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Abstract Background Elevated serum immunoglobulin G4 (IgG4) concentrations are one of the characteristic findings in IgG4-related disease (IgG4-RD). This study investigated the frequency of elevated serum IgG4 levels and associated factors in a general Japanese population. Methods Serum IgG4 concentrations were measured in 1,201 residents of Ishikawa prefecture who underwent general medical examinations. Factors associated with elevated serum IgG4 concentrations were assessed by logistic regression analysis. Participants with elevated serum IgG4 were subjected to secondary examinations. Results The mean serum IgG4 concentration was 44 mg/dL, with 42 (3.5%) participants having elevated serum IgG4 levels. Age- and sex-adjusted logistic regression analyses showed that male sex, older age, and lower intake of lipids and polyunsaturated fatty acids and higher intake of carbohydrates in daily diet were associated with elevated serum IgG4 concentration. Subgroup analyses in men showed that older age, lower estimated glomerular filtration rates based on serum cystatin C (eGFR-cysC) levels, and higher hemoglobin A1c (HbA1c) levels were associated with elevated serum IgG4 concentration. Analyses in women showed that lower intake of lipids and fatty acids and higher intake of carbohydrates were significantly associated with elevated serum IgG4 concentration. One of the 15 participants who underwent secondary examinations was diagnosed with possible IgG4-related retroperitoneal fibrosis. Conclusions Elevated serum IgG4 levels in a Japanese general population were significantly associated with older age, male gender, and dietary intake of nutrients, with some of these factors identical to the epidemiological features of IgG4-RD.

We previously reported that myeloperoxidase-deficient (MPO-/-) mice develop more severe neutrophil-rich lung inflammation than wild-type mice following intranasal Zymosan administration. Interestingly, we found that these mutant mice with severe lung inflammation also displayed pronounced neutrophilia and anemia, characterized by increased granulopoiesis and decreased erythropoiesis in the bone marrow, compared to wild-type mice. This condition was associated with higher concentrations of granulocyte-colony stimulating factor (G-CSF) in both the lungs and serum, a factor known to enhance granulopoiesis. Neutrophils accumulating in the lungs of MPO-/- mice produced greater amounts of G-CSF than those in wild-type mice, indicating that they are a significant source of G-CSF. In vitro experiments using signal transduction inhibitors and Western blot analysis revealed that MPO-/- neutrophils express higher levels of G-CSF mRNA in response to Zymosan, attributed to the upregulation of the IκB kinase/nuclear factor (NF)-κB pathway and the extracellular-signal-regulated kinase/NF-κB pathway. These findings highlight MPO as a critical regulator of granulopoiesis and erythropoiesis in inflamed tissues.

Abstract Background Scleroderma renal crisis (SRC) is a critical kidney involvement of systemic sclerosis (SSc), often resulting in end-stage renal disease. Although the recurrence of SRC in the allograft has been reported, the development of de novo SRC after kidney transplantation has not been reported. Furthermore, normotensive SRC, which rarely occurs, makes prompt diagnosis more challenging. This fact should be recognized widely among nephrologists. Case presentation We report a 37-year-old Japanese man with overlapping SSc/systemic lupus erythematous syndrome who developed normotensive SRC in the transplanted kidney shortly after glucocorticoid escalation. Six years prior to admission, he underwent an ABO-compatible living donor kidney transplantation because of lupus nephritis. He was admitted to our hospital for gradually worsening kidney dysfunction. A kidney biopsy showed idiopathic granulomatous interstitial nephritis and high-dose prednisolone was prescribed. Although renal function improved tentatively, it deteriorated again a week later. A secondary kidney biopsy revealed acute thrombotic microangiopathy, leading to the diagnosis of normotensive SRC because all other causes were excluded, and blood pressure was within normal range. Adding an angiotensin-converting enzyme inhibitor and tapering glucocorticoid slowed the speed of deterioration of his kidney function, but he finally required hemodialysis induction. Conclusions SRC can newly develop even in the transplanted kidney, especially when high-dose glucocorticoid is administered. Normotensive SRC makes the diagnosis challenging, so nephrologists should carefully monitor patients with SSc and transplanted kidneys to treat SRC promptly.

