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Recently, interest in cancer immunotherapy has increased over traditional anti-cancer therapies such as chemotherapy or targeted therapy. Natural killer (NK) cells are part of the immune cell family and essential to tumor immunotherapy as they detect and kill cancer cells. However, the disadvantage of NK cells is that cell culture is difficult. In this study, porous microgels have been fabricated using microfluidic channels to effectively culture NK cells. Microgel fabrication using microfluidics can be mass-produced in a short time and can be made in a uniform size. Microgels consist of photo cross-linkable polymers such as methacrylic gelatin (GelMa) and can be regulated via controlled GelMa concentrations. NK92 cell-laden three-dimensional (3D) microgels increase mRNA expression levels, NK92 cell proliferation, cytokine release, and anti-tumor efficacy, compared with two-dimensional (2D) cultures. In addition, the study confirms that 3D-cultured NK92 cells enhance anti-tumor effects compared with enhancement by 2D-cultured NK92 cells in the K562 leukemia mouse model. Microgels containing healthy NK cells are designed to completely degrade after 5 days allowing NK cells to be released to achieve cell-to-cell interaction with cancer cells. Overall, this microgel system provides a new cell culture platform for the effective culturing of NK cells and a new strategy for developing immune cell therapy.

Abstract Background Patients face a serious threat if a solid tumor leaves behind partial residuals or cannot be completely removed after surgical resection. Immunotherapy has attracted attention as a method to prevent this condition. However, the conventional immunotherapy method targeting solid tumors, that is, intravenous injection, has limitations in homing in on the tumor and in vivo expansion and has not shown effective clinical results. Method To overcome these limitations, NK cells (Natural killer cells) were encapsulated in micro/macropore-forming hydrogels using 3D bioprinting to target solid tumors. Sodium alginate and gelatin were used to prepare micro-macroporous hydrogels. The gelatin contained in the alginate hydrogel was removed because of the thermal sensitivity of the gelatin, which can generate interconnected micropores where the gelatin was released. Therefore, macropores can be formed through bioprinting and micropores can be formed using thermally sensitive gelatin to make macroporous hydrogels. Results It was confirmed that intentionally formed micropores could help NK cells to aggregate easily, which enhances cell viability, lysis activity, and cytokine release. Macropores can be formed using 3D bioprinting, which enables NK cells to receive the essential elements. We also characterized the functionality of NK 92 and zEGFR-CAR-NK cells in the pore-forming hydrogel. The antitumor effects on leukemia and solid tumors were investigated using an in vitro model. Conclusion We demonstrated that the hydrogel encapsulating NK cells created an appropriate micro–macro environment for clinical applications of NK cell therapy for both leukemia and solid tumors via 3D bioprinting. 3D bioprinting makes macro-scale clinical applications possible, and the automatic process shows potential for development as an off-the-shelf immunotherapy product. This immunotherapy system could provide a clinical option for preventing tumor relapse and metastasis after tumor resection. Graphical Abstract Micro/macropore-forming hydrogel with NK cells fabricated by 3D bioprinting and implanted into the tumor site.

Objectives Using tissue-engineered materials for esophageal reconstruction is a technically challenging task in animals that requires bioreactor training to enhance cellular reactivity. There have been many attempts at esophageal tissue engineering, but the success rate has been limited due to difficulty in initial epithelialization in the special environment of peristalsis. The purpose of this study was to evaluate the potential of an artificial esophagus that can enhance the regeneration of esophageal mucosa and muscle through the optimal combination of a double-layered polymeric scaffold and a custom-designed mesenchymal stem cell-based bioreactor system in a canine model. Methods We fabricated a novel double-layered scaffold as a tissue-engineered esophagus using an electrospinning technique. Prior to transplantation, human-derived mesenchymal stem cells were seeded into the lumen of the scaffold, and bioreactor cultivation was performed to enhance cellular reactivity. After 3 days of cultivation using the bioreactor system, tissue-engineered artificial esophagus was transplanted into a partial esophageal defect (5×3 cm-long resection) in a canine model. Results Scanning electron microscopy (SEM) showed that the electrospun fibers in a tubular scaffold were randomly and circumferentially located toward the inner and outer surfaces. Complete recovery of the esophageal mucosa was confirmed by endoscopic analysis and SEM. Esophagogastroduodenoscopy and computed tomography also showed that there were no signs of leakage or stricture and that there was a normal lumen with complete epithelialization. Significant regeneration of the mucosal layer was observed by keratin-5 immunostaining. Alpha-smooth muscle actin immunostaining showed significantly greater esophageal muscle regeneration at 12 months than at 6 months. Conclusion Custom-designed bioreactor cultured electrospun polyurethane scaffolds can be a promising approach for esophageal tissue engineering.

