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Reversible multielectron-transfer materials are of considerable interest because of the potential impact to advance present electrochemical energy storage technology by boosting energy density. To date, a few oxide-based materials can reach an electron-transfer number per metal-cation (e M ) larger than 2 upon a (de)intercalation mechanism. However, these materials suffer from degradation due to irreversible rearrangements of the cation-oxygen bonds, and are based on precious metals, for example, Ir and Ru. Hence, a design of the non-oxide-based reversible multielectron-transfer materials with abundant elements can provide a promising alternative. Herein, it is demonstrated that the bis(diimino)copper framework can show e M  = 3.5 with cation/anion co-redox mechanism together with a dual-ion mechanism. In this study, the role of the cation-anion interactions is unveiled by using an experiment/theory collaboration applied to a series of the model non-oxide abundant electrode systems based on different metal-nitrogen bonds. These models provide designer multielectron-transfer due to the tunable π-d conjugated electronic structures. It is found that the Cu-nitrogen bonds show a unique reversible rearrangement upon Li-intercalation, and this process responds to acquire a significant reversible multielectron-transfer. This work provides new insights into the affordable multielectron-transfer electrodes and uncovers an alternative strategy to advance the electrochemical energy storage reactions., (© 2022 Wiley-VCH GmbH.)

Coordination nanosheets are an emerging class of 2D, bottom-up materials having fully π-conjugated, planar, graphite-like structures with high electrical conductivities. Since their discovery, great effort has been devoted to expand the variety of coordination nanosheets; however, in most cases, their low crystallinity in thick films hampers practical device applications. In this study, mixtures of nickel and copper ions are employed to fabricate benzenehexathiolato (BHT)-based coordination nanosheet films, and serendipitously, it is found that this heterometallicity preferentially forms a structural phase with improved film crystallinity. Spectroscopic and scattering measurements provide evidence for a bilayer structure with in-plane periodic arrangement of copper and nickel ions with the NiCu 2 BHT formula. Compared with homometallic films, heterometallic films exhibit more crystalline microstructures with larger and more oriented grains, achieving higher electrical conductivities reaching metallic behaviors. Low dependency of Seebeck coefficient on the mixing ratio of nickel and copper ions supports that the large variation in the conductivity data is not caused by change in the intrinsic properties of the films. The findings open new pathways to improve crystallinity and to tune functional properties of 2D coordination nanosheets., (© 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Two-dimensional coordination nanosheets (CONASHs) are grown at the spherical liquid-liquid interface of a dichloromethane droplet in water to form zero-dimensional nano- and micro-capsules using a simple dropping method, a syringe-pump method, and an emulsion method. Reaction of 1,3,5-tris[4-(4'-2,2':6',2″-terpyridyl)phenyl]benzene (1) with Fe(BF 4 ) 2 affords electrochromic Fe(tpy) 2 CONASH capsules and that of ligand 1 with ZnSO 4 does photoluminescent Zn 2 (μ-O 2 SO 2 ) 2 (tpy) 2 CONASH capsules. Fe(tpy) 2 CONASH capsules containing magnetite particles were produced by the syringe-pump method by adding magnetite to the aqueous phase, with the assembly and dispersion of the magnetite-containing CONASH capsules being easily controlled with a magnet. This indicates that physicochemically functional CONASH capsules are suitable for incorporating other functional materials to develop hybrid systems.

Bis(diimino)metal coordination frameworks (MDI, M = transition metal), which are a class of metal organic frameworks with two-dimensional anisotropy, high electric conductivity, and redox activity, are attractive platforms for tailoring electrochemical properties by introducing a heterometallic composition. In this study, we synthesized heterometallic Co x Ni 1- x DI coordination frameworks for electrochemical energy storage applications and investigated their electrochemical properties by experimental and theoretical techniques. Ni atoms were embedded into CoDI, and the crystal structure of Co x Ni 1- x DI was modified, especially along the interlayer axis, which activated the kinetically impeded redox reactions accompanied by PF 6 - insertion/extraction. Furthermore, upon charge/discharge with Li + transport, Co x Ni 1- x DI with a specific composition exhibited higher specific capacity (248 mAh g -1 ) than CoDI and NiDI in the potential window of 1.0-3.5 V versus Li + /Li. Density functional theory calculations indicate that the energy levels of the antibonding orbitals around the metals and interlayer spaces are important factors in tailoring the electrochemical properties of Co x Ni 1- x DI.

