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1.
ACS Nano ; 18(18): 11769-11777, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38648369

RESUMO

Twist-controlled moiré superlattices (MSs) have emerged as a versatile platform for realizing artificial systems with complex electronic spectra. The combination of Bernal-stacked bilayer graphene (BLG) and hexagonal boron nitride (hBN) can give rise to an interesting MS, which has recently featured a set of unexpected behaviors, such as unconventional ferroelectricity and the electronic ratchet effect. Yet, the understanding of the electronic properties of BLG/hBN MS has, at present, remained fairly limited. Here, we combine magneto-transport and low-energy sub-THz excitation to gain insights into the properties of this MS. We demonstrate that the alignment between BLG and hBN crystal lattices results in the emergence of compensated semimetals at some integer fillings of the moiré bands, separated by van Hove singularities where the Lifshitz transition occurs. A particularly pronounced semimetal develops when eight holes reside in the moiré unit cell, where coexisting high-mobility electron and hole systems feature strong magnetoresistance reaching 2350% already at B = 0.25 T. Next, by measuring the THz-driven Nernst effect in remote bands, we observe valley splitting, indicating an orbital magnetization characterized by a strongly enhanced effective gv-factor of 340. Finally, using THz photoresistance measurements, we show that the high-temperature conductivity of the BLG/hBN MS is limited by electron-electron umklapp processes. Our multifaceted analysis introduces THz-driven magnetotransport as a convenient tool to probe the band structure and interaction effects in van der Waals materials and provides a comprehensive understanding of the BLG/hBN MS.

2.
Int J Mol Sci ; 25(4)2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38396804

RESUMO

Unlike other vitamins, vitamin D3 is synthesised in skin cells in the body. Vitamin D3 has been known as a bone-related hormone. Recently, however, it has been considered as an immune vitamin. Vitamin D3 deficiency influences the onset of a variety of diseases. Vitamin D3 regulates the production of proinflammatory cytokines such as tumour necrosis factor-α (TNF-α) through binding to vitamin D receptors (VDRs) in immune cells. Since blood levels of vitamin D3 (25-OH-D3) were low in coronavirus disease 2019 (COVID-19) patients, there has been growing interest in the importance of vitamin D3 to maintaining a healthy condition. On the other hand, phytochemicals are compounds derived from plants with over 7000 varieties and have various biological activities. They mainly have health-promoting effects and are classified as terpenoids, carotenoids, flavonoids, etc. Flavonoids are known as the anti-inflammatory compounds that control TNF-α production. Chronic inflammation is induced by the continuous production of TNF-α and is the fundamental cause of diseases like obesity, dyslipidaemia, diabetes, heart and brain diseases, autoimmune diseases, Alzheimer's disease, and cancer. In addition, the ageing process is induced by chronic inflammation. This review explains the cooperative effects of vitamin D3 and phytochemicals in the suppression of inflammatory responses, how it balances the natural immune response, and its link to anti-ageing effects. In addition, vitamin D3 and phytochemicals synergistically contribute to anti-ageing by working with ageing-related genes. Furthermore, prevention of ageing processes induced by the chronic inflammation requires the maintenance of healthy gut microbiota, which is related to daily dietary habits. In this regard, supplementation of vitamin D3 and phytochemicals plays an important role. Recently, the association of the prevention of the non-disease condition called "ME-BYO" with the maintenance of a healthy condition has been an attractive regimen, and the anti-ageing effect discussed here is important for a healthy and long life.


Assuntos
Colecalciferol , Fator de Necrose Tumoral alfa , Humanos , Colecalciferol/farmacologia , Envelhecimento , Flavonoides , Inflamação/prevenção & controle , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Vitamina D/farmacologia
3.
ACS Nano ; 18(5): 4320-4328, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38277645

