mRNA-HPV vaccine encoding E6 and E7 improves therapeutic potential for HPV-mediated cancers via subcutaneous immunization.

The E6 and E7 proteins of specific subtypes of human papillomavirus (HPV), including HPV 16 and 18, are highly associated with cervical cancer as they modulate cell cycle regulation. The aim of this study was to investigate the potential antitumor effects of a messenger RNA-HPV therapeutic vaccine (mHTV) containing nononcogenic E6 and E7 proteins. To achieve this, C57BL/6j mice were injected with the vaccine via both intramuscular and subcutaneous routes, and the resulting effects were evaluated. mHTV immunization markedly induced robust T cell-mediated immune responses and significantly suppressed tumor growth in both subcutaneous and orthotopic tumor-implanted mouse model, with a significant infiltration of immune cells into tumor tissues. Tumor retransplantation at day 62 postprimary vaccination completely halted progression in all mHTV-treated mice. Furthermore, tumor expansion was significantly reduced upon TC-1 transplantation 160 days after the last immunization. Immunization of rhesus monkeys with mHTV elicited promising immune responses. The immunogenicity of mHTV in nonhuman primates provides strong evidence for clinical application against HPV-related cancers in humans. All data suggest that mHTV can be used as both a therapeutic and prophylactic vaccine.

Rhodium(II)-Catalyzed Highly Selective 1,3-Insertion Reactions Using N-Sulfonyl-1,2,3-Triazoles with Heteroaryl Ethers or Heteroaryl Alcohols.

The transformation of N-sulfonyl-1,2,3-triazoles via insertion/rearrangement is achieved using 2-hydroxybenzimidazole or 2-alkoxybenzothiazole over 3 mol % Rh2(Oct)4 for the synthesis of α-((1H-benzo[d]imidazol-2-yl)amino) ketones or (Z)-2-alkoxy-2-phenylethenamines. This regio- and stereoselective reaction proceeds under mild conditions, is tolerant of functional groups, and has a broad substrate scope. Notably, while the general rhodium-catalyzed reaction involves sigmatropic rearrangement from an allyl vinyl ether, the present synthetic methodology prevents rearrangement owing to the benzimidazole group, allowing access to (Z)-olefins.

Innovative C-Arm-Free Navigation Technique for Posterior Spinal Fixation for Atlantoaxial Subluxation: A Technical Note.

Study design: Technical note. Objectives: To present a novel C-arm-free technique guided by navigation to insert and place a C1 lateral mass screw. Background and Objectives: Atlantoaxial subluxation (AAS) is a relatively common sequelae in patients with rheumatoid arthritis (RA) and upper cervical trauma. If they present with severe symptoms, surgical intervention such as posterior fusion is indicated. The established treatment for AAS is fixation with a C1 lateral mass screw and C2 pedicle screw (modified Goel technique) to achieve bony fusion. However, this technique requires fluoroscopy for C1 screw insertion. To avoid exposing the operating team to radiation, we present here a novel C-arm-free C1 lateral mass screw insertion technique for AAS. Materials and Methods: A 67-year-old man was referred to our hospital with neck pain, quadriparesis, and clumsiness and numbness of both upper and lower limbs. He had undergone C3-6 posterior fusion previously in another hospital. In physical examination, he had severe muscle weakness of bilateral upper limbs and hypoesthesia of all four limbs. He had hyper-reflexia of bilateral lower limbs and pollakiuria. His Japanese orthopedic score was 8 points out of 17. Preoperative radiograms showed AAS with an atlantodental interval (ADI) of 7 mm. MRI indicated retro-odontoid pseudotumor and severe spinal cord compression at the C1-2 level. The patient underwent posterior atlantoaxial fixation under navigation guidance. To prevent epidural bleeding during the insertion and placement of a C1 lateral mass screw, we have here defined a novel screw insertion technique. Results: The surgical time was clocked as 127 min and blood loss was 100 mL. There were no complications per-operatively or in the postoperative period. The patient showed almost full recovery (JOA 16/17) at two months follow-up and a solid bony fusion was noticed in the radiograms at one year follow-up. Conclusions: This novel surgical procedure and C1 lateral mas screw placement technique is a practical and safe method in recent advances of AAS treatment. Procedurally, the technique helps prevent epidural bleeding from the screw entry point and also allows for proper C1 screw insertion under navigation guidance without exposing surgeons and staff to the risk of fluoroscopic radiation.

