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Filter-based offline analysis of atmospheric aerosol hygroscopicity coupled to composition analysis provides information complementary to that obtained from online analysis. However, its application itself and comparison to online analysis have remained limited to date. In this study, daily submicrometer aerosol particles (PM0.95, 50 % cutoff diameter: 0.95 μm) were collected onto quartz fiber filters in Okinawa Island, a receptor of East Asian outflow, in the autumn of 2015. The chemical composition of water-soluble matter (WSM) in PM0.95 and PM0.95 itself, and their respective hygroscopicities were characterized through the offline use of an aerosol mass spectrometer and a hygroscopicity tandem differential mobility analyzer. Thereafter, results were compared with those obtained from online analyses. Sulfate dominated the WSM mass (60 %), followed by water-soluble organic matter (WSOM, 20 %) and ammonium (13 %). WSOM accounted for most (93 %) of the mass of extracted organic matter (EOM) and the atomic O to C ratios (O : C) of WSOM and EOM were high (mean ± standard deviation were, respectively, 0.84 ± 0.08 and 0.79 ± 0.08), both of which indicate highly aged characteristics of the observed aerosol. The hygroscopic growth curves showed clear hysteresis for most samples. At 85 % RH, the calculated hygroscopicity parameter κ of the WSM (κWSM), WSOM, EOM, and PM0.95 (κPM0.95) were, respectively, 0.50 ± 0.03, 0.22 ± 0.12, 0.20 ± 0.11, and 0.47 ± 0.03. An analysis using the thermodynamic E-AIM model shows, on average, that inorganic salts and WSOM respectively contributed 88 % and 12 % of the κWSM (or κPM0.95). High similarities were found between offline and online analysis for chemical compositions that are related to particle hygroscopicity (the mass fractions and O : C of organics, and the degree of neutralization), and also for aerosol hygroscopicity. As possible factors governing the variation of κWSM, the influences of WSOM abundance and the neutralization of inorganic salts were assessed. At high RH (70–90 %), the hygroscopicity of WSM and PM0.95 was affected considerably by the presence of organic components; at low RH (20–50 %), the degree of neutralization could be important. This study not only characterized aerosol hygroscopicity at the receptor site of East Asian outflow, but also shows that the offline hygroscopicity analysis is an appropriate method, at least for aerosols of the studied type. The results encourage further applications to other environments and to more in-depth hygroscopicity analysis, in particular for organic fractions.

The Dispatched protein, which is related to the NPC1 and PTCH1 cholesterol transporters1,2 and to H+-driven transporters of the RND family3,4, enables tissue-patterning activity of the lipid-modified Hedgehog protein by releasing it from tightly -localized sites of embryonic expression5–10. Here we determine a cryo-electron microscopy structure of the mouse protein Dispatched homologue 1 (DISP1), revealing three Na+ ions coordinated within a channel that traverses its transmembrane domain. We find that the rate of Hedgehog export is dependent on the Na+ gradient across the plasma membrane. The transmembrane channel and Na+ binding are disrupted in DISP1-NNN, a variant with asparagine substitutions for three intramembrane aspartate residues that each coordinate and neutralize the charge of one of the three Na+ ions. DISP1-NNN and variants that disrupt single Na+ sites retain binding to, but are impaired in export of the lipid-modified Hedgehog protein to the SCUBE2 acceptor. Interaction of the amino-terminal signalling domain of the Sonic hedgehog protein (ShhN) with DISP1 occurs via an extensive buried surface area and contacts with an extended furin-cleaved DISP1 arm. Variability analysis reveals that ShhN binding is restricted to one extreme of a continuous series of DISP1 conformations. The bound and unbound DISP1 conformations display distinct Na+-site occupancies, which suggests a mechanism by which transmembrane Na+ flux may power extraction of the lipid-linked Hedgehog signal from the membrane. Na+-coordinating residues in DISP1 are conserved in PTCH1 and other metazoan RND family members, suggesting that Na+ flux powers their conformationally driven activities. Cryo-electron microscopy studies show that dynamic coordination of Na+ in the ion channel of Dispatched homologue 1 and the transmembrane Na+ gradient have key roles in exporting lipid-modified Hedgehog protein signal.