Two-dimensional (2D) vdW materials have been integrated into optoelectronic devices to achieve exceptional functionality. However, the integration of large-area 2D thin films into organic light-emitting devices (OLEDs) remains challenging because of the finite number of inorganic 2D materials and the high-temperature requirements of their deposition process. The construction of 2D organometallic materials holds immense potential because of their solution synthesis and unlimited structural and functional diversity. Here, we report a facile route using an oil-water interfacial coordination reaction between organic ligands and divalent metal ions to synthesize crystalline quasi-2D organometallic bis(dithiolato)nickel (NiDT) nanosheets with a centimeter scale and a tunable thickness. The NiDT nanosheets can be directly integrated into OLEDs for use as a hole buffer layer and a fluorescent mounting medium without the aid of a transfer process. Moreover, OLEDs with NiDT nanosheets show not only comparable efficiency to conventional OLEDs but also prolonged device lifetime by nearly 2 times. These results open up a new dimension to use quasi-2D organometallic nanosheets as functional layers in large-area organic devices.

The construction of two-dimensional metal complex materials is fascinating because of the structural and functional diversity of these materials. Previously, we have reported the synthesis of electroconductive nickelladithiolene (NiDT) and palladadithiolene (PdDT) nanosheets using benzenehexathiol (BHT). Down the group from Ni, Pd to Pt, there is a distinct positive shift in the reduction potential; as a result, it becomes synthetically more challenging to stabilize Pt 2+ than to form metallic Pt(0) in the presence of BHT as a reducing agent. Herein, a novel synthetic strategy for the preparation of platinadithiolene nanosheet (PtDT) using a dibutyltin-protected BHT ligand is reported, leading to transmetallation in the presence of dioxygen. Both free-standing stacked sheets and atomic layer sheets were obtained and characterized by microscopic techniques such as AFM, SEM, and TEM. To study the morphology of the sheets and determine their charge neutrality, X-ray photoelectron (XP) and infrared (IR) spectroscopic techniques were used. Powder X-ray diffraction analysis of the multilayer PtDT indicates a half-way slipped hexagonal configuration in the P 3[combining macron]1 m space group. The band structure of this PtDT exhibits a band gap at the Fermi level, which is different from that of NiDT in the staggered configuration, and a Dirac gap, indicating the possibility of 2D topological insulation at room temperature. PtDT is insulating but chemically activated by oxidation with I 2 to increase the conductivity by more than 10 6 folds up to 0.39 S cm -1 . The MDT sheets exhibit electrocatalytic activity for the hydrogen evolution reaction, and the activity order is NiDT < PdDT < PtDT.

Graphdiyne (GDY) comprises an important class in functional covalent organic nanosheets based on carbon-carbon bond formation, and recent focus has collected in the expansion of its variations. Here we report on the synthesis of a GDY analogue, TP-GDY, which has triphenylene as the aromatic core. Our liquid/liquid interfacial synthesis for GDY ( J. Am. Chem. Soc. 2017, 139, 3145) was modified for hexaethynyltriphenylene monomer to afford a TP-GDY film with a free-standing morphology, a smooth texture, a domain size of >1 mm, and a thickness of 220 nm. Resultant TP-GDY is characterized by series of microscopies, spectroscopies, and thermogravimetric and gas adsorption analyses.

Cardio-facio-cutaneous (CFC) syndrome, a genetic disorder caused by germline mutations in BRAF, KRAS, MAP2K1 and MAP2K2, is characterized by growth retardation, heart defects, dysmorphic facial appearance and dermatologic abnormalities. We have previously reported that knock-in mice expressing the CFC syndrome-associated mutation, Braf Q241R, showed growth retardation because of gastrointestinal dysfunction. However, other factors associated with growth retardation, including chondrogenesis and endocrinological profile, have not been examined. Here, we show that 3- and 4-week-old BrafQ241R/+ mice have decreased body weight and length, as well as reduced growth plate width in the proximal tibiae. Furthermore, proliferative and hypertrophic chondrocyte zones of the growth plate were reduced in BrafQ241R/+ mice compared with Braf+/+ mice. Immunohistological analysis revealed that extracellular signal-regulated kinase (ERK) activation was enhanced in hypertrophic chondrocytes in BrafQ241R/+ mice. In accordance with growth retardation and reduced growth plate width, decreased serum levels of insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) were observed in BrafQ241R/+ mice at 3 and 4 weeks of age. Treatment with C-type natriuretic peptide (CNP), a stimulator of endochondral bone growth and a potent inhibitor of the FGFR3-RAF1-MEK/ERK signaling, increased body and tail lengths in Braf+/+ and BrafQ241R/+ mice. In conclusion, ERK activation in chondrocytes and low serum IGF-1/IGFBP-3 levels could be associated with the growth retardation observed in BrafQ241R/+ mice. Our data also suggest that CNP is a potential therapeutic target in CFC syndrome.

