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Bacillus genus produces several secondary metabolites with biocontrol ability against various phytopathogens. Bacillus velezensis AK-0 (AK-0), an antagonistic strain isolated from Korean ginseng rhizospheric soil, was found to exhibit antagonistic activity against several phytopathogens. To further display the genetic mechanism of the biocontrol traits of AK-0, we report the complete genome sequence of AK-0 and compared it with complete genome sequences of closely related strains. We report the biocontrol activity of AK-0 against apple bitter rot caused by Colletotrichum gloeosporioides, which could lead to commercialization of this strain as a microbial biopesticide in Korea. To retain its biocontrol efficacy for a longer period, AK-0 has been formulated with ingredients for commercialization, named AK-0 product formulation (AK-0PF). AK-0PF played a role in the suppression of the mycelial growth of the fungicide-resistant pathogen C. gloeosporioides YCHH4 at a greater level than the non-treated control. Moreover, AK-0PF exhibited greater disease suppression of bitter rot in matured under field conditions. Here, we report the complete genome sequence of the AK-0 strain, which has a 3,969,429 bp circular chromosome with 3808 genes and a G+C content of 46.5%. The genome sequence of AK-0 provides a greater understanding of the Bacillus species, which displays biocontrol activity via secondary metabolites. The genome has eight potential secondary metabolite biosynthetic clusters, among which, ituD and bacD genes were expressed at a greater level than other genes. This work provides a better understanding of the strain AK-0, as an effective biocontrol agent (BCA) against phytopathogens, including bitter rot in apple.

Amyloid-β (Aβ) aggregated forms are highly associated with the onset of Alzheimer's disease (AD). Aβ abnormally accumulates in the brain and induces neuronal damages and symptoms of AD such as cognitive impairment and memory loss. Since an antibody drug, aducanumab, reduces Aβ aggregates and delays clinical decline, clearance of accumulated Aβ in the brain is accounted as a therapeutic approach to treat AD. In this study, we synthesized 17 benzofuran derivatives that may disaggregate Aβ oligomers and plaques into inert monomers. By a series of Aβ aggregation inhibition and aggregates' disaggregation assays utilizing thioflavin T assays and gel electrophoresis, YB-9, 2-((5-methoxy-3-(4-methoxyphenyl)benzofuran-6-yl)oxy)acetic acid, was selected as the final Aβ-disaggregator candidate. When it was orally administered to the 8-month-old male transgenic mouse model with five familial AD mutations (5XFAD) via drinking water daily for two months, Aβ oligomers and plaques in hippocampus were reduced. Consequently, decreased astrogliosis and rescued synaptic dysfunction were observed in the hippocampus of YB-9-treated 5XFAD mice compared with the untreated transgenic control group.

Background This study aimed to investigate the effect of cold plasma treatment on the improvement of seed germination and surface sterilization of ginseng seeds. Methods Dehisced ginseng (Panax ginseng) seeds were exposed to dielectric barrier discharge (DBD) plasma operated in argon (Ar) or an argon/oxygen mixture (Ar/O2), and the resulting germination and surface sterilization were compared with those of an untreated control group. Bacterial and fungal detection assays were performed for plasma-treated ginseng seeds after serial dilution of surface-washed suspensions. The microbial colonies (fungi and bacteria) were classified according to their phenotypical morphologies and identified by molecular analysis. Furthermore, the effect of cold plasma treatment on the in vitro antifungal activity and suppression of Cylindrocarpon destructans in 4-year-old ginseng root discs was investigated. Results Seeds treated with plasma in Ar or Ar/O2 exhibited a higher germination rate (%) compared with the untreated controls. Furthermore, the plasma treatment exhibited bactericidal and fungicidal effects on the seed surface, and the latter effect was stronger than the former. In addition, plasma treatment exhibited in vitro antifungal activity against C. destructans and reduced the disease severity (%) of root rot in 4-year-old ginseng root discs. The results demonstrate the stimulatory effect of plasma treatment on seed germination, surface sterilization, and root rot disease suppression in ginseng. Conclusion The results of this study indicate that the cold plasma treatment can suppress the microbial community on the seed surface root rot in ginseng., Graphical abstract Image 1

