The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation.

Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/ß-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/ß-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.

Exploring Differences in Surgical Outcomes Depending on the Arterial Cannulation Strategy for Acute Type A Aortic Dissection: A Single-Center Study.

Background: Type A aortic dissection (AD) and intramural hematoma (IMH) are critical medical conditions. Emergency surgery is typically performed under cardiopulmonary bypass immediately after diagnosis, which involves lowering the body temperature to induce total circulatory arrest. Selection of the arterial cannulation site is a critical consideration in cardiac surgery and becomes more challenging in patients with AD. This study explored the strengths and weaknesses of different cannulation methods by comparing each cannulation strategy and analyzing the reasons for patients' outcomes, especially mortality and cerebrovascular accidents (CVAs). Methods: This retrospective study reviewed the medical records of patients who underwent surgery for type A AD or IMH between 2008 and 2023, using the moderate hypothermic circulatory arrest approach at a single center. Results: Among the 146 patients reviewed, 32 underwent antegrade cannulation via axillary, innominate artery, aortic, or transapical cannulation, while 114 underwent retrograde cannulation via the femoral artery. The analysis of surgical outcomes revealed a significant difference in the total surgical time, with 356 minutes for antegrade and 443 minutes for retrograde cannulation (p<0.001). The mean length of stay in the intensive care unit was significantly longer in the retrograde group (5±16 days) than in the antegrade group (3±5 days, p=0.013). Nevertheless, no significant difference was found between the groups in the 30-day mortality or postoperative CVA rates (p=0.2 and p=0.7, respectively). Conclusion: Surgeons should consider an appropriate cannulation strategy for each patient instead of adhering strictly to a specific approach in AD surgery.

Boltzmann Switching MoS2 Metal-Semiconductor Field-Effect Transistors Enabled by Monolithic-Oxide-Gapped Metal Gates at the Schottky-Mott Limit.

A gate stack that facilitates a high-quality interface and tight electrostatic control is crucial for realizing high-performance and low-power field-effect transistors (FETs). However, when constructing conventional metal-oxide-semiconductor structures with two-dimensional (2D) transition metal dichalcogenide channels, achieving these requirements becomes challenging due to inherent difficulties in obtaining high-quality gate dielectrics through native oxidation or film deposition. Here, a gate-dielectric-less device architecture of van der Waals Schottky gated metal-semiconductor FETs (vdW-SG MESFETs) using a molybdenum disulfide (MoS2) channel and surface-oxidized metal gates such as nickel and copper is reported. Benefiting from the strong SG coupling, these MESFETs operate at remarkably low gate voltages, <0.5 V. Notably, they also exhibit Boltzmann-limited switching behavior featured by a subthreshold swing of ≈60 mV dec-1 and negligible hysteresis. These ideal FET characteristics are attributed to the formation of a Fermi-level (EF) pinning-free gate stack at the Schottky-Mott limit. Furthermore, authors experimentally and theoretically confirm that EF depinning can be achieved by suppressing both metal-induced and disorder-induced gap states at the interface between the monolithic-oxide-gapped metal gate and the MoS2 channel. This work paves a new route for designing high-performance and energy-efficient 2D electronics.

Angiotensin-converting enzyme inhibition prevents l-dopa-induced dyskinesia in a 6-ohda-induced mouse model of Parkinson's disease.

Parkinson's disease (PD) is characterised by severe movement defects and the degeneration of dopaminergic neurones in the midbrain. The symptoms of PD can be managed with dopamine replacement therapy using L-3, 4-dihydroxyphenylalanine (L-dopa), which is the gold standard therapy for PD. However, long-term treatment with L-dopa can lead to motor complications. The central renin-angiotensin system (RAS) is associated with the development of neurodegenerative diseases in the brain. However, the role of the RAS in dopamine replacement therapy for PD remains unclear. Here, we tested the co-treatment of the angiotensin-converting enzyme inhibitor (ACEI) with L-dopa altered L-dopa-induced dyskinesia (LID) in a 6-hydroxydopamine (6-OHDA)-lesioned mouse model of PD. Perindopril, captopril, and enalapril were used as ACEIs. The co-treatment of ACEI with L-dopa significantly decreased LID development in 6-OHDA-lesioned mice. In addition, the astrocyte and microglial transcripts involving Ccl2, C3, Cd44, and Iigp1 were reduced by co-treatment with ACEI and L-dopa in the 6-OHDA-lesioned striatum. In conclusion, co-treatment with ACEIs and L-dopa, such as perindopril, captopril, and enalapril, may mitigate the severity of L-DOPA-induced dyskinesia in a mouse model of PD.