Graphene oxide (GO) contains various types of oxygen functional groups (e.g., C–OH, C–O–C, C=O, and O=C–OH groups), which provide superior functions such as proton conductivity, catalytic activity,...

Although combination immune checkpoint inhibitor (immuno‐oncology [IO]) therapy is the first‐line treatment for metastatic renal cell carcinoma (mRCC), it mostly causes resistance and tumor regrowth. Therefore, an optimal second‐line therapy is necessary. Such therapy typically comprises vascular endothelial growth factor receptor‐tyrosine kinase inhibitors (VEGFR‐TKIs). This study was aimed at comparing the efficacy of two TKIs—axitinib and sunitinib—in mRCC patients. From January 2008 to October 2018, we registered 703 mRCC patients from 8 Japanese institutes. Of these, 408 patients received axitinib or sunitinib as the first‐line treatment. Thereafter, efficacy and survival rate were compared between the axitinib and sunitinib groups. To reduce the effects of selection bias and potential confounders, propensity score matching analysis was performed. Axitinib and sunitinib were administered in 274 and 134 patients, respectively. More than 25% of the patients received nivolumab sequence therapy. To calculate the propensity scores for each patient, we performed multivariate logistic regression analysis. The objective response rate, progression‐free survival (PFS), cause‐specific survival, and overall survival (OS) were significantly better in the axitinib group than in the sunitinib group. Furthermore, the OS was better in the nivolumab‐treated patients in the axitinib group. Axitinib showed higher efficacy and afforded greater survival benefits than did sunitinib when administered as first‐line therapy in mRCC patients. Thus, from among VEGFR‐TKIs, axitinib might be a possible option for application in the middle of IO drug‐based treatment sequences., Compared to sunitinib, axitinib showed higher efficacy and afforded greater survival benefits as first‐line therapy in patients with metastatic renal cell carcinoma. Axitinib might be better than sunitinib for application in the middle of IO drug‐based treatment sequences.

Lignin-based polycaprolactone (PCL) graft copolymers with various graft ratios were prepared by ring-opening reaction in order to design new lignin derivatives. Molecular length of PCL side chain was varied in a wide range, i.e. caprolactone/hydroxyl group (CL/OH) ratio was varied from 3 to 100 mol mol−1. The effect of lignin on thermal properties of PCL was examined by differential scanning calorimetry (DSC) and thermogravimetry. In DSC heating curves of lignin-based PCL, glass transition, pre-melt crystallization and melting were observed. From DSC results, the phase diagram of lignin-based PCL was established. It was found that glass transition temperature (Tg) decreased until CL/OH ratio reached 20, and then, Tg was maintained at around 200 K. Tg slightly increased when CL/OH ratio became higher than 20. The above facts suggest that the random structure of lignin affects the molecular motion of copolymers in a limited length of PCL chains, and that with increasing PCL chain length, free molecular motion is restricted by crystallization. The amorphous region of lignin–PCL was reorganized at pre-melt crystallization, and crystallinity increased. When CL/OH ratio increased more than 20, two melting peaks were observed; the low-temperature side is PCL crystallite affected by lignin and the high-temperature side melting peak is attributed to melting PCL crystal. The effect of lignin on thermal decomposition is apparently observed for lignin-based PCL when CL/OH ratio is smaller than 20. The above results suggest that lignin-based PCL graft copolymers have the potential of an applicant of novel nature-friendly polymers.

