This study aimed to analyze the safety and applicability of a 90-min duration of infusion (SDI) of obinutuzumab in patients with B-cell non-Hodgkin's lymphoma (NHL) in a tertiary hospital in China. This exploratory clinical trial was performed at Jiangsu Province Hospital. All patients were treated with the standard infusion regimen for the first infusion. If no grade ≥3 infusion-related reactions (IRRs) occurred, the subsequent infusions were given as SDI. The primary endpoint was the incidence of IRR during the standard infusion (3-4 h) and 90-min SDI regimens. This study enrolled 208 patients and all completed cycle 1. Forty-one patients (19.71%) had IRRs: five (2.40%) with grade 1, twenty-eight (13.46%) with grade 2, and eight (3.85%) with grade 3. The 41 patients had 71 IRRs, mainly fever (40.85%), chest pain/tightness (12.68%), and dyspnea (9.86%). The occurrence of IRRs in the first infusion was significantly lower in patients who received oral acetaminophen prophylaxis than those who did not (10.72% vs 30.21%, P<0.001). For the subsequent cycles with 90-min SDI, only two (0.25%) IRRs occurred among 814 infusions (one grade 1 hand numbness and one grade 2 chill/fever). The 90-min obinutuzumab SDI might be safe and feasible in patients with B-cell NHL in China. 90min min 90 (SDI Bcell B cell nonHodgkins non Hodgkin s (NHL China Hospital 3 ≥ infusionrelated related (IRRs 34 4 (3- h regimens 20 Fortyone Forty 19.71% 1971 19 (19.71% 2.40% 240 40 (2.40% twentyeight twenty 13.46% 1346 13 46 (13.46% 3.85% 385 85 (3.85% 7 40.85%, 4085 40.85% , (40.85%) paintightness pain tightness 12.68%, 1268 12.68% 12 68 (12.68%) 9.86%. 986 9.86% . 9 86 (9.86%) 10.72% 1072 10 72 (10.72 3021 30 21 30.21% P<0.001. P0001 P P<0.001 0 001 P<0.001) 0.25% 025 25 (0.25% 81 chill/fever. chillfever chill/fever chill chill/fever) (3 19.71 197 (19.71 2.40 24 (2.40 13.46 134 (13.46 3.85 38 8 (3.85 408 40.85 (40.85% 126 12.68 6 (12.68% 98 9.86 (9.86% 10.72 107 (10.7 302 30.21 P000 P<0.00 00 0.25 02 (0.25 ( 19.7 (19.7 2.4 (2.4 13.4 (13.4 3.8 (3.8 40.8 (40.85 12.6 (12.68 9.8 (9.86 10.7 (10. 30.2 P00 P<0.0 0.2 (0.2 19. (19. 2. (2. 13. (13. (3. 40. (40.8 12. (12.6 9. (9.8 10. (10 30. P0 P<0. 0. (0. (19 (2 (13 (40. (12. (9. (1 P<0 (0 (40 (12 (9 P< (4

RESUMO Objetivo: O efeito regulador do microRNA em doenças tem sido confirmado, e este artigo tentou avaliar a expressão do microRNA-210-3p na catarata relacionada à idade e avaliar o efeito da expressão anormal do miR-210-3p em células SAR01/04 induzidas por H2O2. Métodos: O método de transcrição reversa seguida de reação em cadeia da polimerase (RT-PCR) quantitativa foi realizado para avaliar os níveis de miR-210-3p em amostras de humor aquoso. Análise de características operacionais do receptor foi feita para avaliar a capacidade de discriminação do miR-210-3p entre pacientes com catarata relacionada à idade e pessoas saudáveis. A análise de correlação de Pearson identificou a correlação do miR-210-3p e índices de estresse oxidativo, como superóxido dismutase, glutationa peroxidase, malonaldeído. O ensaio de contagem de células kit-8 (cck-8) e o ensaio no sistema Transwell foram utilizados para estimar a função biológica do formato de células de catarata relacionada com a idade induzida por H2O2. Os níveis de índices de estresse oxidativo como superóxido dismutase, glutationa peroxidase e malonaldeído foram detectados para avaliar o grau de dano do estresse oxidativo em formato de células de catarata relacionada à idade. A relação entre miR-210-3p e seu gene alvo foi verificada por análise do gene repórter luciferase. Resultados: A expressão miR-210-3p foi elevada no humor aquoso de pacientes com catarata relacionada à idade. A expressão miR-210-3p altamente expressiva mostrou alto valor diagnóstico para catarata relacionada à idade e foi significativamente associado ao nível de marcadores de estresse oxidativo em pacientes com catarata relacionada à idade. A inibição de miR-210-3p pode reverter a estimulação do estresse oxidativo e os efeitos adversos da função celular induzida por H2O2. Conclusões: Esses dados sugeriram que a expressão miR-210-3p poderia promover a viabilidade celular, migração celular e estresse oxidativo ao direcionar genes ATG 7 relacionados à autofagia em modelo in vitro de células de catarata relacionadas à idade. Objetivo confirmado microRNA2103p microRNAp 210 3p p miR2103p miRp miR SAR0104 SAR SAR01 04 SAR01/0 H2O2 HO H Métodos RTPCR RT PCR (RT-PCR saudáveis dismutase kit8 kit 8 kit- cck8 cck (cck-8 luciferase Resultados Conclusões 21 SAR010 SAR0 0 SAR01/ H2O (cck- 2 (cck

