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Within the phospholipase A2 (PLA2) family that hydrolyzes phospholipids to yield fatty acids and lysophospholipids, secreted PLA2 (sPLA2) enzymes comprise the largest group containing 11 isoforms in mammals. Individual sPLA2s exhibit unique tissue or cellular distributions and enzymatic properties, suggesting their distinct biological roles. Although PLA2 enzymes, particularly cytosolic PLA2 (cPLA2α), have long been implicated in inflammation by driving arachidonic acid metabolism, the precise biological roles of sPLA2s have remained a mystery over the last few decades. Recent studies employing mice gene-manipulated for individual sPLA2s, in combination with mass spectrometric lipidomics to identify their target substrates and products in vivo, have revealed their roles in diverse biological events, including immunity and associated disorders, through lipid mediator-dependent or -independent processes in given microenvironments. In this review, we summarize our current knowledge of the roles of sPLA2s in various immune responses and associated diseases. [ABSTRACT FROM AUTHOR]

Social movement is a battlefield of meanings; a movement campaign contains a cluster of diverse meanings given by those participating in the campaign. Stimulated by such theoretical concepts as “network of meanings”, scholars have attempted to seize the collective meaning attribution process and resultant meaning clusters, as well as central/dominant and peripheral meanings in social movement campaigns. However, such a meaning cluster in the actual movement campaign has never been captured to date. This paper is an attempt to draw what we call “mental map,” mapping a cluster of meanings the movement campaign accommodates. Employing network analysis technique, we draw a network graph showing a cluster of meanings present in the movement campaign. We used the 2012 anti-nuclear movement campaign in Japan as a research site where we collected empirical data. The analysis of the 2012 network graph clearly showed central meanings considered to dominate the signification process of the 2012 campaign and a cluster of meanings that constituted a subset in the entire web of meanings. To ensure the capability of our research technique to differentiate meaning clusters from one movement campaign to another, we compared the 2012 campaign against the 1954 campaign. The differences were stark: the 2012 campaign was strongly driven by motherhood mentality to protect children and a concern over local environments, while the 1954 campaign dominantly drew its signification from collective memory of Hiroshima and Nagasaki and risk on food safety. The mental map approach can help us understand “why” of the movement campaign from yet another perspective; it can also assist us in understanding the change in the mentality and meaning attribution processes of social movements, as, given the data exist, it can be applied to the past campaigns

Problems on the polymerization and condensation reaction of N-methylolacrylamide within cotton fabrics in which K2S2O8, (NH4) 2S 2O8, or H2O2 was used as initiator and NH4 Cl or (NH4 )2HPO4 used as the acid condensation catalyst were investigated primarily from the standpoint of the crease resistance of the treated fahric. The results obtained are as follows.The pre-drying process can be neglected, as almost the same result could be obtained even in the case of direct curing procedure, in which care should be taken not to over- cure.Crease recovery and abrasion resistance (flat) of the treated fabric increased with higher value of resin content ; tear strength, on the contrary, decreased presumably with some intrinsic cause.The effect of the addition of acid catalysts such as NH4Cl on the extent of the crease resistance was considerable, although some marked improvement was obtained in neutral catalysts such as K2S2O8 alone.The addition of comonomers such as acrylamide and hexamethylene diamine HCl-salt as well as softeners to the treating bath was effective in improving the strength losses induced by this treatment. Aftertreatment of the N-methylolacrylamide-treated fabric with hexamethylenediamine or thereafter with formalin was also effective, since some what continuous distribution of the different kinds of network-structures within the fiber could be obtained by this procedure.Durability of the treated fabric for boiling-alkali launderings was excellent. [ABSTRACT FROM PUBLISHER]

