizing the aptamer-nanosheet sensing platform is rapid and can be easily completed within 10 min. In addition, the developed biomolecular sensor is capable of detecting the target malarial biomarker in homogeneous protein solutions as well as in heterogeneous mixtures of proteins. We anticipate that the ultrathin MoS2 nanosheet-based biosensor will facilitate the further development of biomolecular nanosensors for the detection of a wide range of biomarkers for malaria and other diseases.

We develop a novel triple-state liquid-based resistive microfluidic tactile sensor with high flexibility, durability, and sensitivity. It comprises a platinum-cured silicone microfluidic assembly filled with 2 μL liquid metallic alloy interfacing two screen-printed conductive electrodes on a polyethylene terephthalate (PET) film. This flexible tactile sensor is highly sensitive ((2–20) × 10–3 kPa–1) and capable of distinguishing compressive loads with an extremely large range of pressure (2 to 400 kPa) as well as bending loads. Owing to its unique and durable structure, the sensor can withstand numerous severe mechanical load, such as foot stomping and a car wheel rolling over it, without compromising its electrical signal stability and overall integrity. Also, our sensing device is highly deformable, wearable, and able to differentiate and quantify pressures exerted by distinct bodily actions, such as a finger touch or footstep pressure. As a proof-of-concept of the applicability of our tactile sensor, w...

We investigate the molecular interactions between graphene oxide (GO) and blood plasma proteins, in particular, the influence of GO on the intrinsic fluorescence of these proteins. We observe that GO acts as an efficient quencher of the intrinsic fluorescence of albumin, globulin, and fibrinogen. Interestingly, we also note for the first time that, in addition to the robust fluorescence quenching, GO is capable of selectively amplifying the fluorescence emission of fibrinogen up to approximately 30% or 1.3 fold under certain concentrations but not those of albumin and globulin. We suggest that GO may possibly play a dual role in controlling the intrinsic fluorescence emission of the plasma proteins. Furthermore, this role switching may be influenced by the competition between the aggregation and encapsulation effects. We propose that the GO-induced intrinsic fluorescence quenching is driven by the physical encapsulation of the plasma proteins by GO nanosheets. Contrastingly, the GO-mediated fluorescence amplification is promoted by an aggregation of fibrinogen.

Tissue engineering generally utilizes natural or synthetic scaffolds to repair or replace damaged tissues. However, due to the lack of guidance of biological signals, most of the implanted scaffolds have always suffered from poor in vivo cellularization. Herein, we demonstrate a bio-orthogonal reaction-based strategy to realize in situ specific and fast cellularization of tissue engineering scaffold. DBCO-modified PCL-PEG (PCL-PEG-DBCO) polymer was synthesized and then fabricated into PCL-PEG-DBCO film through electrospinning. Meanwhile, azide-labeled macrophages (N3 (+) macrophages) were obtained through metabolic glycoengineering. Through a series of in vitro dynamic and in vivo characterization, DBCO-modified films were noted to dramatically increase the selective capture efficiency and survival rate of N3 (+) cells. Additionally, there is negligible influence of covalent conjugation on cell viability and proliferation, indicating the feasibility of the bio-orthogonal click reaction-based tissue engineering strategy. Overall, this work shows the advantages of an in situ bio-orthogonal click reaction in realizing highly specific, efficient, and long-lasting scaffold cellularization. We anticipate that this general strategy would be widely applicable and useful in tissue engineering and regenerative medicine in the near future.

Bio-orthogonal tumor labeling is more effective in delivering imaging agents or drugs to a tumor site than active targeting strategy owing to covalent ligation. However, to date, tumor-specific imaging through bio-orthogonal labeling largely relies on body clearance to differentiate target from the intrinsic probe signal owing to the lack of light-up probes for in vivo bio-orthogonal labeling. Now the first light-up probe based on a fluorogen with aggregation-induced emission for in vivo bio-orthogonal fluorescence turn-on tumor labeling is presented. The probe has low background fluorescence in aqueous media, showing negligible non-specific interaction with normal tissues. Once it reacts with azide groups introduced to tumor cells through metabolic engineering, the probe fluorescence is lightened up very quickly, enabling rapid tumor-specific imaging. The photosensitizing ability was also used to realize effective image-guided photodynamic tumor therapy.

The near-infrared window between 1000 and 1700 nm, commonly termed the "second near-infrared (NIR-II) window," has quickly emerged as a highly attractive optical region for biological imaging. In contrast to conventional imaging in the visible region between 400 and 700 nm, as well as in the first NIR (NIR-I) window between 700 and 900 nm, NIR-II biological imaging offers numerous merits, including higher spatial resolution, deeper penetration depth, and lower optical absorption and scattering from biological substrates with minimal tissue autofluorescence. Noninvasive imaging techniques, specifically NIR-II fluorescence and photoacoustic (PA) imaging, have embodied the attractiveness of NIR-II optical imaging, with several NIR-II contrast agents demonstrating superior performance to the clinically approved NIR-I agents. Consequently, NIR-II biological imaging has been increasingly explored due to its tremendous potential for preclinical studies and clinical utility. Herein, the progress of optical imaging in the NIR-II window is reported. Starting with highlighting the importance of biological imaging in the NIR-II spectral region, the emergence and latest development of various NIR-II fluorescence and PA imaging probes and their applications are then discussed. Perspectives on the promises and challenges facing this nascent yet exciting field are then given.