Studies were conducted on a current-biased Nb-(constrictions)-NbN (S-c-S') contacts to demonstrate that its low-frequency voltage noise properties have been described by current mesoscopic two-terminal conductor theories. The theory based on the single Andreev reflection model without heating was used to analyze the quasiparticle characteristics of the contacts. Results reveal that there is no significant excess noise contribution related with the Andreev reflection.

The rheological properties of a polyamide (PA) resin with low crystallinity were modified by melt-mixing it with a small amount of an alternative α-olefin–maleic anhydride copolymer as a reactive compound. Because PA has a low melting point, rheological characterization was performed over a wide temperature range. Owing to the reaction between PA and the alternative α-olefin–maleic anhydride copolymer, the blend sample behaved as a long-chain branched polymer in the molten state. The thermo-rheological complexity was obvious owing to large flow activation energy values in the low modulus region, i.e., the rheological time–temperature superposition principle was not applicable. The primary normal stress difference under steady shear was greatly increased in the wide shear rate range, leading to a large swell ratio at the capillary extrusion. Furthermore, strain hardening in the transient elongational viscosity, which is responsible for favorable processability, was clear. Because this is a simple modification method, it will be widely employed to modify the rheological properties of various polyamide resins.

Abstract Background Hemodialysis patients have chronic kidney disease, are often elderly, and have many complications such as hypertension, type 2 diabetes, cardiac disease, and cerebrovascular disease. Therefore, hemodialysis patients infected with COVID-19 are prone to severe disease. Vaccination is the most promising means of preventing the onset and reducing the severity of COVID-19. However, many reports have found that anti-spike antibody titers after two doses of mRNA vaccine are lower in hemodialysis patients than in healthy controls. For this reason, a third vaccination is recommended for hemodialysis patients. In Japan, there are several reports of a third vaccination, especially for hemodialysis patients. In this study, we also examined the antibody response to COVID-19 vaccine in Japanese hemodialysis patients who received the third dose of the vaccine. Methods Study participants received a third vaccination (257 with BNT162b2 vaccine and 5 with mRNA-1273 vaccine) approximately 7–9 months after the second (BNT162b2 vaccine). Anti-SARS-CoV-2 spike IgG antibody titers were measured (Abbott SARS-CoV-2 IgG II Quan) in 185 hemodialysis patients and 109 healthcare workers approximately 2 weeks after the second vaccination and in 162 hemodialysis patients and 100 healthcare workers approximately 2 weeks after the third. Results Following the second vaccination, 97.6% of the hemodialysis group and 100% of the control group were positive for the anti-spike antibody. The median level of the anti-spike antibody was 2728.7 AU/mL (IQR, 1024.2–7688.2 AU/mL) in the hemodialysis group and 10,500 AU/ml (IQR, 9346.1–2,4500 AU/mL) in the controls. Following the third vaccination, 99.4% of the hemodialysis group (only one person tested negative for the antibody) and 100% of the control group were positive for the anti-spike antibody. The median level of the anti-spike antibody was 20,000 AU/mL (IQR, 7729–37,000 AU/mL) in the hemodialysis group and 21,500 AU/ml (IQR, 14,000–32,250 AU/mL) in the control group. The factors involved in the low response to the BNT152b2 vaccine after the second vaccination included old age, low BMI, low Cr index, low nPCR, low GNRI, low lymphocyte count, steroid administration, and complications related to blood disorders. However, in hemodialysis patients, the response after the third vaccination was excellent, and all factors associated with the suppressed response to these vaccines were no longer significant. Conclusions The humoral response of hemodialysis patients to two doses of mRNA vaccine was weaker than that of healthy controls. However, a third vaccination eliminated that difference.