RESUMO

Applying a drain bias to a strongly gate-coupled semiconductor influences the carrier density of the channel. However, practical applications of this drain-bias-induced effect in the advancement of switching electronics have remained elusive due to the limited capabilities of its current modulation known to date. Here, we show strategies to largely control the current by utilizing drain-bias-induced carrier type switching in an ambipolar molybdenum disulfide (MoS2) field-effect transistor with Pt bottom contacts. Our CMOS-compatible device architecture, incorporating a partially gate-coupled p-n junction, achieves multifunctionality. The ambipolar MoS2 device operates as an ambipolar transistor (on/off ratios exceeding 107 for both NMOS and PMOS), a rectifier (rectification ratio of ∼3 × 106), a reversible negative breakdown diode with an adjustable breakdown voltage (on/off ratio exceeding 109 with a maximum current as high as 10-4 A), and a photodetector. Finally, we demonstrate a complementary inverter (gain of ∼24 at Vdd = 1.5 V), which is highly facile to fabricate without the need for complex heterostructures and doping processes. Our study provides strategies to achieve high-performance ambipolar MoS2 devices and to effectively utilize drain bias for electrical switching.

4.
Medicine (Baltimore) ; 102(48): e36191, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38050203

RESUMO

Two representative Kampo formulas, keishibukuryogan and tokishakuyakusan, are frequently prescribed for patients with dysmenorrhea. We previously constructed a model that could predict which of these 2 formulas was most suitable, which is based on 4 subjective symptoms and 3 objective signs. To evaluate the prognosis of patients with dysmenorrhea using the established prediction model and assess the treatment outcomes between those treated in accordance with the prediction model and those who received various other treatments. In this retrospective, observational study, we included patients with menstrual pain who visited the Kampo Clinic at the Keio University Hospital for the first time between October 2014 and December 2020. These patients were monitored over a 90-day follow-up period. Participants were categorized into 2 groups: model-accordance and various-options. The progression of visual analogue scale (VAS) values was evaluated by determining the slopes from regression analysis between these 2 groups, with changes corroborated by the medical records. The study comprised 57 patients: 37 in the model-accordance group and 20 in the various-options group. Notably, the various-options group reported a significantly higher number of subjective symptoms (P = .03). The VAS value showed a decline, as indicated by the negative slope value of the regression line, across both groups - irrespective of their classification. There were no significant differences in the occurrence of adverse events between the 2 groups. The prognosis of patients with dysmenorrhea and the incidence of adverse events remained consistent, regardless of whether the treatment approach was in accordance with the prediction model or varied. Further studies are warranted to assess the prognosis when Kampo formulas are chosen based on the prediction model in the various-options population.


Assuntos
Dismenorreia , Medicina Kampo , Feminino , Humanos , Dismenorreia/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Medição da Dor
5.
Int J Mol Sci ; 24(15)2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37569540

RESUMO

A variety of phytocompounds contained in medical plants have been used as medication, including Kampo (traditional Japanese) medicine. Phytochemicals are one category of the chemical compounds mainly known as antioxidants, and recently, their anti-inflammatory effects in preventing chronic inflammation have received much attention. Here, we present a narrative review of the health-promotion and disease-prevention effects of phytochemicals, including polyphenols, the latter of which are abundant in onions, oranges, tea, soybeans, turmeric, cacao, and grapes, along with the synergetic effects of vitamin D. A phenomenon currently gaining popularity in Japan is finding non-disease conditions, so-called ME-BYO (mibyou) and treating them before they develop into illnesses. In addition to lifestyle-related diseases such as metabolic syndrome and obesity, dementia and frailty, commonly found in the elderly, are included as underlying conditions. These conditions are typically induced by chronic inflammation and might result in multiple organ failure or cancer if left untreated. Maintaining gut microbiota is important for suppressing (recently increasing) intestinal disorders and for upregulating immunity. During the COVID-19 pandemic, the interest in phytochemicals and vitamin D for disease prevention increased, as viral and bacterial infection to the lung causes fatal inflammation, and chronic inflammation induces pulmonary fibrosis. Furthermore, sepsis is a disorder inducing severe organ failure by the infection of microbes, with a high mortality ratio in non-coronary ICUs. However, antimicrobial peptides (AMPs) working using natural immunity suppress sepsis at the early stage. The intake of phytochemicals and vitamin D enhances anti-inflammatory effects, upregulates immunity, and reduces the risk of chronic disorders by means of keeping healthy gut microbiota. Evidence acquired during the COVID-19 pandemic revealed that daily improvement and prevention of underlying conditions, in terms of lifestyle-related diseases, is very important because they increase the risk of infectious diseases. This narrative review discusses the importance of the intake of phytochemicals and vitamin D for a healthy lifestyle and the prevention of ME-BYO, non-disease conditions.