Correlation between the results of two analytical methods for measuring measles virus neutralizing antibodies in source plasma and therapeutic immunoglobulin products.

Patients with primary immunodeficiency disorders are vulnerable to infectious diseases. Intravenous immunoglobulin (IVIG) therapeutic products manufactured from human plasma are employed widely to protect patients from pathogens such as measles virus, which causes a potentially fatal and contagious disease. Therefore, health authorities stipulate a minimum titer of measles neutralizing antibodies (mnAbs) in IVIG products to ensure efficient protection. In general, mnAb titers are measured in a cell-based neutralization assay; however, this assay is labor intensive and time consuming, and the results are variable. Here, we compared a cell-based neutralizing assay with several ELISA tests to evaluate whether ELISAs can overcome the limitations of cell-based assays. The mnAb concentrations measured by the ELISAs showed a strong and significant positive correlation with those measured in a cell-based assay. Also, strong positive correlations were identified for measurement of individual source plasmas, which are used as raw materials for manufacturing IVIG products. Measurement by ELISA revealed that about 80% of 198 source plasmas had mnAb concentrations of <500 mIU/mL. These results suggest that quantitative ELISAs based on relevant antigens allow reliable and comprehensive measurement of mnAb concentrations in source plasmas and drug product; these ELISAs are also faster and more accurate than cell-based assay.

Long-term outcomes of the 2-week schedule of hypofractionated radiotherapy for recurrent hepatocellular carcinoma.

BACKGROUND: The 2-week schedule of hypofractionated radiotherapy as a salvage treatment for hepatocellular carcinoma (HCC) has previously exhibited promising results; this study aimed to assess its long-term clinical outcomes in patients with recurrent HCC ineligible for curative treatments. METHODS: We retrospectively enrolled 77 patients (84 lesions) with HCC who were treated with hypofractionated radiotherapy between December 2008 and July 2013. Primary inclusion criteria were HCC unsuitable for curative treatments and HCC located within 2 cm of a critical normal organ. We administered 3.5-5 Gy/fraction for 2 weeks, resulting in a total dose of 35-50 Gy. RESULTS: The median follow-up period was 33.6 (range, 4.8-78.3) months. The 3- and 5-year overall survival rates were 52.3% and 40.9%, respectively, and local control rates were 79.5% and 72.6% in all treated lesions, respectively. The 5-year local control rate was better in the higher radiation dose group than in the lower radiation dose group (50 Gy: 79.7% vs. < 50 Gy: 66.1%); however, the difference was not statistically significant (P = 0.493). We observed grade ≥ 3 hepatic toxicity in 2 (2.6%) patients and grade 3 gastrointestinal bleeding in 1 (1.3%) patient. However, grade ≥ 4 toxicity was not observed after hypofractionated radiotherapy. CONCLUSIONS: The 2-week schedule of hypofractionated radiotherapy for recurrent HCC exhibited good local control and acceptable treatment-related toxicity during the long-term follow-up period. Thus, this fractionation schedule can be a potential salvage treatment option for recurrent HCC, particularly for tumors located close to a radiosensitive gastrointestinal organ.

Seroprevalence of Encephalitozoon cuniculi in pet rabbits in Korea.