A π-conjugated coordination nanosheet comprising bis(aminothiolato)nickel ( NiAT ) moieties was synthesized by the reaction of Ni(acac) 2 with 1,3,5-triaminobenzene-2,4,6-trithiol at liquid-liquid and gas-liquid interfaces. The sheet thickness could be controlled down to a single layer (0.6 nm). Selected area electron diffraction and grazing incidence X-ray diffraction analyses indicated the formation of a flat crystalline sheet with a kagome lattice stacked in a staggered alignment. NiAT was reversibly interconverted to a bis(iminothiolato)nickel ( NiIT ) nanosheet by the chemical 2H + -2e - reaction, which was accompanied by a drastic change in electrical conductivity from 3 × 10 -6 to 1 × 10 -1 S cm -1 . This change in conductivity was explained by the difference in band structures between NiAT and NiIT . NiAT acted as an efficient electrocatalyst for the hydrogen evolution reaction, showing strong acid durability and an onset overpotential of -0.15 V.

Photoluminescent coordination nanosheets (CONASHs) comprising three-way terpyridine (tpy) ligands and zinc(II) ions are created by allowing the two constitutive components to react with each other at a liquid/liquid interface. Taking advantage of bottom-up CONASHs, or flexibility in organic ligand design and coordination modes, we demonstrate the diversity of the tpy-zinc(II) CONASH in structures and photofunctions. A combination of 1,3,5-tris[4-(4'-2,2':6',2″-terpyridyl)phenyl]benzene (1) and Zn(BF 4 ) 2 affords a cationic CONASH featuring the bis(tpy)Zn complex motif (1-Zn), while substitution of the zinc source with ZnSO 4 realizes a charge-neutral CONASH with the [Zn 2 (μ-O 2 SO 2 ) 2 (tpy) 2 ] motif [1-Zn 2 (SO 4 ) 2 ]. The difference stems from the use of noncoordinating (BF 4 - ) or coordinating and bridging (SO 4 2- ) anions. The change in the coordination mode alters the luminescence (480 nm blue in 1-Zn; 552 nm yellow in 1-Zn 2 (SO 4 ) 2 ). The photophysical property also differs in that 1-Zn 2 (SO 4 ) 2 shows solvatoluminochromism, whereas 1-Zn does not. Photoluminescence is also modulated by the tpy ligand structure. 2-Zn contains triarylamine-centered terpyridine ligand 2 and features the bis(tpy)Zn motif; its emission is substantially red-shifted (590 nm orange) compared with that of 1-Zn. CONASHs 1-Zn and 2-Zn possess cationic nanosheet frameworks with counteranions (BF 4 - ), and thereby feature anion exchange capacities. Indeed, anionic xanthene dyes were taken up by these nanosheets, which undergo quasi-quantitative exciton migration from the host CONASH. This series of studies shows tpy-zinc(II) CONASHs as promising potential photofunctional nanomaterials.

Aromatic groups were incorporated into 9H-9-silafluorene units at the 9-position (mono-9H-silafluorenes) and 9,9'-positions (di-9H-9-silafluorenes). The aryl substituents showed weak conjugation to the 9H-9-silafluorene for 9-aryl substituted ones 1-7 and a 9,9'-phenylene substituted one (compound 8) and they exhibited similar absorption and emission spectra. The 9H-9-silafluorene 10 containing a 5,5'-(2,2'-bithiophenyl) group showed a significantly red-shifted absorption and fluorescence maxima in the solid-state. Single-crystal X-ray diffraction studies found J-type aggregated structures formed by intermolecular CH-π interactions (ca. 2.6-2.7 Å). Density functional theory (DFT), time-dependent DFT (TD-DFT), and configuration interaction single (CIS) calculations were conducted to explain the observed optical properties.