Assuntos
COVID-19 , Vitamina D , Humanos , Idoso , Vitamina D/uso terapêutico , Pandemias , COVID-19/prevenção & controle , Vitaminas/farmacologia , Inflamação/tratamento farmacológico , Anti-Inflamatórios , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico
6.
BMC Med Inform Decis Mak ; 23(1): 119, 2023 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-37442993

RESUMO

BACKGROUND: Kampo medicine is widely used in Japan; however, most physicians and pharmacists have insufficient knowledge and experience in it. Although a chatbot-style system using machine learning and natural language processing has been used in some clinical settings and proven useful, the system developed specifically for the Japanese language using this method has not been validated by research. The purpose of this study is to develop a novel drug information provision system for Kampo medicines using a natural language classifier® (NLC®) based on IBM Watson. METHODS: The target Kampo formulas were 33 formulas listed in the 17th revision of the Japanese Pharmacopoeia. The information included in the system comes from the package inserts of Kampo medicines, Manuals for Management of Individual Serious Adverse Drug Reactions, and data on off-label usage. The system developed in this study classifies questions about the drug information of Kampo formulas input by natural language into preset questions and outputs preset answers for the questions. The system uses morphological analysis, synonym conversion by thesaurus, and NLC®. We fine-tuned the information registered into NLC® and increased the thesaurus. To validate the system, 900 validation questions were provided by six pharmacists who were classified into high or low levels of knowledge and experience of Kampo medicines and three pharmacy students. RESULTS: The precision, recall, and F-measure of the system performance were 0.986, 0.915, and 0.949, respectively. The results were stable even with differences in the amount of expertise of the question authors. CONCLUSIONS: We developed a system using natural language classification that can give appropriate answers to most of the validation questions.


Assuntos
Medicina Kampo , Médicos , Humanos , Processamento de Linguagem Natural , Farmacêuticos , Tecnologia , Japão
7.
Nano Lett ; 23(12): 5617-5624, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37289519

RESUMO

High light absorption (∼15%) and strong photoluminescence (PL) emission in monolayer (1L) transition metal dichalcogenides (TMDs) make them ideal candidates for optoelectronic device applications. Competing interlayer charge transfer (CT) and energy transfer (ET) processes control the photocarrier relaxation pathways in TMD heterostructures (HSs). In TMDs, long-distance ET can survive up to several tens of nm, unlike the CT process. Our experiment shows that an efficient ET occurs from the 1Ls WSe2-to-MoS2 with an interlayer hexagonal boron nitride (hBN), due to the resonant overlapping of the high-lying excitonic states between the two TMDs, resulting in enhanced HS MoS2 PL emission. This type of unconventional ET from the lower-to-higher optical bandgap material is not typical in the TMD HSs. With increasing temperature, the ET process becomes weaker due to the increased electron-phonon scattering, destroying the enhanced MoS2 emission. Our work provides new insight into the long-distance ET process and its effect on the photocarrier relaxation pathways.

8.
Nanomaterials (Basel) ; 13(10)2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37242116

RESUMO

A two-dimensional (2D) atomic crystalline transition metal dichalcogenides has shown immense features, aiming for future nanoelectronic devices comparable to conventional silicon (Si). 2D molybdenum ditelluride (MoTe2) has a small bandgap, appears close to that of Si, and is more favorable than other typical 2D semiconductors. In this study, we demonstrate laser-induced p-type doping in a selective region of n-type semiconducting MoTe2 field effect transistors (FET) with an advance in using the hexagonal boron nitride as passivation layer from protecting the structure phase change from laser doping. A single nanoflake MoTe2-based FET, exhibiting initial n-type and converting to p-type in clear four-step doping, changing charge transport behavior in a selective surface region by laser doping. The device shows high electron mobility of about 23.4 cm2V-1s-1 in an intrinsic n-type channel and hole mobility of about 0.61 cm2V-1s-1 with a high on/off ratio. The device was measured in the range of temperature 77-300 K to observe the consistency of the MoTe2-based FET in intrinsic and laser-dopped region. In addition, we measured the device as a complementary metal-oxide-semiconductor (CMOS) inverter by switching the charge-carrier polarity of the MoTe2 FET. This fabrication process of selective laser doping can potentially be used for larger-scale MoTe2 CMOS circuit applications.