Extrusion-based bioprinting technology is widely used for tissue regeneration and reconstruction. However, the method that uses only hydrogel as the bioink base material exhibits limited biofunctional properties and needs improvement to achieve the desired tissue regeneration. In this study, we present a three-dimensionally printed bioactive microparticle-loaded scaffold for use in bone regeneration applications. The unique structure of the microparticles provided sustained release of growth factor for > 4 weeks without the use of toxic or harmful substances. Before and after printing, the optimal particle ratio in the bioink for cell viability demonstrated a survival rate of ≥ 85% over 7 days. Notably, osteogenic differentiation and mineralization—mediated by human periosteum-derived cells in scaffolds with bioactive microparticles—increased over a 2-week interval. Here, we present an alternative bioprinting strategy that uses the sustained release of bioactive microparticles to improve biofunctional properties in a manner that is acceptable for clinical bone regeneration applications.

Objectives A polydioxanone (PDO) stent was developed to treat tracheomalacia in pediatric patients. However, its safety and efficacy need to be verified in animal studies before clinical trials in patients can be conducted. This study evaluated the safety and efficacy of a PDO stent in normal and tracheomalacia-model rabbits. Methods In total, 29 New Zealand white rabbits were used: 13 for evaluating the biocompatibility of the PDO stent in normal rabbits and 16 for the creation of a tracheomalacia model. The tracheomalacia model was successfully established in 12 rabbits, and PDO stents were placed in eight of those rabbits. Results The PDO stent was successfully positioned in the trachea of the normal rabbits using an endoscopic approach, and its degradation was observed 10 weeks later. The stent fragments did not induce distal airway obstruction or damage, and the mucosal changes that occurred after stent placement were reversed after degradation. The same procedure was performed on the tracheomalacia-model rabbits. The survival duration of the tracheomalacia rabbits with and without stents was 49.0±6.8 and 1.0±0.8 days, respectively. Thus, the PDO stent yielded a significant survival gain (P=0.001). In the tracheomalacia rabbits, stent degradation and granulation tissue were observed 7 weeks after placement, leading to airway collapse and death. Conclusion We successfully developed a PDO stent and an endoscopic guide placement system. The degradation time of the stent was around 10 weeks in normal rabbits, and its degradation was accelerated in the tracheomalacia model. The mucosal changes associated with PDO stent placement were reversible. Placement of the PDO stent prolonged survival in tracheomalacia-model rabbits.

Abalone shells, which contain both organic and inorganic matter, can facilitate bone remodeling and have been used to fabricate three-dimensional (3D)-printed scaffolds for bone regeneration. Herein, polycaprolactone (PCL) scaffolds were fabricated using 3D printing with abalone shell particles (ASPs) used in high-temperature processing. ASPs were heated to approximately the melting point of PCL and thermally embedded in 3D-printed PCL using a relatively simple process. The morphology and roughness of the composite scaffold changed according to the weight of ASPs used. The scaffolds were grouped as follows: ASP25 (25 mg), ASP50 (50 mg), and ASP100 (100 mg). The ASP25 group exhibited optimum cell viability and proliferation because of the direct influence of roughness and rapid pH changes. The ASP25 and ASP100 groups showed the highest alkaline phosphatase activity. This could be attributed to the effect of the alkaline environment, dissolution of calcium ions, and presence of bioactive molecules in the ASPs that could support bone regeneration. Therefore, the ASP25 group was the most suitable for fabricating bone scaffolds. This study revealed the potential applicability of ASP-embedded scaffolds in bone tissue engineering involving natural bio-organisms that self-mineralize in a process similar to human bone formation.