ABSTRACT Purpose: The regulatory effect of microRNA on diseases has been confirmed. This study aimed to evaluate the expression of microRNA-210-3p in age-related cataracts and assess the effect of abnormal miR-210-3p expressions on H2O2-induced SAR01/04 cells. Methods: Reverse-transcription quantitative polymerase chain reaction method was performed to assess the levels of miR-210-3p in aqueous humor samples. Receiver operating characteristic analysis was employed to assess the discrimination ability of miR-210-3p between patients with age-related cataracts and healthy people, and Pearson correlation analysis was used to identify the correlation between miR-210-3p and oxidative stress indices such as superoxide dismutase, glutathione peroxidase, malonaldehyde. Cell counting kit-8 assay and Transwell assay were used to estimate the biological function of H2O2-induced age-related cataract cell model. The levels of oxidative stress indices such as superoxide dismutase, glutathione peroxidase, and malonaldehyde were measured to evaluate the degree of oxidative stress damage in the age-related cataract cell model. The relationship between miR-210-3p and its target gene was verified by luciferase reporter gene analysis. Results: The miR-210-3p expression was elevated in the aqueous humor of patients with age-related cataracts. A high miR-210-3p expression showed a high diagnostic value for age-related cataracts and was significantly associated with the level of oxidative stress markers in patients with age-related cataracts. The inhibition of miR-210-3p can reverse oxidative stress stimulation and adverse effects on H2O2-induced cell function. Conclusions: The results suggested that miR-210-3p could promote cell viability, cell migration, and oxidative stress by targeting autophagy-related gene 7 in in vitro age-related cataract cell model. Purpose confirmed microRNA2103p microRNAp 210 3p p agerelated age related miR2103p miRp miR H2O2induced HOinduced H2O2 induced H O SAR0104 SAR SAR01 04 SAR01/0 cells Methods Reversetranscription Reverse transcription samples people dismutase peroxidase kit8 kit 8 kit- model Results Conclusions viability migration autophagyrelated autophagy 21 HO H2O SAR010 SAR0 0 SAR01/ 2

Abstract Background: This randomized and controlled prospective study tested the hypothesis that closed-loop Target-Controlled Infusion (TCI) of propofol would be associated with better system performance when compared with open-loop controlled delivery of propofol. Methods: Patients scheduled for elective breast surgery were randomly assigned to two groups: a closed-loop group, in which propofol infusion was performed by a closed-loop TCI system that used the Bispectral Index (BIS) as a feedback parameter to titrate the rate of propofol infusion, and an open-loop group, in which propofol infusion was performed manually and guided by the bispectral index. Results: A total of 156 patients were recruited for this study (closed-loop group n = 79; open-loop group n = 77). The Global Score (GS) of the closed-loop group was lower than that of the open-loop group (34.3 and 42.2) (p = 0.044). The proportions of time with a BIS value between 40 and 60 were almost identical in the closed-loop group and the open-loop group (68.7 ± 10.6% and 66.7 ± 13.3%) (p = 0.318). The individuals in the closed-loop group consumed more propofol compared with those in the open-loop group (7.20 ± 1.65 mg.kg−1.h−1 vs. 6.03 ± 1.31 mg.kg−1.h−1, p < 0.001). No intraoperative recall, somatic events or adverse events occurred. No significant difference in heart rate was observed between the two groups (p = 0.169). Conclusion: The closed-loop protocol was associated with lower BIS variability and lower out-of-range BIS values, at the cost of a greater consumption of propofol when compared to the open loop group. Register number:ChiCTR-INR-17010399. Background closedloop closed TargetControlled Target Controlled (TCI openloop Methods (BIS index Results 15 79 77. 77 . 77) GS (GS 34.3 343 34 3 (34. 42.2 422 42 2 0.044. 0044 0.044 0 044 0.044) 4 6 68.7 687 68 7 (68. 106 10 10.6 667 66 66. 13.3% 133 13 0.318. 0318 0.318 318 0.318) 7.20 720 20 (7.2 165 1 65 1.6 mgkg1h1 mgkgh mg kg h mg.kg−1.h− vs 603 03 6.0 131 31 1.3 0.001. 0001 0.001 001 0.001) recall occurred 0.169. 0169 0.169 169 0.169) Conclusion outofrange out range values numberChiCTRINR17010399. numberChiCTRINR17010399 numberChiCTRINR number ChiCTR INR 17010399. 17010399 number:ChiCTR-INR-17010399 34. (34 42. 004 0.04 04 68. (68 10. 13.3 031 0.31 7.2 72 (7. 16 1. mgkg mgkg1h mg.kg−1.h 6. 000 0.00 00 016 0.16 numberChiCTRINR1701039 1701039 number:ChiCTR-INR-1701039 (3 0.0 (6 13. 0.3 7. (7 01 0.1 numberChiCTRINR170103 170103 number:ChiCTR-INR-170103 ( 0. numberChiCTRINR17010 17010 number:ChiCTR-INR-17010 numberChiCTRINR1701 1701 number:ChiCTR-INR-1701 numberChiCTRINR170 170 number:ChiCTR-INR-170 numberChiCTRINR17 17 number:ChiCTR-INR-17 numberChiCTRINR1 number:ChiCTR-INR-1 number:ChiCTR-INR- number:ChiCTR-INR