9.
Front Pharmacol ; 14: 1116260, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36860294

RESUMO

The management of skin wound healing problems is a public health issue in which traditional herbal medicines could play a determining role. Kampo medicine, with three traditionally used ointments, provides interesting solutions for these dermatological issues. These ointments named Shiunko, Chuoko, and Shinsen taitsuko all have in common a lipophilic base of sesame oil and beeswax from which herbal crude drugs are extracted according to several possible manufacturing protocols. This review article brings together existing data on metabolites involved in the complex wound healing process. Among them are representatives of the botanical genera Angelica, Lithospermum, Curcuma, Phellodendron, Paeonia, Rheum, Rehmannia, Scrophularia, or Cinnamomum. Kampo provides numerous metabolites of interest, whose content in crude drugs is very sensitive to different biotic and abiotic factors and to the different extraction protocols used for these ointments. If Kampo medicine is known for its singular standardization, ointments are not well known, and research on these lipophilic formulas has not been developed due to the analytical difficulties encountered in biological and metabolomic analysis. Further research considering the complexities of these unique herbal ointments could contribute to a rationalization of Kampo's therapeutic uses for wound healing.

11.
Adv Mater ; 34(51): e2203990, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36271514

RESUMO

Robust room-temperature interfacial ferroelectricity has been formed in the 2D limit by simply twisting two atomic layers of non-ferroelectric hexagonal boron nitride (hBN). A thorough understanding of this newly discovered ferroelectric system is required. Here, twisted hBN is used as a tunneling junction and it is studied at the nanometer scale using conductive atomic force microscopy. Three properties unique to this system are discovered. First, the polarization dependence of the tunneling resistance contrasts with the conventional theory. Second, the ferroelectric domains can be controlled using mechanical stress, highlighting the original meaning of the emergent "slidetronics". Third, ferroelectric hysteresis is highly spatially dependent. The hysteresis is symmetric at the domain walls. A few nanometers away, the hysteresis shifts completely to the positive or negative side, depending on the original polarization. These findings reveal the unconventional ferroelectricity in this 2D system.

12.
Comput Biol Med ; 146: 105619, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35598353

RESUMO

OBJECTIVE: To establish a prediction model of qi stagnation referring to two existing models. DESIGN: Prospective observational study. SETTING: We recruited patients who visited the Kampo Clinic at Keio University from February 2011 to March 2013. METHODS: We constructed a random forest algorithm with 202 items as independent variables to predict qi stagnation patterns using full agreement data of the physicians' diagnosis and the result of two existing scores as a reference standard. To compare the new model with the two existing models, we calculated the discriminant ratio (prediction accuracy), precision, sensitivity (recall), specificity, and F-measure of these models. RESULTS: The number of eligible participants was 1,194, and 29.1% of them were diagnosed with qi stagnation by Kampo physicians. The discriminant ratio, precision, sensitivity, specificity, and F-measure in our new model were 0.960, 0.672, 0.911, 0.964, and 0.774, respectively. Our new model had a significantly higher discriminant ratio than the two existing models. CONCLUSIONS: We constructed a better qi stagnation prediction model than the previously established ones. Our results can be utilized to reach an international agreement on qi stagnation pattern diagnosis in traditional East Asian medicine.


Assuntos
Medicina Kampo , Qi , Humanos , Medicina Tradicional Chinesa , Estudos Prospectivos
13.
Complement Med Res ; 29(5): 373-381, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35550377

RESUMO

BACKGROUND: We aimed to explore standardized scales and serum biomarkers for tracking changes in the symptoms and severity of pruritus due to eczema in patients treated with Kampo formulas. PATIENTS AND METHODS: This prospective, single-arm, pre-post comparison case series recruited patients with pruritus mostly due to eczema who consulted the Kampo Clinic at the Keio University Hospital from June 2019 to March 2020. The participants were prescribed a personalized Kampo formula for 12 weeks. Patient profiles and symptoms were assessed every 4 weeks using the visual analog scale (VAS), patient-oriented eczema measure (POEM) scale, 5-D itch scale (5D), Skindex-16, and eczema area and severity index (EASI). Blood biomarkers and intestinal permeability indicators were measured at the first consultation and 12 weeks later. RESULTS: Pruritus and eczema severity improved significantly over time. The VAS, POEM, 5D, and Skindex-16 scores were well-correlated. The serum interleukin-31 levels decreased significantly after a 12-week intervention. Changes in the interleukin-31 level correlated with the diamine oxidase level at week 0, suggesting the involvement of the Th2 immune system and intestinal permeability in the mechanism of Kampo formulas. CONCLUSION: The evaluated scales are suitable for evaluating subjective symptoms and eczema severity after Kampo treatment; further studies are required to verify the study findings.