The origin and spread of novel agronomic traits during crop domestication are complex events in plant evolution. Wild rice (Oryza rufipogon) has red grains due to the accumulation of proanthocyanidins, whereas most cultivated rice (Oryza sativa) varieties have white grains induced by a defective allele in the Rc basic helix-loop-helix (bHLH) gene. Although the events surrounding the origin and spread of black rice traits remain unknown, varieties with black grains due to anthocyanin accumulation are distributed in various locations throughout Asia. Here, we show that the black grain trait originated from ectopic expression of the Kala4 bHLH gene due to rearrangement in the promoter region. Both the Rc and Kala4 genes activate upstream flavonol biosynthesis genes, such as chalcone synthase and dihydroflavonol-4-reductase, and downstream genes, such as leucoanthocyanidin reductase and leucoanthocyanidin dioxygenase, to produce the respective specific pigments. Genome analysis of 21 black rice varieties as well as red- and white-grained landraces demonstrated that black rice arose in tropical japonica and its subsequent spread to the indica subspecies can be attributed to the causal alleles of Kala4. The relatively small size of genomic fragments of tropical japonica origin in some indica varieties indicates that refined introgression must have occurred by natural crossbreeding in the course of evolution of the black trait in rice., (© 2015 American Society of Plant Biologists. All rights reserved.)

PDE4B was previously shown to be a dominant PDE4 subtype of neutrophils. However, its physiological role in the neutrophil function has not been evaluated. In this study, the inhibitory effects of a phosphodiesterase 4B (PDE4B)- selective inhibitor (compound A) and subtype non-selective PDE4 inhibitors (roflumilast and cilomilast) were evaluated in human peripheral blood cells. Compound A, roflumilast and cilomilast in a similar manner inhibited TNF-α production by LPS-stimulated human mononuclear cells. However, the inhibitory effect of compound A on IL-8 or LTB4-induced chemotactic response of neutrophils was modest even at the highest concentration (10 μmol L(-1)), whereas roflumilast and cilomilast inhibited IL-8 or LTB4-induced neutrophil chemotaxis. Our results suggest that PDE4B does not play an important role during the chemotactic response of human neutrophils.

Purpose: To find a subgroup that benefits most from transarterial chemoembolization (TACE) in terms of tumor number and size and liver profile in patients with intermediate-stage hepatocellular carcinoma (HCC)., Materials and Methods: Data of 325 intermediate-stage HCC patients who received TACE as the initial treatment were gathered. Four tumor numbers (3-6 tumors) and five maximum tumor diameters (3-7 cm) as well as all of their combinations but one (3 tumors and 3 cm) and Child-Pugh grade were used as variables to ascertain prognostic factors., Results: The respective 1-, 3-, and 5-year overall survival rates in all patients were 86.5, 47.0, and 23.7%, respectively. Tumor numbers of 4 (P = 0.00145) and 5 (P = 0.036), and tumor size of 7 cm (P = 0.015), and 12 other combinations of tumor number and size, and Child-Pugh grade (P = 0.0015) were identified as significant prognostic factors in univariate analysis, and 4 tumors of 7 cm (P = 0.0008) and Child-Pugh grade (P = 0.0036) remained significant in the stepwise Cox proportional hazard model. The overall survival was significantly better in a patient subgroup having two factors other than patient subgroups having one or no prognostic factors., Conclusion: A patient subgroup having two prognostic factors benefited most from TACE in intermediate-stage HCC patients.

Interfacial electron transfer at bis(tpy)–iron(II) complexes (tpy=2,2’:6’,2’’-terpyridine) on Si(111) electrodes was investigated by using four types of surfaceanchor terpyridine ligands. Despite the greater distance, electron transfer between the bis(tpy)–iron(II) unit and the electrode is accelerated in surface-anchor ligands with an additional phenylene group.

A bis(terpyridine)iron network polymer was fabricated by electropolymerisation on a glassy carbon electrode. The modified electrode allowed high-speed charging and discharging with a minor capacity decay (only 5% after 3000 cycles at 1 V s(-1)).

