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Plant pathogenic viruses cause a number of economically important diseases in food, fuel, and fiber crops worldwide. As obligate parasites with highly reduced genomes, viruses rely heavily on their hosts for replication, assembly, intra- and intercellular movement, and attraction of vectors for dispersal. Therefore, viruses must influence or directly utilize many host proteins and processes. While many general effects of virus infection have long been known (e.g., reduction in photosynthesis, alterations in carbon metabolism and partitioning, increased expression of pathogenesis-related proteins), the precise underlying mechanisms and functions in the viral life cycle are largely a mystery. Proteomic studies, including studies of differential protein regulation during infection as well as studies of host–viral protein–protein interactions, can help shed light on the complex and varied molecular interactions between viruses and plant hosts. In this review, we summarize current literature in plant-virus proteomics and speculate on why viruses have been selected to manipulate these diverse biochemical pathways in their plant hosts.

Abstract Introduction Given the increase in the primary care nursing workforce and the need to further grow nursing roles in the community understanding how this is included in undergraduate education is important. This study aimed to explore the inclusion of primary care in the undergraduate nursing education curriculum of four countries. Method A mixed‐method design was employed to obtain a broader context of primary care nursing in nursing education and teaching approaches relating to primary care nursing. Subsequently, Australia, Canada, Spain, and Ireland were selected for this study because primary healthcare systems are established as a part of their healthcare system. Results In total, 136 nursing faculties (40 in Australia, 35 in Canada, 46 in Spain, and 15 in Ireland) were invited to participate in this study. Of these, 27 responses were obtained (19.8% response rate). Following the survey phase, in‐depth interviews were conducted with 13 participants. The results indicated that the highest number was coded within the theme of “Understanding of PHC in the curriculum” (n = 108). The second highest number (n = 87) was within the theme of “Interpretation differences of PHC in curriculum,” and the third highest (n = 31) was coded within “Policy impact on health by national government and others.” Conclusion The results emphasized the ambiguity of primary care within the undergraduate nursing curriculum and that interpretation and implementation into the curriculum largely depended on the school's intentions.

Objective This article evaluates the ability of low-energy (40 keV) virtual monoenergetic images (VMIs) in the local diagnosis of cervical cancer compared with that of conventional computed tomography (C-CT) and magnetic resonance imaging (MRI), using clinicopathologic staging as a reference.

Abstract Developmental synapse elimination is crucial for shaping mature neural circuits. In the neonatal mouse cerebellum, Purkinje cells (PCs) receive excitatory synaptic inputs from multiple climbing fibers (CFs) and synapses from all but one CF are eliminated by around postnatal day 20. Heterosynaptic interaction between CFs and parallel fibers (PFs), the axons of cerebellar granule cells (GCs) forming excitatory synapses onto PCs and molecular layer interneurons (MLIs), is crucial for CF synapse elimination. However, mechanisms for this heterosynaptic interaction are largely unknown. Here we show that deletion of AMPA-type glutamate receptor functions in GCs impairs CF synapse elimination mediated by metabotropic glutamate receptor 1 (mGlu1) signaling in PCs. Furthermore, CF synapse elimination is impaired by deleting NMDA-type glutamate receptors from MLIs. We propose that PF activity is crucial for CF synapse elimination by directly activating mGlu1 in PCs and indirectly enhancing the inhibition of PCs through activating NMDA receptors in MLIs.

Monoclonal antibody (mAb) technology has significantly contributed to basic research and clinical settings for various purposes, including protective and therapeutic drugs. However, a rapid and convenient method to generate high-affinity antigen-specific mAbs has not yet been reported. Here, we developed a rapid, easy, and low-cost protocol for antigen-specific mAb production from single memory B cells. Using this method, high-affinity IgG1 mAbs specific to the hapten 4-hydroxy-3-nitrophenylacetyl (NP) were established from NP-CGG immunized C57BL/6 mice within 6 days. Our mAb production system allows flexible switching of IgG1 to any other isotype with the same paratope, enabling the absolute quantification of antigen-specific serum antibody titers and affinity maturation. Additionally, we established a protocol for the production of IgM and IgA, retaining their functional pentamer and dimer structures. This method is also effective against human antigens and pathogens, making it a powerful tool for mAb development in both research and clinical settings.