For further advance a functionality of three-dimensional (3D) printing techniques using biopolymers, graphene oxide (GO) as a carbon-based nanomaterial has received much attention recently due to its superior properties. However, the ability to synergistically affect the resulting 3D-printed structures has been limited by difficulty controlling the nanomaterial ratio in which biological stability is achieved, as well as by the use of noxious solvents applied to the nanomaterials during scaffold fabrication. To address these issues, we demonstrate the use of an ecofriendly mussel-inspired GO coating for 3D-printed scaffolds to enhance the scaffold’s functionality and bioactivity. We used polydopamine for deposition using 1, 3, and 6 mg/mL GO in solution on the surface of the scaffold. By this coating method, we efficiently regulated the degree of GO deposition on the surface of scaffold strands under non-toxic conditions, which revealed by microscope. Furthermore, the surface roughness, hydrophilicity, and functional groups were increased after GO coating process. Especially, we identified that the GO coated scaffold was shown improved properties for promoting osteogenesis compared to a bare scaffold by in vitro analyses. Therefore, we suggest that the GO coated scaffold has the potential as a bone substitute for tissue engineering.

Abstract Objectives Photocrosslinking systems of polymers have been widely studied using UV or visible light irradiation. However, the photodegradation behavior derived from light irradiation was rarely reported, comparing with the photocrosslinking. In this study, the tyramine-modified hyaluronic acid (HA/Tyr) hydrogel was prepared using riboflavin (RF) as a photoinitiator, and the degradation behavior of HA by the reactive oxygen species (ROS) generated in photochemical process was investigated. Materials and methods The HA/Tyr conjugate was synthesized by EDC/NHS chemistry to introduce phenol group. Degree of substitution (DS, %) of phenol group to HA molecule was about 25%. The structural change of HA/Tyr was measured by proton nuclear magnetic resonance (1H-NMR) and attenuated total reflectance infrared spectroscopy (ATR-FTIR), and the rheological properties of photocrosslinked HA/Tyr hydrogel were investigated by rheometer. Results The HA/Tyr solution with 25% substitution formed a stable hydrogel via visible light irradiation in the presence of RF photoinitiator. Rheological data of HA/Tyr solution showed that the storage modulus (G’) was increased with increasing HA concentration. Additionally, it was found that RF initiated by visible light irradiation induced the degradation of HA molecular chain, and consequently reduced the viscosity of HA/Tyr solutions. Conclusion The results indicate that RF-based photoinitiator system caused the degradation of HA molecule by ROS generated in photochemical process as well as the crosslinking of HA/Tyr.

Self-expanding metal stents (SEMSs) are preferred over plastic stents (PSs) in patients with life expectancy of >3 months. However, SEMSs for biliary application can become obstructed over time due to tumor overgrowth or ingrowth. Uncovered stents used for malignant obstructions in the biliary tree, especially in the hilar area, are prone to obstruction by tumor ingrowth. In comparison, full-covered stents may block bile duct branches and are at risk of migration. Moreover, metal stents merely promote biliary drainage and have no antitumor effect. In contrast, a drug-eluting self-expandable metallic stent (DES) may provide continuous tumor control and relief of malignant obstructive jaundice. In this study, a new design of SEMS was created and fabricated as advanced stent applications of material extrusion (ME) 3D printing for palliative treatment of unresectable malignant hilar biliary obstruction according to various paclitaxel (PTX)/poly ε-caprolactone (PCL) weight ratios. As a result, PTX-containing groups had significant effectiveness for inhibiting biliary tumor growth compared with the control group. The PTX-containing groups showed a controlled drug release profile, and its safety and efficacy were verified through in vivo testing. In conclusion, a new design of SEMS would be potential for palliative treatment of unresectable malignant hilar biliary obstruction.