Coenzyme Q10 (CoQ10) is a potent antioxidant that is implicated in the inhibition of osteoclastogenesis, but the underlying mechanism has not been determined. We explored the underlying molecular mechanisms involved in this process. RAW264.7 cells received receptor activator of NF-κB ligand (RANKL) and CoQ10, after which the differentiation and viability of osteoclasts were assessed. After the cells were treated with CoQ10 and/or H2O2 and RANKL, the levels of reactive oxygen species (ROS) and proteins involved in the PI3K/AKT/mTOR and MAPK pathways and autophagy were tested. Moreover, after the cells were pretreated with or without inhibitors of the two pathways or with the mitophagy agonist, the levels of autophagy-related proteins and osteoclast markers were measured. CoQ10 significantly decreased the number of TRAP-positive cells and the level of ROS but had no significant impact on cell viability. The relative phosphorylation levels of PI3K, AKT, mTOR, ERK, and p38 were significantly reduced, but the levels of FOXO3/LC3/Beclin1 were significantly augmented. Moreover, the levels of FOXO3/LC3/Beclin1 were significantly increased by the inhibitors and mitophagy agonist, while the levels of osteoclast markers showed the opposite results. Our data showed that CoQ10 prevented RANKL-induced osteoclastogenesis by promoting autophagy via inactivation of the PI3K/AKT/mTOR and MAPK pathways in RAW264.7 cells. Q Q1 CoQ (CoQ10 determined process RAW2647 RAW RAW264 7 RAW264. NFκB NF κB RANKL (RANKL assessed CoQ1 andor HO H O H2O (ROS PI3KAKTmTOR PIKAKTmTOR PI3K AKT mTOR PI K tested Moreover agonist autophagyrelated related measured TRAPpositive TRAP positive PIK ERK p p3 reduced FOXO3LC3Beclin1 FOXOLCBeclin FOXO3 LC3 Beclin1 FOXO LC Beclin FOXO3/LC3/Beclin augmented results RANKLinduced induced (CoQ1 RAW26 KAKTmTOR FOXO3LC3Beclin (CoQ RAW2

Abstract Objective This study explored the pharmacological mechanism of Tanshinone IIA (TAN IIA) in the treatment of Osteoarthritis (OA), which provided a certain reference for further research and clinical application of Tan IIA in OA. Methods CHON-001 cells were stimulated with 10 μg/mL IL-1β for 48 h and treated with 10 μM TAN IIA for 48 h. Cellular viability and apoptosis were evaluated by CCK-8 assay and flow cytometry, and Cleaved caspase-3 was measured by Immunoblot assay and RT-qPCR. TNF-α, IL-6, and iNOS in CHON-001 cells were determined by RT-qPCR and ELISA. To further verify the effect of TAN IIA on OA, a rat model of OA in vivo was established by right anterior cruciate ligament transection. TAN IIA was administered at 50 mg/kg or 150 mg/kg for 7 weeks. The degree of cartilage destruction in OA rats was observed by TUNEL and HE staining. Cleaved caspase-3 and FBXO11 were measured by immunohistochemical staining, RT-qPCR, and Immunoblot. TNF-α, IL-6, and iNOS in chondrocytes of OA rats were detected by ELISA. Results IL-1β stimulated CHON-001 cell apoptosis and inflammation, and TAN IIA had anti-apoptosis and anti-inflammatory effects on IL-1β-regulated CHON-001 cells. TAN IIA down-regulated FBXO11 and inhibited PI3K/AKT and NF-κB pathways, thereby alleviating apoptotic and inflammatory reactions in CHON-001 cells under IL-1β treatment. Moreover, TAN IIA treatment improved chondrocyte apoptosis and inflammations in OA rats. Conclusion TAN IIA inhibits PI3K/Akt and NF-κB pathways by down-regulating FBXO11 expression, alleviates chondrocyte apoptosis and inflammation, and delays the progression of OA. , (OA) CHON001 CHON 001 CHON-00 1 μgmL μg mL IL1β ILβ IL 1β β 4 CCK8 CCK 8 CCK- cytometry caspase3 caspase 3 caspase- RTqPCR. RTqPCR RT qPCR. qPCR TNFα, TNFα TNF α, α TNF-α IL6, IL6 6, 6 IL-6 ELISA transection 5 mgkg mg kg 15 weeks staining FBXO FBXO1 RTqPCR, qPCR, inflammation antiapoptosis anti antiinflammatory IL1βregulated ILβregulated regulated downregulated down PI3KAKT PIKAKT PI3K AKT PI K NFκB NF κB Moreover PI3KAkt PIKAkt Akt downregulating regulating expression (OA CHON00 00 CHON-0 IL- βregulated KAKT PIK KAkt CHON0 0 CHON-