Nitrogen-Rich Molybdenum Nitride Synthesized in a Crucible under Air.

The triple bond in N2 is significantly stronger than the double bond in O2, meaning that synthesizing nitrogen-rich nitrides typically requires activated nitrogen precursors, such as ammonia, plasma-cracked atomic nitrogen, or high-pressure N2. Here, we report a synthesis of nitrogen-rich nitrides under ambient pressure and atmosphere. Using Na2MoO4 and dicyandiamide precursors, we synthesized nitrogen-rich γ-Mo2N3 in an alumina crucible under an ambient atmosphere, heated in a box furnace between 500 and 600 °C. Byproducts of this metathesis reaction include volatile gases and solid Na(OCN), which can be washed away with water. X-ray diffraction and neutron diffraction showed Mo2N3 with a rock salt structure having cation vacancies, with no oxygen incorporation, in contrast to the more common nitrogen-poor rock salt Mo2N with anion vacancies. Moreover, an increase in temperature to 700 °C resulted in molybdenum oxynitride, Mo0.84N0.72O0.27. This work illustrates the potential for dicyandiamide as an ambient-temperature metathesis precursor for an increased effective nitrogen chemical potential under ambient conditions. The classical experimental setting often used for solid-state oxide synthesis, therefore, has the potential to expand the nitride chemistry.

Differences in Treatment Outcomes According to the Insertion Method Used in Extracorporeal Cardiopulmonary Resuscitation: A Single-Center Experience.

Background: Venoarterial extracorporeal membrane oxygenation (ECMO) is a key treatment method used with patients in cardiac arrest who do not respond to medical treatment. A critical step in initiating therapy is the insertion of ECMO cannulas. Peripheral ECMO cannulation methods have been preferred for extracorporeal cardiopulmonary resuscitation (ECPR). Methods: Patients who underwent ECPR at Daegu Catholic University Medical Center between January 2017 and May 2023 were included in this study. We analyzed the impact of 2 different peripheral cannulation strategies (surgical cutdown vs. percutaneous cannulation) on various factors, including survival rate. Results: Among the 99 patients included in this study, 66 underwent surgical cutdown, and 33 underwent percutaneous insertion. The survival to discharge rates were 36.4% for the surgical cutdown group and 30.3% for the percutaneous group (p=0.708). The ECMO insertion times were 21.3 minutes for the surgical cutdown group and 10.3 minutes for the percutaneous group (p<0.001). The factors associated with overall mortality included a shorter low-flow time (hazard ratio [HR], 1.045; 95% confidence interval [CI], 1.019-1.071; p=0.001) and whether return of spontaneous circulation was achieved (HR, 0.317; 95% CI, 0.127-0.787; p=0.013). Low-flow time was defined as the time from the start of cardiopulmonary resuscitation to the completion of ECMO cannula insertion. Conclusion: No statistically significant difference in in-hospital mortality was observed between the surgical and percutaneous groups. However, regardless of the chosen cannulation strategy, reducing ECMO cannulation time was beneficial, as a shorter low-flow time was associated with significant benefits in terms of survival.

ERRγ-inducible FGF23 promotes alcoholic liver injury through enhancing CYP2E1 mediated hepatic oxidative stress.

Fibroblast growth factor 23 (FGF23) is a member of endocrine FGF family, along with FGF15/19 and FGF21. Recent reports showed that under pathological conditions, liver produces FGF23, although the role of hepatic FGF23 remains nebulous. Here, we investigated the role of hepatic FGF23 in alcoholic liver disease (ALD) and delineated the underlying molecular mechanism. FGF23 expression was compared in livers from alcoholic hepatitis patients and healthy controls. The role of FGF23 was examined in hepatocyte-specific knock-out (LKO) mice of cannabinoid receptor type 1 (CB1R), estrogen related receptor γ (ERRγ), or FGF23. Animals were fed with an alcohol-containing liquid diet alone or in combination with ERRγ inverse agonist. FGF23 is mainly expressed in hepatocytes in the human liver, and it is upregulated in ALD patients. In mice, chronic alcohol feeding leads to liver damage and induced FGF23 in liver, but not in other organs. FGF23 is transcriptionally regulated by ERRγ in response to alcohol-mediated activation of the CB1R. Alcohol induced upregulation of hepatic FGF23 and plasma FGF23 levels is lost in ERRγ-LKO mice, and an inverse agonist mediated inhibition of ERRγ transactivation significantly improved alcoholic liver damage. Moreover, hepatic CYP2E1 induction in response to alcohol is FGF23 dependent. In line, FGF23-LKO mice display decreased hepatic CYP2E1 expression and improved ALD through reduced hepatocyte apoptosis and oxidative stress. We recognized CBIR-ERRγ-FGF23 axis in facilitating ALD pathology through hepatic CYP2E1 induction. Thus, we propose FGF23 as a potential therapeutic target to treat ALD.