Introduction Advances in treatment have transformed cancer from a fatal to a chronic illness. This requires healthcare professionals, particularly nurses, to have advanced knowledge and collaborative skills. However, challenges persist in implementing patient-centered care in the context of evolving treatment complexity. Objectives This study aimed to clarify nurses’ support practices in providing cancer pharmacotherapy at a university hospital in Japan and compare these practices based on nurses’ years of experience. Methods A questionnaire survey was conducted from February to April 2023 among 430 nurses involved in provision of cancer pharmacotherapy at a Japanese university hospital. Nurses were asked about the types of support they provided during care for patients undergoing cancer pharmacotherapy. Nurses’ cancer pharmacotherapy support practices were extracted using factor analysis, and differences in support scores by years of experience were examined. Results Responses were received from 184 nurses (42.8% response rate). Three support factors were identified: “Providing patient-centered cancer pharmacotherapy,” “Management of continued cancer pharmacotherapy treatment,” and “Assessment of and response to physical symptoms.” Scores for “Providing patient-centered cancer pharmacotherapy” were significantly lower than those for the other two factors ( p

Summary: Functional refinement of neural circuits is a crucial developmental process in the brain. However, how synaptic maturation and axon wiring proceed cooperatively to establish reliable signal transmission is unclear. Here, we combined nanotopography of release machinery at the active zone (AZ), nanobiophysics of neurotransmitter release, and single-neuron reconstruction of axon arbors of lemniscal fibers (LFs) in the developing mouse somatosensory thalamus. With development, the cluster of Cav2.1 enlarges and translocates closer to vesicle release sites inside the bouton, and LFs drastically shrink their arbors and form larger boutons on the perisomatic region of target neurons. Experimentally constrained simulations show that the nanotopography of mature synapses enables not only rapid vesicular release but also reliable transmission following repetitive firing. Sensory deprivation impairs the developmental shift of molecular nanotopography and axon wiring. Thus, we uncovered the cooperative nanotopographical and morphological mechanisms underlying the developmental establishment of reliable synaptic transmission.

The case report describes the management of endometriotic cysts in a woman taking adjuvant tamoxifen. A diagnosis of endometriosis was made at the age of 38, and the condition was initially managed with a low-dose estrogen-progestogen combination; the patient then switched to dienogest at the age of 45. Following a diagnosis of breast cancer at the age of 46, dienogest was stopped and adjuvant tamoxifen treatment started. After 4 months the patient was diagnosed with bilateral ovarian cysts and underwent laparoscopic bilateral salpingo-oophorectomy. Endometriosis was diagnosed in both ovaries on histopathological examination. This case report describes progression of endometriosis in a tamoxifen user.

Abstract Background Rosmarinic acid (RA) has a wide range of beneficial effects on human health. On the other hand, RA has been reported to induce metal-mediated reactive oxygen species (ROS) generation and DNA damage. However, its mechanism remains unknown. In this study, to clarify the underlying mechanism, we analyzed metal-mediated DNA damage in isolated DNA treated with RA and its analog isorinic acid. Results RA plus Cu(II), but not Fe(III), significantly increased 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) formation, an indicator of oxidative DNA damage, in calf thymus DNA. Furthermore, a comparison of the 8-oxodG formation induced by RA and its analog isorinic acid suggested that the catechol groups in RA could be associated with their abilities to form 8-oxodG. Interestingly, the 8-oxodG formation induced by RA and isorinic acid plus Cu(II) was markedly enhanced by the addition of NADH, an endogenous reductant. To elucidate the mechanism of RA plus Cu(II)-induced oxidative DNA damage, we examined DNA damage in 32P-labeled DNA treated with RA in the presence of Cu(II). RA plus Cu(II) caused DNA cleavage, which was enhanced by piperidine treatment, suggesting that RA causes not only DNA strand breakage but also base modification. RA plus Cu(II)-induced DNA damage was inhibited by catalase (H2O2 scavenger), bathocuproine (Cu(I) chelator), and methional (scavenger of a variety of ROS other than •OH) but not by typical •OH scavengers and SOD, indicating the involvement of H2O2, Cu(I), and ROS other than •OH. DNA cleavage site analysis showing RA-induced site-specific DNA damage (frequently at thymine and some cytosine residues) supports the involvement of ROS other than •OH, because •OH causes DNA cleavage without site specificity. Based on these results, Cu(I) and H2O2 generation with concomitant RA autoxidation could lead to the production of Cu(I)-hydroperoxide, which induces oxidative DNA damage. o-Quinone and o-semiquinone radicals are likely to be again reduced to RA by NADH, which dramatically increases oxidative DNA damage, particularly at low concentrations of RA. Conclusions In this study, physiologically relevant concentrations of RA effectively induced oxidative DNA damage in isolated DNA through redox cycle reactions with copper and NADH.