Abstract: We report a case of diffuse sclerosing osteomyelitis of the mandible responded to alendronate, after a poor response to intravenous antibiotics, antibiotic irrigation-perfusion, and decortication. The patient was given an intravenous infusion of 10mg of alendronate. Pain resolved within 24h. There were no severe adverse events. Increased uptake of 99mTc in the mandible almost completely disappeared 3 months after treatment. [Copyright &y& Elsevier]

Background/aim: Nab-paclitaxel is used to treat patients with pancreatic cancer. However, it frequently induces peripheral neuropathy. Notably, pharmacokinetic factors may be associated with neuropathic symptoms as the onset depends on the cumulative dose. Therefore, we prospectively examined the association between the cumulative dose of nab-paclitaxel at the onset of peripheral neuropathy and polymorphisms of hepatic transporter genes., Patients and Methods: Patients with pancreatic cancer receiving nab-paclitaxel (125 mg/m 2 ) and gemcitabine (1,000 mg/m 2 ) were enrolled. Peripheral neuropathy was assessed using the Common Terminology Criteria for Adverse Events (CTCAE), Patient-Reported Outcomes CTCAE (PRO-CTCAE), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), every 2-12 weeks, and every 4 weeks thereafter. solute carrier organic anion transporter family member 1B1 (SLCO1B1) 521T>C, 388A>G; SLCO1B3 rs11045585; ATP-binding cassette transporters, subfamily B, member 1 (ABCB1) 1236C>T, 2677G>T/A, 3435C>T; ABCC1 rs2644983; ABCC2 24C>T; and ABCG2 421C>A were analyzed by direct sequencing. Correlations between transporter genotypes and cumulative dose at symptom onset were assessed using Kaplan-Meier and log-rank tests., Results: In total, 25 patients were enrolled. The lowest median cumulative dose for nab-paclitaxel at peripheral neuropathy onset using PRO-CTCAE was 593 mg. By CTCAE it was 800 mg, and by FACT/GOG-Ntx it was 1,090 mg (p<0.0001). At symptom onset, patients with ABCC2 -24C/T genotype had received a significantly lower median cumulative dose by PRO-CTCAE (540 mg) than those with C/C (720 mg) (p=0.0188). However, the other polymorphisms studied were not associated with symptoms., Conclusion: Herein, we found for the first time that ABCC2 -24C/T genotype was significantly associated with the onset of nab-paclitaxel-induced peripheral neuropathy detected with PRO-CTCAE., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The gut microbiota influences physiological functions of the host, ranging from the maintenance of local gut homeostasis to systemic immunity and metabolism. Secreted phospholipase A 2 group X (sPLA 2 -X) is abundantly expressed in colonic epithelial cells but is barely detectable in metabolic and immune tissues. Despite this distribution, sPLA 2 -X-deficient (Pla2g10 -/- ) mice displayed variable obesity-related phenotypes that were abrogated after treatment with antibiotics or cohousing with Pla2g10 +/+ mice, suggesting the involvement of the gut microbiota. Under housing conditions where Pla2g10 -/- mice showed aggravation of diet-induced obesity and insulin resistance, they displayed increased colonic inflammation and epithelial damage, reduced production of polyunsaturated fatty acids (PUFAs) and lysophospholipids, decreased abundance of several Clostridium species, and reduced levels of short-chain fatty acids (SCFAs). These obesity-related phenotypes in Pla2g10 -/- mice were reversed by dietary supplementation with ω3 PUFAs or SCFAs. Thus, colonic sPLA 2 -X orchestrates ω3 PUFA-SCFA interplay via modulation of the gut microbiota, thereby secondarily affecting systemic metabolism., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Treatment with regorafenib, which inhibits vascular endothelial growth factor (VEGF) receptor, frequently results in hand-foot skin reaction (HFSR), requiring treatment discontinuation or dose reduction. In our prospective study of regorafenib on patients with metastatic colorectal cancer, 17% of patients developed grade 3 HFSR. Herein, we retrospectively examined genetic polymorphisms associated with regorafenib-induced