The extracellular matrix (ECM) is critical to cell attachment, proliferation, and differentiation; therefore, development of bioadaptive ECM-mimetic cell culture scaffolds is an active area of research in tissue engineering. Collagen (rigid nanofiber morphology) and hyaluronan (carboxy groups displayed in a regular manner) are typical ECM components found in vivo. In this work, we used wood-derived crystalline cellulose nanofibers (CNFs) to provide bioadaptive microenvironments for cell culture. Catalytic oxidation of wood CNFs using 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) afforded crystalline nanofibrous scaffolds with various carboxy contents, ranging from 0.31 to 1.60 mmol g–1, of the TEMPO-oxidized CNFs (TOCNFs). Mouse fibroblast cells were subjected to the hydrophilic TOCNF-coated substrates, which were transparent and exhibited a native cellulose I crystalline structure; good cell proliferation was observed for the TOCNFs with carboxy content of 0.8–1.0 mmol g–1, although intact CNF was bioinert and an excess of carboxylates negatively impacted cell growth. Neither mercerized TOCNFs with a cellulose II structure nor carboxymethylated CNFs with irregular surface carboxy groups contributed to cell proliferation. Therefore, the rigid nanofiber morphology of xeno-free, crystalline TOCNFs with regular alignment of surface carboxy groups would hold the key to providing bioadaptive, ECM-mimetic cellular microenvironments.

Patients with primary aldosteronism have a higher risk of chronic kidney disease. Visceral fat tissue is hypothesized to stimulate the adrenal glands to overproduce aldosterone, and aldosterone promotes visceral fat tissue to produce inflammatory cytokines. However, it is unclear whether the volume of accumulated visceral fat tissue is associated with renal impairment among patients with hyperaldosteronism. We conducted a single-center cross-sectional study to assess the association between the estimated glomerular filtration rate and the ratio of the visceral-to-subcutaneous fat volume calculated by computed tomography. One hundred eighty patients with primary aldosteronism were enrolled. The mean ± SD age was 52.7 ± 11.0 years, and 60.0% were women. The ratio of visceral-to-subcutaneous fat volume was highly correlated with the estimated glomerular filtration rate (r = 0.49, p, The ratio of visceral-to-subcutaneous fat tissue volume was significantly associated with eGFR among 180 primary aldosteronism patients, showing an interaction between the ratio and plasma aldosterone concentration.

The post-translational acetylation of lysine residues is found in many nonhistone proteins and is involved in a wide range of biological processes. Recently, we showed that the nucleoprotein of the influenza A virus is acetylated by histone acetyltransferases (HATs), a phenomenon that affects viral transcription. Here, we report that the PA subunit of influenza A virus RNA-dependent RNA polymerase is acetylated by the HATs, P300/CREB-binding protein-associated factor (PCAF), and general control nonderepressible 5 (GCN5), resulting in accelerated endonuclease activity. Specifically, the full-length PA subunit expressed in cultured 293T cells was found to be strongly acetylated. Moreover, the partial recombinant protein of the PA N-terminal region containing the endonuclease domain was also acetylated by PCAF and GCN5 in vitro, which facilitated its endonuclease activity. Mass spectrometry analyses identified K19 as a candidate acetylation target in the PA N-terminal region. Notably, the substitution of the lysine residue at position 19 with glutamine, a mimic of the acetyl-lysine residue, enhanced its endonuclease activity in vitro; this point mutation also accelerated influenza A virus RNA-dependent RNA polymerase activity in the cell. Our findings suggest that PA acetylation is important for the regulation of the endonuclease and RNA polymerase activities of the influenza A virus.

Positive suppression of photocatalytic activity of TiO2 used for an antireflection film or UV-light protection material is required while maintaining its white color and transmittance of visible li...

Despite progress in the use of hyperthermia in clinical practice, the thermosensitivity of cancer cells is poorly understood. In a previous study, we found that sensitivity to hyperthermia varied between ovarian and uterine cancer cell lines. Upon hyperthermia, glycolytic enzymes decreased in hyperthermia-resistant SKOV3 cells. However, the mechanisms of glycolysis inhibition and their relationship with thermoresistance remain to be explored. In this study, metabolomic analysis indicated the downregulation of glycolytic metabolites in SKOV3 cells after hyperthermia. Proteomic and pathway analyses predicted that the ubiquitin pathway was explicitly activated in resistant SKOV3 cells, compared with hyperthermia-sensitive A2780 cells, and STUB1, a ubiquitin ligase, potentially targeted PKM, a glycolytic rate-limiting enzyme. PKM is degraded via ubiquitination upon hyperthermia. Although glycolysis is inactivated by hyperthermia, ATP production is maintained. We observed that oxygen consumption and mitochondrial membrane potential were activated in SKOV3 cells but suppressed in A2780 cells. The activation of mitochondria could compensate for the loss of ATP production due to the suppression of glycolysis by hyperthermia. Although the physiological significance has not yet been elucidated, our results demonstrated that metabolomic adaptation from the Warburg effect to mitochondrial oxidative phosphorylation could contribute to thermoresistance in ovarian and uterine cancer cells.