Abstract Objective To explore the value of serum Dickkopf-3 (sDKK3) in predicting Early Neurological Deterioration (END) and in-hospital adverse outcomes in acute ischemic stroke (AIS) patients. Methods AIS patients (n = 200) were included and assessed by the National Institutes of Health Stroke Rating Scale. Serum Dkk3 levels were assessed by ELISA. END was defined as an increase of ≥ 4 points in NIHSS score within 72h. The biological threshold of sDKK3 level and END occurrence were predicted based on X-tile software. Primary outcomes were END and all-cause death, and the secondary outcome was ICU admission during hospitalization. The logistic regression model and Cox risk regression model were applied to evaluate the relationship between DKK3 level and END incidence, all-cause in-hospital mortality, and in-hospital adverse outcomes (ICU admission). Results During hospitalization, the incidence of END in patients with AIS was 13.0 %, and the mortality rate within 7 days after END was 11.54 % (3/26). In patients below the serum DKK3 cutoff (93.0 pg/mL), the incidence of END was 43.5 % (20/48). Patients with lower sDKK3 levels were associated with a 1.188-fold increased risk of developing END (OR = 1.188, 95 % CI 1.055‒1.369, p < 0.0001). However, there was no significant association with admission to the ICU. sDKK3 below the threshold (93.0 pg/mL) was a risk factor for death. Conclusion Predictive threshold levels of serum DKK3 based on X-tile software may be a potential predictive biomarker of in-hospital END in patients with AIS, and low levels of DKK3 are independently associated with increased in-hospital mortality. Dickkopf3 Dickkopf 3 Dickkopf- sDKK (sDKK3 (END inhospital hospital (AIS n 200 Scale Dkk ELISA 72h h Xtile X tile allcause all cause death hospitalization DKK admission. . admission) 130 13 0 13. 1154 11 54 11.5 3/26. 326 3/26 26 (3/26) 93.0 930 93 (93. pg/mL, pgmL pg/mL , pg mL 435 43 5 43. 20/48. 2048 20/48 20 48 (20/48) 1.188fold 1188fold fold 1.188 1 188 OR 1188 9 10551369 055 369 1.055‒1.369 0.0001. 00001 0.0001 0001 0.0001) However (sDKK 115 11. 32 3/2 2 (3/26 93. (93 204 20/4 (20/48 188fold 1.18 18 118 1055136 05 36 1.055‒1.36 0000 0.000 000 3/ (3/2 (9 20/ (20/4 1.1 105513 1.055‒1.3 0.00 00 (3/ ( (20/ 1. 10551 1.055‒1. 0.0 (3 (20 1055 1.055‒1 0. (2 105 1.055‒ 10 1.055 1.05 1.0

Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is a key transcription factor in the antioxidant response and is associated with various chronic diseases. The aim of this study was to explore the action of esculetin, a natural dihydroxy coumarin, on attenuating middle cerebral artery occlusion (MCAO) and reperfusion, and whether its effect is dependent on Nrf2 activation, as well as nuclear factor-kappa B (NF-κB) inhibition. Two doses of esculetin (20 and 40 mg/kg) were tested on rats with MCAO reperfusion. Neurological deficiency, oxidative stress, and pathological analyses were performed to evaluate its effect. An in vitro analysis was also used to confirm whether its action was dependent on the Nrf2/HO-1/NQO-1 pathway. Compared with MCAO reperfusion rats, esculetin improved infarct volume and increased normal-shaped neuron cells by decreasing tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-1β levels. The oxidative stress parameter malondialdehyde (MDA) decreased and the activity of superoxide dismutase (SOD) and glutathione/glutathione disulfide (GSH/GSSG) ratio increased after esculetin treatment. Moreover, esculetin inhibited NF-κB activation induced by MCAO. In vitro, hypoxia/reoxygenation (H/R) impaired the viability of rat neuron cells and esculetin showed a neuron protection effect on cells. Nrf2 inhibitor Brusatol inhibited the activation of Nrf2, heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase 1 (NQO-1) caused by esculetin and abolished its protection effect. Esculetin protected cerebral neurons from ischemia-reperfusion injury by inhibiting NF-κB and Nrf2/HO-1/NQO-1 activation. NFE2related NFErelated NF E2 related E Nrf (Nrf2 diseases coumarin (MCAO factorkappa kappa NFκB κB (NF-κB inhibition 20 (2 4 mg/kg mgkg mg kg deficiency Nrf2/HO1/NQO1 Nrf2HO1NQO1 NrfHONQO Nrf2/HO 1/NQO HO NQO Nrf2/HO-1/NQO- pathway normalshaped normal shaped factoralpha alpha TNFα, TNFα TNF α , (TNF-α) IL6, IL6 IL 6, 6 (IL)-6 IL1β ILβ 1β β levels MDA (MDA SOD (SOD glutathioneglutathione glutathione GSH/GSSG GSHGSSG GSH GSSG (GSH/GSSG treatment Moreover hypoxiareoxygenation hypoxia reoxygenation H/R HR H R (H/R oxygenase1 oxygenase oxygenase- HO1, HO1 (HO-1) NADPH NAD P NQO1 (NQO-1 ischemiareperfusion ischemia NFE (Nrf ( Nrf2/HO1/NQO Nrf2HO1NQO Nrf2HO NrfHO 1NQO Nrf2/HO-1/NQO (TNF-α (IL)- (HO-1 (NQO- (IL) (HO- (NQO (IL (HO

Designing highly efficient dialkylphosphinic acid extractant for zirconium/hafnium separation relies on systematic structure-property studies. In this paper, dialkylphosphinic acids with different substituents at β-C, γ-C and δ-C for zirconium and hafnium extraction and separation from H2SO4 media were investigated. The results show that substituents at β-C, γ-C and δ-C reduce the extraction ability of dialkylphosphinic acids for both zirconium and hafnium. The substituent effect at β-C is greater than that at γ-C and δ-C. The larger steric hindrance of the substituents (ethyl > methyl > H), the weaker extraction ability of the dialkylphosphinic acids. The zirconium and hafnium separation behavior is related to the extraction ability of dialkylphosphinic acids. Dialkylphosphinic acids with stronger extraction ability show better zirconium/hafnium separation performance at higher acidity of 2.0 mol L-1 H2SO4, while those with weaker extraction ability show better zirconium and hafnium separation performance at lower acidity of 0.25 mol L-1 H2SO4. The highest hafnium/zirconium separation factor (βHf/Zr) in the current study occurs with (2-ethylhexyl)(2,4,4-trimethylpentyl)phosphinic acid (USTB-1), which reaches 19.2. zirconiumhafnium structureproperty structure property studies paper βC, βC β C, C γC γ δC δ HSO H SO H2SO investigated δC. C. ethyl H, , H) 20 2 0 2. L1 L 1 L- 025 25 0.2 hafniumzirconium βHf/Zr βHfZr βHf Zr (βHf/Zr 2ethylhexyl2,4,4trimethylpentylphosphinic 2ethylhexyl244trimethylpentylphosphinic ethylhexyltrimethylpentylphosphinic ethylhexyl 2,4,4 trimethylpentyl phosphinic 4 USTB1, USTB1 USTB (USTB-1) 192 19 19.2 02 0. 2ethylhexyl2 4trimethylpentylphosphinic trimethylpentylphosphinic 244 2,4, (USTB-1 19. 2ethylhexyl 24 2,4 (USTB- 2, (USTB

Abstract Background Oxidative stress is strongly associated with cellular senescence. Numerous studies have indicated that microRNAs (miRNAs) play a critical part in cellular senescence. MiR-181a was reported to induce cellular senescence, however, the potential mechanism of miR-181a in hydrogen peroxide (H2O2)-induced cellular senescence remains obscure. Objective The aim of this study is to investigate the role and regulatory mechanism of miR-181a in H2O2-induced cellular senescence. Methods Human foreskin fibroblasts (HFF) transfected with miR-181a inhibitor/miR-NC with or without H2O2 treatment were divided into four groups: control + miR-NC/miR-181a inhibitor, H2O2 + miR-NC/miR-181a inhibitor. CCK-8 assay was utilized to evaluate the viability of HFF. RT-qPCR was used to measure the expression of miR-181a and its target genes. Protein levels of protein disulfide isomerase family A member 6 (PDIA6) and senescence markers were assessed by western blotting. Senescence-associated β-galactosidase (SA-β-gal) staining was applied for detecting SA-β-gal activity. The activities of SOD, GPx, and CAT were detected by corresponding assay kits. The binding relation between PDIA6 and miR-181a was identified by luciferase reporter assay. Results MiR-181a inhibition suppressed H2O2-induced oxidative stress and cellular senescence in HFF. PDIA6 was targeted by miR-181a and lowly expressed in H2O2-treated HFF. Knocking down PDIA6 reversed miR-181a inhibition-mediated suppressive impact on H2O2-induced oxidative stress and cellular senescence in HFF. Study limitations Signaling pathways that might be mediated by miR-181a/PDIA6 axis were not investigated. Conclusion Downregulated miR-181a attenuates H2O2-induced oxidative stress and cellular senescence in HFF by targeting PDIA6. miRNAs (miRNAs MiR181a MiRa MiR 181a however miR181a miRa miR H2O2induced HOinduced induced H O obscure (HFF inhibitor/miRNC inhibitormiRNC inhibitor/miR NC inhibitor HO H2O groups miRNC/miR181a miRNCmiR181a miRNCmiRa NC/miR CCK8 CCK 8 CCK- RTqPCR RT qPCR genes PDIA (PDIA6 blotting Senescenceassociated Senescence βgalactosidase β galactosidase SAβgal SA gal (SA-β-gal activity SOD GPx kits H2O2treated HOtreated treated inhibitionmediated miR181a/PDIA6 miR181aPDIA6 miRaPDIA 181a/PDIA6 miR-181a/PDIA investigated miRNC inhibitormiR miRNCmiR NCmiR (PDIA miR181a/PDIA aPDIA miR181aPDIA 181aPDIA6 181a/PDIA 181aPDIA