Purpose: To investigate the feasibility of a polycaprolactone (PCL) scaffold fabricated by three-dimensional (3D) printing for tissue engineering applications for tunica albuginea. Materials and Methods: PCL scaffolds were fabricated by use of a 3D printing system. Two scaffolds were fabricated that differed in the architecture of the lay-down pattern: a 90°PCL scaffold and a 45°PCL scaffold. Mechanical properties were measured to compare tensile strength between the two scaffold types. The scaffolds were characterized by scanning electron microscope (SEM) images. The scaffolds were seeded with fibroblast cells, and the ability of these scaffolds to support the cells was evaluated by immunofluorescence staining. Results: The PCL scaffolds had well-structured shapes, regular arrays, and good interconnection in SEM images. The horizontal and vertical Young’s modulus coefficients were 13 and 12 MPa for the 90°PCL scaffold and 19 and 21 MPa for the 45°PCL scaffold, respectively. Microscopy images revealed that human fibroblast cells covered the entire scaffold surface. Immunofluorescence staining of ER-TR7 confirmed that the fibroblast cells remained viable and proliferated throughout the time course of the culture. Conclusions: This preliminary study provides experimental evidence for the feasibility of 3D printing of PCL scaffolds for tissue engineering applications of tunica albuginea.

Background/AimsChronic liver disease is a major widespread cause of death, and whole liver transplantation is the only definitive treatment for patients with end-stage liver diseases. However, many problems, including donor shortage, surgical complications and cost, hinder their usage. Recently, tissue-engineering technology provided a potential breakthrough for solving these problems. Three-dimensional (3D) printing technology has been used to mimic tissues and organs suitable for transplantation, but applications for the liver have been rare.Methods : A 3D bioprinting system was used to construct 3D printed hepatic structures using alginate. HepG2 cells were cultured on these 3D structures for 3 weeks and examined by fluorescence microscopy, histology and immunohistochemistry. The expression of liver-specific markers was quantified on days 1, 7, 14, and 21.Results : The cells grew well on the alginate scaffold, and liver-specific gene expression increased. The cells grew more extensively in 3D culture than two-dimensional culture and exhibited better structural aspects of the liver, indicating that the 3D bioprinting method recapitulates the liver architecture.Conclusion : sThe 3D bioprinting of hepatic structures appears feasible. This technology may become a major tool and provide a bridge between basic science and the clinical challenges for regenerative medicine of the liver.

Coupling between osteoblast-mediated bone formation and osteoclast-mediated bone resorption maintains both mechanical integrity and mineral homeostasis. Zinc is required for the formation, mineralization, growth, and maintenance of bones. We examined the effects of zinc sulfate on osteoblastic differentiation of human periosteum-derived cells (hPDCs) and osteoclastic differentiation of THP-1 cells. Zinc sulfate enhanced the osteoblastic differentiation of hPDCs; however, it did not affect the osteoclastic differentiation of THP-1 cells. The levels of extracellular signaling-related kinase (ERK) were strongly increased during osteoblastic differentiation in zinc sulfate-treated hPDCs, compared with other mitogen-activated protein kinases (MAPKs). Zinc sulfate also promoted osteogenesis in hPDCs and THP-1 cells co-cultured with the ratio of one osteoclast to one osteoblast, as indicated by alkaline phosphatase levels, mineralization, and cellular calcium contents. In addition, the receptor activator of nuclear factor kappa B ligand (RANKL)/osteoprotegerin (OPG) ratio was decreased in the zinc sulfate-treated co-cultures. Our results suggest that zinc sulfate enhances osteogenesis directly by promoting osteoblastic differentiation and osteogenic activities in osteoblasts and indirectly by inhibiting osteoclastic bone resorption through a reduced RANKL/OPG ratio in co-cultured osteoblasts and osteoclasts.

