Deubiquitination and Stabilization of PD-L1 by CSN5

Lim, Seung-Oe,Li, Chia-Wei,Xia, Weiya,Cha, Jong-Ho,Chan, Li-Chuan,Wu, Yun,Chang, Shih-Shin,Lin, Wan-Chi,Hsu, Jung-Mao,Hsu, Yi-Hsin,Kim, Taewan,Chang, Wei-Chao,Hsu, Jennifer L.,Yamaguchi, Hirohito,Ding Elsevier 2016 Cancer cell Vol.30 No.6

<P><B>Summary</B></P> <P>Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TNF-α stabilizes cancer cell PD-L1 in response to chronic inflammation </LI> <LI> Activation of NF-κB by TNF-α induces CSN5 expression leading to PD-L1 stabilization </LI> <LI> CSN5 enzyme activity controls T cell suppression via PD-L1 deubiquitination </LI> <LI> Destabilization of PD-L1 by CSN5 inhibitor curcumin benefits anti-CTLA4 therapy </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>

A new constructive neural network method for noise processing and its application on stock market prediction

Xi, L.,Muzhou, H.,Lee, M.H.,Li, J.,Wei, D.,Hai, H.,Wu, Y. Elsevier Science, B.V 2014 Applied soft computing Vol.15 No.-

In this paper, in order to optimize neural network architecture and generalization, after analyzing the reasons of overfitting and poor generalization of the neural networks, we presented a class of constructive decay RBF neural networks to repair the singular value of a continuous function with finite number of jumping discontinuity points. We proved that a function with m jumping discontinuity points can be approximated by a simplest neural network and a decay RBF neural network in L<SUP>2</SUP>(@?) by each @? error, and a function with m jumping discontinuity point y=f(x),x@?E@?@?<SUP>d</SUP> can be constructively approximated by a decay RBF neural network in L<SUP>2</SUP>(@?<SUP>d</SUP>) by each ε>0 error. Then the whole networks will have less hidden neurons and well generalization in the same of the first part. A real world problem about stock closing price with jumping discontinuity have been presented and verified the correctness of the theory.

High Sustained Virologic Response with Daclatasvir plus Asunaprevir in HCV GT-1b Chinese, Korean and Taiwanese without Baseline NS5A Polymorphisms

( F. Mcphee ),( L. Wei ),( Q. Xie ),( Y. Suzuki ),( J. Toyota ),( Y. Karino ),( K. Chayama ),( Y. Kawakami ),( M. L. Yu ),( S. H. Ahn ),( N. Zhou ),( H. Kumada ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Daclatasvir (DCV) plus asunaprevir (ASV) has demonstrated highsustained virologic response (SVR) in HCV genotype (GT-)1b infection.NS5A-Y93H and NS5A-L31 resistance-associated polymorphisms(RAPs) to DCV are known to impact DCV+ASV response in GT-1b-infectedJapanese. The effect of RAPs on SVR at posttreatment week12 (SVR12) to DCV+ASV was explored in mainland Chinese, Korean,and Taiwanese.Methods: Pooled data from 2 studies of DCV (60 mg daily) + ASV(100 mg capsule, twice-daily) for 24 weeks in GT-1b-infected interferon/ribavirin-naive and -experienced patients from mainland China,Korea, and Taiwan. Similar Japanese data (4 studies; n=445) werepooled for comparison. SVR12 with versus without baseline Y93Hand/or L31 RAPs was compared by age (<65 vs ≥65 years), cirrhosisstatus, and baseline HCV-RNA.Results: SVR12 and baseline NS5A sequences were available for 282patients (126 mainland Chinese [45%〕, 80 Koreans [28%〕, 76Taiwanese [27%〕). NS5A-Y93H and/or -L31 RAPs were observed pretreatmentin 8% mainland Chinese, 14% Korean, and 18%Taiwanese patients, compared with 19% in Japanese. SVR12 in allnon-Japanese patients is shown (Figure); rates were broadly similarbetween countries and with Japanese data (Japanese: 96% overallwithout RAPs, 41% with RAPs). Responses were lower among patientswith baseline RAPs. By contrast, SVR12 in patients without RAPs washigh (92-100%), irrespective of cirrhosis, age, or baseline HCV-RNA.Conclusions: At least 95% of HCV GT-1b-infected patients from mainlandChina, Korea or Taiwan without baseline NS5A-Y93H or -L31polymorphisms who had HCV-RNA ≤7 log10 IU/mL achieved SVR12on DCV+ASV, regardless of cirrhosis status and age.