This article completes our comprehensive understanding of the electron transport properties of our original π-conjugated redox-active molecular wires comprising Fe bridged by p-phenylene linkers (tpy=2,2':6',2''-terpyridine). The Fe(tpy)2 oligomer wires comprise three types of tpy ligands: the anchor tpy ligand (A series) makes a junction between the wire and electrode, the bridging bis-tpy ligand (L series) connects the Fe(tpy)2 units, and the terminal tpy ligand (T series) possesses a redox site as a probe for the long-range electron transport ability. Taking advantage of the precise tunability of the composition of the Fe(tpy)2 oligomer wires, thus far we investigated how A and L impacted on the electron-transport ability. The excellent long-range electron transport ability with ultrasmall attenuation constants (β(d), 0.002 Å(-1) as the minimum) depends on L significantly [Chem. Asian J. 2009, 4, 1361], whereas A is unrelated to the β(d) value, but influences the zero-distance electron-transfer rate constant, k(et)(0) [J. Am. Chem. Soc. 2010, 132, 4524]. Herein we study the influence of terminal ligand T(x) (x=1-3). β(d) is independent of T, however, T(3), with a cyclometallated Ru complex as the redox site, gives rise to a k(et)(0) value greater than T(1) and T(2) with ferrocene. This series of simple but definitive conclusions indicates that we have reached the stage of being able to precisely design molecular wires to attain desirable single-molecule electron conduction., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

G protein-coupled receptor 84 (GPR84) is a putative receptor for medium-chain fatty acids (MCFAs), whose pathophysiological roles have not yet been clarified. Here, we show that GPR84 was activated by MCFAs with the hydroxyl group at the 2- or 3-position more effectively than nonhydroxylated MCFAs. We also identified a surrogate agonist, 6-n-octylaminouracil (6-OAU), for GPR84. These potential ligands and the surrogate agonist, 6-OAU, stimulated [(35)S]GTP binding and accumulated phosphoinositides in a GPR84-dependent manner. The surrogate agonist, 6-OAU, internalized GPR84-EGFP from the cell surface. Both the potential ligands and 6-OAU elicited chemotaxis of human polymorphonuclear leukocytes (PMNs) and macrophages and amplified LPS-stimulated production of the proinflammatory cytokine IL-8 from PMNs and TNFα from macrophages. Furthermore, the intravenous injection of 6-OAU raised the blood CXCL1 level in rats, and the inoculation of 6-OAU into the rat air pouch accumulated PMNs and macrophages in the site. Our results indicate a proinflammatory role of GPR84, suggesting that the receptor may be a novel target to treat chronic low grade inflammation associated-disease.

Objective: A phase II trial on neoadjuvant trans-uterine arterial chemotherapy (TUAC) followed by type III radical hysterectomy (RH) was conducted for patients with bulky cervical adenocarcinoma (AC)., Methods: Tumors of >4 cm were eligible. The neoadjuvant regimen comprised paclitaxel (60 mg/m(2) intravenously on days 1, 8, and 15) and cisplatin (70 mg/m(2) TUAC followed by transcatheter embolization with gelatin sponge particles on day 2) repeated every 3 weeks for 3 cycles. The primary endpoints were clinical and pathological responses., Results: Twenty-two patients (median age, 51 years; range, 33-75 years) were enrolled. The International Federation of Gynecology and Obstetrics stages were IB2 (9 patients), IIA-IIB (8), IIIB (3), and IVA (2). The adeno/adenosquamous ratio was 16/6. The overall clinical response rate was 95.4% (95% confidence interval [CI], 86.7-100%). RH was completed in 19 patients (86%), including 2 stage IVA patients who underwent anterior or posterior pelvic exenteration. Of the 19 patients, no residual malignant cells were found pathologically in 4; thus, the pathological complete response rate was 18% (4/22). No patients experienced grade 4 thrombocytopenia or febrile neutropenia or required platelet transfusions. The 5-year progression-free survival and overall survival rates in stages IB2-IIB were 70.0% (95%CI, 48.1-92.1%) and 69.5% (95%CI, 47.0-92.0%), respectively. The 2 patients with stage IVA tumors were alive without recurrence for 72 and 84 months after enrollment., Conclusions: TUAC showed high clinical and pathological response rates. TUAC is promising for stage IB2-IIB and IVA bulky AC., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Phosphodiesterase 4 (PDE4) inhibitors have been developed for the treatment of pulmonary inflammatory diseases, but their clinical use was dose-limited by mainly gastric adverse effects. Recent studies suggested PDE4B-selective inhibitors over PDE4D are supposed to display a wider therapeutic index than subtype non-selective PDE4 inhibitors such as roflumilast. Compound A was identified as an orally active PDE4B-selective inhibitor over PDE4D both in humans (80-fold selective) and mice (29-fold selective). In this study, the therapeutic effects of compound A and roflumilast were evaluated on lipopolysaccaride (LPS) injection-induced plasma TNF-α elevation and on LPS inhalation-induced pulmonary neutrophilia in mice. The inhibitory effect on gastric emptying in mice was evaluated as a gastric adverse effect. The therapeutic index for TNF-α production (TI(TNF) = ID50 in gastric emptying / ID50 in LPS injection-induced plasma TNF-α elevation) of compound A was larger than roflumilast (9.0 and 0.2, respectively), whereas the therapeutic index for pulmonary neutrophilia (TI(Neu) = ID50 in gastric emptying / ID50 in LPS inhalation-induced pulmonary neutrophilia) of compound A was comparable to roflumilast (1.0 and 0.5, respectively). In conclusion, the TI(Neu) of compound A was not superior compared to that of roflumilast in spite of its high selectivity for PDE4B over PDE4D in mice.