Encephalitozoon cuniculi is a microsporidian parasite commonly found in rabbits that can infect humans, causing encephalitozoonosis. The prevalence of encephalitozoonosis is not well documented, even when many clinics suspect pet rabbits as being highly infected. This study investigated the seropositivity of E. cuniculi using ELISA. The examination of 186 rabbits using ELISA showed that 22.6% (42/186) were seropositive against E. cuniculi. In analysis with healthy status, all 42 seropositive sera were collected from clinically normal rabbits. Moreover, the gender and age of pet rabbits did not have anysignificant effect on E. cuniculi infection. To the best of our knowledge, this is the first report to describe the seroprevalence of E. cuniculi in pet rabbits and suggests that pet rabbits could act as an important reservoir of encephalitozoonosis for both pet animals and humans in Korea.

Study on the characteristics of increased mechanical stiffness according to changes in LCP shape to reinforce clavicle fractures.

The clavicle has various anatomic shapes unique to each individual. Additionally, with the increase in high-energy traumas such as sports injuries and traffic accidents, the patterns of fractures become complex and complicated. Thus, there is a need for a variety of shapes of locking compression plates (LCP) to accommodate different types of fractures and facilitate quicker rehabilitation. The aim of this study is to present different types of LCP that secure fracture fragments and distribute stress evenly, in comparison to typical anatomical LCPs, for reinforcing clavicle fractures. Three models were compared in this study: the typical shape, the center hole removed shape, and the double-curved wing shape. The DICOM (Digital Imaging and Communications in Medicine) file obtained from the computed tomography scan of the patient's clavicle was used to extract the three-dimensional (3D) clavicle structure. Finite element analysis (FEA) simulation was employed to analyze the structural changes of the LCP under external forces. A reinforced jig was used to apply the same type of external force to each LCP, and an experiment was conducted to analyze the mechanical impact of the LCP's structural characteristics. When comparing the stress values at the fracture zone point, resulting from the FEA simulation with applied bending forces, it was calculated that the stress dispersion effect was approximately ten times greater when transitioning from a typical LCP shape to a double-curved partial wing structure. Moreover, the ultimate stress increased 3.33 times, from 241.322 to 804.057 N, as the LCP design changed under cantilever bending conditions. This double-curved wing LCP design reduces stress concentration at the fracture site and minimizes stress in the fracture area when subjected to cantilever bending forces. Consequently, this newly designed LCP has the potential to decrease complications related to the plate and accelerate rehabilitation protocols.

Intranasal immunization with the recombinant measles virus encoding the spike protein of SARS-CoV-2 confers protective immunity against COVID-19 in hamsters.

BACKGROUND: As the nasal mucosa is the initial site of infection for COVID-19, intranasal vaccines are more favorable than conventional vaccines. In recent clinical studies, intranasal immunization has been shown to generate higher neutralizing antibodies; however, there is a lack of evidence on sterilizing immunity in the upper airway. Previously, we developed a recombinant measles virus encoding the spike protein of SARS-CoV-2 (rMeV-S), eliciting humoral and cellular immune responses against SARS-CoV-2. OBJECTIVES: In this study, we aim to provide an experiment on nasal vaccines focusing on a measles virus platform as well as injection routes. STUDY DESIGN: Recombinant measles viruses expressing rMeV-S were prepared, and 5 × 105 PFUs of rMeV-S were administered to Syrian golden hamsters via intramuscular or intranasal injection. Subsequently, the hamsters were challenged with inoculations of 1 × 105 PFUs of SARS-CoV-2 and euthanized 4 days post-infection. Neutralizing antibodies and RBD-specific IgG in the serum and RBD-specific IgA in the bronchoalveolar lavage fluid (BALF) were measured, and SARS-CoV-2 clearance capacity was determined via quantitative reverse-transcription PCR (qRT-PCR) analysis and viral titer measurement in the upper respiratory tract and lungs. Immunohistochemistry and histopathological examinations of lung samples from experimental hamsters were conducted. RESULTS: The intranasal immunization of rMeV-S elicits protective immune responses and alleviates virus-induced pathophysiology, such as body weight reduction and lung weight increase in hamsters. Furthermore, lung immunohistochemistry demonstrated that intranasal rMeV-S immunization induces effective SARS-CoV-2 clearance that correlates with viral RNA content, as determined by qRT-PCR, in the lung and nasal wash samples, SARS-CoV-2 viral titers in lung, nasal wash, BALF samples, serum RBD-specific IgG concentration, and RBD-specific IgA concentration in the BALF. CONCLUSION: An intranasal vaccine based on the measles virus platform is a promising strategy owing to the typical route of infection of the virus, the ease of administration of the vaccine, and the strong immune response it elicits.

