In Situ Loading of Ni3ZnC0.7 Nanoparticles with Carbon Nanotubes to 3D Melamine Sponge Derived Hollow Carbon Skeleton toward Superior Microwave Absorption and Thermal Resistance.

The simple and low-cost construction of a 3D network structure is an ideal way to prepare high-performance electromagnetic wave (EMW) absorption materials. Herein, a series of carbon skeleton/carbon nanotubes/Ni3ZnC0.7 composites (CS/CNTs/Ni3ZnC0.7) are successfully prepared by in situ growth of Ni3ZnC0.7 and CNTs on 3D melamine sponge carbon. With the increase of precursor, Ni3ZnC0.7 nanoparticles nucleate and catalyze the generation of CNTs on the surface of the carbon skeleton. The minimum reflection loss (RL) value of the S60min composite (loading time of 60 min) reaches -86.6 dB at 1.6 mm and effective absorption bandwidth (EAB, RL≤-10 dB) is up to 9.3 GHz (8.7-18 GHz). The 3D network sponge carbon with layered micro/nanostructure and hollow skeleton promotes multiple reflection and absorption mechanisms of incident EMW. The N-doping and defects can be equivalent to an electric dipole, providing dipole polarization to increase dielectric relaxation. The uniform Ni3ZnC0.7 nanoparticles and CNTs play a key role in dissipating electromagnetic energy, blocking heat transfer, and enhancing the mechanical properties of the skeleton. Fortunately, the composite displays a quite low thermal conductivity of 0.09075 W m·K-1 and good flexibility, which can provide insulation and quickly recover to its original state after being stressed.

Is Phase Angle Useful in Screening for Sarcopenia in Patients with Hematologic Malignancies?

The purposes of this study were to investigate the relationship between sarcopenia and phase angle (PhA), and to examine whether PhA cutoff values can be used to identify sarcopenia in patients with hematologic malignancies. The study population comprised 108 patients with hematologic malignancies who were admitted for chemotherapy, and were undergoing rehabilitation for exercise therapy. The diagnostic criteria for sarcopenia were determined according to the Asian Working Group for Sarcopenia 2019. Muscle strength, endurance, and body composition (including PhA), were assessed. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to investigate associations between sarcopenia and PhA, and to determine cutoff values. Sarcopenia was found in 17.6% of the participants. PhA was significantly associated with sarcopenia (p < 0.01). The areas under the curve were 0.84 for the males and 0.87 for the females, and the cutoff values were 4.75° for the males (sensitivity 69%, specificity 83%) and 3.95° for the females (sensitivity 78%, specificity 85%). Our results suggest that PhA, which can be measured noninvasively, objectively, and rapidly, can be used as a screening tool for sarcopenia in patients with hematologic malignancies.

Effect of Combined Exercise and Nutrition Interventions During Inpatient Chemotherapy in Acute Leukemia and Malignant Lymphoma Patients: A Randomized Controlled Trial.

The aim of the present study was to determine the effectiveness of combined exercise and nutrition interventions on physical function and quality of life (QOL) in patients with acute leukemia or malignant lymphoma (ML) during inpatient chemotherapy. The study was a randomized controlled trial where patients with acute leukemia or ML who were receiving inpatient chemotherapy and exercise therapy were divided into an intervention group (IG) and a control group (CG). Both groups underwent resistance training and aerobic exercise. The patients in the IG were instructed to take nutritional supplements twice a day. Assessment items were muscle strength (handgrip strength and knee extension strength), 6-min walking test, skeletal muscle mass, QOL, nutritional status, and fatigue. Two-way analysis of variance showed a significant interaction for bilateral handgrip strength and knee extension strength. No significant interactions were found for the other items. The results of the present study showed improved muscle strength in the IG compared to the CG, indicating the effectiveness of combined exercise and nutrition interventions during inpatient chemotherapy in patients with acute leukemia or ML.

Exacerbation of autoimmune hemolytic anemia associated with pure red cell aplasia after COVID-19: A case report.