Assuntos
Amina Oxidase (contendo Cobre) , Eczema , Humanos , Medicina Kampo , Japão , Índice de Gravidade de Doença , Eczema/tratamento farmacológico , Eczema/diagnóstico , Prurido/tratamento farmacológico , Biomarcadores
14.
Artigo em Inglês | MEDLINE | ID: mdl-35542986

RESUMO

Direct top-down nanopatterning of semiconductors is a powerful tool for engineering properties of optoelectronic devices. Translating this approach to two-dimensional semiconductors such as monolayer transition metal dichalcogenides (TMDs) is challenging because of both the small scales required for confinement and the degradation of electronic and optical properties caused by high-energy and high-dose electron radiation used for high-resolution top-down direct electron beam patterning. We show that encapsulating a TMD monolayer with hexagonal boron nitride preserves the narrow exciton linewidths and emission intensity typical in such heterostructures after electron beam lithography, allowing direct patterning of functional optical monolayer nanostructures on scales of a few tens of nanometers. We leverage this fabrication method to study size-dependent effects on nanodot arrays of MoS2 and MoSe2 as well as laterally confined electrical transport devices, demonstrating the potential of top-down lithography for nanoscale TMD optoelectronics.

15.
Lancet Gastroenterol Hepatol ; 7(7): 648-657, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35366419

RESUMO

BACKGROUND: AJM300 is an oral, small-molecule α4-integrin antagonist. We assessed the efficacy and safety of AJM300 in patients with moderately active ulcerative colitis. METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 3 study consisted of two phases: a treatment phase and an open-label re-treatment phase. The study was done at 82 hospitals and clinics in Japan. Patients with a Mayo Clinic score of 6-10, endoscopic subscore of 2 or more, rectal bleeding subscore of 1 or more, and an inadequate response or intolerance to mesalazine were enrolled. Patients were randomly allocated (1:1) via a website to either AJM300 (960 mg) or placebo by the minimisation method, which was adjusted centrally by dynamic assignment against the Mayo Clinic score (≥6 to ≤7, ≥8 to ≤10 points), any use of corticosteroid, anti-TNFα antibody, or immunosuppressants during the disease-active period (yes vs no), duration of induction therapy until randomisation (<4 weeks vs ≥4 weeks) as the minimisation factors. Patients, investigators, site staff, assessors, and the sponsor were masked to treatment assignments. The study drug was administered orally, three times daily, for 8 weeks, and continued for up to 24 weeks if endoscopic remission was not achieved or rectal bleeding did not stop. The primary endpoint was the proportion of patients with a clinical response at week 8, and was analysed in the full analysis set. Clinical response was defined as a reduction in Mayo Clinic score of 30% or more and 3 or more, a reduction in rectal bleeding score of 1 or more or rectal bleeding subscore of 1 or less, and an endoscopic subscore of 1 or less at week 8. The study is registered with ClinicalTrials.gov, NCT03531892, and is closed to recruitment. FINDINGS: Between June 6, 2018, and July 22, 2020, 203 patients were randomly assigned to AJM300 (n=102) or placebo (n=101). At week 8, 46 (45%) patients in the AJM300 group and 21 (21%) patients in the placebo group had a clinical response (odds ratio 3·30, 95% CI 1·73-6·29; p=0·00028). During the 8-week treatment and 16-week extension treatment periods, adverse events occurred in 39 (39%) of 101 patients in the placebo group and 39 (38%) of 102 patients in the AJM300 group. We found no difference in the incidence of adverse events between groups or after repeated administration of AJM300. The most common adverse event was nasopharyngitis (11 [11%] of 101 patients in the placebo group and ten [10%] of 102 patients in the AJM300 group). The most common treatment-related adverse event was also nasopharyngitis (four [4%] of 101 patients in the placebo group and three [3%] of 102 patients in the AJM300 group). Most adverse events were mild-to-moderate in severity. No deaths were reported. A serious adverse event was reported in the AJM300 group (one patient with anal abscess), but this was judged to be unrelated to study drug. INTERPRETATION: AJM300 was well tolerated and induced a clinical response in patients with moderately active ulcerative colitis who had an inadequate response or intolerance to mesalazine. AJM300 could be a novel induction therapy for the treatment of patients with moderately active ulcerative colitis. FUNDING: EA Pharma and Kissei Pharmaceutical. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.


