The diagnosis of liver diseases is generally carried out via ultrasound imaging, computed tomography, and magnetic resonance imaging. The emerging photoacoustic imaging is an attractive alternative ...to diagnose even early stage of liver diseases providing high‐resolution anatomical and functional information in deep tissue noninvasively. However, the liver has insufficient photoacoustic contrast due to low optical absorbance in the near‐infrared windows. Here, a new hyaluronate–silica nanoparticle (HA–SiNP) conjugate for liver‐specific delivery and imaging for the diagnosis of liver diseases is developed. The HA–SiNP conjugates show high liver‐specific targeting efficiency, strong optical absorbance near‐infrared windows, excellent biocompatibility, and biodegradability. The liver‐specific targeting efficiency is verified by in vitro cellular uptake test, and in vivo and ex vivo photoacoustic imaging. In vivo photoacoustic imaging shows that photoacoustic amplitude in the liver injected with HA–SiNP conjugates is 4.4 times higher than that of the liver injected with SiNP. The biocompatibility and biodegradability of HA–SiNP conjugates are verified by cell viability test, optical spectrum analysis of urine, and inductively coupled plasma‐mass spectroscopy (ICP‐MS) analysis. Taken together, HA–SiNP conjugates may be developed as a promising liver targeted photoacoustic imaging contrast agent and liver‐targeted drug delivery agent.
A new hyaluronate–silica nanoparticle (HA–SiNP) conjugate for liver‐specific delivery and imaging for the diagnosis of liver diseases is developed. The HA–SiNP conjugates show high liver‐specific targeting efficiency, strong optical absorbance near‐infrared windows, excellent biocompatibility, and biodegradability. The liver‐specific targeting efficiency is verified by an in vitro cellular uptake test, and in vivo and ex vivo photoacoustic imaging.
Smart contact lenses for continuous glucose monitoring (CGM) have great potential for huge clinical impact. To date, their development has been limited by challenges in accurate detection of glucose ...without hysteresis for tear glucose monitoring to track the blood glucose levels. Here, long‐term robust CGM in diabetic rabbits is demonstrated by using bimetallic nanocatalysts immobilized in nanoporous hydrogels in smart contact lenses. After redox reaction of glucose oxidase, the nanocatalysts facilitate rapid decomposition of hydrogen peroxide and nanoparticle‐mediated charge transfer with drastically improved diffusion via rapid swelling of nanoporous hydrogels. The ocular glucose sensors result in high sensitivity, fast response time, low detection limit, low hysteresis, and rapid sensor warming‐up time. In diabetic rabbits, smart contact lens can detect tear glucose levels consistent with blood glucose levels measured by a glucometer and a CGM device, reflecting rapid concentration changes without hysteresis. The CGM in a human demonstrates the feasibility of smart contact lenses for further clinical applications.
Smart contact lenses containing bimetallic nanocatalysts immobilized in nanoporous hydrogels are developed for long‐term and robust continuous glucose monitoring. The smart contact lenses can accurately monitor increasing and decreasing blood glucose levels with 92.2% acceptable data in diabetic and normal rabbits. Finally, the clinical feasibility and safety of smart contact lenses are evaluated on the eyes of a human patient.
This article presents a controller IC for smart contact lens (SCL). For wireless telemetry, we propose a transmitter supporting dual-mode operations with a single external loop antenna. In the ...wireless-powered backscattering load-shift keying (LSK) mode, the transmitter is configured to use the antenna as an <inline-formula> <tex-math notation="LaTeX">{L} </tex-math></inline-formula> for magnetic resonance coupling. The transmitter switches its configuration to be an active LC oscillator circuit in the RF-radiated transmission mode. To suppress the average power consumption, a 0.2% duty cycling is applied with a controlled timing schedule while minimizing static power consumption in the sleep mode. To reduce the effect of instantaneous discharging, the period of data transmission is shortened by transmitting data with a higher rate. The designed IC is fabricated using 0.18-<inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula> CMOS. For in vitro verifications in both modes, an SCL is implemented by integrating the IC, a glucose sensor, a thin-film battery, a loop antenna, and a supply-regulating capacitor. The IC achieves a power consumption of 143 nW with an input dynamic range of 89 dB.