severe HFSR., Methods: To identify associated polymorphisms, exploratory whole-exome sequencing focusing on factors related to VEGF-mediated signaling pathways was first performed in seven patients each, with grade 3 HFSR and without HFSR. The identified HFSR-associated polymorphisms were analyzed in all the 40 patients., Results: The genotype frequency of rs3025009 G/A or A/A in the gene encoding VEGF-A (VEGFA) in patients with ≥ grade 2 HFSR was significantly higher than in other patients (P = 0.0257, Pc = 0.0771 [Bonferroni correction]). The frequency of C-C motif of chemokine ligand 4-like 2 (CCL4L2) rs3744596 A/T or T/T in patients with grade 3 HFSR was significantly lower than in others (P = 0.00894, Pc = 0.0268). The combination of the risk genotypes VEGFA rs3025009 G/A or A/A and CCL4L2 rs3744596 A/A was significantly associated with a higher incidence of grade 3 (P = 0.000614, Pc = 0.00246) and a longer median progression-free survival (P = 0.0234) than others., Conclusions: These VEGF-related polymorphisms were found to be associated with HFSR and the survival benefits of regorafenib treatment., Trial Registration Number and Date: UMIN000013939, registered on May 12, 2014, when 6 months after the approval by the Institutional Review Board of Showa University., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The awn is a bristle-like appendage that protrudes from the seed tip and plays a critical role in preventing feed damage and spreading habitats in many grass species, including rice. While all wild species in the Oryza genus have awns, this trait has been eliminated in domesticated species due to its obstructive nature to agricultural processes. To date, several genes involved in awn development have been identified in wild rice, Oryza rufipogon and Oryza barthii which are ancestral species of cultivated rice in Asia and Africa, respectively. However, the responsible genes for awn development have not been identified in other wild rice species even though multiple QTLs have been reported previously. In this study, we identified An7 gene responsible for awn development in two wild rice species, Oryza glumaepatula and Oryza meridionalis . An7 encodes a cytochrome P450 enzyme and is homologous to D2/CYP90D2 , a known brassinosteroid biosynthesis enzyme in rice. The identification of An7 provides insight into a distinct molecular mechanism underlying awn development that occurs in geographically separated environments., (Copyright © 2024 by JAPANESE SOCIETY OF BREEDING.)

The aim of this study was to clarify the effectiveness and challenges of applying mesoporous tin oxide (SnO 2 )-based supports for Pt catalysts in the cathodes of polymer electrolyte fuel cells (PEFCs) to simultaneously achieve high performance and high durability. Recently, the focus of PEFC application in automobiles has shifted to heavy-duty vehicles (HDVs), which require high durability, high energy-conversion efficiency, and high power density. It has been reported that employing mesoporous carbon supports improves the initial performance by mitigating catalyst poisoning caused by sulfonic acid groups of the ionomer as well as by reducing the oxygen transport resistance through the Pt/ionomer interface. However, carbon materials in the cathode can degrade oxidatively during long-term operation, and more stable materials are desired. In this study, we synthesized connected mesoporous Sb-doped tin oxides (CMSbTOs) with controlled mesopore sizes in the range of 4-11 nm and tested their performance and durability as cathode catalyst supports. The CMSbTO supports exhibited higher fuel cell performance at a pore size of 7.3 nm than the solid-core SnO 2 -based, solid-core carbon, and mesoporous carbon supports under dry conditions, which can be attributed to the mitigation of the formation of the Pt/ionomer interface and the better proton conductivity within the mesopores even at the low-humidity conditions. In addition, the CMSbTO supports exhibited high durability under oxidative conditions. These results demonstrate the promising applicability of mesoporous tin oxide supports in PEFCs for HDVs. The remaining challenges, including the requirements for improving performance under wet conditions and stability under reductive conditions, are also discussed.