Background: A majority of Japanese care managers lack medical qualifications, feel uncomfortable discussing future medical choices and believe that it is not their responsibility. Objectives: As there is a paucity of care manager intervention studies, this study aimed to measure changes in advance care planning engagement among long-term care service users before and after intervention by care managers with communication training. Design: A multi-institutional pre- and post-pilot comparative study Methods: A multi-institutional pre- and post-trial study was performed from August 2022 to January 2023 (trial ID: 000048573). Nine trained care managers communicated with 30 long-term care service users regarding advance care planning, and the pre- and post-trial advance care planning engagement scores were compared. Additionally, the post-trial impact of events score was investigated. Results: All 30 long-term care service users completed the trial. The advance care planning engagement score increased after the trial. The sample size was considered adequate for future trials. Years of experience as a care manager, impact of events score, and having a clinical frailty scale of ⩾5 were significant explanatory variables that affected the objective variable of the difference between pre- and post-trial advance care planning engagement score. Conclusion: This study on the impact of advance care planning communication interventions by trained care managers offers insights into determining appropriate sample sizes and identifying factors influencing future research outcomes. Advance care planning engagement of long-term care service users might change before and after intervention by care managers through advance care planning communication. Trial registration: University Hospital Medical Information (UMIN) Network Trial ID: 000048573.

Background: Women with gynecologic disorders requiring a hysterectomy often have co-existing psychiatric diagnoses. A change in the dispensing pattern of antidepressant (AD) and antianxiety (AA) medications around the time of hysterectomy may be due to improvement in gynecologic symptoms, such as pelvic pain and abnormal bleeding, or the emotional impact of the hysterectomy. Unfortunately, these dispensing patterns before and after hysterectomy are currently undescribed. Objectives: To model the dispensing patterns of AD and AA medications over time among women with psychiatric disorders before and after benign hysterectomy for endometriosis and uterine fibroids; and to characterize clusters of patients with various dispensing behaviors based on these patterns. Design: Retrospective cohort study. Methods: This is a study of women who underwent a benign hysterectomy using data from the Merative MarkertScan® Research Databases (Ann Arbor, MI, USA). Inclusion criteria were reproductive-aged women (18–50 years), diagnosis of at least one mood or anxiety disorder, and at least one dispensing of AD or AA medications. We measured monthly adherence and persistence of AD/AA medication use over 12 months after hysterectomy. Group-based-trajectory modeling (GBTM) was used to identify trajectory groups of monthly AD/AA medication dispensing over the study period. Multinomial logistic regression was used to identify factors independently associated with individual dispensing trajectory patterns. Results: For a total of 11,607 patients, 6 dispensing trajectory groups were identified during the study period: continuously high (27.0%), continuously moderate (21.9%), continuously low (17.9%), low-to-high (10.0%), moderate-to-low (9.8%), and low-to-moderate (13.4%). Compared with the continuously high group, younger age, no history of a mood disorder, and uterine fibroids were clinical predictors of low dispensing. The discontinuation rate at 3 months after hysterectomy was higher at 88.6% in the continuously low group and at 66.5% in the continuously low-to-moderate group. Conclusions: This study demonstrates that GBTM identified six distinct trajectories of AD/AA medication dispensing in the perioperative period. Trajectory models could be used to identify specific dispensing patterns for targeting interventions.

Abstract Alzheimer’s disease (AD), a chronic neurodegenerative disorder, is the leading cause of dementia. Over-activated microglia is related to amyloid-beta (Aβ) and phosphorylated tau (phospho-tau) accumulation in the AD brain. Taurine is an amino acid with multiple physiological functions including anti-inflammatory effects, and has been reported to be neuroprotective in AD. However, the role of taurine in microglia-mediated AD remains unclear. Here, we examined the effects of taurine on the brains of senescence-accelerated mouse prone 8 (SAMP8) mice by comparing those administered 1% taurine water with those administered distilled water (DW). We observed increased levels of taurine and taurine transporter (TAUT) in the brains of the taurine-treated mice compared with those of control mice. Immunohistochemical and Western blot analyses revealed that taurine significantly reduced the number of activated microglia, levels of phospho-tau and Aβ deposit in the hippocampus and cortex. Triggering receptors expressed on myeloid cells-2 (TREM2) are known to protect against AD pathogenesis. Taurine upregulated TREM2 expression in the hippocampus and cortex. In conclusion, the present study suggests that taurine treatment may upregulate TREM2 to protect against microglia over-activation by decreasing the accumulation of phospho-tau and Aβ; providing an insight into a novel preventive strategy in AD.