Lamin A/C, a core component of the nuclear lamina, forms a mesh-like structure beneath the inner nuclear membrane. While its structural role is well-studied, its involvement in DNA metabolism remains unclear. We conducted sequential protein fractionation to determine the subcellular localization of early DNA damage response (DDR) proteins. Our findings indicate that most DDR proteins, including ATM and the MRE11-RAD50-NBS1 (MRN) complex, are present in the nuclease – and high salt-resistant pellet fraction. Notably, ATM and MRN remain stably associated with these structures throughout the cell cycle, independent of ionizing radiation (IR)-induced DNA damage. Although Lamin A/C interacts with ATM and MRN, its depletion does not disrupt their association with nuclease-resistant structures. However, it impairs the IR-enhanced association of ATM with the nuclear matrix and ATM-mediated DDR signaling, as well as the interaction between ATM and MRN. This disruption impedes the recruitment of MRE11 to damaged DNA and the association of damaged DNA with the nuclear matrix. Additionally, Lamin A/C depletion results in reduced protein levels of CtIP and RAD51, which is mediated by transcriptional regulation. This, in turn, impairs the efficiency of homologous recombination (HR). Our findings indicate that Lamin A/C plays a pivotal role in DNA damage repair (DDR) by orchestrating ATM-mediated signaling, maintaining HR protein levels, and ensuring efficient DNA repair processes.

This study assessed the seasonal distribution and factors associated with PM2.5 in nationwide subway stations in Korea. A total of 229,644 data points collected over one year were used to determine one-day PM2.5 concentrations from 642 subway stations. The geometric mean of indoor PM2.5 concentrations was 26.6 µg/m3. PM2.5 concentrations were higher in the Seoul metropolitan area (SMA) compared to non-Seoul metropolitan areas (NSMA), with the highest level occurring in winter, followed by spring, fall, and summer, similar to the trend observed for outdoor PM2.5 concentrations. In SMA, PM2.5 concentrations were significantly associated with the operation year, number of air cleaners on platforms, and number of passengers. These findings may help in the development of national strategies for managing indoor PM2.5 concentrations in subway stations, taking into account spatial and temporal factors.

Polyhexamethylene guanidine phosphate (PHMG-p), a major ingredient of humidifier disinfectants, is known to induce inflammation, interstitial pneumonitis, and fibrosis in the lungs. While its histopathologic toxicities have been studied in rodents, research on pulmonary function test (PFT) changes following PHMG-p exposure is limited. This study aimed to investigate the acute and chronic effects, as well as the dose and time response, of PHMG-p on the lungs in mice using PFT and histopathologic examinations. In the single instillation model, mice received PHMG-p and were sacrificed at 2, 4, and 8 weeks. In the five-time instillation model, PHMG-p was administered five times at one-week intervals, and mice were sacrificed 10 weeks after the first instillation. Results showed that PHMG-p exposure reduced lung volume, increased resistance, and decreased compliance, indicating a restrictive ventilation defect. Histopathologic examination showed increases in lung inflammation and fibrosis scores. Changes in several lung volume and compliance parameters, as well as histopathology, were dose-dependent. Lung resistance and compliance parameters had significant correlations with lung inflammation and fibrosis scores. PHMG-p exposure in mice resulted in a restrictive ventilation defect with altered lung resistance and compliance, along with histopathologic lung inflammation and fibrosis.