Abstract Kaempferol, an important flavonol, has numerous health-beneficial bioactivities and possesses a great potential for application in medicine, food, and cosmetics industries. To improve the production of kaempferol in an in vitro synthetic biosystem, we designed and constructed a panel of bifunctional enzymes by fusing the flavanone 3-hydroxylase (AtF3H) and the flavonol synthase (AtFLS1) of Arabidopsis thaliana with different orientation and different peptide linker type and length. By comparing the output of kaempferol, we obtained a highly active bifunctional enzyme AtF3H-(GGGGS)2-AtFLS1 with a Km value of 0.129 ± 0.016 mM. After optimization of a series of reaction parameters, kaempferol was produced at 100.54 ± 0.54 mg/L, the currently highest kaempferol output in an in vitro synthetic biosystem, and the substrate conversion rate was 68.26% ± 0.05%. In addition, we observed substrate inhibition for the AtFLS1, which eventually limited the production of kaempferol. This study provides a highly active biocatalyst for production of kaempferol and an insight into biosynthesis of other valuable molecules. Kaempferol healthbeneficial health beneficial medicine food industries biosystem 3hydroxylase hydroxylase 3 AtF3H AtFH AtF H (AtF3H AtFLS1 AtFLS (AtFLS1 length AtF3HGGGGS2AtFLS1 AtFHGGGGSAtFLS GGGGS 2 AtF3H-(GGGGS)2-AtFLS 0129 0 129 0.12 0016 016 0.01 mM parameters 10054 100 54 100.5 054 0.5 mgL mg L mg/L 6826 68 26 68.26 005 05 0.05% addition molecules (AtFLS HGGGGS AtF3HGGGGS2AtFLS 012 12 0.1 001 01 0.0 1005 10 5 100. 0. 682 6 68.2 00 0.05 1 68.

Abstract Polysaccharides are a class of biological macromolecules made up of sugar chains with multiple glycosidic bonds. To explore the extracted, purified, carboxymethylated and phosphorylated modified to obtained carboxymethylated polysaccharides (HSPS) and phosphorylated polysaccharides (HSPP), and the HSPS and HSPP were characterized and analyzed, and their antioxidant activity measured. Response surface design was used for the synthesis process of HSPS and HSPP, the structure characterization and antioxidant activities of HSPS and HSPP were evaluated. The results showed that the Mw and Mn of HSP were 14.66 kDa and 8.39 kDa, respectively. The monosaccharides were mainly galactose, glucose, xylose, and arabinose in a molar ratio of 37.68%: 24.43%: 13.63%: 9.18%. The optimal synthesis conditions for HSPS were as follows: reaction time of 2.01 h, reaction temperature of 44.61°C and the amount of monochloroacetic acid necessary was 1.18 g. The optimal synthesis conditions for HSPP were: reaction time of 4.28 h, reaction temperature of 80.78°C, and reaction pH of 8.98. HSPS and HSPP have scavenging effects on ABTS, super oxideanion and hydroxyl radicals. The HSPS and HSPP were characterized and analyzed, and their antioxidant activity measured. bonds extracted purified (HSPS , (HSPP) analyzed measured evaluated 1466 14 66 14.6 839 8 39 8.3 respectively galactose glucose xylose 37.68% 3768 37 68 24.43% 2443 24 43 13.63% 1363 13 63 918 9 18 9.18% follows 201 2 01 2.0 h 4461C C 44 61 118 1 1.1 g 428 4 28 4.2 8078C 80 78 80.78°C 898 98 8.98 ABTS radicals (HSPP 146 6 14. 83 3 8. 37.68 376 24.43 244 13.63 136 91 9.18 20 0 2. 11 1. 42 4. 7 89 8.9 37.6 24.4 13.6 9.1 37. 24. 13. 9.