Formyl peptide receptor 1 (FPR1) and FPR2/ALX are known to control neutrophil chemotaxis in response to various ligands. In this study, we investigated the inhibitory mechanism of compound 43 (Cpd43), an FPR1 and FPR2/ALX dual agonist, on human neutrophil chemotaxis. Precedent stimulation of human peripheral blood neutrophils with Cpd43 rendered the cells unresponsive in calcium mobilization induced by interleukin-8, C5a, or leukotriene B₄. In addition, neutrophils pretreated with Cpd43 lost their chemotactic responses against these chemoattractants, wherein the expressions of chemoattractant receptors CXCR1, CXCR2, C5a receptor, and leukotriene B₄ receptor 1 on the surface of neutrophils were all diminished significantly by treatment with Cpd43. By evaluating its pharmacological effect on 341 molecules, including receptors and enzymes, we also confirmed that Cpd43 has a highly specific affinity to FPR1 and FPR2/ALX and does not show binding affinity to the other chemoattractant receptors. These results indicate a previously unrecognized inhibitory mechanism of Cpd43 on neutrophil chemotaxis: the induction of cross-desensitization of multiple chemoattractant receptors in human neutrophils through its FPR1 and FPR2/ALX dual agonism.

Background/aims: Intraductal papillary mucinous neoplasms have a better prognosis than ductal adenocarcinomas of the pancreas. The aim of this study was to evaluate the malignant potential of IPMNs by their preoperative images., Methodology: Forty-three intraductal papillary mucinous neoplasms were divided into 3 duct ectatic types using preoperative images (the main duct type, the branch duct type, and the mixed type), and into 2 groups using resected specimens (the malignant group including severe dysplasia based on the WHO classification and the benign group). The diameters of the tumor, main pancreatic duct and mural nodule were measured on the images., Results: Two thirds of main duct type cases were in the malignant group. For the branch duct and mixed types, the diameters of the tumor and detectable mural nodules were larger in the malignant group than in the benign group. A tumor diameter larger than 3.5cm and a mural nodule diameter larger than 6mm were risk factors for malignancy (p < 0.05)., Conclusions: The main duct type, a tumor larger than 3.5cm of the branch duct or mixed type, and a mural nodule larger than 6mm were all indicators of malignancy risk.

Natto, steamed soybeans fermented by Bacillus subtilis natto, is a traditional Japanese food. We derived a purified protein layer, called NKCP as a trade mark, from B. subtilis natto fermentation. In the present study, we examined the fibrinolytic and antithrombotic effects of NKCP and identified its active component to clarify the fibrinolytic effect of NKCP observed in preliminary clinical trials previously. The active component of NKCP was identified as a 34-kilodalton protein designated bacillopeptidase F. NKCP showed direct degradation of artificial blood clot in saline. The protease activity, accounting for the fibrinolytic effect of NKCP, was examined with a chromogenic substrate for plasmin. Dose-dependent prolongations of both prothrombin time and active partial thromboplastin time were observed in rats with intra-duodenum administration of NKCP. Our in vitro and in vivo studies suggest that NKCP has both a fibrinolytic effect and an antithrombotic effect similar to heparin. Because NKCP is derived from food and has safety data demonstrated by previous animal experiments and preliminary clinical trials, NKCP is considered as safe for clinical use.