PurposeTo compare the diagnostic capacity of a color fundus camera (CFC), ultra-wide-field bicolor confocal scanning laser ophthalmoscope (BC-cSLO; OPTOS), and true-color confocal scanning ophthalmoscope (TC-cSO; EIDON) in detecting coexisting retinal diseases in eyes with asteroid hyalosis (AH).MethodsThe medical records of consecutive patients with AH who were referred to a tertiary hospital for subsequent assessment by a vitreoretinal specialist were retrospectively reviewed. Fundus images obtained simultaneously using CFC, BC-cSLO, and TC-cSO were classified into four grades based on their obscuration by asteroid bodies. The proportion of Grade 1 images (minimal obscuration group) was assessed for each imaging modality. The diagnostic and screening abilities for concurrent retinal diseases were compared in terms of the accuracy and sensitivity of each device.ResultsAmong the 100 eyes with AH, 76 had coexisting retinal diseases, such as diabetic retinopathy (DR), retinal vascular occlusion, age-related macular degeneration, epiretinal membrane, and retinitis pigmentosa. TC-cSO had the highest ratio of Grade 1 images (94%, PConclusionsTC-cSO images showed minimal obscuration and a superior ability for diagnosing retinal diseases accompanied by AH over other imaging devices. TC-cSO can be a valuable alternative screening tool for detecting retinal diseases when AH impedes fundus imaging.

Background: Metformin, a drug prescribed for patients with type 2 diabetes, has potential efficacy in enhancing antitumor immunity; however, the detailed underlying mechanisms remain to be elucidated. Therefore, we aimed to identify the inhibitory molecular mechanisms of metformin on programmed death ligand 1 (PD-L1) expression in cancer cells and programmed death 1 (PD-1) expression in immune cells. Methods: We employed a luciferase reporter assay, quantitative real-time PCR, immunoblotting analysis, immunoprecipitation and ubiquitylation assays, and a natural killer (NK) cell-mediated tumor cell cytotoxicity assay. A mouse xenograft tumor model was used to evaluate the effect of metformin on tumor growth, followed by flow-cytometric analysis using tumor-derived single-cell suspensions. Results: Metformin decreased AKT-mediated ß-catenin S552 phosphorylation and subsequent ß-catenin transactivation in an adenosine monophosphate-activated protein kinase (AMPK) activation-dependent manner, resulting in reduced CD274 (encoding PD-L1) transcription in cancer cells. Tumor-derived soluble factors enhanced PD-1 protein stability in NK and T cells via dissociation of PD-1 from ubiquitin E3 ligases and reducing PD-1 polyubiquitylation. Metformin inhibited the tumor-derived soluble factor-reduced binding of PD-1 to E3 ligases and PD-1 polyubiquitylation, resulting in PD-1 protein downregulation in an AMPK activation-dependent manner. These inhibitory effects of metformin on both PD-L1 and PD-1 expression ameliorated cancer-reduced cytotoxic activity of immune cells in vitro and decreased tumor immune evasion and growth in vivo. Conclusions: Metformin blocks both PD-L1 and PD-1 within the tumor microenvironment. This study provided a mechanistic insight into the efficacy of metformin in improving immunotherapy in human cancer. [ABSTRACT FROM AUTHOR]