Reaction pathways and energetics for the dimerization and trimerization reactions of 2-bromo-3-methoxythiophene (2Br-3Met) molecules are investigated using hybrid density functional theory (DFT) calculations to obtain insight into the oligomerization reaction observed in the spontaneous combustion of pure liquid 2Br-3Met. The calculations show that the carbon-bromine bond in a 2Br-3Met molecule elongates easily, and the trans addition of this C-Br bond to a double bond in the neighboring 2Br-3Met molecule occurs easily at room temperature, reflecting the evaluated activation energy of ΔHa = 12.46 kcal/mol (enthalpy) or ΔGa = 35.68 kcal/mol (Gibbs free energy, 298.150 K and 1 atm). The formation process of trimers is calculated in a similar way. A model for the explanation of spontaneous combustion is proposed; large oligomers of the 2Br-3Met molecule are produced spontaneously following the initial formation of dimers or trimers. UV-vis spectra and vibration spectra are obtained for related molecular species, which show reasonable agreement with the experimental results.

Electrochemical (EC) reduction of graphene oxide (GO) serves as a green chemistry pathway to produce reduced GO (rGO). However, the mechanistic understanding of this process is still limited due to the structural complexity of GO-based materials. In the present study, we employ an inductive approach that consists of investigating the structures afforded by alternating EC reduction and oxidation steps to elucidate the electrochemical reduction reactions in aqueous solution. The initial EC reduction of chemically derived GO mainly converts epoxides (C–O–C) to COH/CH pairs. Simultaneously, carbon-centered radicals (C•) are eliminated. Subsequent EC oxidation does not result in restoration of epoxides but reverse dehydrogenation and radical formation. The second EC reduction and oxidation cycle involves reversible C–H formation coupled with radical elimination, suggesting that C• serves as an active site for the hydrogenation. As a result of this study, COH–CH is revealed as a plausible characteristic structure in electrochemically derived rGO. The reversible radical hydrogenation reaction can offer an effective route to manipulate the chemical reactivities of GO-based materials. We demonstrate that the electrons transferred by EC reduction can delocalize in the rGO to some extent, activating the pseudocapacitance that probably originates from COH.

Biomass has been attracting attention as an environmentally friendly energy resource due to concerns about global environmental problems. Chromated copper arsenate-treated wood produced by injecting a solution containing sub-percent of chromium, copper, and arsenic (hereinafter referred to as CCA-treated wood) is one of the construction wastes. As fundamental research on the development of clean gasification process for biomass, pyrolysis (400–800 °C) which is the initial stage of gasification and CO2 gasification (1000 °C, 0–60 min) characteristics of CCA-treated wood were investigated. The release behavior of high-volatile arsenic during pyrolysis and gasification of CCA-treated wood was followed. When the CCA-treated wood was pyrolyzed, the release of arsenic proceeded with increasing temperature and the release extent was 41% at 800 °C. In the case of gasification, the release extent of arsenic increased with gasification time and 90% of the arsenic was released into gas phase within 60 min. Furthermore, it was possible to suppress the release of arsenic by 800 °C during pyrolysis by mixing organic sludge rich in iron and calcium with CCA-treated wood.

Cationic BN-embedded polycyclic aromatic hydrocarbons (BN-PAH+ s) were synthesized from a nitrogen-containing macrocycle via pyridine-directed tandem C-H borylation. Incorporating BN into PAH+ resulted in a remarkable hypsochromic shift due to an increase in the LUMO energy and the symmetry changes of the HOMO and LUMO. Electrophilic substitution or anion exchange of BN-PAH+ possessing tetrabromoborate as a counter anion (BN+ [BBr4- ]) afforded air-stable BN-PAH/PAH+ s. Of these, BN+ [TfO- ] allowed reversible two-electron reduction and the formation of two-dimensional brickwork-type π-electronic ion pair with 1,2,3,4,5-pentacyanocyclopentadienyl anion, demonstrating the potential application of BN-PAH+ as electronic materials.