Assuntos
Colite Ulcerativa , Nasofaringite , Colite Ulcerativa/tratamento farmacológico , Humanos , Quimioterapia de Indução/métodos , Integrina alfa4/antagonistas & inibidores , Mesalamina/efeitos adversos , Fenilalanina/análogos & derivados , Quinazolinonas , Resultado do Tratamento
16.
Front Pharmacol ; 13: 775798, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35300298

RESUMO

In this self-controlled case series, we aimed to investigate the variation in estimated glomerular filtration rate (eGFR) after taking astragalus-containing preparations in patients with mild to moderate chronic kidney disease (CKD) by retrospectively reviewing their charts in our clinic. We set the inclusion criteria as first-visit patients aged 20 years or older presenting to our clinic between 1 October 2014, and 31 June 2019, and who were prescribed astragalus-containing herbal preparations for any reason. We calculated the mean eGFR from the readings taken 6 months before (pre) and after (post) the intake of astragalus-containing preparations for each participant. Among the 37 patients included in our final analysis, we found a statistically significant improvement in the eGFR after prescribing astragalus-containing preparations (pre, 66 ± 12 ml/min/1.73 m2 vs. post, 70 ± 14 ml/min/1.73 m2; p < 0.001 by paired t-test). Our results were consistent regardless of age, sex, CKD stage of the participants (G2 or G3), daily dosage of astragalus root, or duration of astragalus-containing preparations. No severe adverse reactions were recorded in the charts of the study participants. Our results suggest that there is eGFR improvement after taking astragalus-containing preparations in mild to moderate CKD cases as reported previously. The findings should be considered with caution due to major limitations such as small sample size without optimum control, short follow-up period, and incomplete data. Further adequately powered and designed studies are needed to confirm the efficacy and safety of the long-term use of astragalus root in patients with mild to moderate CKD.

17.
Front Nutr ; 8: 719197, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604277

RESUMO

Licorice, the dried root or stolon of Glycyrrhiza glabra or G. ularensis, is commonly used worldwide as a food sweetener or crude drug. Its major ingredient is glycyrrhizin. Hypokalemia or pseudoaldosteronism (PsA) is one of the most frequent side effects of licorice intake. Glycyrrhizin metabolites inhibit type 2 11ß-hydroxysteroid dehydrogenase (11ßHSD2), which decomposes cortisol into inactive cortisone in the distal nephron, thereby inducing mineralocorticoid receptor activity. Among the several reported glycyrrhizin-metabolites, 18ß-glycyrrhetyl-3-O-sulfate is the major compound found in humans after licorice consumption, followed by glycyrrhetinic acid. These metabolites are highly bound to albumin in blood circulation and are predominantly excreted into bile via multidrug resistance-associated protein 2 (Mrp2). High dosage and long-term use of licorice are constitutional risk factors for PsA. Orally administered glycyrrhizin is effectively hydrolyzed to glycyrrhetinic acid by the intestinal bacteria in constipated patients, which enhances the bioavailability of glycyrrhizin metabolites. Under hypoalbuminemic conditions, the unbound metabolite fractions can reach 11ßHSD2 at the distal nephron. Hyper direct-bilirubin could be a surrogate marker of Mrp2 dysfunction, which results in metabolite accumulation. Older age is associated with reduced 11ßHSD2 function, and several concomitant medications, such as diuretics, have been reported to affect the phenotype. This review summarizes several factors related to licorice-induced PsA, including daily dosage, long-term use, constipation, hypoalbuminemia, hyper direct-bilirubin, older age, and concomitant medications.