Autoimmune hemolytic anemia (AIHA) and pure red cell aplasia (PRCA) are rare complications of coronavirus disease 2019 (COVID-19). Herein, we report the case of a 28-year-old Japanese man who showed severe AIHA exacerbation associated with PRCA after COVID-19. AIHA was diagnosed and maintained for 5 years. Approximately 4 weeks after COVID-19, the patient developed severe anemia (hemoglobin level, 3.4 g/dL). Laboratory test results confirmed hemolytic exacerbation of IgG-mediated warm-type AIHA. Despite the hemolysis phase, the bone marrow revealed extreme hypoplasia of erythroblasts with a decreased reticulocyte count, similar to that observed in patients with PRCA. During oral prednisolone treatment, the patient recovered from anemia and showed increased reticulocyte count and reduced hypoplasia of marrow erythroblasts. Exacerbation of AIHA and PRCA was triggered by COVID-19 because other causes were ruled out. Although this case report highlights that COVID-19 could lead to hematological complications such as AIHA and PRCA, the exact mechanisms remain unclear.

Biomass-Derived Carbon Materials for the Electrode of Metal-Air Batteries.

Facing the challenges of energy crisis and global warming, the development of renewable energy has received more and more attention. To offset the discontinuity of renewable energy, such as wind and solar energy, it is urgent to search for an excellent performance energy storage system to match them. Metal-air batteries (typical representative: Li-air battery and Zn-air battery) have broad prospects in the field of energy storage due to their high specific capacity and environmental friendliness. The drawbacks preventing the massive application of metal-air batteries are the poor reaction kinetics and high overpotential during the charging-discharging process, which can be alleviated by the application of an electrochemical catalyst and porous cathode. Biomass, also, as a renewable resource, plays a critical role in the preparation of carbon-based catalysts and porous cathode with excellent performance for metal-air batteries due to the inherent rich heteroatom and pore structure of biomass. In this paper, we have reviewed the latest progress in the creative preparation of porous cathode for the Li-air battery and Zn-air battery from biomass and summarized the effects of various biomass sources precursors on the composition, morphology and structure-activity relationship of cathode. This review will help us understand the relevant applications of biomass carbon in the field of metal-air batteries.

Traditional Chinese medicine Jia Wei Gui Pi Tang improves behavioural and psychological symptoms of dementia and favourable positive emotions in patients.

BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) are challenging to manage, leading to caregiver burden and often to subsequent transfer of patients to a nursing home or psychiatric hospital for treatment. Eliciting favourable positive emotions should be an important goal in the treatment of negative emotions associated with BPSD. To date, no data have indicated that antipsychotic medications can improve positive emotions. BPSD are known to be associated with anxiety in patients with dementia. The traditional Chinese medicine Jia Wei Gui Pi Tang is officially indicated and approved for anxiety treatment in Japan. METHODS: Here, we performed a multicentre, randomised, observer-blind control study of the effect of Jia Wei Gui Pi Tang on BPSD in Alzheimer's disease (AD) patients. Patients with AD or AD with cerebral vascular disease were randomly divided into the Jia Wei Gui Pi Tang treatment group and the control group that received no traditional Chinese medicine. BPSD were scored using the Neuropsychiatric Inventory Nursing Home Version (NPI-NH) and by favourable positive emotions using the Delightful Emotional Index (DEI). RESULTS: A total of 63 participants (18 male and 45 female; mean age: 83.3 ± 6.0 years) were included in the study. Changes in NPI-NH scores differed significantly between the two groups (one-way analysis of variance, P < 0.001). Within the treatment group, there was a significant improvement in the NPI-NH score from 29.8 ± 17.3 at baseline to 13.2 ± 9.4 at the endpoint (paired t-test, P < 0.001), whereas there was no statistically significant change in the control group. Changes in DEI scores differed significantly between the two groups. Within the treatment group, there was a significant improvement in the DEI score from 24.3 ± 23.0 at baseline to 32.5 ± 21.2 at the endpoint (paired t-test, P = 0.001), whereas there was no statistically significant change in the control group. CONCLUSION: The traditional Chinese medicine Jia Wei Gui Pi Tang significantly improved both BPSD and positive emotions.