ABSTRACT This study investigated the effect of resveratrol on the immune and inflammatory responses and the mRNA levels of splenic toll-like receptor (TLR)-4 signaling pathway-related genes of broilers under heat stress (HS). One hundred and sixty-two birds were allocated to three groups, each with 6 replicates, for 21 continuous days. The three treatments were as follows: the control group (22 ± 1 °C), the HS (33 ± 1 °C for 10 h d-1 and 22 ± 1 °C for the remaining time) group and the HS + resveratrol (400 mg kg-1) group. At the end of the trial, one bird per replicate close to the average body weight (BW) was selected, exsanguinated, and slaughtered. Compared with the control group, the HS treatment decreased (p<0.05) final BW, average daily gain (ADG), average daily feed intake (ADFI), relative weight of bursa of Fabricius and spleen, serum immunoglobulin (Ig) Y, IgA and interleukin (IL)-10 contents, and splenic IL-10 mRNA level, while it increased (p<0.05) feed/gain, mRNA levels of splenic tumor necrosis factor-α (TNF-α), TLR-4, nuclear factor-kappa-B (NF-κB), IL-1β, and IL-6. Compared to the HS group, the HS+resveratrol group exhibited increased (p<0.05) final BW, ADG, relative weight of bursa of Fabricius and spleen, serum IgY, IgA and IL-10 contents, and splenic IL-10 mRNA level, while it exhibited lower (p<0.05) TNF-α, IL-1β and IL-6 contents in serum, and splenic TLR4, TNF-α, IL-1β, and NF-κB mRNA levels. In conclusion, resveratrol prevented a HS-impairment of the immune function of broilers by blocking the abnormal activation of the TLR4 signaling pathway. tolllike toll like TLR 4 (TLR)- pathwayrelated pathway related HS. . (HS) sixtytwo sixty two groups replicates 2 days follows (2 °C, C , °C) 33 (3 d1 d d- time 400 (40 kg1 kg kg-1 trial BW (BW selected exsanguinated slaughtered p<0.05 p005 p 0 05 (p<0.05 ADG (ADG) ADFI, ADFI (ADFI) spleen Ig (Ig Y IL10 IL (IL)-1 IL-1 level feedgain feed/gain factorα factor α TNFα, TNFα TNF (TNF-α) 4, TLR-4 factorkappaB kappa B NFκB, NFκB NF κB (NF-κB) IL1β, IL1β ILβ 1β, 1β β IL6. IL6 6. HSresveratrol IgY α, TNF-α IL- conclusion HSimpairment impairment (TLR) (HS ( 3 40 (4 kg- p<0.0 p00 (p<0.0 (ADG (ADFI IL1 (IL)- (TNF-α TLR- (NF-κB (TLR p<0. p0 (p<0. (IL) p<0 (p<0 (IL p< (p< (p

Abstract Objectives: Lung cancer was one of the most common malignancies around the world. It has great significance in to search for the mechanism of occurrence and development of lung cancer. LIM Domain Binding protein 2 (LDB2) belongs to the LIM-domain binding family, it can be used as a binding protein that combined with other transcription factors to form the transcription complex for regulating the expression of target genes. The expression of microRNA-96-5p (miR-96-5p) has been investigated in various tumors. The aim of this study is to investigate the potential role of LDB2 and miR-96-5p in lung cancer. Methods: Real-time quantitative PCR was applied to detect the expression of LDB2 and miR-96-5p. The proliferation, invasion, and metastasis of H1299 cells were analyzed by CCK8, transwell, and wound healing assay after LDB2 or miR-96-5p transfection. Luciferase activities assay and western blot were used to reveal the targeted regulation between LDB2 and miR-96-5p. Results: Here the authors found LDB2 was down-regulated in lung cancer tissues and negatively correlated with miR-96-5p expression, it could promote or inhibit the proliferation, invasion and metastasis of H1299 cells after LDB2 knockdown or overexpression and regulate the expression of cyclinD1, MMP9, Bcl-2, and Bax via ERK1/2 signaling pathway. Furthermore, miR-96-5p exerted its function by directly binding to 3′-UTR of LDB2 and regulating expression of LDB2. miR-96-5p could promote the proliferation, invasion, and metastasis of H1299 cells. Conclusion: These findings demonstrate that LDB2 can act as a new regulator to inhibit cell proliferation, invasion, and metastasis via the ERK1/2 signaling pathway, and miR-96-5p may be a potential promising molecular by targeting LDB2 in lung cancer. Objectives world LDB (LDB2 LIMdomain domain family genes microRNA965p microRNAp microRNA 96 5p p miR965p miRp miR (miR-96-5p tumors Methods Realtime Real time miR965p. 5p. proliferation H H129 CCK8 CCK transwell transfection Results downregulated down regulated cyclinD1 cyclinD MMP9 MMP Bcl2, Bcl2 Bcl 2, Bcl-2 ERK12 ERK ERK1 ERK1/ pathway Furthermore 3′UTR 3UTR UTR 3′ 3 Conclusion (LDB 9 H12 Bcl- H1