The patient was an 85-year-old female who has been treated for hypertension and atrial fibrillation (Af). She has visited outpatient clinic and has received regularly general blood tests for every six months. Hemoglobin (Hb) level was stable as 11.2-12.3 g/dL and MCV 88fL from 2017, but it decreased suddenly to 5.2 g/dL and 64 fL in Sept 2020. She did not feel any symptoms or signs. Further evaluations revealed that occult blood in stool and upper and endoscopic exams were negative. About 40 days after starting sodium ferrous citrate, she developed edema anasarca, bilateral pleural effusion and heart failure. Laboratory test showed hypothyroidism, and then the administration of thyroid hormone and diuretics brought her early improvement. As to this impressive case report, general clinical progress and some discussion of the relationship among anemia, edema anasarca, heart failure and hypothyroidism would be described.

We report a deep generative model for regression tasks in materials informatics. The model is introduced as a component of a data imputer and predicts more than 20 diverse experimental properties of organic molecules. The imputer is designed to predict material properties by "imagining" the missing data in the database, enabling the use of incomplete material data. Even removing 60% of the data does not diminish the prediction accuracy in a model task. Moreover, the model excels at extrapolation prediction, where target values of the test data are out of the range of the training data. Such an extrapolation has been regarded as an essential technique for exploring novel materials but has hardly been studied to date due to its difficulty. We demonstrate that the prediction performance can be improved by >30% by using the imputer compared with traditional linear regression and boosting models. The benefit becomes especially pronounced with few records for an experimental property (

Conjugated linoleic acid (CLA) is an isomer of linoleic acid (LA). The predominant dietary CLA is cis-9, trans-11-CLA (c-9, t-11-CLA), which constitutes up to ~ 90% of total CLA and is thought to be responsible for the positive health benefits associated with CLA. However, the effects of c-9, t-11-CLA on Alzheimer’s disease (AD) remain to be elucidated. In this study, we investigated the effect of dietary intake of c-9, t-11-CLA on the pathogenesis of an AD mouse model. We found that c-9, t-11-CLA diet-fed AD model mice significantly exhibited (1) a decrease in amyloid-β protein (Aβ) levels in the hippocampus, (2) an increase in the number of microglia, and (3) an increase in the number of astrocytes expressing the anti-inflammatory cytokines, interleukin-10 and 19 (IL-10, IL-19), with no change in the total number of astrocytes. In addition, liquid chromatography–tandem mass spectrometry (LC–MS/MS) and gas chromatographic analysis revealed that the levels of lysophosphatidylcholine (LPC) containing c-9, t-11-CLA (CLA-LPC) and free c-9, t-11-CLA were significantly increased in the brain of c-9, t-11-CLA diet-fed mice. Thus, dietary c-9, t-11-CLA entered the brain and appeared to exhibit beneficial effects on AD, including a decrease in Aβ levels and suppression of inflammation.

The venom color variation of Crotalus durissus terrificus (Cdt) is attributed to the presence of the toxin L-amino acid oxidase (LAAO). During the venom milking routine of Instituto Butantan, we have noticed that most venoms of captive Cdt specimens show a yellowish color, while most venoms of wild specimens are white. Here we describe a comparative analysis of long-term captive (LTC) and recently wild-caught (RWC) Cdt, focusing on LAAO variation. For the identification of LAAO in individual venoms, four different approaches were employed: evaluation of the enzymatic activity, SDS-PAGE, Western blotting, and ELISA. In addition, mass spectrometry analysis was performed using pooled samples. Although some variation among these methodologies was observed, it was possible to notice that the presence of LAAO was significantly higher in the venom of LTC individuals. LAAO was identified in 60–80% LTC specimens and in only 10–12% of RWC specimens. Furthermore, this enzyme accounts for 5.6% of total venom proteins of LTC Cdt pooled venom, while it corresponds to only 0.7% of RWC Cdt pooled venom. These findings strongly suggest that captive maintenance increases the expression of LAAO in Cdt venom.