Physical therapy for multiple myeloma patients with severely hindered daily living activities due to bone lesions: a report of two cases.

[Purpose] Physical therapy for patients with multiple myeloma requires appropriate exercise intensity and risk management due to osteolytic lesions. However, the optimal strategy for setting exercise intensity remains unclear. We report cases in which physical therapy was performed using the Borg scale and the Common Terminology Criteria for Adverse Events v4.0 as indicators of improvement in the performance of activities of daily living without causing adverse events. [Participants and Methods] Two patients with multiple myeloma, whose performance status was 4, underwent resistance training of the upper and lower limbs and activities of daily living practice in stages according to their functional status. Each exercise was performed for 20 to 40 minutes twice a day for 6 days a week. The exercise intensity was set to 13 on the Borg scale as a guide, and the allowable bone pain was up to Grade 1 according to Common Terminology Criteria for Adverse Events v4.0. [Results] No adverse events occurred in either patient, and the performance status improved to 1 or 2. Subsequently, autologous peripheral hematopoietic stem cell transplantation was performed. [Conclusion] Physical therapy with exercise intensity set to 13 on the Borg scale and Grade 1 per Common Terminology Criteria for Adverse Events v4.0 may safely improve the performance of activities of daily living of patients with multiple myeloma.

Continuous lenalidomide treatment after bortezomib-melphalan-prednisolone therapy for newly diagnosed multiple myeloma.

These are the results of phase II study of bortezomib-melphalan-prednisolone (VMP) induction therapy followed by lenalidomide-dexamethasone (Rd) consolidation and lenalidomide maintenance in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), overall response rates (ORRs), and safety. Eighty-three eligible patients were enrolled between October 2012 and August 2014. The median PFS was 28.0 months (95% CI 19.6-36.7) and the median OS was 55.3 months (95% CI 51.6-NA). Among the patients who received lenalidomide maintenance therapy, median PFS was significantly improved in patients who had achieved a very good partial response (VGPR) or better (41.8 vs 20.7 months, p = 0.0070). As the best response, the rates of partial response or better were 85.5% comprising stringent complete response (sCR, 21.7%), complete response (CR, 10.8%), VGPR (18.1%), and partial response (PR, 34.9%). The most frequently observed grade 3 or higher adverse events during the VMP therapy were anemia (28.9%), neutropenia (15.6%), thrombocytopenia (6.0%), and peripheral neuropathy (2.4%). The most frequently observed grade 3 or higher adverse events during the Rd therapy were anemia (3.5%), neutropenia (1.8%), and skin rush (5.3%). The most frequently observed grade 3 or higher adverse events during lenalidomide maintenance therapy were anemia (7.4%) and neutropenia (24.1%). Thus, VMP induction therapy followed by Rd consolidation and lenalidomide maintenance is considered a well-tolerated and effective regimen in transplant-ineligible NDMM. This trial is registered with UMIN-CTR with the identification number UMIN000009042.

van der Waals force layered multiferroic hybrid perovskite (CH3NH3)2CuCl4 single crystals.

In inorganic-organic perovskites, the three-dimensional arrangement of the organic group results in more subtle balance of charge, spin and space, thereby providing an attractive route toward new multiferroics. Here we report the existing of multiple ferroic orderings in inorganic-organic layered perovskites with relative strong hydrogen bond ordering of the organic chains intra plane. In addition, the inter plane in perovskite is stacking via van der Waals force. However, such magnetoelectric coupling properties for this compound have not been reported since it is difficult to characterize the properties in single crystals since most of the hybrid perovskites are usually deliquescent and unstable when exposed to air. To deal with these problems, we synthesized a (CH3NH3)2CuCl4 single crystal by using a simple evaporation technique, and demonstrated ferroelectric, magnetic and magneto-electric properties of (CH3NH3)2CuCl4. The internal hydrogen bonding of easily tunable organic unit combined with 3d transition-metal layers in such hybrid perovskites make (CH3NH3)2CuCl4 a multiferroic crystal with magnetoelectrical coupling and offer an new way to engineer multifunctional multiferroic.

