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Up-Regulation of Local TGF-β Contributes to a Decrease in Renal Tubular Na⁺-K⁺ ATPase and Hyperkalemia in a Mouse Model of Crush Syndrome

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Pharmacology & Pharmacy 2016年第12期7卷 481-492页

作者： Shinya mizuno yoko mizuno-horikawa Department of Biochemistry Osaka University Graduate School of Medicine Suita Japan Department of Immunology and Microbiology Osaka University Graduate School of Medicine Suita Japan The Institute of Experimental Animal Sciences Suita Japan

Hyperkalemia is one of the most important risk factors in patients suffering from crush syndrome with rhabdomyolysis. Glycerol-injected animals have been used as an experimental model of rhabdomyolysis-induced acute kidney injury (AKI), but little information is available for the onset and molecular mechanism of hyperkalemia. In our murine model, plasma potassium levels increased after a single injection of 50%-glycerol solution (10 ml/kg, i.m.) during the progression of muscular and renal injuries. Renal tubular Na+-K+-ATPase functions as ion-exchange pomp for potassium clearance from blood into renal tubular epithelial cells. Renal histochemistry revealed an apparent decrease in the tubular Na+-K+-ATPase expression, especially at 24 hours post-glycerol challenge in our AKI model. In contrast to the loss in active Na+-K+-ATPase, there was a significant increase in the renal levels of transforming growth factor-β (TGF-β) that is known to suppress Na+-K+-ATPase production in vitro. When anti-TGF-β antibody was administered in mice after the glycerol challenge, the suppression of renal Na+-K+-ATPase activity was partially restored. As a result, hyperkalemia was improved in the TGF-β-neutralized AKI mice, associated with a significant decrease in plasma potassium concentration. Taken together, we predict that endogenous TGF-β is a key regulator for inhibiting Na+-K+-ATPase production and, in part, enhancing hyperkalemia during progression of rhabdomyolysis-induced AKI. This is, to our knowledge, the first report to determine a critical role of endogenous TGF-β in renal potassium metabolism during crush syndrome.

关键词： Rhabdomyolysis AKI Hyperkalemia Na+-K+-ATPase TGF-β

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Pedestrian trajectory prediction method based on the Social-LSTM model for vehicle collision

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Transportation Safety and Environment 2024年第3期6卷 140-151页

作者： Yong Han Xujie Lin Di Pan Yanting Li Liang Su Robert Thomson Koji mizuno School of Mechanical and Automotive Engineering Xiamen University of TechnologyXiamen 361024China Fujian Province Key Laboratory of Advanced Design and Manufacturing of Buses Xiamen 361024China Engineering Research Institute of Xiamen Kinglong United Automobile Industry Co. Ltd.Xiamen 361000China Chalmers University of Technology Gothenburg 41296Sweden Department of Mechanical Systems Engineering Nagoya UniversityNagoya 464-8603Japan

Techniques for predicting the trajectory of vulnerable road users are important to the development of perception systems for autonomous vehicles to avoid *** most effective trajectory prediction methods,such as Social-LSTM,are often used to predict pedestrian trajectories in normal passage ***,they can produce unsatisfactory prediction results and data redundancy,as well as difficulties in predicting trajectories using pixel-based coordinate systems in collision avoidance *** is also a lack of validations using real vehicle-to-pedestrian *** address these issues,some insightful approaches to improve the trajectory prediction scheme of Social-LSTM were proposed,such methods included transforming pedestrian trajectory coordinates and converting image coordinates to world *** YOLOv5 detection model was introduced to reduce target loss and improve prediction *** DeepSORT algorithm was employed to reduce the number of target transformations in the tracking *** Perspective Transformation(IPT)and Direct Linear Transformation(DLT)theories were combined to transform the coordinates to world coordinates,identifying the collision location where the accident could *** performance of the proposed method was validated by training tests using MS COCO(Microsoft Common Objects in Context)and ETH/UCY *** results showed that the target detection accuracy was more than 90%and the prediction loss tends to decrease with increasing training steps,with the final loss value less than 1%.The reliability and effectiveness of the improved method were demonstrated by benchmarking system performance to two video recordings of real pedestrian accidents with different lighting conditions.