Zinc is an essential micronutrient in human body and a vital cofactor for the function of numerous proteins encoded by the human genome. Zinc has a critical role in maintaining many biochemical and physiological processes at the molecular, cellular, and multiple organ and systemic levels. The alteration of zinc homeostasis causes dysfunction of many organs and systems. In the immune system, zinc regulates the differentiation, proliferation and function of inflammatory cells, including T cells, eosinophils, and B cells, by modifying several signaling pathways such as NFκB signaling pathways and TCR signals. An adequate zinc level is essential for proper immune responses and decreased zinc levels were reported in many allergic inflammatory diseases, including atopic dermatitis, bronchial asthma, and chronic rhinosinusitis. Decreased zinc levels often enhance inflammatory activation. On the other hand, the inflammatory conditions alter the intracellular homeostasis of zinc, often decreasing zinc levels. These findings implied that there could be a vicious cycle between zinc deficiency and inflammatory conditions. In this review, we present recent evidence on the involvement of zinc in atopic dermatitis, bronchial asthma, and chronic rhinosinusitis, with insights into the involvement of zinc in the underlying molecular and cellular mechanisms related to these allergic inflammatory diseases.

Native cellulose is mainly found in phytomass, such as trees and other plants. It has a regular hierarchical nanoarchitecture, in which the extended macromolecular chains are aligned and closely packed in parallel to form the crystalline nanofibrils of cell walls. In the context of material utilization, nanocellulose is a collective term for nano-ordered assemblies of cellulose chains. In recent times, it has been produced in large quantities from woody bioresources. In addition, nanocellulose has some fascinating physicochemical properties, such as high strength, light weight, transparency, birefringence, and low thermal expansion. These properties have enabled broad functional design of nanocellulose-based materials; but most of them are facing serious competition from various products that already exist. However, nanocellulose is not just a green alternative to existing materials. Rather, it is expected to make a profound difference in terms of pioneering novel functions. The present review focuses on the unexpected features of nanocellulose materials, triggered by details of the inherent nanoarchitecture of native cellulose.

This account highlights the development of efficient borylation reactions of arenes toward organoboron-based materials. Upon the introduction of boron substituents, an intramolecular tandem bora-Fr...

The change in the positron annihilation lifetime (PAL) of vacancy clusters before and after electrolysis hydrogen charging was determined using PAL measurements in electron-irradiated F82H. The experimental change indicated 8 hydrogen atoms were trapped in vacancy clusters; whereas the theoretical calculation resulted in approximately 14 atoms. As the samples were left at room temperature for 5 min until the start of the PAL measurements, the de-trapping effect of hydrogen atoms was also considered; approximately 13 hydrogen atoms were captured at each vacancy cluster. The PAL decreased after annealing at 148 K, which could not be explained theoretically. Therefore, further experiments and discussions are needed to obtain a precise change in the PAL of vacancy clusters containing hydrogen atoms in F82H.

The significant progress made in the context of iron-catalyzed cross-coupling reactions in the past several years has boosted competition with well-known nickel and palladium catalyst systems. Iron...

This paper reports that the fully-discharged graphite-fluoride Li primary battery (GF/Li battery) can be regenerated as a hybrid capacitor with a higher energy density than the electric double layer capacitor (EDLC) using an activated carbon electrode. The graphite-fluoride (GF) positive electrode of the GF/Li battery is electrochemically defluorinated during the fully-discharged process to be converted to a nanocomposite consisting of carbon and LiF particles. The nanocomposite as the discharge product behaves as a capacitor-like electrode, so the fully-discharged GF/Li battery can be stably charged/discharged as a hybrid capacitor with the capacitor-type electrode (defluorinated GF electrode) and the battery-type negative electrode (Li metal). This hybrid capacitor, i.e., “graphite-fluoride Li capacitor (GF/Li capacitor)”, exhibited the maximum volumetric energy density of 52 Wh L−1 (at the power density of 71 W L−1), which is higher than that of the EDLC and comparable to that of the Li-ion capacitor. In this paper, the improvement of the cyclability by using the graphite/Li bilayer negative electrode and the charge-discharge mechanism are also discussed for the GF/Li capacitor.