A smart contact lens can be used as an excellent interface between the human body and an electronic device for wearable healthcare applications. Despite wide investigations of smart contact lenses ...for diagnostic applications, there has been no report on electrically controlled drug delivery in combination with real-time biometric analysis. Here, we developed smart contact lenses for both continuous glucose monitoring and treatment of diabetic retinopathy. The smart contact lens device, built on a biocompatible polymer, contains ultrathin, flexible electrical circuits and a microcontroller chip for real-time electrochemical biosensing, on-demand controlled drug delivery, wireless power management, and data communication. In diabetic rabbit models, we could measure tear glucose levels to be validated by the conventional invasive blood glucose tests and trigger drugs to be released from reservoirs for treating diabetic retinopathy. Together, we successfully demonstrated the feasibility of smart contact lenses for noninvasive and continuous diabetic diagnosis and diabetic retinopathy therapy.
The bioflocs technology (BFT) for shrimp production has been proposed as a sustainable practice capable of reducing environmental impacts and preventing pathogen introduction. The microbial community ...associated with BFT not only detoxifies nutrients, but also can improve feed utilization and animal growth. Biofloc system contains abundant number of bacteria of which cell wall consists of various components such as bacterial lipopolysaccharide, peptidoglycan and β‐1, 3‐glucans, and is known as stimulating nonspecific immune activity of shrimp. Bioflocs, therefore, are assumed to enhance shrimp immunity because they consume the bioflocs as additional food source. Although there are benefits for having an in situ microbial community in BFT systems, better understanding on these microorganisms, in particular molecular level, is needed. A fourteen‐day culture trial was conducted with postlarvae of Litopenaeus vannamei in the presence and absence of bioflocs. To determine mRNA expression levels of shrimp, we selected six genes (prophenoloxidase1, prophenoloxidase2, prophenoloxidase activation enzyme, serine proteinase1, masquerade‐like proteinase, and ras‐related nuclear protein) which are involved in a series of responses known as the prophenoloxidase (proPO) cascade, one of the major innate immune responses in crustaceans. Significant differences in shrimp survival and final body weights were found between the clear water and in the biofloc treatments. mRNA expression levels were significantly higher in the biofloc treatment than the clear water control. These results suggest that the presence of bioflocs in the culture medium gives positive effect on growth and immune‐related genes expression in L.vannamei postlarvae.
Accumulating evidence supports the idea that necrotrophic plant pathogens interact with their hosts by controlling cell death. Sclerotinia sclerotiorum is a necrotrophic ascomycete fungus with a ...broad host range (>400 species). Previously, we established that oxalic acid (OA) is an important pathogenicity determinant of this fungus. In this report, we describe a mechanism by which oxalate contributes to the pathogenic success of this fungus; namely, that OA induces a programmed cell death (PCD) response in plant tissue that is required for disease development. This response exhibits features associated with mammalian apoptosis, including DNA laddering and TUNEL reactive cells. Fungal mutants deficient in OA production are nonpathogenic, and apoptotic-like characteristics are not observed following plant inoculation. The induction of PCD by OA is independent of the pH-reducing abilities of this organic acid, which is required for sclerotial development. Moreover, oxalate also induces increased reactive oxygen species (ROS) levels in the plant, which correlate to PCD. When ROS induction is inhibited, apoptotic-like cell death induced by OA does not occur. Taken together, we show that Sclerotinia spp.-secreted OA is an elicitor of PCD in plants and is responsible for induction of apoptotic-like features in the plant during disease development. This PCD is essential for fungal pathogenicity and involves ROS. Thus, OA appears to function by triggering in the plant pathways responsible for PCD. Further, OA secretion by Sclerotinia spp. is not directly toxic but, more subtly, may function as a signaling molecule.
Noninvasive real-time biosensors to measure glucose levels in the body fluids have been widely investigated for continuous glucose monitoring of diabetic patients. However, they suffered from low ...sensitivity and reproducibility due to the instability of nanomaterials used for glucose biosensors. Here, we developed a hyaluronate–gold nanoparticle/glucose oxidase (HA–AuNP/GOx) complex and an ultralow-power application-specific integrated circuit chip for noninvasive and robust wireless patch-type glucose sensors. The HA–AuNP/GOx complex was prepared by the facile conjugation of thiolated HA to AuNPs and the following physical binding of GOx. The wireless glucose sensor exhibited slow water evaporation (0.11 μL/min), fast response (5 s), high sensitivity (12.37 μA·dL/mg·cm2) and selectivity, a low detection limit (0.5 mg/dL), and highly stable enzymatic activity (∼14 days). We successfully demonstrated the strong correlation between glucose concentrations measured by a commercially available blood glucometer and the wireless patch-type glucose sensor. Taken together, we could confirm the feasibility of the wireless patch-type robust glucose sensor for noninvasive and continuous diabetic diagnosis.