Abstract Osteoarthritis (OA) is an age-related degenerative joint disease that causes progressive cartilage loss. Chondrocyte senescence is a fundamental mechanism that contributes to the imbalance of matrix homeostasis in OA by inducing senescence-associated secretory phenotype (SASP). Although OA chondrocytes are mainly exposed to oxidative and inflammatory stresses, the role of these individual stresses in chondrocyte senescence remains unclear. In this study, we compared the effects of these stresses on the senescence of rat chondrocytes. Rat chondrocytes were treated with H2O2 and a combination of IL-1β and TNF-α (IL/TNF) to compare their in vitro effect on senescent phenotypes. For in vivo evaluation, H2O2 and IL/TNF were injected into rat knee joints for 4 weeks. The in vitro results showed that H2O2 treatment increased reactive oxygen species, γ-H2AX, and p21 levels, stopped cell proliferation, and decreased glycosaminoglycan (GAG)-producing ability. In contrast, IL/TNF increased the expression of p16 and SASP factors, resulting in increased GAG degradation. Intraarticular injections of H2O2 did not cause any changes in senescent markers; however, IL/TNF injections reduced safranin O staining and increased the proportion of p16- and SASP factor-positive chondrocytes. Our results indicate that oxidative and inflammatory stresses have significantly different effects on the senescence of rat chondrocytes.

Utilities of whey powder (WP) and whey protein concentrate 34% powder (WPC34) prepared as dairy-processing residues were evaluated using a green alga Chlamydomonas reinhardtii. Analysis of C. reinhardtii growth showed that the strain used WP and WPC34 as nitrogen sources. Its specific growth rate and maximum cell density in WP-containing medium were higher than those in WPC34-containing medium; growth with WPC34 was improved by adding KCl or K2HPO4, which content was decreased as a result of WPC34’s preparation from WP. Although the lipid contents in media containing dairy-processing residues were 2.72 ± 0.31 wt% and 2.62 ± 0.20 wt% with no significant difference, the composition ratio of fatty acid C14 with WPC34 was higher than that with WP and the composition ratio of the sum of fatty acid-C16 and -C18 with WPC34 tended to be lower than that with WP. Additionally, analyses of gene transcription showed that the transcription level of acetyl-CoA carboxylase biotin carboxyl carrier protein in WPC34-containing medium was lower than that in WP-containing medium, possibly affecting the ratios of the chain lengths of fatty acids. The transcription of genes involved in glycolysis and the TCA cycle was outstandingly lower in algae grown in WPC34-containing medium when compared to those cultivated in the presence of WP, resulting in differences in energy production for cell proliferation.

Abstract Background Hemodialysis patients are more likely to be severely affected if infected by COVID-19. Contributing factors include chronic kidney disease, old age, hypertension, type 2 diabetes, heart disease, and cerebrovascular disease. Therefore, action against COVID-19 for hemodialysis patients is an urgent issue. Vaccines are effective in preventing COVID 19 infection. In hemodialysis patients, however, responses to hepatitis B and influenza vaccines are reportedly weak. The BNT162b2 vaccine has shown an efficacy rate of about 95% in the general population, but as far as we know there are only several reports of efficacy data in hemodialysis patients in Japan. Methods We assessed serum anti-SARS-CoV-2 IgG antibody (Abbott SARS-CoV-2 IgG II Quan) in 185 hemodialysis patients and 109 health care workers. The exclusion criterion was positivity for SARS-CoV-2 IgG antibody before vaccination. Adverse reactions to BNT162b2 vaccine were evaluated through interviews. Results Following vaccination, 97.6% of the hemodialysis group and 100% of the control group were positive for the anti-spike antibody. The median level of anti-spike antibody was 2,728.7 AU/mL (IQR, 1,024.2–7,688.2 AU/mL) in the hemodialysis group and 10,500 AU/ml (IQR, 9,346.1–2,4500 AU/mL) in the health care workers group. The factors involved in the low response to the BNT152b2 vaccine included old age, low BMI, low Cr index, low nPCR, low GNRI, low lymphocyte count, steroid administration, and complications related to blood disorders. Conclusions Humoral responses to BNT162b2 vaccine in hemodialysis patients are weaker than in a healthy control sample. Booster vaccination is necessary for hemodialysis patients, especially those showing a weak or non-response to the two-dose BNT162b2 vaccine. Trial registration UMIN, UMIN000047032. Registered 28 February 2022, https://center6.umin.ac.jp/cgi-bin/ctr/ctr_reg_rec.cgi.