Pungent traits caused by capsaicinoids are characteristic of chili peppers (Capsicum spp.), and the pungent-variable sweet chili pepper 'Shishito' (Capsicum annuum) is unique in being known for the pungency in fruits with few seeds. In the present study, we tried to clarify the relationship between the number of seeds and pungency in 'Shishito'. First, we investigated the pungency of 'Shishito' by simple sensory evaluations and quantifications of capsaicinoids by high-performance liquid chromatography. As a result, few-seeded fruits had a larger fluctuation of capsaicinoid content than many-seeded ones. This indicates that the number of seeds, in particular a decrease of the seeds, has some sort of connection with the pungency of 'Shishito'. Then, we analyzed the relationship between pungency and gene expression involving capsaicinoid biosynthesis at the individual fruit level. We vertically separated the placental septum in which capsaicinoids are synthesized and performed quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for 18 genes involved in capsaicinoid biosynthesis. We also used the placental septum for capsaicinoid quantification so that the gene expression levels and capsaicinoid contents in the same fruits were obtained, and their correlations were analyzed using 20 biological replicates. Among the 18 genes, expression levels of 11 genes (WRKY9, CaMYB31, AT3, BCAT, BCKDH, KAS I, KAS III, ACL, CaKR1, FAT, and pAMT) had a significant positive correlation with the capsaicinoid concentration, and they were considered to upregulate capsaicinoid biosynthesis. These results provide new insights regarding the environmental variation of the pungency traits in chili peppers and the relationship between pungency, the number of seeds, and gene expression involved in capsaicinoid biosynthesis.

Objective To evaluate temporal trends in neoadjuvant chemotherapy (NAC) utilisation and outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC). Patients and methods We included 289 patients from seven hospitals who underwent radical nephroureterectomy (RNU) for locally advanced UTUC (≥cT3 or cN+) between 2000 and 2020. These patients received RNU alone or two to four courses of NAC with either a cisplatin- or carboplatin-based regimen. We evaluated the temporal changes in NAC use and compared the visceral recurrence-free, cancer-specific, and overall survival rates. The effect of NAC on oncological outcomes was examined using multivariate Cox regression analysis with inverse probability of treatment weighting (IPTW) models. Results Of 289 patients, 144 underwent NAC followed by RNU (NAC group) and 145 underwent RNU alone (Control [Ctrl] group). NAC use increased significantly from 19% (2006-2010), 58% (2011-2015), to 79% (2016-2020). Pathological downstaging was significantly higher in the NAC group than in the Ctrl group. The IPTW-adjusted multivariable analyses showed that NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group. Moreover, carboplatin-based NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group among patients with chronic kidney disease Stage ≥3. There were no significant differences in oncological outcomes between the cisplatin- and carboplatin-based regimens. Conclusions The use of NAC for high-risk UTUC increased significantly after 2010. Platinum-based short-term NAC followed by immediate RNU may not impede and potentially improves oncological outcomes.

Selective destruction of senescent cells Senescent cells are associated with a variety of age-related medical conditions and thus have been proposed as potential targets for therapy, but we do not yet have a full understanding of the underlying mechanisms. Johmura et al. used RNA interference to screen for enzymes essential to the survival of senescent cells (see the Perspective by Pan and Locasale). The authors identified a key role for glutamine metabolism, particularly the enzyme glutaminase 1, and demonstrated that inhibition of this pathway induced the death of senescent cells. Glutaminase targeting also ameliorated aging-related organ dysfunction and obesity-related disorders in mouse models, suggesting the potential therapeutic value of this approach. Science , this issue p. 265 ; see also p. 234