Abstract DNA methylation is crucial for chromatin structure and gene expression and its aberrancies, including the global “hypomethylator phenotype”, are associated with cancer. Here we show that an underlying mechanism for this phenotype in the large proportion of the highly lethal brain tumor glioblastoma (GBM) carrying receptor tyrosine kinase gene mutations, involves the mechanistic target of rapamycin complex 2 (mTORC2), that is critical for growth factor signaling. In this scenario, mTORC2 suppresses the expression of the de novo DNA methyltransferase (DNMT3A) thereby inducing genome-wide DNA hypomethylation. Mechanistically, mTORC2 facilitates a redistribution of EZH2 histone methyltransferase into the promoter region of DNMT3A, and epigenetically represses the expression of DNA methyltransferase. Integrated analyses in both orthotopic mouse models and clinical GBM samples indicate that the DNA hypomethylator phenotype consistently reprograms a glutamate metabolism network, eventually driving GBM cell invasion and survival. These results nominate mTORC2 as a novel regulator of DNA hypomethylation in cancer and an exploitable target against cancer-promoting epigenetics.

Abstract Background Carbendazim (methyl 2-benzimidazolecarbamate, CASRN: 10605-21-7) exhibits spindle poisoning effects and is widely used as a fungicide. With respect to genotoxicity, carbendazim is deemed to be non-mutagenic in vitro, but it causes indicative DNA damage in vivo and chromosome aberrations in vitro and in vivo. In this study, we examined the mutagenicity of carbendazim in vivo. Results MutaMice were treated with carbendazim orally at doses of 0 (corn oil), 250, 500, and 1,000 mg/kg/day once a day for 28 days. A lacZ assay was used to determine the mutant frequency (MF) in the liver and glandular stomach of mice. MutaMice were administered up to the maximum dose recommended by the Organization for Economic Co-operation and Development Test Guidelines for Chemicals No. 488 (OECD TG488). The lacZ MFs in the liver and glandular stomach of carbendazim-treated animals were not significantly different from those in the negative control animals. In contrast, positive control animals exhibited a significant increase in MFs in both the liver and glandular stomach. Conclusions Carbendazim is non-mutagenic in the liver and glandular stomach of MutaMice following oral treatment.

Introduction: Imperforate hymen and transverse vaginal septum are conditions characterized by obstructive defects, typically leading to hematometrocolpos detected around the time of puberty. We encountered a patient who had undergone hymenotomy in infancy to treat pyocolpos due to an imperforate hymen and later developed hematometrocolpos in puberty due to a transverse vaginal septum. Case presentation: A 13-year-old female presented with hypomenorrhea and hematometrocolpos-induced dysmenorrhea. She had a history of pyocolpos with a urinary tract infection at 3 months of age. At that time, no vaginal opening was found on perineal examination, and imperforate hymen was diagnosed. When hymenotomy was performed, the external cervical os was not detected by intravaginal bronchoscopic examination. However, this abnormal finding was not fully investigated. The postoperative course after hymenotomy was free of complications, and the patient remained asymptomatic until menarche. When she presented 3 months after menarche, genital examination revealed a bulging transverse septum inside the vagina, 5 cm from the hymen. Ultrasound and magnetic resonance imaging revealed a distended uterus, distended upper vagina, and collapsed lower vagina. Transverse vaginal septum was considered, and vaginoscopy was performed to exclude vaginal reclosure or adhesion caused by the previous surgery. A diagnosis of transverse vaginal septum was confirmed, and total excision of the septum was performed. The patient underwent regular postoperative follow-ups for stenosis prevention. Conclusion: Considering the rarity of these concurrent conditions, clinicians must always consider the possibility of several complex anomalies. Vaginoscopy using a hysteroscope may be useful for definitive diagnosis and determining appropriate treatments.