Genistein Decreases food Intake, Body Weight, and Fat Pad Weight and Causes Adipose Tissue Apoptosis in Ovariectomized Female Mice

Hye-Kyeong Kim,Cassandra Nelson-Dooley,Mary Anne Della-Fera,Jeong-Yeh Yang,Wei Zhang.y Jiuhua Duan,Diane L. Hartzell,Mark W. Hamrick,Clifton A. Baile,성소희 전주국제발효식품엑스포 조직위원회 2006 발효 : 맛있는 잡지 Vol.2 No.2

Poster Session:PS 0479 ; Nephrology : Hypotonic Versus Isotonic Fluid Maintenance Therapy on Biochemical Outcomes after Major Surgery

( Wei Ying Jen ),( Margaret L Teng ),( Wee Chuan Hing ),( Valerie Ma ),( Shridhar Ganpathi Iyer ),( Chung Cheen Chai ),( Horng Ruey Chua ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Premixed hypotonic solutions of 0.33% saline + 5% dextrose + 10mmol/ L potassium-chloride (0.33S, tonicity 133mEq/L) and 0.9% saline ±dextrose (NS, tonicity 308mEq/L) are common peri-operative maintenance fiuids, but their effects on serum biochemistry are unclear. Methods: Using a single-centre, prospectively-maintained electronic database, we retrospectively examined post-operative biochemistry in adults maintained on exclusively 0.33S or NS peri-operatively, from March 2012 to September 2013. Outcomes included new-onset post-operative hyponatremia, hypokalaemia, hypoglycaemia, and acute kidney injury (AKI, =1.5x increase in serum creatinine); multivariate analyses were adjusted for demographics, comorbidities, surgery-types/duration, infusion time/ volumes, and hospital length-of-stay. Results: We studied 279 patients given 0.33S, and 279 NS controls matched for cumulative infusion volume. Mean age was 59(±18) years. More NS patients had diabetes mellitus, ischemic heart disease and chronic kidney disease (p<0.05). Surgery types included gastrointestinal/hepatobiliary (43%), orthopaedic (30%) and nephrectomy (3%). Mean fi uid volumes administered were 6.9(±3.3)L of 0.33S and 7.1(±5.6)L of NS (p=0.57), with 100% versus 52% of drips containing dextrose, respectively. More 0.33S patients (versus NS) developed hyponatremia (30% versus 17%, p<0.001); this difference was signifi cant for gastrointestinal/hepatobiliary (p=0.001) but not orthopaedic (p=0.74) surgeries. Less 0.33S patients (versus NS) had hypokalaemia (1% versus 10%, p<0.001), hypoglycaemia (1% versus 4%, p=0.01), and AKI (3% versus 8%, p=0.007). On multivariate analyses, 0.33S, gastrointestinal/hepatobiliary surgeries and nephrectomy were independently associated with hyponatremia; while NS, hypertension, longer infusion hours, and nephrectomy were independently associated with AKI (p<0.05). Conclusions: 0.33S infusion in post-surgical patients, especially post-gastrointestinal/ hepatobiliary surgeries, is strongly associated with hyponatremia, but with less hypokalaemia or hypoglycaemia, compared with NS. The association between NS administration and AKI is heavily confounded by baseline comorbidities and requires further prospective evaluation. Both fi uid types are not appropriate for isolated use, and more balanced maintenance fi uids are desired.

Effects of Iron from an Amino Acid Complex on the Iron Status of Neonatal and Suckling Piglets

Wei, K.Q.,Xu, Z.R.,Luo, X.G.,Zeng, L.L.,Chen, W.R.,Timothy, M.F. Asian Australasian Association of Animal Productio 2005 Animal Bioscience Vol.18 No.10

This experiment was conducted to investigate the effects of iron from an amino acid complex (Availa-$Fe^{\circledR}$) on the iron status of neonatal and suckling piglets. A total of 24 gestating sows (Landrace${\times}$Large White) were randomly allocated to three dietary treatments. The control diet contained 80 mg $kg^{-1}$ Fe from ferrous sulfate heptahydrate ($FeSO_4$.$7H_2O$), while the two experimental diets were supplemented with an additional 120 mg $kg^{-1}$ Fe from Availa-$Fe^{(R)}$ or $FeSO_4$.$7H_2O$, respectively. The lactating sows remained the same iron treatments as gestating sows, while neonatal piglets of 24 litters born from the above sows were allotted to another three treatments. Piglets from the sows of the control treatment were fed basal diet with no supplemental Fe as control treatment, but were injected with 100 mg Fe as Fe dextran at birth. Piglets from the sows of Availa-$Fe^{(R)}$ or $FeSO_4$.$7H_2O$ treatments were supplemented with 120 mg $kg^{-1}$ iron from Availa-$Fe^{(R)}$ or $FeSO_4$.$7H_2O$, respectively. The total born alive and weaned, and the average piglets weight at birth and at weaning were not significantly affected by the sow' dietary treatments (p>0.05). Iron from Availa-$Fe^{(R)}$ did not demonstrate a statistically significant improvement in hemoglobin concentration, hematocrit and plasma iron of sows on day 90 and 105 of pregnancy and the milk iron of sows during lactation (p>0.05). Neonatal piglets in the Availa-$Fe^{(R)}$ treatment had a significantly higher hemoglobin concentration (p<0.05) and higher hematocrit and plasma iron (p>0.05) than those in the other two treatments, respectively. The hemoglobin of suckling piglets in the Availa-$Fe^{(R)}$ treatment was higher than that of piglets in $FeSO_4$.$7H_2O$ treatment on day 28 (p<0.05). The total iron binding capacity of piglets in Availa-$Fe^{(R)}$ treatment was lower than that of piglets in the control and $FeSO_4$.$7H_2O$ treatment on day 14 (p<0.05), but there was not a statistically significant difference among three treatments on day 28 (p>0.05). However, the hemoglobin and hematocrit of suckling piglets injected with Fe were higher than those of piglets in the other two treatments (p<0.05). This study indicated that the addition of 120 mg $kg^{-1}$ iron from amino acid complex into the diets improved iron status of neonatal and nursing piglets more effectively than the addition of 120 mg $kg^{-1}$ iron from $FeSO_4$.$7H_2O$, however, this improvement of the organic Fe was not sufficient to replace the Fe injection for prevention of iron-deficiency anemia.