18.
Nature ; 600(7888): 240-245, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34670267

RESUMO

The emergence of superconductivity and correlated insulators in magic-angle twisted bilayer graphene (MATBG) has raised the intriguing possibility that its pairing mechanism is distinct from that of conventional superconductors1-4, as described by the Bardeen-Cooper-Schrieffer (BCS) theory. However, recent studies have shown that superconductivity persists even when Coulomb interactions are partially screened5,6. This suggests that pairing in MATBG might be conventional in nature and a consequence of the large density of states of its flat bands. Here we combine tunnelling and Andreev reflection spectroscopy with a scanning tunnelling microscope to observe several key experimental signatures of unconventional superconductivity in MATBG. We show that the tunnelling spectra below the transition temperature Tc are inconsistent with those of a conventional s-wave superconductor, but rather resemble those of a nodal superconductor with an anisotropic pairing mechanism. We observe a large discrepancy between the tunnelling gap ΔT, which far exceeds the mean-field BCS ratio (with 2ΔT/kBTc ~ 25), and the gap ΔAR extracted from Andreev reflection spectroscopy (2ΔAR/kBTc ~ 6). The tunnelling gap persists even when superconductivity is suppressed, indicating its emergence from a pseudogap phase. Moreover, the pseudogap and superconductivity are both absent when MATBG is aligned with hexagonal boron nitride. These findings and other observations reported here provide a preponderance of evidence for a non-BCS mechanism for superconductivity in MATBG.

19.
Med Educ Online ; 26(1): 1938504, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34134610

RESUMO

In May 2019, the World Health Assembly, in an unprecedented move, endorsed the inclusion of traditional medicine in the International Classification of Diseases, 11th Revision. In Japan, traditional medicine (known as Kampo) is regulated by the government and prescribed by over 90% of physicians along with modern medicine under the national health insurance system. Although Kampo education must be included in Japan's core medical curricula, there are significant challenges to implementation. In the educational context, the flipped classroom teaching method has received considerable attention in recent years. This study developed a Kampo e-learning program and verified the effectiveness of a flipped classroom using Kampo e-learning. The Kampo e-learning Committee determined three courses and assigned an administrator for each. The administrators appointed lecturers who developed Kampo e-learning lessons. Physicians, pharmacists, medical students, and pharmacy students were asked to participate in the e-learning program, and their comments and suggestions were collected after program completion. The flipped classroom was evaluated by implementing Kampo e-learning in the Kampo session with fourth-year students at Keio University School of Medicine in Japan. Seven courses were created, including four based on volunteer suggestions. The 'Systematic Kampo Curricula' featured 88 lessons developed by 54 Kampo specialists. Out of 118 fourth-year medical students who participated in the flipped classroom, 113 registered for the Kampo e-learning program, 100 attended the session, and 88 answered the post-session questionnaire. Among the students who answered the questionnaire, 86.4% were satisfied with the flipped classroom, 79.5% replied that the program made them understand Kampo and 80.7% stated that it should be adopted. The flipped classroom using Kampo e-learning program was shown to be attractive in one medical school. Further expanded study is necessary in the near future to reveal the usefulness of the flipped classroom of Kampo learning.


Assuntos
Educação a Distância , Pessoal de Saúde/educação , Medicina Kampo/métodos , Currículo , Humanos , Internet , Japão , Aprendizagem , Aprendizagem Baseada em Problemas/métodos , Universidades
20.
Nano Lett ; 21(12): 5301-5307, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34096736

RESUMO

The allotropic affinity for bulk silicon and unique electronic and optical properties make silicene a promising candidate for future high-performance devices compatible with mature complementary metal-oxide-semiconductor technology. However, silicene's outstanding properties are not preserved on its most prominent growth templates, due to strong substrate interactions and hybridization effects. In this letter, we report the optical properties of silicene epitaxially grown on Au(111). A novel in situ passivation methodology with few-layer hexagonal boron nitride enables detailed ex situ characterization at ambient conditions via µ-Raman spectroscopy and reflectance measurements. The optical properties of silicene on Au(111) appeared to be in accordance with the characteristics predicted theoretically for freestanding silicene, allowing the conclusion that its prominent electronic properties are preserved. The absorption features are, however, modified by many-body effects induced by the Au substrate due to an increased screening of electron-hole interactions.

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