Heterotrophic microorganism Escherichia coli LS5218 was cultured with flesh green alga Chlamydomonas reinhardtii C-9: NIES-2235 as a nutrient supplier. In order to evaluate the cell response of Escherichia coli with Chlamydomonas reinhardtii, Escherichia coli was evaluated with microbial methods and comprehensive gene transcriptional analyses. Escherichia coli with Chlamydomonas reinhardtii showed a specific growth rate (µmax) of 1.04 ± 0.27, which was similar to that for cells growing in Luria–Bertani medium (µmax = 1.20 ± 0.40 h−1). Furthermore, comparing the cellular responses of Escherichia coli in a green-algae-containing medium with those in the Luria–Bertani medium, transcriptomic analysis showed that Escherichia coli upregulated gene transcription levels related to glycolysis, 5-phospho-d-ribosyl-1-diphosphate, and lipid synthesis; on the other hand, it decreased the levels related to lipid degradation. In particular, the transcription levels were increased by 103.7 times on pgm (p * < 0.05 (p = 0.015)) in glycolysis, and decreased by 0.247 times on fadE (p * < 0.05 (p = 0.041)) in lipolysis. These genes are unique and could regulate the direction of metabolism; these responses possibly indicate carbon source assimilation as a cellular response in Escherichia coli. This paper is the first report to clarify that Escherichia coli, a substance-producing strain, directly uses Chlamydomonas reinhardtii as a nutrient supplier by evaluation of the cellular responses analyzed with microbial methods and transcriptome analysis.

The experiment conducted to prepare four kinds of 1:1 and 1:3 salts of 3-[4-(trimethylammonio)phenyl]-1,5-diphenyl-6-oxoverdazyl radical cation ([1]+) and its mono-and dimethyl derivatives ([2]+ and [3]+) with Ni(dmit)2 anions (dmit)=1,3-dithiol-2-thione-4,5-dithiolate)([1]+[Ni(dmit)2]-, [2]+[Ni(dmit)2]-, and [1]+[Ni(dmit)2]3 is presented.

Ceftriaxone (CRO) is a long-acting third-generation cephalosporin antibiotic. We present a case of CRO-induced encephalopathy in an 84-year-old male patient with a solitary right kidney, admitted with bilateral pneumonia and right pyelonephritis. Intravenous CRO (2 g, every 24 hours) was started for the infection, but tonic-clonic seizures of the left face and left upper extremity appeared on the eighth day. To examine the relationship between CRO administration and the seizures, we measured CRO concentrations in the patients’ plasma/serum and cerebrospinal fluid. The CRO concentration in blood at the onset of encephalopathy was estimated to have been approximately 60 μg/ml based on a simulation curve. We also calculated the pharmacokinetic parameters after CRO administration. The patient had about one-tenth of the total body clearance and one-third of the volume of distribution compared with healthy adults, and the elimination half-life was about three times longer.

Wheat bran has high nutritional values and is also cheaper than yeast nitrogen base as an important component of a medium. Although its use in microbial cultivations is expected, research and development has hardly progressed so far. In this study, with experimental Saccharomyces cerevisiae BY4741, the cell responses to wheat bran as a nutrient were evaluated by analyses of cell growth, ethanol production, and comprehensive gene transcription levels. Comparing wheat bran and yeast nitrogen base, BY4741 showed specific growth rates of 0.277 ± 0.002 and 0.407 ± 0.035 as a significant difference. Additionally, wheat bran could be used as a restricted media component like yeast nitrogen base. However, in 24 h of cultivation with wheat bran and yeast nitrogen base, although conversion ratios of ethanol productions showed no significant difference at 63.0 ± 7.2% and 62.5 ± 8.2%, the ratio of cell production displayed a significant difference at 7.31 ± 0.04% and 4.90 ± 0.16%, indicating a different cell response. In fact, the comprehensive evaluation of transcription levels strongly suggested major changes in glucose metabolism. This study indicated that BY4741 could switch transcription levels efficiently to use wheat bran.