A strong convergence theorem for common fixed points of two relatively nonexpansive mappings and?its?applications

Wei, L.,Cho, Y. J.,Zhou, H. Korean Society for Computational Applied Mathemati 2009 Journal of applied mathematics & computing Vol.29 No.1

Gradual electroforming and memristive switching in Pt/CuO_<i>x</i>/Si/Pt systems

Wei, L L,Shang, D S,Sun, J R,Lee, S B,Sun, Z G,Shen, B G IOP Pub 2013 Nanotechnology Vol.24 No.32

<P>We report a memristive switching effect in Pt/CuO<SUB><I>x</I></SUB>/Si/Pt devices prepared by the rf sputtering technique at room temperature. Differently from other Cu-based metal filament switching systems, a gradual electroforming process, marked by a gradual increase of the device resistance and a gradual decrease of the device capacitance, was observed in the current–voltage and capacitance characteristics. After the gradual electroforming, the devices show a uniform memristive switching behavior. By Auger electron spectroscopy analysis, a model based on the thickness change of the SiO<SUB><I>x</I></SUB> layer at the CuO<SUB><I>x</I></SUB>/Si interface and Cu ion migration is proposed for the gradual electroforming and uniform memristive switching, respectively. This work should be meaningful for the preparation of forming-free and homogeneous memristive devices.</P>

Quantitative Study of the Reformation of Excess Sludge by Intense Aeration Under Nutrient-poor Conditions

L Guang Wei,Chen Liming,Toda Kiyoshi,Zhang Shuting The Korean Society for Biotechnology and Bioengine 2004 Biotechnology and Bioprocess Engineering Vol.9 No.6

In the course of anaerobic storage of excess sludge, odors due to chemicals such as hydrogen sulfide are produced. These odors cause many problems. Many methods have been developed to eliminate odors, but all current methods are not only costly, but also largely inef­fective. In this paper, we investigate the process of transformation of sludge microorganism cul­tures through intense aeration under nutrient-poor conditions, in terms of the selective adjust­ment and control of microorganism culture. The aerated sludge is subsequently returned to the adjusting pool, where the microorganisms inhibit odors, thus the excess sludge itself will act as an odor inhibitor. The process can be verified in terms of viability, in that the degradation capac­ity of the sludge was maintained after the intensely-aerated sludge was returned to the treat­ment system.

Integrated Safety and Tolerability of Daclatasvir plus Asunaprevir in Patients with Chronic HCV Genotype 1b Infection

( L. Wei ),( K. Chayama ),( W. L. Chuang ),( S. H. Bae ),( J. Y. Jang ),( R. Bhore ),( V. Vazquez ),( L. Mo ),( M. Linaberry ),( M. Treitel ),( H. Kumada ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: The combination of daclatasvir (DCV) plus asunaprevir (ASV)has demonstrated high sustained virologic response (SVR) rates andis generally well tolerated in clinical studies. This integrated analysisevaluated the safety profile of DCV (60mg once daily) and ASV (100mgsoftgel capsule or 200mg tablets twice daily in genotype 1b (GT1b)infected patients enrolled in four phase 3 and two phase 2 clinicalstudies conducted globally, including Asia.Methods: Integrated safety data from 1218 treatment-naive or treatment-experienced patients were analyzed for adverse events (AEs),serious AEs, discontinuations due to AEs and grade 3/4 AEs andlaboratory abnormalities reported on-treatment.Results: Patients were 58% female, median age was 58 years and23% had compensated cirrhosis. DCV+ASV was associated with infrequentserious AEs and discontinuations due to AEs (Table). Twelvepatients reported treatment-related serious AEs. The most commonAEs (any grade) were diarrhea, nausea, fatigue, and headache. Onepatient died due to coronary heart disease (not treatment-related).The most common grade 3/4 laboratory abnormalities were aminotransferaseelevations (more frequent among Japanese patients); however,all grade 3/4 laboratory abnormality occurred in <5% of patientsoverall. Grade 3/4 total bilirubin elevations were reported in <1%of patients. The DCV+ASV safety profile was similar in patients withor without cirrhosis.Conclusions: DCV+ASV was generally well tolerated across globalnon-Asian patient populations and in Asian patients from Japan, mainlandChina, Korea, and Taiwan.