Mechanisms of Impaired Neutrophil Migration by MicroRNAs in Myelodysplastic Syndromes.

In myelodysplastic syndromes (MDS), functional defects of neutrophils result in high mortality because of infections; however, the molecular basis remains unclear. We recently found that miR-34a and miR-155 were significantly increased in MDS neutrophils. To clarify the effects of the aberrant microRNA expression on neutrophil functions, we introduced miR-34a, miR-155, or control microRNA into neutrophil-like differentiated HL60 cells. Ectopically introduced miR-34a and miR-155 significantly attenuated migration toward chemoattractants fMLF and IL-8, but enhanced degranulation. To clarify the mechanisms for inhibition of migration, we studied the effects of miR-34a and miR-155 on the migration-regulating Rho family members, Cdc42 and Rac1. The introduced miR-34a and miR-155 decreased the fMLF-induced active form of Cdc42 to 29.0 ± 15.9 and 39.7 ± 4.8% of that in the control cells, respectively, although Cdc42 protein levels were not altered. miR-34a decreased a Cdc42-specific guanine nucleotide exchange factor (GEF), dedicator of cytokinesis (DOCK) 8, whereas miR-155 reduced another Cdc42-specific GEF, FYVE, RhoGEF, and PH domain-containing (FGD) 4. The knockdown of DOCK8 and FGD4 by small interfering RNA suppressed Cdc42 activation and fMLF/IL-8-induced migration. miR-155, but not miR-34a, decreased Rac1 protein, and introduction of Rac1 small interfering RNA attenuated Rac1 activation and migration. Neutrophils from patients showed significant attenuation in migration compared with healthy cells, and protein levels of DOCK8, FGD4, and Rac1 were well correlated with migration toward fMLF (r = 0.642, 0.686, and 0.436, respectively) and IL-8 (r = 0.778, 0.659, and 0.606, respectively). Our results indicated that reduction of DOCK8, FGD4, and Rac1 contributes to impaired neutrophil migration in MDS.

Alternative pathway of H2S and polysulfides production from sulfurated catalytic-cysteine of reaction intermediates of 3-mercaptopyruvate sulfurtransferase.

It has been known that hydrogen sulfide and/or polysulfides are produced from a (poly)sulfurated sulfur-acceptor substrate of 3-mercaptopyruvate sulfurtransferase (MST) via thioredoxin (Trx) reduction in vitro. In this study, we used thiosulfate as the donor substrate and the catalytic reaction was terminated on the formation of a persulfide or polysulfides. We can present alternative pathway of production of hydrogen sulfide and/or polysulfides from (poly)sulfurated catalytic-site cysteine of reaction intermediates of MST via Trx reduction. Matrix-assisted laser desorption ionization tandem time-of-flight mass spectrometric analysis revealed that after prolonged incubation of MST with thiosulfate, a trisulfide adduct becomes predominant at the sulfurated catalytic-site cysteine. When these adducts were reduced by Trx with reducing system (MST:Escherichia coli Trx:E. coli Trx reductase:NADPH = 1:5:0.02:12.5 molar ratio), liquid chromatography with tandem mass spectrometric analysis for monobromobimane-derivatized H2Sn revealed that H2S2 first appeared, and then H2S and H2S3 did later. The results were confirmed by high-performance liquid chromatography-fluorescence analysis.

Treatment-free remission after two-year consolidation therapy with nilotinib in patients with chronic myeloid leukemia: STAT2 trial in Japan.