Abstract Our purpose was to compare the efficacy of liver and splenic volumetry (LV and SV), extracellular volume (ECV) on dual-layer spectral-detector CT scoring systems for estimating liver fibrosis (LF) in 45 patients with pathologically staged LF. ECV measured on CT value (HU-ECV), iodine density (ID-ECV), atomic number (Zeff-ECV), and electron density (ED-ECV), LV or SV/body surface area (BSA), albumin bilirubin grade (ALBI), model for end-stage liver disease (MELD) score, aspartate aminotransferase platelet ratio index (APRI), and fibrosis index based on the four factors (FIB-4) were recorded. Transient elastography was measured in 22 patients, and compared to ECV. No correlation was found between transient elastography and all ECVs. Area under the curve (AUC) for estimating F4 on transient elastography was 0.885 (95% CI 0.745–1.000). ALBI was weakly associated with LF (p = 0.451), while MELD (p

Abstract Background tert-Butyl hydroperoxide (TBHP; CAS 75–91-2), a hydroperoxide, is mainly used as a polymerization initiator to produce polyethylene, polyvinyl chloride, and unsaturated polyester. It is a high-production chemical, widely used in industrial countries, including Japan. TBHP is also used as an additive for the manufacturing of food utensils, containers, and packaging (UCP). Therefore, there could be consumer exposure through oral intake of TBHP eluted from UCPs. TBHP was investigated in various in vitro and in vivo genotoxicity assays. In Ames tests, some positive results were reported with and/or without metabolic activation. As for the mouse lymphoma assay, the positive result was reported, regardless of the presence or absence of metabolic activation enzymes. The results of some chromosomal aberrations test and comet assay in vitro also demonstrated the genotoxic positive results. On the other hand, in in vivo tests, there are negative results in the bone marrow micronucleus test of TBHP-administered mice by single intravenous injection and the bone marrow chromosomal aberration test using rats exposed to TBHP for 5 days by inhalation. Also, about dominant lethal tests, the genotoxic positive results appeared. In contrast, there is little information about in vivo mutagenicity and no information about carcinogenicity by oral exposure. Results We conducted in vivo gene mutation assay using MutaMice according to the OECD Guidelines for the Testing of Chemicals No. 488 to investigate in vivo mutagenicity of TBHP through oral exposure. After repeated dosing for 28 days, there were no significant differences in the mutant frequencies (MFs) of the liver and glandular stomach up to 300 mg/kg/day (close to the maximum tolerable dose (MTD)). The positive and negative controls produced the expected responses. Conclusions These findings show that orally administrated TBHP is not mutagenic in the mouse liver and glandular stomach under these experimental conditions.

The marine environment represents a formidable source of biodiversity, is still largely unexplored, and has high pharmacological potential. Indeed, several bioactive marine natural products (MNPs), including immunomodulators, have been identified in the past decades. Here, we review how this reservoir of bioactive molecules could be mobilized to develop novel anti-inflammatory compounds specially produced by or derived from marine microorganisms. After a detailed description of the MNPs exerting immunomodulatory potential and their biological target, we will briefly discuss the challenges associated with discovering anti-inflammatory compounds from marine microorganisms.

Abstract Background The transferrin receptor (TfR) encoded by TFRC gene is the main cellular iron importer. TfR is highly expressed in many cancers and is expected to be a promising new target for cancer therapy; however, its role in nasopharyngeal carcinoma (NPC) remains unknown. Methods The TfR levels were investigated in NPC tissues and cell lines using immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. Knockdown of TFRC using two siRNA to investigate the effects on intracellular iron level and biological functions, including proliferation by CKK-8 assay, colony formation, cell apoptosis and cell cycle by flow cytometry, migration and invasion, and tumor growth in vivo by nude mouse xenografts. RNA sequencing was performed to find possible mechanism after TFRC knockdown on NPC cells and further verified by western blotting. Results TfR was overexpressed in NPC cell lines and tissues. Knockdown of TFRC inhibited cell proliferation concomitant with increased apoptosis and cell cycle arrest, and it decreased intracellular iron, colony formation, migration, invasion, and epithelial-mesenchymal transition in HK1-EBV cells. Western blotting showed that TFRC knockdown suppressed the levels of the iron storage protein FTH1, anti-apoptotic marker BCL-xL, and epithelial-mesenchymal transition markers. We confirmed in vivo that TFRC knockdown also inhibited NPC tumor growth and decreased Ki67 expression in tumor tissues of nude mouse xenografts. RNA sequencing and western blotting revealed that TFRC silencing inhibited the PI3K/Akt/mTOR signaling pathway. Conclusions These results indicated that TfR was overexpressed in NPC, and TFRC knockdown inhibited NPC progression by suppressing the PI3K/Akt/mTOR signaling pathway. Thus, TfR may serve as a novel biomarker and therapeutic target for NPC.