Characteristics and functional outcomes of varus displaced proximal humerus fractures.

BACKGROUND: The purpose of this study was to compare fracture characteristics and functional outcomes between patients with proximal humerus fractures with and without initial varus displacement. METHODS: A retrospective review of 325 patients with proximal humerus fractures was performed. Patients with initial varus displacement were placed in Varus cohort and were age- and sex-matched 1:1 with a second cohort presenting proximal humerus fractures without varus displacement, referred to as Fracture cohort. Varus fracture displacement was defined when the most proximal aspect of humeral head was below the most proximal aspect of greater tuberosity on initial radiographs, and the head shaft angle was <130°. RESULTS: There were 60 patients in V cohort and 60 patients in F cohort. Statistical analysis revealed that there were significant differences in initial horizontal offset (38.8 vs. 45.9 mm), initial anterior angulation angle (36.5° vs. 16.4°), postoperative head shaft angle (132.2° vs. 141.3°), last head shaft angle (122.2° vs. 138.5°), difference for head shaft angles (10.0° vs. 2.7°), postoperative horizontal offset (43.4 vs. 45.3 mm), last horizontal offset (38.4 vs. 42.8 mm), difference for offsets (4.9 vs. 2.5 mm), complications (15 vs. 7 cases), and revision surgery (7 vs. 1 case) between two cohorts. Overall satisfactory results were achieved in most patients regardless of varus displacement, pain-VAS and Constant scores in V cohort were inferior to the scores in F cohort. The cut-off value of postoperative head shaft angle for good/excellent outcomes was 135.5° using receiver operating characteristic curve analyses. CONCLUSION: Varus displaced proximal humerus fractures were accompanied by decreased horizontal offset and increased anterior angulation angle, and had a course of more varization and horizontal shortening compared with those without initial varus displacement. Patients with varus displaced fractures were associated with worse functional outcomes, and these factors might affect functional outcomes. LEVEL OF EVIDENCE: Prognostic, cohort study, Level III.

Electrically Confined Electroluminescence of Neutral Excitons in WSe2 Light-Emitting Transistors.

Monolayer transition metal dichalcogenides (TMDs) have drawn significant attention for their potential in optoelectronic applications due to their direct band gap and exceptional quantum yield. However, TMD-based light-emitting devices have shown low external quantum efficiencies as imbalanced free carrier injection often leads to the formation of non-radiative charged excitons, limiting practical applications. Here, electrically confined electroluminescence (EL) of neutral excitons in tungsten diselenide (WSe2) light-emitting transistors (LETs) based on the van der Waals heterostructure is demonstrated. The WSe2 channel is locally doped to simultaneously inject electrons and holes to the 1D region by a local graphene gate. At balanced concentrations of injected electrons and holes, the WSe2 LETs exhibit strong EL with a high external quantum efficiency (EQE) of ≈8.2 % at room temperature. These experimental and theoretical results consistently show that the enhanced EQE could be attributed to dominant exciton emission confined at the 1D region while expelling charged excitons from the active area by precise control of external electric fields. This work shows a promising approach to enhancing the EQE of 2D light-emitting transistors and modulating the recombination of exciton complexes for excitonic devices.

Macrophage stimulating protein is a novel transcriptional target of estrogen related receptor gamma in alcohol-intoxicated mice.