Water Skating Miniature Robot Propelled by Acoustic Bubbles.

This paper presents a miniature robot designed for monitoring its surroundings and exploring small and complex environments by skating on the surface of water. The robot is mainly made of extruded polystyrene insulation (XPS) and Teflon tubes and is propelled by acoustic bubble-induced microstreaming flows generated by gaseous bubbles trapped in the Teflon tubes. The robot's linear motion, velocity, and rotational motion are tested and measured at different frequencies and voltages. The results show that the propulsion velocity is proportional to the applied voltage but highly depends on the applied frequency. The maximum velocity occurs between the resonant frequencies for two bubbles trapped in Teflon tubes of different lengths. The robot's maneuvering capability is demonstrated by selective bubble excitation based on the concept of different resonant frequencies for bubbles of different volumes. The proposed water skating robot can perform linear propulsion, rotation, and 2D navigation on the water surface, making it suitable for exploring small and complex water environments.

Acoustic Bubble and Magnetic Actuation-Based Microrobot for Enhanced Multiphase Drug Delivery Efficiency.

This paper proposes an acoustic bubble and magnetic actuation-based microrobot for enhancing multiphase drug delivery efficiency. The proposed device can encapsulate multiphase drugs, including liquids, using the two bubbles embedded within the microtube. Additionally, using the magnetic actuation of the loaded magnetic liquid metal, it can deliver drugs to target cells. This study visualized the flow patterns generated by the oscillating bubble within the tube to validate the drug release principle. In addition, to investigate the effect of the oscillation properties of the inner bubble on drug release, the oscillation amplitude of the inner bubble was measured under various experimental variables using a high-speed camera. Subsequently, we designed a microrobot capable of encapsulating bubbles, drugs, and magnetic liquid metal and fabricated it using microfabrication technology based on ultra-precision 3D printing. As a proof of concept, we demonstrated the transport and drug release of the microrobot encapsulating the drug in a Y-shaped channel simulating a blood vessel. The proposed device is anticipated to enhance the efficiency of drug therapy by minimizing drug side effects, reducing drug administration frequency, and improving the stability of the drug within the body. This paper is expected to be applicable not only to targeted drug delivery but also to various biomedical fields, such as minimally invasive surgery and cell manipulation, by effectively delivering multiphase drugs using the simple structure of a microrobot.

Exploring Physical Lumbar Microvascular Geometry Through Endoscopy and Illustrations: Implications for Clinical Interpretation.

STUDY DESIGN: Retrospective Study. OBJECTIVES: Minimally invasive endoscopic spinal surgery is gaining popularity, but our understanding of the lumbar spine's microvascular geometry relies heavily on cadaver studies and textbook illustrations. Additionally, inconsistent nomenclature of vessels in the literature hampers effective communication among surgeons. This study aims to improve the clarity and comprehensibility of the lumbar spinal microvascular geometry under endoscopic view. METHODS: The study included 400 patients who underwent endoscopic spinal surgery for lumbar spinal canal stenosis and foraminal stenosis. The surgeries were performed by an experienced surgeon using either the interlaminar or transforaminal approach. Endoscopic video recordings were further analyzed to map the microvascular geometry and common bleeding foci. The observed results were cross-referenced with existing literature to reconstruct a comprehensive view of the vascular anatomy. RESULTS: The transforaminal approach commonly encounters bleeding foci originating from the major branches of the segmental lumbar artery and the emissary veins within the foramen. The interlaminar approach primarily encounters bleeding foci from the muscle vessels in the dorsal lamina, which are believed to be located near the ends of the three main branches. In the intracanal region, epidural vessels form a rotary loop above the disc, which can contribute to most of the bleeding during discectomy. CONCLUSIONS: This study provides a comprehensive understanding of the microvascular anatomy in the lumbar spine during endoscopic spinal surgery. Recognizing the geometry will help surgeons anticipate and control bleeding, reducing the risk of complications. The findings contribute to the improvement of surgical techniques and patient safety in endoscopic spinal surgery.