Purpose: Glycated hemoglobin (HbA1c) as a glycemic index may have limited value in pediatric patients with acute leukemia as they often present with anemia and/ or pancytopenia. To address this issue, we evaluated the usefulness of glycated albumin (GA) as a glycemic monitoring index in pediatric patients with acute leukemia. Methods: Medical records of 25 patients with type 2 diabetes mellitus (T2DM), 63 patients with acute leukemia, and 115 healthy children from Seoul St. Mary's Hospital, The Catholic University of Korea, were retrospectively investigated for serum GA, HbA1c, and fasting blood glucose (FBG) levels, along with demographic data. Results: GA, HbA1c, and FBG levels did not differ between the control and acute leukemia groups. In the T2DM group, positive correlations were observed among GA, HbA1c, and FBG (P<0.01). Although GA level was not associated with the HbA1c level in the control group, GA and HbA1c levels showed a positive correlation in the acute leukemia group (P=0.045). Regression analysis revealed GA and HbA1c levels to be positively correlated in the acute leukemia and T2DM groups even after adjusting for age, sex, and body mass index z-score (P=0.007, P<0.01). Conclusion: GA may be a useful complementary parameter to HbA1c for glycemic monitoring in pediatric patients with acute leukemia, similar to its use in patients with T2DM. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated changes in psychological and physiological indices in cancer survivors who participated in a forest therapy camp in Korea. Methods: A total of 37 cancer survivors (19 and 18 in the experimental and control groups, respectively) participated in this study. Over a 2-night and 3-day period, the participants in the experimental group took part in a forest therapy camp that included activities such as gymnastics, walking, five-senses experiences, and meditation. Both groups completed self-report questionnaires that measured their stress levels and profile of mood states, both before and after the forest therapy camp. Blood samples were collected to measure the levels of cortisol, serotonin, and natural killer (NK) cells. Results: After the forest therapy camp, the experimental group exhibited reduced stress levels (p = .031) and a significant improvement in total mood disturbance (p = . 047) when compared with the control group. The level of serotonin also significantly increased (p < .001). However, in contrast to the prediction, a significant increase in cortisol was noted in the experimental group relative to the control group (p = .016). Moreover, no significant difference in NK cells was noted between the two groups. Conclusion: Forest therapy can be easily applied to cancer survivors. The positive psychological effects of the forest therapy camp were confirmed by improvements in stress and mood states and the increased level of serotonin in forest therapy camp participants. However, there is a need for a follow-up evaluation of cortisol and NK cells due to the absence of significant between-group differences. [ABSTRACT FROM AUTHOR]

BACKGROUND With the continuous increasing availability of new filler products, each hyaluronic acid filler brand has distinctive pharmacokinetics, which may be associated with different complications. Therefore, the long-term safety of new generations of fillers should be evaluated. OBJECTIVE This prospective, multicenter, observational, postmarketing study (ClinicalTrials.gov identifier: NCT04738019) aimed to investigate the incidence of delayed-onset nodules and adverse reactions after the injection of new hyaluronic acid fillers (YYS series) into the facial skin. METHODS Subjects scheduled to receive an injection YYS series filler were followed up for 52 weeks. The authors aimed to determine the incidence of a self-reported delayed-onset nodule--a visible or palpable nodule or mass at the injection site that was detected beyond the 14th day following the injection--during the 1-year follow-up period. RESULTS Among the 1,022 subjects who received an injection of the YYS series, the incidences of delayed-onset nodules were 0% for YYS 360, YYS 540, and YYS 720. A 0.21% incidence (1 delayed hypersensitivity reaction) of a delayed-onset adverse reaction was noted for YYS 720, although none were reported for YYS 360 and YYS 540. CONCLUSION In this study, a notably low frequency of adverse reactions associated with the YYS series was observed. [ABSTRACT FROM AUTHOR]

Background: In rabbits, renal abscesses (pus-filled sores) are rare and diagnosis remains challenging. Therefore, in this study, we aimed to determine the clinical manifestation and diagnostic tests associated with renal abscess identification in rabbits. Case Description: A four-and-a-half-year-old castrated male Lionhead rabbit with a history of poor appetite and abdominal distension was admitted to the animal hospital. Blood analysis, radiography, ultrasonography, and computed tomography scans revealed a kidney abscess found within the renal parenchyma, with severe loss of the cortex and medulla, extending toward the capsule. Consequently, the rabbit underwent nephrectomy. The enlarged right kidney was surgically removed. Histopathological examination of the affected kidney showed severe necrosis and ischemic zones, atrophy of the renal tubules, and prominent heterophils with mixed inflammatory cell infiltrates. Immunohistochemistry and polymerase chain reaction confirmed Encephalitozoon cuniculi and Escherichia coli infections, respectively. Conclusion: This report provides novel insights into the diagnosis of renal abscesses in Lionhead rabbits. [ABSTRACT FROM AUTHOR]