Abstract Introduction Previous studies in 2018 and 2022 have suggested increasing inpatient burden of pneumothorax and widespread variation in management. Local trends have never been elucidated. Northumbria Healthcare NHS Foundation Trust (NHCT) has a well-established pleural service, serving just over 600,000. Thus, we set up a local retrospective study to look at trends in pneumothorax presentation, management strategies, length of stay, and recurrence. Methods A coding search for ‘pneumothorax’ was performed for all patients attending NHCT between 2010 and 2020 was performed with local Caldicott approval. A total of 1840 notes were analysed to exclude iatrogenic, traumatic, and paediatric events. After excluding those cases, 580 remained for further analysis, consisting of 183 primary pneumothoraces (PSP) and 397 secondary pneumothoraces (SSP). Results Median age for PSP was 26.5 years (IQR 17) with 69% male, and for SSP 68 years (IQR 11.5), 62% male; 23.5% of PSP and 8.6% of SSP were never smokers. The proportion of smokers and ex-smokers has not really changed over time: > 65% every year have been smokers or ex-smokers. Yearly pneumothorax incidence shows a downward trend for PSP but upwards for SSP. Median length of stay (LoS) for PSP was 2 days (IQR 2), and SSP 5 days (IQR 8), with a clear downward trend. From 2010 to 2015 > 50% PSP were managed with drain, but in 2019–2020 at least 50% managed conservatively, with a significant reduction in aspiration. Trends of recurrence for PSP are increasing, whereas for SSP is decreasing. Seventy-six (20 PSP, 56 SSP) went for surgery at the index time with 5.3% recurrence (20% recurrence in those without surgery). Conclusions This is the first known analysis of pneumothorax trends in a large trust in the northeast of England. The data in this study have certain limitations, including the lack of information on the size of pneumothorax and frailty indicators that may influence the decision for conservative management. Additionally, there is a reliance on clinical coding, which can introduce potential inaccuracies, and not all patient notes were accessible for analysis. Updated larger datasets should help elucidate trends better.

Abstract Background/purpose: The most widely utilized irrigation solution in endodontic therapy is sodium hypochlorite (NaOCl). The purpose of this study was to assess the effects of NaOCl on the bond strength of four universal adhesives and one two-step self-etch adhesive to pulp chamber dentin. Materials and methods: One hundred sixteen extracted sound human third molars were used in this study. All the teeth were divided into two groups: (1) with NaOCl treatment and (2) without NaOCl treatment. These two groups were subdivided into five bonding groups: G-Premio Bond (GP), Beautibond Xtreme (BBX), Scotchbond Universal (SBU), Clearfil Universal Bond Quick (UBQ), and Clearfil Megabond 2 (MB2). The microtensile bond strength (μTBS), the fracture mode analysis, resin-dentin interface and dentin surface were observed by SEM. Two-way ANOVA was performed to analyze the μTBS (α = 0.05). Results: The μTBS of the NaOCl group significantly decreased for GP and MB2 (P

We previously demonstrated that glycyrrhizin (GL) suppressed inflammation and carcinogenesis in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced murine model of colorectal cancer (CC). In this study, we found an accumulation of regulatory T cells (Tregs) in the spleen and suppression by GL in model mice. ICR mice were divided into four groups: Control, GL, CC, and GL-treated CC (CC+GL), and were sacrificed 20 weeks after AOM/DSS treatment. We measured spleen weight, areas of white and red pulp, and CD8+ T cells (cytotoxic T lymphocytes, CTL), and CD11c-positive cells (dendritic cells) in splenic tissues and forkhead box protein 3 (FoxP3)-positive cells (Tregs) in colorectal and splenic tissues. In all cases, the CC group showed a significant increase compared with those in Control group, and GL administration significantly attenuated this increase. These results indicate that Tregs accumulated in the spleen may participate in inflammation-related carcinogenesis by suppressing CTL. We also suggest that GL which binds to high-mobility group box 1 (HMGB1), suppresses carcinogenesis with decreasing Tregs in the spleen. Furthermore, there was an expression of FoxP3 in cancer cells, indicating that it may be involved in the malignant transformation of cancer cells.