In this study, we developed an X-ray detector module (XDM) that includes two readout electronic units and a 64-channel data acquisition system for X-ray imaging systems. The readout electronic unit comprises eight X-ray sensor arrays (two CdWO4 scintillators and four Si-PIN photodiodes per detector array), 32 charge integrators, 32 sample-and-holds (S/H), 4 shift registers, and a buffer. The data acquisition system comprises line drivers and receivers, a multiplexer, an analog-to-digital converter, and a 32-kB static random-access memory. All the control signals for module operation are implemented in a field-programmable gate array. The module operates with a single 24 V DC supply and transfers each channel’s data to the host computer through an Ethernet port. We fabricated a 64-channel electronic module and evaluated its performance in terms of the relative offset and linearity. By connecting 14 XDMs, air-cargo container images were successfully acquired through X-ray irradiation at an energy of 6-MeV.

Although the pathological contributions of reactive astrocytes have been implicated in Alzheimer's disease (AD), their in vivo functions remain elusive due to the lack of appropriate experimental models and precise molecular mechanisms. Here, we show the importance of astrocytic reactivity on the pathogenesis of AD using GiD, a newly developed animal model of reactive astrocytes, where the reactivity of astrocytes can be manipulated as mild (GiDm) or severe (GiDs). Mechanistically, excessive hydrogen peroxide (H2O2) originated from monoamine oxidase B in severe reactive astrocytes causes glial activation, tauopathy, neuronal death, brain atrophy, cognitive impairment and eventual death, which are significantly prevented by AAD-2004, a potent H2O2 scavenger. These H2O2--induced pathological features of AD in GiDs are consistently recapitulated in a three-dimensional culture AD model, virus-infected APP/PS1 mice and the brains of patients with AD. Our study identifies H2O2 from severe but not mild reactive astrocytes as a key determinant of neurodegeneration in AD.

Background: Hemorrhoids are a common anal disorder and are more frequent in women than in men. Urinary incontinence (UI) also occurs more frequently in women than in men. Although both diseases share similar risk factors, research on the association between the two diseases is lacking. This study aimed to investigate the relationship between hemorrhoids and UI in adult Korean women. Methods: This study was based on the data of the 2008-2009 Korean National Health and Nutrition Examination Survey. Logistic regression test was performed to determine the relationship between hemorrhoids and UI after adjusting for age, body mass index (BMI), smoking, heavy drinking, physical activity, education level, income, diabetes mellitus, and hypertension. Results: Analysis of the data of 8,139 adult women revealed that the prevalence of hemorrhoids, which were self-reported and diagnosed by a physician, was 17.5% and 7.9%, respectively. Both types of hemorrhoids were more prevalent in older women with spouses, those with a large waist circumference, and those with a high BMI. The prevalence of UI was significantly high in the hemorrhoid group, regardless of whether it was self-reported or diagnosed by a physician. Multiple logistic regression analyses revealed a significant association between the prevalence of UI and hemorrhoids, both of which were found to peak at 19-39 years of age. Conclusions: Our findings demonstrate that hemorrhoids are significantly correlated with UI in adult Korean women. When treating adult women with hemorrhoids, it is, therefore, necessary to consider other pelvic floor diseases such as UI.

Radiation-based imaging systems comprise multiple radiation sensors that are assembled with coupled Si PIN (positive — intrinsic — negative) photodetectors and scintillators. This paper describes the fabrication and characterization of a four-channel array Si PIN photodetector for security inspection systems. The Si PIN photodetector was fabricated using conventional (CMOS) processes at the Radiation Equipment Fab. The junction depth, passivation, and anti-reflection layer of the photodetector were controlled to maximize the light detection efficiency and the signal-to-noise ratio. The spectral responsivity obtained was 0.28 A/W for the cadmium tungstate (CWO) emission at a wavelength of 475 nm. Finally, a line pattern image was acquired using the fabricated Si PIN sensor and a self-developed readout and data acquisition system. The significance of this study is it confirms the feasibility of using the developed array-type Si PIN photodetectors in radiation-based imaging systems.