关键词： vehicle-to-pedestrian collisions pedestrian trajectory prediction YOLOvB DeepSORT Social-LSTM

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Steroidal scaffold decorations in Solanum alkaloid biosynthesis

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Molecular Plant 2024年第8期17卷 1236-1254页

作者： Rosalind Lucier Mohamed O.Kamileen yoko Nakamura Sofiia Serediuk Ranjit Barbole Jens Wurlitzer Maritta Kunert Sarah Heinicke Sarah E.O'Connor Prashant D.Sonawane Department of Natural Product Biosynthesis Max Planck Institute for Chemical Ecology07745 JenaGermany Research Group Biosynthesis and NMR Max Planck Institute for Chemical Ecology07745 JenaGermany Biochemical Sciences Division CSIR-National Chemical LaboratoryPune 411008MaharashtraIndia

Steroidal glycoalkaloids(SGAs)are specialized metabolites produced by hundreds of Solanum species,including important vegetable crops such as tomato,potato,and *** it has been known that SGAs play important roles in defense in plants and“anti-nutritional"effects(e.g.,toxicity and bitterness)to humans,many of these molecules have documented anti-cancer,anti-microbial,antiinflammatory,anti-viral,and anti-pyretic *** these,α-solasonine andα-solamargine isolated from black nightshade(Solanum nigrum)are reported to have potent anti-tumor,anti-proliferative,and anti-inflammatory ***,α-solasonine andα-solamargine,along with the core steroidal aglycone solasodine,are the most widespread SGAs produced among the Solanum ***,it is still unknown how plants synthesize these bioactive steroidal *** comparative metabolomictranscriptome-guided approach,biosynthetic logic,combinatorial expression in Nicotiana benthamiana,and functional recombinant enzyme assays,here we report the discovery of 12 enzymes from *** that converts the starting cholesterol precursorto solasodine aglycone,and the downstreamα-solasonine,α-solamargine,and malonyl-solamargine SGA *** further identified six enzymes from cultivated eggplant that catalyze the production ofα-solasonine,α-solamargine,and malonyl-solamargine SGAs from solasodine aglycone via glycosylation and atypical malonylation *** work provides the gene tool box and platform for engineering the production of high-value,steroidal bioactive molecules inheterologoushosts usingsyntheticbiology.

关键词： steroidal glycoalkaloids Solanum biosynthetic pathway α-solamargine malonyl-solamargine specialized metabolites

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Enzyme-linked immunosorbent assay of 3 Screen Islet Cell Autoantibody in patients with autoimmune thyroid disease

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World Journal of Diabetes 2024年第5期15卷 935-944页

作者： Eiji Kawasaki Hidekazu Tamai Takahiro Fukuyama yoko Sagara Ryutaro Hidaka Aira Uchida Masayuki Tojikubo Narihito Tatsumoto Yuko Akehi Yuji Hiromatsu The Diabetes Thyroid and Endocrine CenterShin-Koga HospitalKurume 830-8577Japan

BACKGROUND In recent years,the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediated type 1 diabetes(T1D).While it has been established that 20%-30%of T1D patients suffer from autoimmune thyroid disease(AITD),there is limited available data regarding the presence of anti-islet autoantibodies in AITD *** commercially available anti-islet autoantibodies,glutamic acid decarboxylase 65 autoantibodies(GADAs)are often the first marker measured in general clinical *** To investigate the frequency of anti-islet autoantibodies in AITD *** Our study involved four hundred ninety-five AITD patients,categorized into three distinct groups:AITD with T1D(n=18),AITD with phenotypic type 2 diabetes(T2D)(n=81),and AITD without diabetes(n=396),and the enzyme-linked immunosorbent assay(ELISA)was employed to determine the frequencies of 3 Screen Islet Cell Autoantibody(3 Screen ICA),GADA,insulinoma-associated antigen-2 autoantibodies(IA-2As),and zinc transporter 8 autoantibodies(ZnT8As)within these *** The frequency of 3 Screen ICA in AITD patients with T1D,T2D,and those without diabetes were 88.9%,6.2%,and 5.1%,respectively,with no significant difference seen between the latter two ***,the frequency of 3 Screen ICA was 11.1%higher in AITD patients with T1D,1.3%higher in AITD patients with T2D,and 1.1%higher in AITD patients without diabetes compared to GADA,***,12.5%,20.0%,and 20.0%of the 3 Screen ICA-positive patients were negative for ***,1.3%of the AITD patients who tested negative for 3 Screen ICA in both the AITD with T2D and non-diabetic AITD groups were found to be positive for individual *** the 3 Screen ICA-positive patients,there was a significantly higher proportion of individuals with multiple autoantibodies in AITD patients with T1D com