Analyzing immune responses to varied mRNA and protein vaccine sequences.

In response to the COVID-19 pandemic, different types of vaccines, such as inactive, live-attenuated, messenger RNA (mRNA), and protein subunit, have been developed against SARS-CoV-2. This has unintentionally created a unique scenario where heterologous prime-boost vaccination against a single virus has been administered to a large human population. Here, we aimed to analyze whether the immunization order of vaccine types influences the efficacy of heterologous prime-boost vaccination, especially mRNA and protein-based vaccines. We developed a new mRNA vaccine encoding the hemagglutinin (HA) glycoprotein of the influenza virus using the 3'-UTR and 5'-UTR of muscle cells (mRNA-HA) and tested its efficacy by heterologous immunization with an HA protein vaccine (protein-HA). The results demonstrated higher IgG2a levels and hemagglutination inhibition titers in the mRNA-HA priming/protein-HA boosting (R-P) regimen than those induced by reverse immunization (protein-HA priming/mRNA-HA boosting, P-R). After the viral challenge, the R-P group showed lower virus loads and less inflammation in the lungs than the P-R group did. Transcriptome analysis revealed that the heterologous prime-boost groups had differentially activated immune response pathways, according to the order of immunization. In summary, our results demonstrate that the sequence of vaccination is critical to direct desired immune responses. This study demonstrates the potential of a heterologous vaccination strategy using mRNA and protein vaccine platforms against viral infection.

Unstable fracture of fusion mass in old healed tuberculous kyphosis: Case report.

INTRODUCTION AND IMPORTANCE: Old healed spinal tuberculosis sometimes makes bony ankylosis with kyphotic deformity. This bony ankylosis with adjacent vertebra is like ankylosing spinal disorders (ASDs) such as ankylosing spondylitis and diffuse idiopathic skeletal hyperostosis. There is lots of report which revealed that conservative management might be failed in thoracolumbar fracture in ASDs. However, there is no report which shows surgical treatment was finally done because conservative management was failed in fracture healing of fusion mass caused by old spinal tuberculosis. CASE PRESENTATION: A 68 year-old male patient has suffered from spinal tuberculosis about fifty years ago and then has bony kyphotic ankylosis. He fell off a ladder and was conducted conservative treatment under diagnosis of a sprain at a doctor's office. He was diagnosed with fracture of fusion mass after computed tomography and magnetic resonance image scans in our hospital due to persistent back pain. At first, he refused operation strongly, but underwent eventually posterior fixation without anterior support and angle correction for persistent pain and fracture nonunion. We finally achieved bone union after postoperative nine months. CLINICAL DISCUSSION: The characteristics of old healed spinal tuberculosis with kyphotic deformity is similar to that of ASDs. The spine fractures among the patients with ASDs can be easily missed. So, Checking whole spine CT or MRI is recommended for fracture screening to ASD patients with back or neck pain after trauma. For unstable AOSpine type B- or C-type injuries, conservative management is not recommended. This recommendations should also apply to patients with spinal tuberculosis. CONCLUSION: In patients with bony kyphotic ankylosis due to spinal tuberculosis, minor trauma can cause unstable fracture. If there's found unstable fracture, surgery should be underwent as soon as possible for preventing neurologic deficits. Hence, we would like to report this case with literature reviews.