Rhizolutin (1) was discovered as a natural product of ginseng-rhizospheric Streptomyces sp. WON17. Its structure features an unprecedented 7/10/6-tricyclic dilactone carbon skeleton composed of dimethylcyclodecatriene flanked by a 7-membered and a 6-membered lactone ring based on spectroscopic analysis. During an unbiased screening of natural product libraries, this novel compound was found to dissociate amyloid-β (Aβ) plaques and tau tangles, which are key pathological hallmarks of Alzheimer's disease (AD). Rhizolutin treatment of APP/PS1 double transgenic mice with AD significantly dissociated hippocampal plaques. In vitro, rhizolutin substantially decreased Aβ-induced apoptosis and inflammation in neuronal and glial cells. Our findings introduce a unique chemical entity that targets Aβ and tau concurrently by mimicking misfolded protein clearance mechanisms of immunotherapy, which is prominently investigated in clinical trials.

Latency and amplitude are the measurement parameters of mismatch negativity (MMN). The values of the parameters vary sensitively with the stimulus paradigm. A paradigm using the frequency difference of sounds for the MMN study is well known. This study obtained the reference values of the parameters in healthy young adults by performing the MMN study using the frequency paradigm. The authors recruited ten healthy adults. Their average age was 25.5 years; three were female, and seven were male. On the auditory paradigm for the MMN study, the frequency of sound was 1000 Hz for the standard stimulus, and 1032 Hz for the deviant stimulus. The mean values of latency and amplitude of MMN were 202 ms and 1.88 μV at Fz, 207 ms, and 1.46 μV at Cz, 212 ms, and 1.10 μV at C3, and 214 ms and 1.45 μV at C4. There was no correlation between the latency and amplitude of MMN. This study presented the reference values of the latency and amplitude of the MMN using a standard paradigm that is easy to apply. This information may make the MMN useful for clinical applications and basic research.

Background and purpose The increased demand for donor organs has made it crucial to keep the organs of patients with impending brain death (PWIBDs) suitable for transplantation during the process of determining brain death. This study aimed to identify the time taken to determine brain death (TT-BD) in PWIBDs and the associated influencing factors. Methods This study analyzed data collected by the Korean Organ Donation Agency from 15 hospitals in the Yeongnam region of South Korea. There were 414 PWIBDs eligible for inclusion in this study. The data consisted of the TT-BD for PWIBDs and the potential variables influencing the TT-BD. Results The mean age of the 414 PWIBDs was 48.9 years, and 120 of them were female (29.0%). The mean TT-BD was 8.5 days. The presence of spontaneous movements (SMs) and craniotomy significantly affected the TT-BD. The mean TT-BDs were 13.9 and 8.2 days in the PWIBDs with and without SMs, respectively, and 9.8 and 8.0 days in the PWIBDs with and without craniotomy, respectively. Conclusions The SMs in PWIBDs and a craniotomy performed immediately before starting the process of determining brain death seem to be related to lengthening the TT-BD.

BackgroundThe blood-brain barrier has been a hindrance to developing blood-based diagnostic tests for dementias, as it limits the appearance of brain biomarkers in the blood. Our aim was to see if the natural opening of the blood-brain barrier induced by ischemic stroke would increase serum levels of inflammatory biomarkers known to be elevated in the brains of patients with Alzheimer’s disease and other neurodegenerative dementias.MethodsForty-three patients with acute ischemic stroke presenting to Stony Brook University Hospital were prospectively enrolled in the study. Eight of these patients were clinically diagnosed as having an underlying neurodegenerative dementia. Blood was drawn acutely within 72 h of stroke symptom onset, and serum levels of the classic inflammatory biomarkers, interleukin-6 (IL-6) and C-reactive protein (CRP) were measured, along with levels of S100B protein (S100B) and complement C3 (CC3).ResultsSerum levels of IL-6 and CRP in patients with acute ischemic stroke and underlying dementia (AIS + D) were significantly higher (p = 0.002 and 0.003, respectively) than in patients with acute ischemic stroke alone (AIS). Serum levels of S100B and CC3 did not differ significantly between the groups.ConclusionsThis study supports the possibility that opening of the blood-brain barrier may enhance the blood appearance of brain tissue markers of inflammation associated with neurodegenerative dementia. Further study is warranted to test this possibility, given the recent emergence of methods to open the blood-brain barrier for diagnostic or therapeutic purposes.