Purpose: Capecitabine is a prodrug that converts to 5-fluorouracil (5-FU) in three steps. A previous study showed that ABCA2 rs2271862 (C > T) and ABCG5 rs6720173 were associated with increased clearance of 5-FU and 5'-deoxy-5-fluorouridine, respectively, in Spanish patients with colorectal cancer (CRC) (Br J Clin Pharmacol 2021) and reported that ABCA2 rs2271862 was associated with decreased risk of capecitabine-induced neutropenia. Other studies have reported that ABCB1 rs1128503, rs2032592, and rs1045642 were associated with capecitabine-induced toxicity in Spanish CRC patients (Oncotarget 2015, Phamacogenomics 2010). Here, we prospectively examined the effects of ABC transporter genes polymorphisms on capecitabine pharmacokinetics and toxicity., Methods: We enrolled patients with postoperative CRC treated with adjuvant capecitabine plus oxaliplatin (CapeOX) and patients with metastatic CRC receiving CapeOX. Pharmacokinetic analysis of the first capecitabine dose (1000 mg/m 2 ) was performed on day 1. We analyzed plasma concentrations of capecitabine and its three metabolites by high-performance liquid chromatography and ABC transporter genes polymorphisms using direct sequencing., Results: Patients with ABCA2 rs2271862 T/T genotype had significantly lower area under the plasma concentration-time curve of capecitabine, but not of its metabolites, which were divided by the dose of the parent drug, than patients with C/C or C/T genotype (P = 0.0238). Frequency of ≥ grade 2 neutropenia was significantly lower in patients with ABCA2 rs2271862 T/T genotype (P = 0.00915). Polymorphisms in ABCG5 and ABCB1 were not associated with capecitabine pharmacokinetics and toxicity., Conclusions: We found that ABCA2 polymorphism was significantly associated with systemic exposure to capecitabine and capecitabine-induced neutropenia in Japanese patients with CRC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Regorafenib improves the survival of patients with metastatic colorectal cancer (mCRC); however, it is also characterized by detrimental dermal side effects that may require treatment cessation or modified dosing. In our previous prospective pharmacokinetic, pharmacodynamic, and pharmacogenetic studies, 17.5% (7/40) of the patients with mCRC had grade 3 erythema multiforme (EM) that caused treatment discontinuation. Haplotypes in genes encoding human leukocyte antigen (HLA) are associated with EM following the administration of drugs, such as allopurinol. This study examined the association between HLA haplotypes and regorafenib-induced EM. Regorafenib was administered orally at 160 mg/body once daily for weeks 1-3 of each 4-week cycle. To determine the HLA haplotypes, we used the WAKFlow HLA Typing Kit HLA-A, -B, or -C. The carrier frequency of HLA-C*01:02 in patients with EM (6/7) was higher than that in tolerant controls (8/33; odds ratio [OR] = 18.8, 95% confidence interval [CI] = 1.95-180, p = 0.00437). HLA-B*46:01 was also associated with EM (OR = 11.6, 95% CI = 1.47-92.1, p = 0.0299). These associations were no longer significant after Bonferroni correction for multiple testing. Therefore, regorafenib-induced EM in Japanese patients appears to be associated with specific HLA haplotypes but further validation is needed., (© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Patients undergoing total knee arthroplasty (TKA) surgery are at high risk of chronic postsurgical pain (CPSP). Accumulating evidence suggests an active role of neuroinflammation in chronic pain. However, its role in the progression to CPSP following TKA surgery remains unanswered. Here, we examined the associations between preoperative neuroinflammatory states and pre- and postsurgical chronic pain in TKA surgery., Methods: The data of 42 patients undergoing elective TKA surgery for chronic knee arthralgia at our hospital were analyzed in this prospective study. Patients completed the following questionnaires: brief pain inventory (BPI), hospital anxiety and depression scale, painDETECT, and pain catastrophizing scale (PCS). Cerebrospinal fluid (CSF) samples were collected preoperatively and concentrations of IL-6, IL-8, TNF, fractalkine, and CSF-1 were measured by electrochemiluminescence multiplex immunoassay. CPSP severity was ascertained, using the BPI, 6 months postsurgery., Results: While no significant correlation was observed between the preoperative CSF mediator levels and preoperative pain profiles, the preoperative fractalkine level in the CSF showed