The purpose of this trial was to evaluate the efficacy of 2-year consolidation therapy with nilotinib, at a dose of 300 mg twice daily, for achieving treatment-free remission in chronic myeloid leukemia patients with a deep molecular response (BCR-ABL1IS ≤0.0032%). Successful treatment-free remission was defined as no confirmed loss of deep molecular response. We recruited 96 Japanese patients, of whom 78 sustained a deep molecular response during the consolidation phase and were therefore eligible to discontinue nilotinib in the treatment-free remission phase; of these, 53 patients (67.9%; 95% confidence interval: 56.4-78.1%) remained free from molecular recurrence in the first 12 months. The estimated 3-year treatment-free survival was 62.8%. Nilotinib was readministered to all patients (n=29) who experienced a molecular recurrence during the treatment-free remission phase. After restarting treatment, rapid deep molecular response returned in 25 patients (86.2%), with 50% of patients achieving a deep molecular response within 3.5 months. Tyrosine kinase inhibitor withdrawal syndrome was reported in 11/78 patients during the early treatment-free remission phase. The treatment-free survival curve was significantly better in patients with undetectable molecular residual disease than in patients without (3-year treatment-free survival, 75.6 versus 48.6%, respectively; P=0.0126 by the log-rank test). There were no significant differences in treatment-free survival between subgroups based on tyrosine kinase inhibitor treatment before the nilotinib consolidation phase, tyrosine kinase inhibitor-withdrawal syndrome, or absolute number of natural killer cells. The results of this study indicate that it is safe and feasible to stop tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia who have achieved a sustained deep molecular response with 2 years of treatment with nilotinib. This study was registered with UMIN-CTR (UMIN000005904).

Integrating radiation protection criteria for radioactive waste management into remediation procedures in existing exposure situations after a nuclear accident.

Experience after the accident at the Fukushima Daiichi nuclear power station has shown that there is a need to establish radiation protection criteria for radioactive waste management consistent with the criteria adopted for the remediation of existing exposure situations. A stepwise approach to setting such criteria is proposed. Initially, a reference level for the annual effective dose from waste management activities in the range 1-10 mSv should be set, with the reference level being less than the reference level for the ambient dose. Subsequently, the reference level for the annual effective dose from waste management activities should be reduced in one or more steps to achieve a final target value of 1 mSv. The dose criteria at each stage should be determined with relevant stakeholder involvement. Illustrative case studies show how this stepwise approach might be applied in practice.

Silencing of eIF3e promotes blood perfusion recovery after limb ischemia through stabilization of hypoxia-inducible factor 2α activity.

OBJECTIVE: We previously observed that silencing of eukaryotic translation initiation factor 3 subunit e (eIF3e), a hypoxia-independent downregulator of hypoxia-inducible factor 2α (HIF-2α), led to neoangiogenesis by promoting HIF-2α activity under normoxic conditions. In the current study, we investigated whether temporary silencing of eIF3e in muscles affects blood flow recovery in a mouse ischemic limb model. METHODS: eIF3e silencing was performed using small interfering RNA (siRNA), and changes in gene transcription and protein expression were analyzed in vitro using murine primary skeletal muscle myoblast and human primary skeletal muscle myoblast cell cultures. In unilateral femoral artery ligation experiments, eIF3e siRNA-expressing plasmids were injected into the muscles of BALB/c mice near the ligation sites, and tissue damage and loss of limb function were scored for 28 days while serial measurements of limb perfusions were performed with laser Doppler perfusion imaging. RESULTS: Silencing of eIF3e in murine primary skeletal muscle myoblasts led to stabilization of HIF-2α and upregulation of angiogenic transcripts, including basic fibroblast growth factor and platelet-derived growth factor B (P < .05), and the supernatant of eIF3e-silenced human primary skeletal muscle myoblasts triggered the tube formation of human umbilical vein endothelial cells. The in vivo mouse model of hindlimb ischemia revealed that single intramuscular injections of eIF3e siRNA-expressing plasmids significantly enhanced perfusion of ischemia-damaged limbs (P < .05) at days 7 and 14 and functional recovery at days 7, 14, and 21 (P < .05). CONCLUSIONS: eIF3e is an angiogenesis suppressor and may be a therapeutic target for promoting angiogenesis after ischemic injuries.