In the present study, in order to enhance the performance of ceramic microfiltration (MF) water treatment process, several pre-treatment processes such as adsorption, coagulation, flocculation, and sedimentation were examined under harsh conditions (kaolin of 50 mg/L with a humic acid of 1000 mg/L). A jar-test of batch coagulation/flocculation (C/F) experiments showed that the optimum coagulant (A-PAC, 10.6 % as Al2O3) dosage was 5 mg/L. Moreover, batch adsorption experiments revealed that the powdered activated carbon dosage of 20 mg/L with stirring for 30 min was the optimum condition. When the ceramic MF process was operated at the flux of 5 m3/m2/d, the implication of integrated coagulation/flocculation/adsorption (C/F/A-Mem) could lead to a better improvement of the removal ratio (DOC, UV254, and turbidity) compared with other integrated procedures. In terms of the filtration resistances, the integrated pre-treatment and ceramic MF processes are mitigating fouling problems compared with the single ceramic MF process, which means that the single ceramic MF process was not effective to operate with a stable TMP and produce suitable water qualities of the permeate water. Based on the results, the integrated C/F/A followed by the ceramic MF process was the best approach to produce better qualities water with long-term stability.

This study was performed to verify the possibility of manufacturing Rhizopus oligosporus ‘Koji’, which is cultured using a range of different substrates. The growth characteristics of R. oligosporus were therefore investigated for the preparation of R. oligosporus ‘Koji’, and the optimal incubation conditions were determined to be 30 °C for 24 h, with an optimal NaCl concentration were 5%. Based on these results, R. oligosporus was incubated using three substrates, namely beans, rice and a mixture of beans and rice, for 6 d, and the enzyme activities and volatile compounds of the fermentation products were investigated. On the fourth day of incubation, the α-amylase activities of the rice and the mixed substrates were 155 and 42 unit/mL, respectively, while on the fifth day of incubation, the neutral protease activities of the beans and the mixed substrate were 14 and 15 unit/mL, respectively. In terms of the lipase activity, the mixed substrate resulted in a higher activity than the other substrates. Various volatile flavor compounds, including alcohols, ketones, esters, aldehydes, and pyrazines, were identified in R. oligosporus ‘Koji’ cultured using the mixed substrate.

Considering that earthquakes are largely unpredictable and unpreventable by nature, it is critical to evacuate victims promptly to a safe location in case of a sudden occurrence. The lessons from Japan indicate a crucial role of urban parks perform as a safe shelter for earthquake evacuation, but urban parks in South Korea have not yet served such a role. This paper studies the need to improve and reform the legal system of South Korea to bolster the function of urban parks to prevent earthquake disasters. This study finds that the current legal framework has a limitation in installing disaster prevention facilities to assist evacuation and relief activities. In order to establish the function of earthquake disaster prevention in South Korea, the Urban Park Act should be amended to include urban parks as well as theme parks as a disaster prevention facility. In addition, the Framework Act on the National Land should include clauses on earthquakes. Lastly, the National Land Planning and Utilization Act should incorporate the prevention of earthquake and other disasters into its basic principles of land planning and management.

The demand for display technology is expected to increase with the continuous spread of portable electronics and with the expected emergence of flexible, wearable, and transparent display devices. A touch screen is a critical component in display technology that enables user interface operations, and the future generation of touch screens, the so-called 3D touch screens, is expected to be able to detect multiple levels of pressure. To enable 3D touch screens, transparent pressure sensors with high linearity over a working range that encompasses the pressure range of human touch (10-100 kPa) are required. In this work, a transparent and linear capacitive pressure sensor is reported with a transmittance over 85% and high linearity (R2 = 0.995) over 5-100 kPa of pressure. To render the sensor transparent, a microstructured "hard" elastomer layer was filled in with a refractive index matching a "soft" elastomer layer, through which light scattering was minimized. High linearity was attained from the sensor's unique architecture that increases the effective area of the capacitor with applied pressure. These attributes render our sensor highly suitable for future 3D touch screen applications.

In this paper, the athermal performance of a long-range oblique photography (LOROP) sensor with an all-SiC telescope is described. The dual-band LOROP sensor includes a visible and nearinfrared (VNIR) band and a mid-wave infrared (MWIR) band, which use a common reflective mirror system. The Cassegrain telescope is composed entirely of SiC to achieve an athermal characteristic. During the flight, a thermal effect on the optical system is observed to be negligible, and the athermal performance was found to be extremely stable. Particularly, no performance degradations due to the temperature gradient were observed.