a significant correlation with CPSP severity (Spearman's rho = -0.525; p = .002). Furthermore, multivariate linear regression analysis revealed that the preoperative PCS score (standardized β coefficient [β]: .11; 95% confidence interval [CI]: 0.06-0.16; p < .001) and CSF fractalkine level (β: -.62; 95% CI: -1.10 to -0.15; p = .012) were independent predictors of CPSP severity 6 months after TKA surgery., Conclusions: We identified the CSF fractalkine level as a potential predictor for CPSP severity following TKA surgery. In addition, our study provided novel insights into the potential role of neuroinflammatory mediators in the pathogenesis of CPSP., (© 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

A prolonged length of hospital stay (LOS) has become an important issue among patients undergoing cardiovascular surgery in our aging society. However, there are no established prediction models for a prolonged LOS. We therefore created a prediction model of a prolonged LOS using a deep learning software program (Prediction One; Sony Network Communications Inc., Tokyo, Japan) using preoperative data. Subjects were 157 patients (121 for training data, 36 for validation data). A prolonged LOS was defined as a more than 30-day postoperative stay due to physical inactivity. The area under the receiver operating characteristic curve and the accuracy of the model in the validation data were 0.806 and 67%, respectively. In conclusion, the preliminary model demonstrated acceptable performance for the prediction of a prolonged LOS after cardiovascular surgery., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Two species of rice have been independently domesticated from different ancestral wild species in Asia and Africa. Comparison of mutations that underlie phenotypic and physiological alterations associated with domestication traits in these species gives insights into the domestication history of rice in both regions. Asian cultivated rice, Oryza sativa, and African cultivated rice, Oryza glaberrima , have been modified and improved for common traits beneficial for humans, including erect plant architecture, nonshattering seeds, nonpigmented pericarp, and lack of awns. Independent mutations in orthologous genes associated with these traits have been documented in the two cultivated species. Contrary to this prevailing model, selection for awnlessness targeted different genes in O. sativa and O. glaberrima . We identify Regulator of Awn Elongation 3 ( RAE3 ) a gene that encodes an E3 ubiquitin ligase and is responsible for the awnless phenotype only in O. glaberrima . A 48-bp deletion may disrupt the substrate recognition domain in RAE3 and diminish awn elongation. Sequencing analysis demonstrated low nucleotide diversity in a ~600-kb region around the derived rae3 allele on chromosome 6 in O. glaberrima compared with its wild progenitor. Identification of RAE3 sheds light on the molecular mechanism underlying awn development and provides an example of how selection on different genes can confer the same domestication phenotype in Asian and African rice.

Backgrounds: The endoplasmic reticulum (ER) is a crucial organelle that regulates both the folding, modification and transport of many proteins and senses certain stimuli inside and outside of cells. ER-associated degradation (ERAD), including SEL1L is a crucial mechanism to maintain homeostasis. In this study, we performed comparative proteome analysis in wild-type (wt) and SEL1L-deficient cells., Methods and Results: We found constitutively high expression of thioredoxin domain-containing protein 11 (TXNDC11) mRNA and protein in our SEL1L-deficient HEK293 cells by RT-PCR and Western blot analysis. The TXNDC11 gene possesses a well-conserved unfolded protein response element (UPRE) around its transcription start site, and ER stress increased TXNDC11 mRNA and luciferase reporter activity via this putative UPRE in HEK293 cells. The amounts of TXNDC11 protein in wild-type and SEL1L-deficient cells with or without thapsigargin (Tg) treatment were parallel to their mRNAs in these cells, which was almost proportional to spliced XBP1 (sXBP1) mRNA expression. The establishment and characterization of TXNDC11-deficient HEK293 cells revealed that the expression of three different ER resident stress sensors, ATF6α, CREB3 and CREB3L2, is regulated by TXNDC11. The rate of disappearance of the three proteins by CHX treatment in wt cells was remarkably different, and the full-length CREB3L2 