IntroductionVaricocelectomy is well known to improve the pregnancy outcome of patients with clinical varicoceles in assisted reproductive technologies as well as spontaneous conception. Therefore, this study aimed to evaluate the additional effects of oral antioxidant therapy after varicocelectomy on the pregnancy outcome in the assisted reproductive technology setting.MethodsThis study was a retrospective cohort study. The subjects were couples among whom the male partner had undergone varicocelectomy and was scheduled for subsequent assisted reproductive technology. Pregnancy outcomes were followed retrospectively in 62 couples with male partners who received tocopherol (antioxidant group) and 37 couples who did not (control group). The tocopherol and control groups were assigned dependent on the decision of the physician in charge and the patient's request. The clinical pregnancy rates per couple and embryo transfer, time to pregnancy, and the number of cycles during transfer to pregnancy were evaluated.ResultsNo significant differences were observed in the pregnancy rate per couple (antioxidant group 70.9% vs. control group 64.9%, P = 0.55) and per embryo transfer (50.4% vs. 39.6%, P = 0.22). Regarding the time to event analyzed by adjusted restricted mean survival time, the mean time to pregnancy was significantly shorter in the antioxidant (tocopherol) group (14.2 vs. 17.4 months, P = 0.025). No significant difference was observed in the embryo transfer cycle to pregnancy (mean embryo transfer cycles: 2.6 vs. 3.0, P = 0.238).ConclusionsAdditional oral tocopherol nicotinate as antioxidant therapy after varicocelectomy was shown to shorten the time to pregnancy. It is recommended that add-on effects be tested in more well-designed randomized controlled trials to examine whether it improves assisted reproductive outcomes.

Abstract Background Styrene (CAS 100-42-5) is widely used as polystyrene and acrylonitrile–butadiene–styrene resin such as plastic, rubber, and paint. One of the primary uses of styrene is food utensils and containers, but a small amount of styrene transferred into food can be ingested by eating. Styrene is metabolized into styrene 7,8-oxide (SO). SO is mutagenic in bacteria and mouse lymphoma assays. It is clastogenic in cultured mammalian cells. However, styrene and SO are not clastogenic/aneugenic in rodents, and no rodent in vivo gene mutation studies were identified. Methods To investigate the mutagenicity of orally administered styrene, we used the transgenic rodent gene mutation assay to perform an in vivo mutagenicity test (OECD TG488). The transgenic MutaMouse was given styrene orally at doses of 0 (corn oil; negative control), 75, 150, and 300 mg/kg/day for 28 days, and mutant frequencies (MFs) were determined using the lacZ assay in the liver and lung (five male mice/group). Results There were no significant differences in the MFs of the liver and lung up to 300 mg/kg/day (close to maximum tolerable dose (MTD)), when one animal with extremely high MFs that were attributed to an incidental clonal mutation was omitted. Positive and negative controls produced the expected results. Conclusions These findings show that styrene is not mutagenic in the liver and lung of MutaMouse under this experimental condition.

Photoelectrodes have attracted significant attention in green hydrogen production via water electrolysis. Among others, titanium oxide (TiO2) is a representative photoelectrode for the conversion of solar energy in the ultravisible region into electrical and chemical energies. However, the poor solar adsorption of this material and the low anode reaction rate have limited the efficiency of hydrogen production via water electrolysis. In addition, there is an urgent need for more ecofriendly hydrogen production systems. The composite films of TiO2 and electronically conductive materials with various structures have been investigated to improve the photoelectrochemical activity of TiO2 by increasing the effective surface area of TiO2 and electronic conductivity of the films, which suppress the electron–hole pair combination. Herein, TiO2 and multiwalled carbon nanotube (MWCNT) composite films with various structures are prepared using the sol–gel method and electrophoretic deposition simultaneously, i.e., sol–gel electrophoretic deposition, under different solution conditions. Scanning electron microscopy (SEM)/energy dispersive X-ray spectroscopy (EDS) results reveals that additives and the mixing ratio of TiO2 sol and MWCNT dispersion solution in the electrophoresis bath affect film structure. Thin-film electrodes with different structures show different photoelectrochemical activities. Most as-fabricated TiO2/MWCNT composite thin-film electrodes outperform pristine TiO2 thin-film electrodes. TiO2 deposition on the MWCNT network surface with an antenna-like shape yields the best photoelectrochemical activity, achieving a low film resistance and ∼80 % anatase/rutile ratio.