ABSTRACT Poultry is frequently contaminated by Salmonella, a pathogen leading to human health concern worldwide. This study aimed to evaluate the effect of Bacillus subtilis (BS)strain 048 (BS048) on the activation, phagocytosis, sterilization, cytokine secretion, and nitrogen oxide synthesis of HD11 chicken macrophages subjected to Salmonella enteritidis challenge, using lipopolysaccharide treatment as a negative control. The results showed: (1) BS048 had no significant effect on extracellular lactate dehydrogenase activity (p>0.05), while lipopolysaccharide treatment significantly increased extracellular lactate dehydrogenase activity (p<0.05);(2)BS048 significantly upregulated the expression levels of pro-inflammatory cytokines (interleukin (IL)-1â and IL-6), anti-inflammatory cytokines(IL-10 and transforming growth factor-â1), and anti-viral cytokine, interferon-â (p<0.01); (3)BS048 significantly upregulated the mRNA expression level of the inducible nitric oxide synthase and its activity as well as extracellular nitrogen oxide level (p<0.01). In conclusion, BS048 could improve anti-inflammatory and immune functions of HD11 chicken macrophages, without cytotoxic effects on these cells. worldwide BSstrain BS strain 04 (BS048 activation phagocytosis sterilization secretion HD HD1 challenge control showed 1 (1 BS04 p>0.05, p005 p p>0.05 , 0 05 (p>0.05) p<0.052BS048 p0052BS048 pBS p<0.05 2 (p<0.05);(2)BS04 proinflammatory pro inflammatory interleukin IL1â ILâ IL 1â â IL6, IL6 6 IL-6) antiinflammatory anti cytokinesIL10 cytokinesIL 10 cytokines(IL-1 factorâ1, factorâ1 factorâ factor â1 factor-â1) antiviral viral interferonâ interferon p<0.01 p001 01 (p<0.01) 3BS048 3 (3)BS04 p<0.01. . conclusion cells (BS04 ( BS0 p00 p>0.0 (p>0.05 052BS048 p<0.052BS04 p0052BS04 p<0.0 (p<0.05);(2)BS0 IL-6 cytokinesIL1 cytokines(IL- factor-â1 (p<0.01 3BS04 (3)BS0 (BS0 p0 p>0. (p>0.0 052BS04 p<0.052BS0 p0052BS0 p<0. (p<0.05);(2)BS IL- cytokines(IL factor-â (p<0.0 3BS0 (3)BS (BS p>0 (p>0. 052BS0 p<0.052BS p0052BS p<0 (p<0. 3BS p> (p>0 052BS p< (p<0 (p> (p< (p

Abstract We aimed to compare the effects of oxycodone hydrochloride and dezocine on hemodynamics and inflammatory factors in patients receiving gynecological laparoscopic surgery under general anesthesia. A total of 246 patients were divided into group A and B (n=123). Hemorheology indices were recorded 5 min after anesthesia (T0), 1 min after pneumoperitoneum (T1), when position was changed 5 min after pneumoperitoneum (T2), 15 min after pneumoperitoneum (T3), 1 min (T4) and 5 min (T5) after position was restored. Visual analogue scale scores 1, 2, 6, 12, 24 and 48 h after operation were recorded. Postoperative adverse reactions and visceral pain were observed. The expression levels of inflammatory factors were detected by enzyme-linked immunosorbent assay 12 h after operation. Compared with group A, group B had higher heart rate and mean arterial pressure at T2, lower central venous pressure and cardiac output at T1-T3, and higher systemic vascular resistance at T1-T5 (P<0.05). The incidence rate of pain syndrome in group A was lower (P<0.05). Group A had lower tumor necrosis factor-alpha and interleukin-6 expression levels and higher interleukin-10 level than those of group B (P<0.05). For gynecological laparoscopic surgery, oxycodone preemptive analgesia has superior outcomes to those of dezocine. n=123. n123 n n=123 . 123 (n=123) T0, T0 T , (T0) T1, T1 (T1) T2 (T2) T3, T3 (T3) T4 (T4 T5 (T5 restored 2 6 4 observed enzymelinked enzyme linked T1T3, T1T3 TT T1-T3 T1T5 T1-T P<0.05. P005 P P<0.05 0 05 (P<0.05) factoralpha factor alpha interleukin6 interleukin interleukin- interleukin10 10 interleukin-1 n12 n=12 (n=123 (T0 (T1 (T2 (T3 (T T1T P00 P<0.0 (P<0.05 interleukin1 n1 n=1 (n=12 P0 P<0. (P<0.0 n= (n=1 P<0 (P<0. (n= P< (P<0 (n (P< (P