protein was almost completely degraded within 15 min after CHX treatment. TXNDC11 deficiency increased the expression of each full-length form under resting conditions and delayed their disappearance by CHX treatment. Interestingly, the degree of increase in full-length CREB3/CREB3L2 by TXNDC11 deficiency was apparently higher than that in full-length ATF6α. The increase in these proteins by TXNDC11 deficiency was hardly correlated with the expression of each mRNA. Treatment with ER stress inducers influenced each full-length mature form, and the difference in each full-length form observed in wt and TXNDC11-deficient cells was smaller., Conclusion: This study demonstrated that TXNDC11 is an ER stress-inducible gene regulated by the IRE1-sXBP1 pathway. In addition, TXNDC11 is involved in the regulation of ATF6α, CREB3 and CREB3L2 protein expression, although the contribution to the stability of these proteins is quite variable. Therefore, its further characterization will provide new insights for understanding protein homeostasis in ER physiology and pathology., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: Several therapeutic agents have been found to prevent myocardial ischemic and reperfusion (I/R) injury after cardiac surgery; however, no drug is routinely used to afford cardioprotective benefits in clinical settings. Herein, we aimed to determine whether chloroquine (CQ) pretreatment attenuates I/R injury after global ischemia in isolated rat hearts and elucidate mechanisms underlying the effects of CQ., Methods: Isolated rat hearts were subjected to 30-min global ischemia, followed by 60-min reperfusion with Krebs-Henseleit buffer (KHB). Immediately before ischemia, 10 mL of pretreatment solutions (KHB, n = 4 or KHB + CQ [100 μM], n = 4) were injected through the aortic root. Cardiac function was examined based on the rate pressure product (RPP). Myocardial apoptosis was evaluated using TUNEL staining. To assess the reperfusion ischemia salvage kinase pathway, protein expression levels of AKT and extracellular signal-regulated kinase (ERK1/2) were determined using western blotting. To investigate the role of ERK1/2, an ERK1/2 selective inhibitor was used in eight additional rats., Results: The recovery rate of the RPP was higher in the KHB + CQ group than in the KHB group 60 min after I/R (KHB, 44 ± 3% vs. KHB + CQ, 69 ± 7%; P = 0.019, d = 2.2). CQ pretreatment reduced apoptosis and enhanced the phosphorylation of ERK1/2; however, AKT phosphorylation was unaltered. In addition, the ERK1/2 inhibitor abolished CQ-mediated cardioprotective effects., Conclusions: CQ pretreatment showed protective effects on cardiac function after I/R by activating ERK1/2., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

The two-dimensional (2-D) framework, [Cu(BTDAT)(MeOH)] {BTDAT = bis-[1,2,5]-thiadiazolo-tetracyanoquinodimethane}, possesses remarkable multi-step redox properties, with electrochemical studies revealing six quasi-stable redox states in the solid state. In situ electron paramagnetic resonance and visible-near infrared spectroelectrochemistry elucidated the mechanism for these multi-step redox processes, as well as the optical and electrochromic behavior of the BTDAT ligand and framework. In studying the structural, spectroscopic, and electronic properties of [Cu(BTDAT)(MeOH)], the as-synthesized framework was found to exist in a mixed-valence state with thermally-activated semiconducting behavior. In addition to pressed pellet conductivity measurements, single-crystal conductivity measurements using a pre-patterned polydimethylsiloxane layer on a silicon substrate provide important insights into the anisotropic conduction pathways. As an avenue to further understand the electronic state of [Cu(BTDAT)(MeOH)], computational band structure calculations predicted delocalized electronic transport in the framework. On the balance of probabilities, we propose that [Cu(BTDAT)(MeOH)] is a Mott insulator (i.e., electron correlations cause a metal-insulator transition). This implies that the conductivity is incoherent. However, we are unable to distinguish between activated transport due to Coulombically bound electron-hole pairs and a hopping mechanism. The combined electrochemical, electronic, and optical properties of [Cu(BTDAT)(MeOH)] shine a new light on the experimental and theoretical challenges for electroactive framework materials, which are implicated as the basis of advanced optoelectronic and electrochromic devices.