Numerical simulation and biomechanical analysis of locking screw caps on clavicle locking plates.

BACKGROUND: The risk of displaced and comminuted midshaft clavicle fractures is increased in high-energy traumas such as sport injuries and traffic accidents. Open reduction and plate fixation have been widely used for midshaft clavicle fractures. Among various plates for clavicle shaft fractures, superior locking compression plates (LCPs) have been mostly used. In plate fixation, nonunion caused by implant failure is the most difficult complication. The most common reasons for metal plate failure are excessive stress and stress concentration caused by cantilever bending. These causes were easily addressed using a locking screw cap (LSC). METHODS: The clavicle 3-dimensional image was made from a computed tomography scan, and the clavicle midshaft fracture model was generated with a 10-mm interval. The fracture model was fixed with a superior LCP, and finite element analysis was conducted between the presence (with LSC model) and absence (without LSC model) of an LSC on the site of the fracture. The stresses of screw holes in models with and without LSCs were measured under 3 forces: 100 N cantilever bending force, 100 N axial compression force, and 1 N·m axial torsion force. After the finite element analysis, a validation test was conducted on the cantilever bending force known as the greatest force applied to superior locking plates. RESULTS: The mean greatest stress under the cantilever bending force was significantly greater than other loading forces. The highest stress site was the screw hole edge on the fracture site in both models under the cantilever bending and axial compression forces. Under the axial torsional force, the maximum stress point was the lateral first screw hole edge. The ultimate plate stress of the with LSC model is completely lower than that of the without LSC model. According to the validation test, the stiffness, ultimate load, and yield load of the with LSC model were higher than those of the without LSC model. CONCLUSIONS: Therefore, inserting an LSC into an empty screw hole in the fracture area reduces the maximum stress on an LCP and improves biomechanical stability.

AI-Based Drug Discovery of TKIs Targeting L858R/T790M/C797S-Mutant EGFR in Non-small Cell Lung Cancer.

Lung cancer has a high mortality rate, and non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Patients have been observed to acquire resistance against various anticancer agents used for NSCLC due to L858R (or Exon del19)/T790M/C797S-EGFR mutations. Therefore, next-generation drugs are being developed to overcome this problem of acquired resistance. The goal of this study was to use artificial intelligence (AI) to discover drug candidates that can overcome acquired resistance and reduce the limitations of the current drug discovery process, such as high costs and long durations of drug design and production. To generate ligands using AI, we collected data related to tyrosine kinase inhibitors (TKIs) from accessible libraries and used LSTM (Long short term memory) based transfer learning (TL) model. Through the simplified molecular-input line-entry system (SMILES) datasets of the generated ligands, we obtained drug-like ligands via parameter-filtering, cyclic skeleton (CSK) analysis, and virtual screening utilizing deep-learning method. Based on the results of this study, we are developing prospective EGFR TKIs for NSCLC that have overcome the limitations of existing third-generation drugs.

Reliability of Processing Map and Influence of Sigma Phase Precipitation on Hot Workability of Duplex Stainless Steel.

The hot deformation characteristics of an UNS No. S32205 grade duplex stainless steel with nitrogen content of 0.17 ms% was studied over the ranges of temperature from 800 to 1200 °C and strain rates from 0.001 to 1.0 s-1 at the total strain of 0.5 by the hot compression test to draw the processing map. The obtained map was discussed in combinations of microstructural observations and TEM analysis. The optimum hot working region is the temperatures from 950 to 1200 °C regardless of the strain rates without cracks and sigma precipitates.

The Effect of Aronia Berry on Type 1 Diabetes In Vivo and In Vitro.