关键词： Anti-islet autoantibodies Autoimmune thyroid disease Real-world practice Retrospective study Type 1 diabetes

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Real-world efficacy and safety of tofacitinib treatment in Asian patients with ulcerative colitis

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World Journal of Gastroenterology 2024年第13期30卷 1871-1886页

作者： Kentaro Kojima Kenji Watanabe Mikio Kawai Soichi Yagi Koji Kaku Maiko Ikenouchi Toshiyuki Sato Koji Kamikozuru yoko yokoyama Tetsuya Takagawa Masahito Shimizu Shinichiro Shinzaki Department of Gastroenterology Hyogo Medical UniversityNishinomiya 663-8501Japan Department of Gastroenterology Gifu University Graduate School of MedicineGifu 501-1194Japan Department of Internal Medicine for Inflammatory Bowel Disease The University of ToyamaToyama 930-0194Japan Center for Clinical Research and Education Hyogo Medical UniversityNishinomiya 663-8501Japan

BACKGROUND Real-world data on tofacitinib(TOF)covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis(UC)are *** To investigate the long-term efficacy and safety of TOF treatment for UC,including clinical *** We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease *** consecutive UC patients who received TOF between May 2018 and February 2020 were *** were followed up until August *** primary outcome was the clinical response rate at week *** outcomes included clinical remission at week 8,cumulative persistence rate of TOF administration,colectomy-free survival,relapse after tapering of TOF and predictors of clinical response at week 8 and week *** The clinical response and remission rates were 66.3%and 50.5%at week 8,and 47.1%and 43.5%at week 48,*** overall cumulative clinical remission rate was 61.7%at week 48 and history of anti-tumor necrosis factor-alpha(TNF-α)agents use had no influence(P=0.25).The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8(30.9%vs 88.1%;P<0.001).Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8(odds ratio:0.61,95%confidence interval:0.45-0.82,P=0.001).Relapse occurred in 45.7%of patients after TOF tapering,and 85.7%of patients responded within 4 wk after *** 6 patients with herpes zoster(HZ)developed the infection after achieving remission by *** TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-α*** relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off *** attention is needed for tapering and H

关键词： Ulcerative colitis Tofacitinib Janus kinase inhibitor Real-world Biologics

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Usefulness of Newly Devised Clomiphene Citrate Administration Method Compared with the Conventional Method in Ovulation and Pregnancy

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Open Journal of Obstetrics and Gynecology 2024年第4期14卷 637-649页

作者： Makoto Kawamura Misaki Akiyama Remi Nakajima Eri Satoi yoko Ogaki Rieko Kanda Department of Obstetrics and Gynecology Kohseichuo General Hospital Tokyo Japan

Objective: Since not all women wish to conceive a child through aggressive treatment, we investigated the usefulness of modified repeated intracyclic clomiphene citrate (CC) therapy (repeated CC therapy) as a newly devised administration method. Methods: We evaluated the effects of CC administration on menstrual cycle length and retrospectively compared ovulation and pregnancy in 220 women who received CC at our hospital. Patients in the conventional method group received 50 mg per day for five days, starting on the fifth day of menstruation (withdrawal bleeding). Groups with and without menstrual cycle shortening after conventional CC administration were compared. The repeated CC therapy group was also compared with the non-shortened group. Repeated CC therapy was administered for the first five days as in the conventional method, and a second five-day repeat treatment was administered after an interval of five to seven days. Pregnancy rates, including indirect pregnancies, were evaluated by three different methods. Results: Ovulation and pregnancy rates were significantly better in the shortened group than in the non-shortened group (P < 0.001 and P = 0.010, respectively). Even in the non-shortened group, ovulation and pregnancy rates including indirect pregnancies were significantly improved when ovulation was observed with repeated CC therapy (P < 0.001 and P = 0.022, respectively). Conclusions: For patients whose menstrual cycle was not improved or shortened, repeated CC therapy as the newly devised CC administration method is useful as the next step after the conventional CC administration method.