Electrical conduction among metallocycles has been unexplored because of the difficulty in creating electronic transport pathways. In this work, we present an electrocrystallization strategy for synthesizing an intrinsically electron-conductive metallocycle, [Ni 6 (NDI-Hpz) 6 (dma) 12 (NO 3 ) 6 ]·5DMA· n H 2 O (PMC-hexagon) (NDI-Hpz = N , N '-di(1 H -pyrazol-4-yl)-1,4,5,8-naphthalenetetracarboxdiimide). The hexagonal metallocycle units are assembled into a densely packed ABCABC… sequence (like the fcc geometry) to construct one-dimensional (1D) helical π-stacked columns and 1D pore channels, which were maintained under the liberation of H 2 O molecules. The NDI cores were partially reduced to form radicals as charge carriers, resulting in a room-temperature conductivity of (1.2-2.1) × 10 -4 S cm -1 (pressed pellet), which is superior to that of most NDI-based conductors including metal-organic frameworks and organic crystals. These findings open up the use of metallocycles as building blocks for fabricating conductive porous molecular materials., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background/aim: Carboplatin is a key drug in the treatment of ovarian cancer, but hypersensitivity reactions (HSRs) may occur with repeated use., Patients and Methods: Thirty-seven ovarian cancer patients treated with carboplatin desensitization therapy were reviewed retrospectively. The treatment completion rate and toxicity were examined., Results: The carboplatin desensitization completion rate was 86.5%. Toxicity was Grade 0, 1, 2, and 3 in 17, 5, 10, and 5 patients, respectively. Erythema was the most frequent toxicity (36.8%), most commonly affecting the arm (23.5%). Furthermore, all HSRs were classified into: skin, respiratory, digestive, circulatory, and neurological. The completion rate of desensitization was significantly lower in patients with two or more target organs affected (p<0.001)., Conclusion: The main symptoms of HSRs, the most common sites of HSRs, and the criteria for discontinuing desensitization therapy identified in this study are useful information for the safe implementation of carboplatin desensitization therapy., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Tissue-resident mast cells (MCs) have important roles in IgE-associated and -independent allergic reactions. Although microenvironmental alterations in MC phenotypes affect the susceptibility to allergy, understanding of the regulation of MC maturation is still incomplete. We previously reported that group III secreted phospholipase A 2 (sPLA 2 -III) released from immature MCs is functionally coupled with lipocalin-type prostaglandin D 2 (PGD 2 ) synthase in neighboring fibroblasts to supply a microenvironmental pool of PGD 2 , which in turn acts on the PGD 2 receptor DP1 on MCs to promote their proper maturation. In the present study, we reevaluated the role of sPLA 2 -III in MCs using a newly generated MC-specific Pla2g3 -deficient mouse strain. Mice lacking sPLA 2 -III specifically in MCs, like those lacking the enzyme in all tissues, had immature MCs and displayed reduced local and systemic anaphylactic responses. Furthermore, MC-specific Pla2g3 -deficient mice, as well as MC-deficient Kit W-sh mice reconstituted with MCs prepared from global Pla2g3- null mice, displayed a significant reduction in irritant contact dermatitis (ICD) and an aggravation of contact hypersensitivity (CHS). The increased CHS response by Pla2g3 deficiency depended at least partly on the reduced expression of hematopoietic PGD 2 synthase and thereby reduced production of PGD 2 due to immaturity of MCs. Overall, our present study has confirmed that MC-secreted sPLA 2 -III promotes MC maturation, thereby facilitating acute anaphylactic and ICD reactions and limiting delayed CHS response.

Background: We previously reported that cannabidiol (CBD), a cannabinoid with a low toxicity profile, downregulated the expression of the prometastatic gene inhibitor of DNA binding 1 ( ID1 ) in cancer cells, leading to inhibition of tumor progression in vivo . While CBD is broadly used, including in the self-medication of cancer patients, and CBD-based therapies are undergoing clinical evaluation for cancer treatment, its mechanisms of action are still poorly understood. Methods: In this study, using microarray analysis and Western blot analysis for validation, we attempted to identify the full spectrum of genes regulated by CBD across various aggressive cancer cell lines, including the breast, brain, head and neck, and prostate. Results: We confirmed that ID1 was a major target downregulated by CBD and also discovered that CBD inhibited FOXM1 (Forkhead box M1), a transcriptional activator involved in cell proliferation, while simultaneously upregulating GDF15 (growth differentiation factor 15), a cytokine associated with tissue differentiation. Conclusion: Our results suggest that, by modulating expression of shared key cancer-driving genes, CBD could represent a promising nontoxic therapeutic for treating tumors of various origins., Competing Interests: No competing financial interests exist., (Copyright 2021, Mary Ann Liebert, Inc., publishers.)