Water electrolysis is an environment-friendly process of producing hydrogen with zero-carbon emission. Herein, we studied the water vapor electrolysis using a proton-conducting membrane composed of graphene oxide (GO) nanosheets intercalated with cations (Al3+ and Ce3+). We examined the effect of cation introduction on the physical and chemical structures, morphology, thermal and chemical stabilities, and the proton conductivity of stacked GO nanosheet membranes by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), X-ray photoemission spectroscopy (XPS), Raman spectroscopy, atomic force microscopy (AFM), dynamic light scattering (DLS), thermogravimetric-differential thermal analysis (TG-DTA), and electrochemical impedance spectroscopy (EIS). Concentration cell measurements revealed that the cation-modified membranes are pure proton conductors at room temperature. The proton conductivity of a GO membrane was much improved by cation modification. The cation-modified GO membranes, sandwiched with Pt/C electrodes as the cathode and anode, electrolyzed humidified air to produce hydrogen at room temperature, indicating the feasibility of this carbon-based electrochemical device.

An amendment to this paper has been published and can be accessed via the original article.

Electrocatalysts with metal–nitrogen–carbon (M–N–C) sites have recently attracted much attention as potential catalysts for the oxygen reduction reaction (ORR), and a hybrid of iron phthalocyanine (FePc) and reduced graphene oxide (rGO) is one of the promising candidates. Herein, a FePc/GO nanocomposite was synthesized by electrostatic deposition on the electrode. The electrochemically reduced FePc/GO nanocomposite (ER(FePc/GO)) contained Fe2+ centers in well reduced graphene sites without agglomeration. The ER(FePc/GO) exhibited high ORR activity with an ORR onset (Eonset) and half-wave potential (E1/2) of 0.97 and 0.86 V, respectively. Furthermore, the ORR activity successfully improved by adding an electrolyte such as KCl or KNO3. The small H2O2 yield of 2%, superior tolerance to methanol addition and high-durability indicate that the ER(FePc/GO) is a promising electrocatalyst. Theoretical studies, indicating that the presence of Cl− and NO3− ions lowered the conversion energy barrier, strongly supported the experimental results.

Carbazole-based DABNA analogues (CzDABNAs) were synthesized from triarylamine by regioselective one-shot single and double borylation. The reaction proceeded selectively at the ortho position of the carbazolyl group, where the highest occupied molecular orbital is mainly localized owing to the difference in the electron-donating abilities of the diarylamino and carbazolyl groups. The facile and scalable method enabled synthesis of CzDABNAs, exhibiting narrowband thermally activated delayed fluorescence with emission spectra ranging from deep blue to green. The organic light-emitting diode devices employing these products as emitters exhibited deep-blue, sky-blue, and green emission with high external quantum efficiencies of 19.5, 21.8, and 26.7 %, respectively.

Nitroxide radicals are considered as ideal redox species in all-organic redox flow batteries due to their redox potential of ∼2 V. These radicals are predominantly used in their polymerized form as...

Redox potentials of various redox-active molecules were examined in highly concentrated electrolytes. At the high concentration regions, the shifts were significantly larger than the conventional t...

Phosphatidylserine (PS)-normally present on the inner leaflet of the plasma membrane-translocates to the outer leaflet at an early stage of apoptosis. PS-containing liposomes (PSLs) can mimic the effect of apoptotic cells in inducing the secretion of prostaglandin E2 from phagocytes and inhibiting the maturation of dendritic cells and osteoclast precursors. The present study attempted to evaluate the effect of calcium phosphate (in the form of hydroxyapatite [HAP]) in the presence or absence of PSLs for repair of rat calvarial bone defects. The defects, each 5 mm in diameter, were created in the calvaria parietal bone of 8-week-old Wistar rats and subjected to one of the following treatments: no augmentation (Sham), HAP alone, or a mixture of HAP and PSL (HAP+PSL). Micro-computed tomography data showed that the HAP+PSL complexes promoted greater bone regeneration in comparison with either the Sham procedure or HAP alone at 4 and 8 weeks after implantation. The regeneration of calvarial bone defects induced by PSLs was mediated partly through upregulation of the osteogenic marker Alkaline Phosphatase, Type I collagen, osteocalcin, Runx2, and Osterix mRNAs. These data are the first to show that PSLs can influence bone regeneration by regulating osteoblast differentiation.