We investigated the impact of acute kidney injury (AKI) in elderly deceased-donors (DDs) vs. AKI in young DDs on post-transplant clinical outcomes. A total of 709 kidney transplant recipients (KTRs) from 602 DDs at four transplant centers were enrolled. KTRs were divided into young-DDKT and elderly-DDKT groups according to the age of DD of 60 years. Both groups were subdivided into non-AKI-KT and AKI-KT subgroups according to AKI in DDs. We investigated short-term and long-term clinical outcomes of non-AKI-DDKT and AKI-DDKT subgroups within young-DDKT and elderly-DDKT groups. The incidence of DGF in the AKI-DDKT subgroup was higher and the allograft function within 12 months after KT in the AKI-DDKT subgroup was lower than those in the non-AKI-DDKT subgroup in both young-DDKT and elderly-DDKT groups. Death-censored allograft survival rate was significantly lower in the AKI-elderly-DDKT subgroup than that in the non-AKI-elderly-DDKT subgroup, but it did not differ between AKI-young-DDKT and non-AKI-young-DDKT subgroup. In multivariable analysis, AKI-elderly-DDKT was an independent risk factor for allograft failure (hazard ratio: 2.648, 95% CI: 1.170–5.994, p = 0.019) and a significant interaction between AKI and old age in DDs on allograft failure was observed (p = 0.001). AKI in elderly DDs, but not in young DDs, can significantly affect long-term allograft outcomes of KTRs.

Objective: To evaluate the effect of different extracts of Diospyros lotus leaves in atopic dermatitis Methods: Diospyros lotus leaves were extracted in ethanol and treated with or without hydrochloric acid or α-rhamnosidase to obtain three different extracts-ethanol, acid-hydrolyzed, and enzyme-hydrolyzed leaf extracts of date plum. The myricitrin content in all samples was measured using HPLC analysis. In vitro antioxidant and anti-inflammatory activities of the extracts were determined by measuring DPPH radical scavenging activities and nitric oxide production in RAW264.7 cells, respectively. Seven- week-old male hairless mice were used to evaluate the anti-atopic dermatitis effects of three extracts in vivo. Splenocytes and mast cells were used to further determine the anti-atopic dermatitis effects of the major compound in the ethanol leaf extract. Results: Enzyme-hydrolyzed leaf extract showed significant in vitro antioxidant and anti-inflammatory activities, and attenuated atopic dermatitis-like skin symptoms and clinical signs more significantly than ethanol and acid-hydrolyzed leaf extracts in 1-fluoro-2,4- dinitrobenzene and house dust mite antigen-treated hairless mice. Enzyme-hydrolyzed leaf extract also suppressed the serum level of immunoglobulin E, interleukin (IL)-4, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, thymic stromal lymphopoietin, and thymus and activation-regulated chemokine in mice with atopic dermatitis. Furthermore, histological analysis revealed that enzyme- hydrolyzed leaf extract suppressed the increased epidermal thickness, dermal infiltration of inflammatory cells, and infiltration and degranulation of mast cells more markedly than the other two extracts in atopic dermatitis-like skin lesions. In addition, this extract effectively inhibited the production of IFN-γ, IL-4,and thymus and activation-regulated chemokine compared with the other two extracts in concanavalin A-stimulated splenocytes. Myricitrin, a major compound of enzyme-hydrolyzed leaf extract, suppressed atopic dermatitis biomarkers in stimulated mouse splenocytes and HMC-1 human mast cells. Conclusions: These results suggest that enzyme-hydrolyzed leaf extract might be a potential candidate to treat atopic dermatitis.