Transferrin receptor (TfR) is overexpressed on the surface of many cancer cells due to its vital roles in iron circulation and cellular respiration. Soluble transferrin receptor (sTfR), a truncated extracellular form of TfR in serum, is an important marker of iron deficiency anemia (IDA) and bone marrow failure in cancer patients. More recently, sTfR level in urine has been related to a specific kidney disease of Henoch-Schönlein purpura nephritis (HSPN). Despite the universal significance of sTfR, there is still a lack of a simple and sensitive method for the quantification of sTfR. Furthermore, it is desirable to have a probe that can detect both TfR and sTfR for further comparison study. In this work, we developed a water-soluble AIE-peptide conjugate with aggregation-induced emission (AIE) characteristics. Taking advantage of the negligible emission from molecularly dissolved tetraphenylethene (TPE), probe TPE-2T7 was used for the light-up detection of sTfR. The probe itself is nonemissive in aqueous solution, but it turns on its fluorescence upon interaction with sTfR to yield a detection limit of 0.27 μg/mL, which is much lower than the sTfR level in IDA patients. Furthermore, a proof-of-concept experiment validates the potential of the probe for diagnosis of HSPN by urine test.

Sinusoidal wrinkles develop in compressively stressed film as a means to release stored elastic energy. Here, a simple way to fabricate large-area, periodic, hexagonal wrinkled pattern on nanocrystalline graphitic films grown on c-plane sapphire (

Reduced graphene oxide (rGO) has been fabricated into a microelectrode array (MEA) using a modified nanoimprint lithography (NIL) technique. Through a modified NIL process, the rGO MEA was fabricated by a self-alignment of conducting Indium Tin Oxide (ITO) and rGO layer without etching of the rGO layer. The rGO MEA consists of an array of 10μm circular disks and microelectrode signature has been found at a pitch spacing of 60μm. The rGO MEA shows a sensitivity of 1.91nAμm(-1) to dopamine (DA) without the use of mediators or functionalization of the reduced graphene oxide (rGO) active layer. The performance of rGO MEA remains stable when tested under highly resistive media using a continuous flow set up, as well as when subjecting it to mechanical stress. The successful demonstration of NIL for fabricating rGO microelectrodes on flexible substrate presents a route for the large scale fabrication of highly sensitive, flexible and thin biosensing platform.

There has been an increased use of silicone gel for applications such as cell traction force measurements as well as lab- and organ-on-chip systems. However, silicone gel is a viscoelastic material which tends to undergo non-elastic deformation and displays time-dependent and strain rate-dependent responses. Here, we evaluated the mechanical responses of two types of commonly used silicone gels, Sylgard-184 and CY52-276, when subjected to nanoNewton force and micrometer displacement length scales. Using different mechanical characterization tools and theoretical models, we characterized and quantified the viscoelastic parameters of these substrates. Our experimental results showed that silicone substrates with high stiffness and elasticity and negligible strain rate-dependency and creep responses will be most suited for use at the nanoNewton force and micrometer displacement length scales such as that encountered in cell traction force assays.

Bacterial infection is one of the most serious physiological conditions threatening human health. There is an increasing demand for more effective bacterial diagnosis and treatment through noninvasive theranostic approaches. Herein, a new strategy is reported to achieve in vivo metabolic labeling of bacteria through the use of MIL-100 (Fe) nanoparticles (NPs) as the nanocarrier for precise delivery of 3-azido-d-alanine (d-AzAla). After intravenous injection, MIL-100 (Fe) NPs can accumulate preferentially and degrade rapidly within the high H2 O2 inflammatory environment, releasing d-AzAla in the process. d-AzAla is selectively integrated into the cell walls of bacteria, which is confirmed by fluorescence signals from clickable DBCO-Cy5. Ultrasmall photosensitizer NPs with aggregation-induced emission characteristics are subsequently designed to react with the modified bacteria through in vivo click chemistry. Through photodynamic therapy, the amount of bacteria on the infected tissue can be significantly reduced. Overall, this study demonstrates the advantages of metal-organic-framework-assisted bacteria metabolic labeling strategy for precise bacterial detection and therapy guided by fluorescence imaging.

There has been growing interest in the development of paper-based biosensors because their simplicity and low cost are attractive for point-of-care diagnosis, especially in low-resource areas. However, only a limited range of paper materials – primarily chromatography papers – have been incorporated into diagnostics thus far. Here, we investigate the performance of different types of paper in order to develop an aptamer- and MoS2 nanosheet-based sensor relying on fluorescence resonance energy transfer (FRET) to signal the presence of a target protein. An aptamer which binds to a malarial biomarker, Plasmodium lactate dehydrogenase (pLDH), is chosen for this study, as point-of-care diagnostics would be especially advantageous in low-resource areas, such as those where malaria is prevalent. We observe that of all papers tested, a measurable and specific fluorescence recovery can only be produced on the sensor created with printer paper, while no significant fluorescence recovery is generated on sensors made from other types of paper, including chromatography, lens, and filter papers. Therefore, our findings demonstrate the importance of careful material selection for the development of a paper-based diagnostic test, and suggest that commercially-available products such as printer paper may serve as viable materials to develop cost-effective and simple diagnostics.

Aptamer-based biosensing, which uses short, single-stranded nucleic acid segments to bind to a target, can be advantageous over antibody-based diagnostics due to the ease of synthesis and high stability of aptamers. However, the development of most aptamer-based sensors (aptasensors) is still in its initial stages and many factors affecting their performance have not been studied in great detail. Here, we enhance the sensing specificity of a fluorescence resonance energy transfer (FRET)-based MoS