Hydrogen polysulfide (H2S n ) signaling along with hydrogen sulfide (H2S) and nitric oxide (NO).

Hydrogen sulfide (H2S) is a physiological mediator with various roles, including neuro-modulation, vascular tone regulation, and cytoprotection against ischemia-reperfusion injury, angiogenesis, and oxygen sensing. Hydrogen polysulfide (H2S n ), which possesses a higher number of sulfur atoms than H2S, recently emerged as a potential signaling molecule that regulates the activity of ion channels, a tumor suppressor, transcription factors, and protein kinases. Some of the previously reported effects of H2S are now attributed to the more potent H2S n . H2S n is produced by 3-mercaptopyruvate sulfurtransferase (3MST) from 3-mercaptopyruvate (3MP) and is generated by the chemical interaction of H2S with nitric oxide (NO). H2S n sulfhydrates (sulfurates) cysteine residues of target proteins and modifies their activity, whereas H2S sulfurates oxidized cysteine residues as well as reduces cysteine disulfide bonds. This review focuses on the recent progress made in studies concerning the production and physiological roles of H2S n and H2S.

Polysulfide evokes acute pain through the activation of nociceptive TRPA1 in mouse sensory neurons.

BACKGROUND: Hydrogen sulfide (H2S) is oxidized to polysulfide. Recent reports show that this sulfur compound modulates various biological functions. We have reported that H2S is involved in inflammatory pain in mice. On the other hand, little is known about the functional role of polysulfide in sensory neurons. Here we show that polysulfide selectively stimulates nociceptive TRPA1 and evokes acute pain, using TRPA1-gene deficient mice (TRPA1(-/-)), a heterologous expression system and a TRPA1-expressing cell line. RESULTS: In wild-type mouse sensory neurons, polysulfide elevated the intracellular Ca concentration ([Ca(2+)]i) in a dose-dependent manner. The half maximal effective concentration (EC50) of polysulfide was less than one-tenth that of H2S. The [Ca(2+)]i responses to polysulfide were observed in neurons responsive to TRPA1 agonist and were inhibited by blockers of TRPA1 but not of TRPV1. Polysulfide failed to evoke [Ca(2+)]i increases in neurons from TRPA1(-/-) mice. In RIN-14B cells, constitutively expressing rat TRPA1, polysulfide evoked [Ca(2+)]i increases with the same EC50 value as in sensory neurons. Heterologously expressed mouse TRPA1 was activated by polysulfide and that was suppressed by dithiothreitol. Analyses of the TRPA1 mutant channel revealed that cysteine residues located in the internal domain were related to the sensitivity to polysulfide. Intraplantar injection of polysulfide into the mouse hind paw induced acute pain and edema which were significantly less than in TRPA1(-/-) mice. CONCLUSIONS: The present data suggest that polysulfide functions as pronociceptive substance through the activation of TRPA1 in sensory neurons. Since the potency of polysulfide is higher than parental H2S and this sulfur compound is generated under pathophysiological conditions, it is suggested that polysulfide acts as endogenous ligand for TRPA1. Therefore, TRPA1 may be a promising therapeutic target for endogenous sulfur compound-related algesic action.

Dysregulation of the MIRLET7/HMGA2 axis with methylation of the CDKN2A promoter in myeloproliferative neoplasms.