During the year 2018, the symptoms of bunch rot on Shine Muscat (Vitis vinifera L.) were observed in Kimcheon-si, Gyeongbuk province in Korea. The disease appears on the Shine Muscat as a black rot due to prolific fungal sporulation after it has invaded into the Shine Muscat which look completely empty and dryness. Colonies of these fungi are present on the Shine Muscat skin from fruit setting and increase in amount from early season to harvest, while become peak at ripening stage. To isolate the causal agent, small fragments (2 to 3 mm) of decayed tissue from the lesion margin were placed onto potato dextrose agar (PDA) plates. Fungal colonies on PDA produced dense white aerial mycelium and then covered with dark black conidial heads. These heads were large and radiate, and vesicles were globose (2.12–32.0×2.0–3.1 μm). Based on morphological and cultural characteristics, this fungus was identified as Aspergillus tubingensis. To confirm its identity, the internal transcribed spacer, β-tubulin, and RNA polymerase II was sequenced for molecular identification. BLAST search indicated 99% identity with A. tubingensis. The pathogenicity test on healthy grape of Shine Muscat produced bunch rot, as the original symptoms. To select effective fungicides for the control of brunch rot, an in vitro antifungal activity of seven fungicides were evaluated against the growth of A. tubingensis. Five fungicides (dipenoconazole, tebuconazole, metconazole, iminoctadine, and captan) exhibited significantly strong suppression of the mycelial growth of A. tubingensis.

The first complete chloroplast genome sequence of Jeju Island endemic diploid dandelion, Taraxacum hallaisanense, is reported in this study. The plastome size is 151,554 bp in total length, with on...

Immunoglobulin M nephropathy (IgMN) is an idiopathic glomerulonephritis characterized by diffuse deposits of IgM in the glomerular mesangium. However, its renal prognosis remains unknown. We compared renal outcomes of IgMN patients with those of patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or mesangial proliferative glomerulonephritis (MsPGN) from a prospective observational cohort, with 1791 patients undergoing native kidney biopsy in eight hospitals affiliated with The Catholic University of Korea between December 2014 and October 2020. IgMN had more mesangial proliferation and matrix expansion than MsPGN and more tubular atrophy and interstitial fibrosis than MCD. IgMN patients had decreased eGFR than MCD patients in the earlier follow-up. However, there was no significant difference in urine protein or eGFR among all patients at the last follow-up. When IgMN was divided into three subtypes, patients with FSGS-like IgMN tended to have lower eGFR than those with MCD-like or MsPGN-like IgMN but higher proteinuria than MsPGN-like IgMN without showing a significant difference. The presence of hypertension at the time of kidney biopsy predicted ≥20% decline of eGFR over two years in IgMN patients. Our data indicate that IgMN would have a clinical course and renal prognosis similar to MCD, FSGS, and MsPGN.

Purpose Disruption of the tumor-brain barrier in meningioma is a crucial factor in peritumoral brain edema (PTBE). We previously reported the possible effect of osteoporosis on the integrity of the arachnoid trabeculae because both the bone and the arachnoid trabeculae are composed of type 1 collagen. We hypothesized that osteoporotic conditions may be associated with PTBE occurrence after radiation treatment in patients with meningioma. Methods A receiver operating characteristic curve analysis was used to identify the optimal cut-off values of mean skull Hounsfield unit for predicting osteopenia and osteoporosis in patients from our registry. Multivariate Cox regression analysis was used to determine whether possible osteoporosis independently predicted PTBE development in patients with meningioma after radiation. Results A total of 106 intracranial meningiomas were included for the study. All patients received linear accelerator-based radiation therapy in our hospital over an approximate 6-year period. Multivariate Cox regression analysis identified that hypothetical osteoporosis was an independent predictive factor for the development of PTBE in patients with meningioma after linear accelerator-based radiation treatment (hazard ratio 5.20; 95% confidence interval 1.11–24.46; p = 0.037). Conclusions Our study suggests that possible osteoporotic conditions may affect PTBE development after linear accelerator-based radiation treatment for intracranial meningioma. However, due to the study’s small number of patients, these findings need to be validated in future studies with larger cohorts, before firm recommendations can be made. Graphic abstract

Cancer immunotherapy, or the utilization of a patient's own immune system to treat cancer, has shifted the paradigm of cancer treatment. Despite meaningful responses being observed in multiple studies, currently available immunotherapy platforms have only proven effective to a small subset of patients. To address this, nanoparticles have been utilized as a novel carrier for immunotherapeutic drugs, achieving robust anti-tumor effects with increased adaptive and durable responses. Specifically, dendrimer nanoparticles have attracted a great deal of scientific interest due to their versatility in various therapeutic applications, resulting from their unique physicochemical properties and chemically well-defined architecture. This review offers a comprehensive overview of dendrimer-based immunotherapy technologies, including their formulations, biological functionalities, and therapeutic applications. Common formulations include: (1) modulators of cytokine secretion of immune cells (adjuvants); (2) facilitators of the recognition of tumorous antigens (vaccines); (3) stimulators of immune effectors to selectively attack cells expressing specific antigens (antibodies); and (4) inhibitors of immune-suppressive responses (immune checkpoint inhibitors). On-going works and prospects of dendrimer-based immunotherapies are also discussed. Overall, this review provides a critical overview on rapidly growing dendrimer-based immunotherapy technologies and serves as a guideline for researchers and clinicians who are interested in this field. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