GPCR kinases (GRKs) phosphorylate active-form G-protein-coupled receptors (GPCRs). Here, the authors reveal that Gq heterotrimer coupled with the angiotensin II type-1 receptor (AT1R) determines the GRK subtypes recruited to the complex in a microdomain, thus defining subsequent AT1R phosphorylation patterns, β-arrestin conformation and functionality.

Rosai-Dorfman disease (RDD), a rare form of non-Langerhans cell histiocytosis, can involve systemic extranodal lesions. Skin lesions are the most common, whereas intrapelvic, cardiac, and hepatic lesions are infrequent. The present study describes a 74-year-old woman with multiple extranodal lesions in the pelvis, heart, liver, and skin that were successfully treated with glucocorticoid therapy. She had experienced fever and persistent inflammation without cervical lymphadenopathy for several months and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) showed abnormal FDG uptake in the left cheek; cervical, axillary, inguinal lymph nodes; periatrium; and pelvis. She was diagnosed with RDD based on skin and pelvic biopsies. Although this was an atypical case without bilateral cervical lymphadenopathy, the FDG-PET detection of inflammatory lesions led to selection of suitable biopsy sites, and pathological examination led to a correct diagnosis. Findings in this patient indicate that RDD can present with an atypical distribution of infrequent extranodal lesions, with attention required to prevent a delayed diagnosis.

Tocopheryl succinate (Tsuc) is a succinic acid ester of the well-known antioxidant α-tocopherol (T). Tsuc exhibits various biological activities, including tumor growth suppression via activation of cell signaling and prevention of lipid accumulation in mouse adipocyte 3T3-L1 cells. The latter findings suggest that Tsuc may be a drug candidate for the treatment of obesity. However, Tsuc was found to induce apoptosis of normal cells (in addition to cancer cells), demonstrating the need to reduce the cytotoxicity of Tsuc without losing the suppression effect on lipid accumulation. Based on our previous findings, we focused on the ester structure of Tsuc for controlling cytotoxicity. Herein, we examined the cytotoxicity and lipid accumulation suppression effect of various T ester derivatives. We found that the terminal carboxylic group is necessary for suppression of lipid accumulation. We synthesized tocopheryl glutarate (Tglu) and tocopheryl adipate (Tadi) by elongation of carbon atoms 1 and 2 of the dicarboxylic moiety, respectively. Tglu and Tadi did not show any cytotoxicity, and both esters suppressed lipid accumulation, although their suppression activities were weaker than that of Tsuc. Tadi showed a more potent lipid accumulation inhibitory effect than Tglu. Although Tadi inhibited lipogenesis and promoted lipolysis, lipolysis was induced at lower concentrations than inhibition of lipogenesis, suggesting that Tadi mainly affects lipolysis. Taken together, we succeeded in the reduction of cytotoxicity, without loss of the suppression effect on lipid accumulation, by elongation of the dicarboxylic moiety of Tsuc. Tadi may be a promising candidate as an anti-obesity drug.

Allergies to dogs and cats can cause enormous damage to human health and the economy. Dog and cat allergens are mainly found in dog and cat dander and are present in small particles in the air and in carpets in homes with dogs and cats. Cleaning houses and washing pets are the main methods for reducing allergens in homes; however, it is difficult to eliminate them completely. Therefore, we aimed to investigate whether a TiO2 photocatalyst could degrade dog and cat allergens. Under wet conditions, exposure to the TiO2 photocatalyst for 24 h degraded Can f1, which is a major dog allergen extracted from dog dander, by 98.3%, and Fel d1, which is a major cat allergen extracted from cat dander, by 93.6–94.4%. Furthermore, under dry conditions, the TiO2 photocatalyst degraded Can f1 and Fel d1 by 92.8% and 59.2–68.4%, respectively. The TiO2 photocatalyst abolished the binding of dog and cat allergens to human IgE by 104.6% and 108.6%, respectively. The results indicated that the TiO2 photocatalyst degraded dog and cat allergens, causing a loss in their allergenicity. Our results suggest that TiO2 photocatalysis can be useful for removing indoor pet allergens and improving the partnership between humans and pets.