关键词： Clomiphene Citrate Infertility Menstrual Cycle Ovulation Induction

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Six Amino Acids among Natural Moisturizing Factors Responsible for Skin Hydration: Improvement and Anti-Aging of Skin by Galactomyces Ferment Filtrate-PiteraTM Containing Skin Moisturizer

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Journal of Cosmetics, Dermatological Sciences and Applications 2024年第2期14卷 113-127页

作者： Kukizo Miyamoto yoko Munakata Keisuke Fujii Wang Summer Ley Yang Suda Sudarsana Masutaka Furue Research and Development Kobe Innovation Center Procter and Gamble Innovation GK Kobe Japan Global Scientific Communications P & G Guangzhou Ltd. Guangzhou China Department of Dermatology Graduate School of Medical Sciences Kyushu University Fukuoka Japan

Background: Natural moisturizing factors (NMFs) are filaggrin-derived components in the cornified layer that are critical for maintaining healthy skin moisturization and barrier function. However, studies have reported conflicting findings on the relationship between NMF levels and aging, while few studies have investigated this relationship clinically. To fill this research gap, we determined the levels of major NMF components such as free amino acids, pyrrolidone carboxylic acid, and urocanic acids, and individually verified their relationships with skin hydration, barrier function, age, and skin aging. Purpose: The objective of this study was to clinically investigate the relationship between NMF components levels and skin aging in facial skin. The main NMF components were obtained from facial skin and quantified. We then selected NMF components showing strong relationships to skin hydration, and analyzed the relationships of the levels of these selected NMF components with signs of skin aging, namely, texture, pores, wrinkles, and dullness (L-value). We also examined the efficacy of treatment with a skin care formula (SK-II Facial Treatment Essence, called SK-II FTE hereafter) including Galactomyces ferment filtrate (GFF, PiteraTM) on the selected NMF component levels associated with skin hydration and barrier function, and the signs of skin aging of texture, pores, wrinkles, and dullness (L-value). Method: We conducted two clinical trials in this research. In Study 1, we measured 23 NMF components using tape-stripped cornified layer to quantify them via an HPLC method in 196 Asian females aged 20 to 59 (mean S.D., 38.6 9.4). Facial visual aging parameters [texture, pores, wrinkles, and dullness (L-value)], as well as elasticity (R7), skin hydration, and TEWL, were quantified using facial skin imaging and skin physical property measurement devices. Study 2 was performed to evaluate whether the facial application of SK-II FTE affects the NMF levels and skin aging

关键词： NMF Amino Acid Visual Aging Parameter Hydration Aging Texture Pore Wrinkle Dullness Galactomyces Ferment Filtrate PiteraTM SK-II Facial Treatment Essence

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Quantification of In Vivo Epidermal Keratinocyte Architecture Associated with the Signs of Skin Aging and the Skin Benefit Evaluation by Application of Galactomyces Ferment Filtrate (Pitera)-Containing Skin Care Product

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Journal of Cosmetics, Dermatological Sciences and Applications 2024年第1期14卷 12-28页

作者： Kukizo Miyamoto yoko Munakata Keisuke Fujii Chenlu Lei Ley Yang Suda Sudarsana Masutaka Furue Research and Development Kobe Innovation Center Procter and Gamble Innovation GK Kobe Japan Global Scientific Communications P & G Guangzhou Ltd. Guangzhou China Department of Dermatology Graduate School of Medical Sciences Kyushu University Fukuoka Japan

Background: Aged skin exhibits visual alterations such as wrinkles, rough texture, pore dilation, and dull skin tone, as well as physiological aging, namely, decreased hydration and increased transepidermal water loss (TEWL). Recent advances in coherence tomography have also revealed that skin aging affects in vivo epidermal keratinocyte architecture. However, the interconnectivity between spatial architectural aging and visual/physiological aging parameters remains largely unknown. Purpose: To elucidate whether the tomographic keratinocyte architectural aging is correlated with visual and physiological skin aging parameters and to quantitatively evaluate the improvements of the architectural, visual, and physiological aging parameters by the daily treatment of the skin care formula containing Galactomyces Ferment Filtrate (GFF, 8X PiteraTM). Method: We measured the in vivo keratinocyte cellular architecture with two-photon stereoscopic tomography obtaining by-layer epidermal section images in 78 Asian females of various ages. Visual aging parameters were analyzed using a portable image capture system. Hydration and TEWL were also assessed. The anti-aging effects of GFF-containing skin moisturizer (SK-II LXP CreamTM) were also examined in two studies after twice-daily application for 2 (N = 35) and 4 (N = 32) weeks. Results: As for the keratinocyte cellular architecture, skin aging was significantly associated with decreased cell density and increased cell uniformity. These architectural aging parameters were significantly correlated with visual and physiological aging parameters, namely, rough texture, wrinkles, pore dilation, dull skin tone, dehydration, and increased TEWL. The strong interconnectivity allowed us to develop formulae to estimate the keratinocyte architecture from visual aging parameters. Moreover, twice-daily application of SK-II significantly improved the keratinocyte architecture associated with multiple skin aging visual an