We performed a comparative analysis of two ER-resident CREB3 family proteins, CREB3 and CREB3L2, in HEK293 cells using pharmacological and genome editing approaches and identified several differences between the two. Treatment with brefeldin A (BFA) and monensin induced the cleavage of full-length CREB3 and CREB3L2; however, the level of the full-length CREB3 protein, but not CREB3L2 protein, was not noticeably reduced by the monensin treatment. On the other hand, treatment with tunicamycin (Tm) shifted the molecular weight of the full-length CREB3L2 protein downward but abolished CREB3 protein expression. Thapsigargin (Tg) significantly increased the expression of only full-length CREB3L2 protein concomitant with a slight increase in the level of its cleaved form. Treatment with cycloheximide and MG132 revealed that both endogenous CREB3 and CREB3L2 are proteasome substrates. In addition, kifunensine, an α-mannosidase inhibitor, significantly increased the levels of both full-length forms. Consistent with these findings, cells lacking SEL1L, a crucial ER-associated protein degradation (ERAD) component, showed increased expression of both full-length CREB3 and CREB3L2; however, cycloheximide treatment downregulated full-length CREB3L2 protein expression more rapidly in SEL1L-deficient cells than the full-length CREB3 protein. Finally, we investigated the induction of the expression of several CREB3 and CREB3L2 target genes by Tg and BFA treatments and SEL1L deficiency. In conclusion, this study suggests that both endogenous full-length CREB3 and CREB3L2 are substrates for ER-associated protein degradation but are partially regulated by distinct mechanisms, each of which contributes to unique cellular responses that are distinct from canonical ER signals.

A series of stable radical 2D metal-organic frameworks has been assembled. (m-TTFTB) 3 (m-Tetrathiafulvalene-tetrabenzoate) trimer building blocks are beneficial for the stability of the radicals due to delocalization of the unpaired electron. Hexanuclear rare-earth-cluster-based 1D chains further enhance the stability of the frameworks. The radical state of the middle TTF in the trimer has been observed by the change of central C-C and C-S bond distances and the configuration of the TTF by single-crystal X-ray diffraction. The radical characteristics are also confirmed by electron paramagnetic resonance, UV/Vis-NIR absorption, and X-ray photoelectron spectroscopy experiments. Stability tests showed that the radicals are stable even in solutions and under acid/base environments (pH 1-12). Owing to efficient light absorption due to intramolecular charge transfer, low thermal conductivity, and outstanding stability, the radical 2D Dy-MOF shows excellent photothermal properties, an increase of 34.7 °C within 240 s under one-sun illumination., (© 2020 Wiley-VCH GmbH.)

Toward a sustainable synthesis of value-added chemicals, the method of CO 2 utilization attracts great interest in chemical process engineering. Biotechnological CO 2 fixation is a promising technology; however, efficient methods that can fix carbon dioxide are still limited. Instead, some parts of microbial decarboxylases allow the introduction of carboxy group into phenolic compounds using bicarbonate ion as a C1 building block. Here, we identified a unique decarboxylase from Arthrobacter sp. K8 that acts on resorcinol derivatives. A high-throughput colorimetric decarboxylase assay facilitated gene cloning of orsellinic acid decarboxylase from genomic DNA library of strain K8. Sequence analysis revealed that the orsellinic acid decarboxylase belonged to amidohydrolase 2 family, but shared low amino acid sequence identity with those of related decarboxylases. Enzymatic characterization unveiled that the decarboxylase introduces a carboxy group in a highly regio-selective manner. We applied the decarboxylase to enzymatic carboxylation of resorcinol derivatives. Using Escherichia coli expressing the decarboxylase gene as a whole cell biocatalyst, orsellinic acid, 2,4-dihydroxybenzoic acid, and 4-methoxysalicylic acid were produced in the presence of saturated bicarbonate. These findings could provide new insights into the production of useful phenolic acids from resorcinol derivatives., (Copyright © 2020 Elsevier B.V. All rights reserved.)