We investigated whether the development of delayed graft function (DGF) in pre-sensitized patients affects the clinical outcomes after deceased-donor kidney transplantation (DDKT).The study included 709 kidney transplant recipients (KTRs) from three transplant centers. We divided KTRs into four subgroups (highly sensitized DGF, highly sensitized non-DGF, low-sensitized DGF, and low-sensitized non-DGF) according to panel reactive antibody level of 50%, or DGF development. We compared post-transplant clinical outcomes among the four subgroups.Incidence of biopsy-proven acute rejection (BPAR) was higher in two highly sensitized subgroups than in low-sensitized subgroups. It tended to be higher in highly sensitized DGF subgroups than in the highly sensitized non-DGF subgroups. In addition, the highly sensitized DGF subgroup showed the highest risk for BPAR (hazard ratio, 3.051; P=0.005) and independently predicted BPAR. Allograft function was lower in the two DGF subgroups than in the non-DGF subgroup until one month after transplantation, but thereafter it was similar. Death-censored graft loss rates and patient mortality tended to be low when DGF developed, but it did not reach statistical significance.DGF development in highly sensitized patients increases the risk for BPAR in DDKT compared with patients without DGF, suggesting the need for strict monitoring and management of such cases.

The visualization of misfolded Aβ peptides by using fluorescence chemical dyes is very important in Alzheimer’s disease (AD) diagnosis. Here, we describe the fluorescent substance, fucoxanthin, which detects Aβ aggregates in the brain of AD transgenic mouse models. We found that fucoxanthin from the microalgae Phaeodactylum tricornutum has fluorescent excitation and emission wavelengths without any interference for Aβ interaction. Thus, we applied it to monitor Aβ aggregation in AD transgenic mouse models. Aβ plaques were visualized using fucoxanthin in the brain tissue of APP/PS1 and 5×FAD mice by histological staining with different staining methods. By comparing fucoxanthin-positive and thioflavin S-positive stained regions in the brains, we found that they are colocalized and that fucoxanthin can detect Aβ aggregates. Our finding suggests that fucoxanthin from P. tricornutum can be a new Aβ fluorescent imaging reagent in AD diagnosis.

Apium graveolens (celery) of the family Apiaceae contains bioactive compounds including luteolin and apigenin. The purpose of this study was to increase the extraction yield of apigenin and luteolin in celery extract using green technology and to evaluate their biological activities. The results showed that CA and β-glucosidase-assisted celery extraction transformed apiin in the celery to apigenin with an increase in luteolin concentration. The CA and β-glucosidase-treated celery extract (CAGE) improved the anti-inflammatory properties of celery extract by inhibiting the expression and production of inflammatory cytokines (IL-6, IL-8, IL-31, and TNF-α) in IL-33-stimulated mast cells (HMC-1.2 cells). Their mechanism of action was tied to the inhibition of ERK, JNK, IKKα, IκBα, and NF-κB activation by CAGE in the stimulated cells. In conclusion, CA and enzyme treatment can be considered as a useful biotechnology tool for the improvement of bioactive compounds in celery and hence improve on their bioactivity. PRACTICAL APPLICATIONS: Apium graveolens commonly called celery is an edible agricultural product cultivated throughout the world and known as a "superfood." Celery contains bioactive compounds including apigenin and luteolin that contribute to their described biological activities. However, extracting celery using normal extraction procedures such as hot water and ethanol methods yields only a small amount of apigenin and luteolin. In the present study, we introduced an eco-friendly method using citric and β-glucosidase to obtain apigenin and luteolin-rich celery extract with improved anti-inflammatory activities. The present work will spark studies on the conversion of less biologically active compounds in functional food materials to more active compounds using CA and β-glucosidase, and the development of functional food with specifically enriched bioactive substances at the industrial levels.