关键词： Facial Skin Aging In Vivo Keratinocyte Cellular Architecture Visual Aging Pa-rameter Dehydration Interconnectivity New Trajectory Galactomyces Fer-ment Filtrate PiteraTM SK-II LXP CreamTM

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Reliability of urinary tests for antibody to Helicobacterpylori in patients with pulmonary tuberculosis

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World Journal of Gastroenterology 2005年第3期11卷 412-414页

作者： Takatsugu Yamamoto Taro Ishii Tomotaka Kawakami yoko Sase Chiaki horikawa Nozomu Aoki Masaki Sanaka Yasushi Kuyama Department of Internal Medicine Hospital attached to the Institute of Chemotherapy

AIM: Although the quality of currently available urinary tests for detecting antibody to Helicobacter pylori(H pylori) have been proved in some populations, the accuracy has not been studied regarding patients who suffer from pulmonary tuberculosis with multi-drug treatments. The present study was conducted to evaluate the accuracy of these urinary tests for antibody to H pylori in these patients. METHODS: Serum samples from 61 inpatients with pulmonary tuberculosis were tested using enzyme immunoassay, and urine samples were assayed by enzyme-linked immunosorbent assay method (URINELISA) and immunochromatography method (RAPIRAN). Medicines prescribed to the patients were recorded for medical charts, to evaluate the influences on the results of urinary tests. RESULTS: The sensitivity, specificity, and consistency of URINELJSA against the serum test were 93.1%, 65.6%, and 78.6% respectively, and those of RAPIRAN were 86.2%, 93.7%, and 90.1% respectively, which were almost equal to the data previously reported. Prescribed medicines had little influence on the results. CONCLUSION: The two urinary tests for detecting H pylori antibody have a diagnostic accuracy in patients with pulmonary tuberculosis given multiple anti-tuberculosis drugs.

关键词： Helicobacter pylori Pulmonary Tuberculosis Helicobacter pylori antibody Urinary tests

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Current perspectives of viral hepatitis

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World Journal of Gastroenterology 2024年第18期30卷 2402-2417页

作者： Daisuke Usuda Yuki Kaneoka Rikuo Ono Masashi Kato Yuto Sugawara Runa Shimizu Tomotari Inami Eri Nakajima Shiho Tsuge Riki Sakurai Kenji Kawai Shun Matsubara Risa Tanaka Makoto Suzuki Shintaro Shimozawa Yuta Hotchi Ippei Osugi Risa Katou Sakurako Ito Kentaro Mishima Akihiko Kondo Keiko mizuno Hiroki Takami Takayuki Komatsu Tomohisa Nomura Manabu Sugita Department of Emergency and Critical Care Medicine Juntendo University Nerima HospitalNerima 177-8521TokyoJapan Department of Sports Medicine Faculty of MedicineJuntendo UniversityBunkyo 113-8421TokyoJapan

Viral hepatitis represents a major danger to public health,and is a globally leading cause of *** five liver-specific viruses:Hepatitis A virus,hepatitis B virus,hepatitis C virus,hepatitis D virus,and hepatitis E virus,each have their own unique epidemiology,structural biology,transmission,endemic patterns,risk of liver complications,and response to antiviral *** remain few options for treatment,in spite of the increasing prevalence of viral-hepatitiscaused liver ***,chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality,even though effective treatments are available that could reduce or prevent most patients’*** 2016,the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030,along with a discussion of current gaps and prospects for both regional and global eradication of viral ***,treatment is sufficiently able to prevent the disease from reaching advanced ***,future therapies must be extremely safe,and should ideally limit the period of treatment necessary.A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral *** review aims to summarize the current state of knowledge on each type of viral hepatitis,together with major innovations.

关键词： Hepatitis A virus Hepatitis B virus Hepatitis C virus Hepatitis D virus Hepatitis E virus Current perspectives

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