The number of diabetic patients worldwide is increasing, and complications such as stroke and cardiovascular disease are becoming a serious cause of death. Diabetes mellitus is classified into two types according to the etiopathogenic mechanism and insulin dependence. Type 1 diabetes (T1D), an insulin-dependent diabetes mellitus, is caused by damage and destruction of pancreatic ß cells that produce insulin. It is a disease that is characterized by hyperglycemia and hypoinsulinemia. Aronia berry has been used as a medicinal food in Europe. Aronia contains a variety of ingredients such as polyphenols, anthocyanins, flavonoids, and tannins. Especially, anthocyanin content in aronia berry is known to be much higher than in other plants and berries. It is known for exerting antioxidant, anti-inflammation, and anti-aging effects. Therefore, this study was conducted to investigate the effects of aronia berry extract intake in multiple low-dose streptozotocin (STZ)-induced T1D and to confirm the functional properties of aronia berry. ICR mice (6-week male) were divided into four groups: control (normal control group), STZ (100 mg/kg of STZ-induced T1D group), AR 10 (STZ with oral administration of aronia 10 mg/kg), and AR 100 (STZ with oral administration of aronia 100 mg/kg). Afterward, STZ was injected in a single dose to induce T1D, and the extract was orally administered daily. Dietary intake and body weight were measured twice a week. We confirmed that aronia berry has the effect of decreasing the increase of blood glucose level and also has the protection effect of pancreas ß cell (RINm5F cell). This study confirms the anti-diabetic activity of aronia berry, and it can be expected to increase the utilization according to the results.

Aronia Berry Extract Ameliorates the Severity of Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice.

Inflammatory bowel disease, including Crohn's disease and ulcerative colitis (UC), is a group of inflammatory conditions of the colon and small intestine. UC is a chronic inflammatory disorder of the colon and rectum that includes intervals of acute exacerbation. Although recent studies have suggested that proinflammatory cytokines might have initiated the inflammatory responses in UC, its etiology remains unclear. Aronia berries are rich in dietary polyphenols such as phenolic acids, anthocyanins, flavonoids, and proanthocyanidins with various health benefits, including antioxidant, anti-inflammatory, and antiaging activities. The objective of this study was to determine whether Aronia berry can be an effective intervention for the treatment of UC. BALB/c mice were administered 5% dextran sulfate sodium (DSS) to induce UC. They were then given Aronia berry extracts at concentrations of 10 or 100 mg/kg. During the induction of UC, the expression levels of nuclear factor-kappa B were increased in colonic epithelial cells and immune cells, leading to increased proinflammatory cytokine levels. Aronia berry extract significantly improved the clinical signs of DSS-induced UC, including body weight loss, colon length shortening, and disease activity index increase, with histological markers of colon injury. Furthermore, oral administration of Aronia berry extract inhibited prostaglandin E2 production in DSS-induced colitis and decreased the levels of nitric oxide, interleukin-6, and tumor necrosis factor-α in lipopolysaccharide-stimulated macrophages. These results suggest that Aronia berry extract could efficiently ameliorate clinical signs and inflammatory mediators of UC. Therefore, Aronia berry might be a promising natural treatment for UC.

Molecular Architecture of Yeast Chromatin Assembly Factor 1.

Chromatin Assembly Complex 1 (CAF-1) is a major histone chaperone involved in deposition of histone H3 and H4 into nucleosome. CAF-1 is composed of three subunits; p150, p60 and p48 for human and Cac1, Cac2 and Cac3 for yeast. Despite of its central role in chromatin formation, structural features of the full CAF-1 in complex with histones and other chaperones have not been well characterized. Here, we dissect molecular architecture of yeast CAF-1 (yCAF-1) by cross-linking mass spectrometry (XL-MS) and negative stain single-particle electron microscopy (EM). Our work revealed that Cac1, the largest subunit of yCAF-1, might serve as a major histone binding platform linking Cac2 and Cac3. In addition, EM analysis showed that yCAF-1 adopts a bilobal shape and Cac1 connecting Cac2 and Cac3 to generate a platform for binding histones. This study provides the first structural glimpse of the full CAF-1 complex and a structural framework to understand histone chaperoning processes.