Macrophage stimulating protein (MSP) is a multifunctional serum protein produced in the liver, belonging to the plasminogen-related kringle protein family. It exerts diverse biological functions by activating a transmembrane receptor protein-tyrosine kinase known as RON in humans and SKT in mice. MSP plays a pivotal role in innate immunity and is involved in various activities such as cell survival, migration, and phagocytosis. Elucidating the regulatory mechanisms governing MSP gene expression is of great importance. In this study, we comprehensively elucidate the molecular mechanism underlying hepatic MSP gene expression in response to alcoholism. Exposure to ethanol specifically upregulated the expression of ERRγ and MSP in the liver, while not in other organs. Liver-specific knockout of the cannabinoid receptor type 1 (CB1R), an upstream regulator of ERRγ, inhibited the alcohol-induced upregulation of MSP expression. Overexpression of ERRγ alone was sufficient to enhance MSP expression in hepatic cell lines and in mice. Conversely, knockdown of ERRγ in cell lines or liver-specific knockout of ERRγ in mice reversed ethanol-induced MSP gene expression. Promoter studies revealed the direct binding of ERRγ to the MSP gene promoter at the ERR response element (ERRE), resulting in the positive regulation of MSP gene expression in response to alcohol. This finding was further supported by ERRE-mutated MSP-luciferase reporter assays. Notably, treatment with GSK5182, an ERRγ-specific inverse agonist, significantly suppressed alcohol-induced hepatic MSP expression. Collectively, we exposed a novel mechanistic understanding of how alcohol-induced ERRγ controls the transcriptional regulation of MSP gene expression in the liver.

Agathobaculum butyriciproducens improves ageing-associated cognitive impairment in mice.

AIMS: The gut microbiota is increasingly recognised as a pivotal regulator of immune system homeostasis and brain health. Recent research has implicated the gut microbiota in age-related cognitive impairment and dementia. Agathobaculum butyriciproducens SR79 T (SR79), which was identified in the human gut, has been reported to be beneficial in addressing cognitive deficits and pathophysiologies in a mouse model of Alzheimer's disease. However, it remains unknown whether SR79 affects age-dependent cognitive impairment. MAIN METHOD: To explore the effects of SR79 on cognitive function during ageing, we administered SR79 to aged mice. Ageing-associated behavioural alterations were examined using the open field test (OFT), tail suspension test (TST), novel object recognition test (NORT), Y-maze alternation test (Y-maze), and Morris water maze test (MWM). We investigated the mechanisms of action in the gut and brain using molecular and histological analyses. KEY FINDINGS: Administration of SR79 improved age-related cognitive impairment without altering general locomotor activity or depressive behaviour in aged mice. Furthermore, SR79 increased mature dendritic spines in the pyramidal cells of layer III and phosphorylation of CaMKIIα in the cortex of aged mice. Age-related activation of astrocytes in the cortex of layers III-V of the aged brain was reduced following SR79 administration. Additionally, SR79 markedly increased IL-10 production and Foxp3 and Muc2 mRNA expression in the colons of aged mice. SIGNIFICANCE: These findings suggest that treatment with SR79 may be a beneficial microbial-based approach for enhancing cognitive function during ageing.

Mucosal TLR5 activation controls healthspan and longevity.

Addressing age-related immunological defects through therapeutic interventions is essential for healthy aging, as the immune system plays a crucial role in controlling infections, malignancies, and in supporting tissue homeostasis and repair. In our study, we show that stimulating toll-like receptor 5 (TLR5) via mucosal delivery of a flagellin-containing fusion protein effectively extends the lifespan and enhances the healthspan of mice of both sexes. This enhancement in healthspan is evidenced by diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis. Additionally, this fusion protein boosts intestinal mucosal integrity by augmenting the surface expression of TLR5 in a certain subset of dendritic cells and increasing interleukin-22 (IL-22) secretion. In this work, we present observations that underscore the benefits of TLR5-dependent stimulation in the mucosal compartment, suggesting a viable strategy for enhancing longevity and healthspan.

Novel Signal Peptides and Episomal Plasmid System for Enhanced Protein Secretion in Engineered Bacteroides Species.

The genus Bacteroides, a predominant group in the human gut microbiome, presents significant potential for microbiome engineering and the development of live biotherapeutics aimed at treating gut diseases. Despite its promising capabilities, tools for effectively engineering Bacteroides species have been limited. In our study, we have made a breakthrough by identifying novel signal peptides in Bacteroides thetaiotaomicron and Akkermansia muciniphila. These peptides facilitate efficient protein transport across cellular membranes in Bacteroides, a critical step for therapeutic applications. Additionally, we have developed an advanced episomal plasmid system. This system demonstrates superior protein secretion capabilities compared to traditional chromosomal integration plasmids, making it a vital tool for enhancing the delivery of therapeutic proteins in Bacteroides species. Initially, the stability of this episomal plasmid posed a challenge; however, we have overcome this by incorporating an essential gene-based selection system. This novel strategy not only ensures plasmid stability but also aligns with the growing need for antibiotic-free selection methods in clinical settings. Our work, therefore, not only provides a more robust secretion system for Bacteroides but also sets a new standard for the development of live biotherapeutics.