Biofloc technology (BFT) has recently gained considerable attention as a sustainable method in shrimp aquaculture. In a successful BFT system, microbial communities are considered a crucial component ...in their ability to both improve water quality and control microbial pathogens. Yet, bacterioplankton diversity in rearing water and how bacterioplankton community composition changes with shrimp growth are rarely documented. In this study, the Pacific white shrimp,
Litopenaeus vannamei
was cultivated in a greenhouse-enclosed BFT system. Rearing water samples were collected on a weekly basis for 5 months (152 days) and water quality variables such as physicochemical parameters and inorganic nutrients were monitored. In parallel, 16S rRNA gene pyrosequencing was employed to investigate the temporal patterns of rearing-water microbiota. The productivity, survival rate, and feed conversion ratio were 3.2–4.4 kg/m
3
, 74%–89%, and 1.2–1.3, respectively, representing successful super-intensive cultures. The metataxonomic results indicated a highly dynamic bacterioplankton community, with two major shifts over the culture. Members of the phylum
Planctomycetes
dominated in rearing water during the early stages, while
Actinobacteria
dominated during the middle stages, and
Chloroflexi
and
TM7
dominated during the late stages of culture. The bacterioplankton community fluctuated more in the beginning but stabilized as the culture progressed. Intriguingly, we observed that certain bacterioplankton groups dominated in a culture-stage-specific manner; these groups include
Rhodobacteraceae
,
Flavobacteriaceae
,
Actinobacteria,
and
Chloroflexi
, which either contribute to water quality regulation or possess probiotic potential. Altogether, our results indicate that an operationally successful BFT-based aquaculture system favors the growth and dynamics of specific microbial communities in rearing water. Our study expands the scientific understanding of the practical utilization of microbes in sustainable aquaculture. A thorough understanding of rearing-water microbiota and factors influencing their dynamics will help to establish effective management strategies.
Diospyros kaki Thunb. is widely distributed in East Asian countries, its leaves being mainly used for making tea. In this study, coussaric acid (CA) and betulinic acid (BA), both triterpenoid ...compounds, were obtained from D. kaki leaf extracts through bioassay-guided isolation. CA and BA showed anti-inflammatory effects via inhibition of the nuclear factor-κB (NF-κB) pathway, providing important information on their anti-inflammatory mechanism. Furthermore, they markedly inhibited nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages, and suppressed tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) levels. Furthermore, they decreased protein expression of inducible nitric oxide synthase and cyclooxygenase-2. Pre-treatment with CA and BA inhibited LPS-induced NF-κB. We further examined the effects of CA and BA on heme oxygenase (HO)-1 expression in RAW 264.7 macrophages: BA induced HO-1 protein expression in a dose-dependent manner, while CA had no effect. We also investigated whether BA treatment induced nuclear translocation of Nrf2. BA inhibited LPS-induced NF-κB-binding activity, as well as pro-inflammatory mediator and cytokine production (e.g., NO, PGE₂, TNF-α, IL-1β, IL-6), by partial reversal of this effect by SnPP, an inhibitor of HO-1. These findings further elucidate the anti-inflammatory mechanism of CA and BA isolated from D. kaki.
Diabetic retinopathy is currently treated by highly invasive repeated therapeutic injections and surgical interventions without complete vision recovery. Here, a noninvasive smart wireless far ...red/near‐infrared (NIR) light emitting contact lens developed successfully for the repeated treatment of diabetic retinopathy with significantly improved compliance. A far red/NIR light emitting diode (LED) is connected with an application‐specific integrated circuit chip, wireless power, and communication systems on a PET film, which is embedded in a silicone elastomer contact lens by thermal crosslinking. After in vitro characterization, it is confirmed that the retinal vascular hyper‐permeability induced by diabetic retinopathy in rabbits is reduced to a statistically significant level by simply repeated wearing of smart far red/NIR LED contact lens for 8 weeks with 120 µW light irradiation for 15 min thrice a week. Histological analysis exhibits the safety and feasibility of LED contact lenses for treating diabetic retinopathy. This platform technology for smart LED contact lens would be harnessed for various biomedical photonic applications.
A noninvasive smart wireless far red/near‐infrared (NIR) light emitting contact lens is developed for the repeated treatment of diabetic retinopathy. The diabetic retinopathy in rabbits is reduced to a statistically significant level by simple repeated wearing of smart far red/NIR light emitting diode contact lens for 8 weeks with 120 µW light irradiation for 15 min thrice a week.
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