Overexpression of high mobility group AT-hook 2 (Hmga2), which is negatively regulated by MIRLET7 micro RNAs through 3'-untranslated region (3'UTR), causes proliferative haematopoiesis mimicking myeloproliferative neoplasms (MPNs) and contributes to progression of myelofibrosis in mice. Thus, we investigated HMGA2 mRNA expression in 66 patients with MPNs including 23 polycythaemia vera (PV), 33 essential thrombocythaemia (ET) and 10 primary myelofibrosis (PMF). HMGA2 mRNA expression, especially variant 1 with 3'UTR that contains MIRLET7-specific sites, rather than variant 2 lacking 3'UTR, is frequently deregulated due to decreased MIRLET7 expression in granulocytes from over 20% of PV and ET, and in either granulocytes or CD34(+) cells from 100% of PMF. Patients with deregulated HMGA2 mRNA expression were significantly more likely to show splenomegaly, high serum lactate dehydrogenase values, and methylation of the CDKN2A promoter compared with other patients without deregulation of HMGA2. A histone deacetylase inhibitor, panobinostat, significantly increased MIRLET7 expression and reduced variant 1 of HMGA2 mRNA expression, but not variant 2, in both U937 cells and PMF-derived CD34(+) cells. Moreover, both panobinostat and small interfering RNA of HMGA2 demethylated the CDKN2A promoter in U937 cells. In conclusion, the frequently dysregulated MIRLET7/HMGA2 axis could be a therapeutic target in MPNs.

Polysulfide promotes neuroblastoma cell differentiation by accelerating calcium influx.

Polysulfides are a typical type of bound sulfur, which is physiologically stable form of sulfur species, derived from the hydrogen sulfide (H2S) that is generated endogenously in cells. We previously reported that bound sulfur protects neuronal cells from oxidative injury. In the present study, we demonstrated that polysulfides inhibited cell growth and promoted neurite outgrowth in mouse neuroblastoma Neuro2A (N2A) cells. However, Na2S showed no effect on neurite outgrowth in N2A cells. Furthermore, 2-APB and SKF96365, which are typical transient receptor potential (TRP) channel inhibitors, suppressed the neurite outgrowth induced by Na2S4. These new findings suggest that bound sulfur could induce neurite outgrowth and cell differentiation of N2A cells by accelerating calcium influx.

H2S2014 in Kyoto: the 3rd International Conference on H2S in Biology and Medicine.

About 20 years ago, a pungent gas was found to be the physiological mediator of cognitive function and vascular tone. Since then, studies on hydrogen sulfide (H2S) have uncovered its numerous physiological roles such as protecting various tissues/organs from ischemia and regulating inflammation, cell growth, oxygen sensing, and senescence. These effects of H2S were extensively studied, and some of the corresponding mechanisms were also studied in detail. Previous studies on the synergistic interaction between H2S and nitric oxide (NO) have led to the discovery of several potential signaling molecules. Polysulfides are considerably potent and are one of the most active forms of H2S. H2S has a significant therapeutic potential, which is evident from the large number of novel H2S-donating compounds and substances developed for manipulating endogenous levels of H2S. The Third International Conference on H2S was held in Kyoto in June 2014. One hundred and sixty participants from 21 countries convened in Kyoto to report new advances, discuss conflicting findings, and make plans for future research. This article summarizes each oral presentation presented at the conference.

Physiological Roles of Hydrogen Sulfide and Polysulfides.

Hydrogen sulfide (H2S) has been recognized as a signaling molecule as well as a cytoprotective molecule. H2S modulates neurotransmission, regulates vascular tone, protects various tissues and organs, regulates inflammation, induces angiogenesis, and detects cellular oxygen levels. H2S is produced from L-cysteine by cystathionine ß-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) together with cysteine aminotransferase (CAT). Recently, a novel pathway for the production of H2S from D-cysteine was identified, involving D-amino acid oxidase (DAO) together with 3MST. Sulfuration (also called sulfhydration), which adds sulfur atoms to the cysteine residues of target proteins to modify protein activity, has been extensively studied as a mode of H2S action. Recently, hydrogen polysulfides (H2Sn, where n=3-7; n=2 is termed as persulfide) have been found to sulfurate target proteins in the brain, including transient receptor potential ankyrin 1 (TRPA1) channels, Kelch-like ECH-associating protein 1 (Keap1), and phosphatase and tensin homolog (PTEN), much more potently than H2S. The physiological stimuli that trigger the production of H2S and polysulfides, and the mechanisms maintaining their local levels, remain unknown. Understanding the regulation of H2Sn (including H2S) production, and the specific stimuli that induce their release, will provide new insight into the biology of H2S and will provide novel avenues for therapeutic development in diseases involving H2S-related substances.