All-Solution-Processed High-Performance MoS2 Thin-Film Transistors with a Quasi-2D Perovskite Oxide Dielectric.

Assembling solution-processed van der Waals (vdW) materials into thin films holds great promise for constructing large-scale, high-performance thin-film electronics, especially at low temperatures. While transition metal dichalcogenide thin films assembled in solution have shown potential as channel materials, fully solution-processed vdW electronics have not been achieved due to the absence of suitable dielectric materials and high-temperature processing. In this work, we report on all-solution-processedvdW thin-film transistors (TFTs) comprising molybdenum disulfides (MoS2) as the channel and Dion-Jacobson-phase perovskite oxides as the high-permittivity dielectric. The constituent layers are prepared as colloidal solutions through electrochemical exfoliation of bulk crystals, followed by sequential assembly into a semiconductor/dielectric heterostructure for TFT construction. Notably, all fabrication processes are carried out at temperatures below 250 °C. The fabricated MoS2 TFTs exhibit excellent device characteristics, including high mobility (>10 cm2 V-1 s-1) and an on/off ratio exceeding 106. Additionally, the use of a high-k dielectric allows for operation at low voltage (∼5 V) and leakage current (∼10-11 A), enabling low power consumption. Our demonstration of the low-temperature fabrication of high-performance TFTs presents a cost-effective and scalable approach for heterointegrated thin-film electronics.

Beta-lapachone ameliorates the progression of primary sclerosing cholangitis pathogenesis in rodent models.

AIMS: Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by chronic inflammation and severe fibrosis for which effective treatment options are currently lacking. In this study, we explored the potential of beta-lapachone (ßL) as a drug candidate for PSC therapy. MATERIALS AND METHODS: We employed an animal model fed a diet containing 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) to assess the preventive and therapeutic effects of ßL. The beneficial effects of ßL on PSC pathogenic characteristics, including blood biomarkers, inflammation, and fibrosis, were determined by assessing relevant parameters. Differential gene expression between each group was analyzed by RNA sequencing of liver tissues. Mdr2-/- mice were utilized to explore the involvement of Abcb4 in the ßL-induced improvement of PSC pathogenesis. KEY FINDINGS: ßL effectively inhibited key features of PSC pathogenesis, as demonstrated by reduced blood biomarkers and improved pathogenic characteristics. Treatment with ßL significantly mitigated DDC-induced apoptosis, cell proliferation, inflammation, and fibrosis. Analysis of differential gene expression confirmed a new insight that ßL could stimulate the expression of genes related to NAD synthesis and Abcb4. Indeed, ßL-induced NAD exhibited effective functioning, as evidenced by enhanced sirt1/3 and acetyl-lysine levels, leading to improved mitochondrial stability. The role of Abcb4 in response to ßL was confirmed in Mdr2/Abcb4 KO mice, where the beneficial effects of ßL were abolished. SIGNIFICANCE: This study provided a new concept for PSC treatment, suggesting that pharmacological stimulation of the NAD synthetic pathway and Abcb4 via ßL ameliorates PSC pathogenesis.

Low-Temperature Chiral Crystal Structure and Superconductivity in (Pt0.2Ir0.8)3Zr5.

We report the observation of superconductivity in (Pt0.2Ir0.8)3Zr5 with a chiral space group (P6122) at low temperatures. The bulk nature of the superconductivity at a transition temperature of 2.2 K was confirmed using specific heat measurements. We revealed that (Pt0.2Ir0.8)3Zr5 obeys the weak-coupling Bardeen-Cooper-Schrieffer model, and the dominant mechanism in the upper critical field is the orbital pair-breaking limit rather than the Pauli-Clogston limit. This indicates that the antisymmetric spin-orbit coupling caused by the chiral crystal structure does not significantly affect the superconductivity of (Pt0.2Ir0.8)3Zr5.

Gadd45ß is critical for regulation of type I interferon signaling by facilitating G3BP-mediated stress granule formation.

Stress granules (SGs) constitute a signaling hub that plays a critical role in type I interferon responses. Here, we report that growth arrest and DNA damage-inducible beta (Gadd45ß) act as a positive regulator of SG-mediated interferon signaling by targeting G3BP upon RNA virus infection. Gadd45ß deficiency markedly impairs SG formation and SG-mediated activation of interferon signaling in vitro. Gadd45ß knockout mice are highly susceptible to RNA virus infection, and their ability to produce interferon and cytokines is severely impaired. Specifically, Gadd45ß interacts with the RNA-binding domain of G3BP, leading to conformational expansion of G3BP1 via dissolution of its autoinhibitory electrostatic intramolecular interaction. The acidic loop 1- and RNA-binding properties of Gadd45ß markedly increase the conformational expansion and RNA-binding affinity of the G3BP1-Gadd45ß complex, thereby promoting assembly of SGs. These findings suggest a role for Gadd45ß as a component and critical regulator of G3BP1-mediated SG formation, which facilitates RLR-mediated interferon signaling.

Rb(Zn,Cu)4As3 as a New High-Efficiency Thermoelectric Material.

The thermoelectric performance of RbZn4-xCuxAs3 crystallized in the KCu4S3-type structure was investigated. Samples were synthesized via solid-state reactions, followed by hot pressing. Hole carriers were doped by substituting Zn with Cu until x = 0.02, resulting in an increase of the power factor from 0.049 to 0.52 mW/mK2 at T = 797 K. The lattice thermal conductivity was substantially low, with a value of 1.61 W/mK at T = 312 K, independent of doping. This can be attributed to the large vibration of the Rb atoms, as demonstrated by the neutron diffraction analysis. The maximum dimensionless figure of merit, ZT, was 0.53 at T = 797 K, representing the highest value for the 143-Zintl compounds. The result indicated that the 143-Zintl compounds could be a new class of high-performance thermoelectric materials.

Calorimetric evidence for two phase transitions in Ba1-xKxFe2As2 with fermion pairing and quadrupling states.

Materials that break multiple symmetries allow the formation of four-fermion condensates above the superconducting critical temperature (Tc). Such states can be stabilized by phase fluctuations. Recently, a fermionic quadrupling condensate that breaks the Z2 time-reversal symmetry was reported in Ba1-xKxFe2As2. A phase transition to the new state of matter should be accompanied by a specific heat anomaly at the critical temperature where Z2 time-reversal symmetry is broken ([Formula: see text]). Here, we report on detecting two anomalies in the specific heat of Ba1-xKxFe2As2 at zero magnetic field. The anomaly at the higher temperature is accompanied by the appearance of a spontaneous Nernst effect, indicating the breakdown of Z2 symmetry. The second anomaly at the lower temperature coincides with the transition to a zero-resistance state, indicating the onset of superconductivity. Our data provide the first example of the appearance of a specific heat anomaly above the superconducting phase transition associated with the broken time-reversal symmetry due to the formation of the novel fermion order.

Humulus japonicus ameliorates irritant contact dermatitis by suppressing NF­κB p65­dependent inflammatory responses in mice.

As a type of contact dermatitis (CD), irritant CD (ICD) is an acute skin inflammation caused by external irritants, such as soap, water and chemicals. Humulus japonicus (HJ) is a herbal medicine widely distributed in Asian countries and has anti-inflammatory, antimicrobial and antioxidant effects. The current study aimed to investigate the anti-dermatitis effect of HJ on ICD and determine the molecular basis of this effect using 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced dermatitis mice models and lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Mice were orally administered HJ and luteolin, the major compound in HJ, and topically administered TPA on the right ear to induce dermatitis. Topical application of TPA induced ear redness, oedema and increased infiltration of neutrophils and macrophages, which ameliorated following HJ and luteolin administration. The gene expression levels of inflammatory cell migrating chemokines, chemokine ligand 3 (CCL3) and chemokine (C-X-C motif) ligand 2 (CXCL2), and pro-inflammatory cytokine, IL-1ß, were reduced in the ears of HJ- and luteolin-treated mice. HJ and luteolin also inhibited the gene expression of chemokines, CCL3 and CXCL2, and pro-inflammatory cytokines, IL-1ß, IL-6 and TNF-α, in LPS-stimulated RAW264.7 cells. Moreover, HJ and luteolin decreased the expression levels of two key inflammatory enzymes, cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS), and total and active phosphorylation of NF-κB p65. These results suggest that HJ could have a protective effect against ICD by suppressing inflammatory responses; therefore, HJ is a promising therapeutic strategy for ICD treatment.