Abstract The incidence of non-alcoholic fatty liver (NAFLD) remains high, and many NAFLD patients suffer from severe ischemia-reperfusion injury (IRI). Currently, no practical approach can be used to treat IRI. Puerarin plays a vital role in treating multiple diseases, such as NAFLD, stroke, diabetes, and high blood pressure. However, its role in the IRI of the fatty liver is still unclear. We aimed to explore whether puerarin could protect the fatty liver from IRI. C57BL/6J mice were fed with a high‐fat diet (HFD) followed by ischemia reperfusion injury. We showed that hepatic IRI was more severe in the fatty liver compared with the normal liver, and puerarin could significantly protect the fatty liver against IRI and alleviate oxidative stress. The PI3K-AKT signaling pathway was activated during IRI, while liver steatosis decreased the level of activation. Puerarin significantly protected the fatty liver from IRI by reactivating the PI3K-AKT signaling pathway. However, LY294002, a PI3K-AKT inhibitor, attenuated the protective effect of puerarin. In conclusion, puerarin could significantly protect the fatty liver against IRI by activating the PI3K-AKT signaling pathway. nonalcoholic non alcoholic (NAFLD ischemiareperfusion . (IRI) Currently diseases stroke diabetes pressure However unclear C57BL6J CBLJ C57BL 6J C BL J highfat fat HFD (HFD stress PI3KAKT PIKAKT PI3K AKT PI K activation LY294002 LY inhibitor conclusion (IRI CBL KAKT PIK LY29400 LY2940 LY294 LY29 LY2

BiOCl nanosheets modified with AuCu nanoparticles were successfully designed and fabricated for water reduction of CO2. The AuxCuy/BiOCl composites exhibited enhanced visible light absorption ability due to a surface plasmon resonance (SPR) effect. The AuxCuy/BiOCl composites could convert carbon dioxide to ethane (C2H6), while only CO was obtained over pure BiOCl nanosheets. In this study, the rate of C2H6 production (12.2 μmol h-1 g-1) and selectivity of C2H6 (75.7%) were obtained over the Au1Cu1/BiOCl photocatalyst under simulated sunlight illumination. The AuCu nanoparticles played the dual role of electron traps and hot electron donors, facilitating efficient separation and migration of the carriers. The photocatalyst exhibited steady photocatalytic activity over the test duration of 9 h. CO2 AuxCuyBiOCl AuxCuy SPR (SPR effect C2H6, CH , C H (C2H6) study C2H 12.2 122 12 2 (12. h1 h 1 h- g1 g g-1 75.7% 757 75 7 (75.7% Au1Cu1BiOCl AuCuBiOCl Au1Cu1 Au Cu illumination donors carriers (C2H6 12. (12 g- 75.7 (75.7 Au1Cu (C2H (1 75. (75. ( (75 (7

Silicon catalysts have very low catalytic activity in polyester (PET). However, titanium catalysts have high catalytic activity in polyester. The simultaneous use of titanium and silicon catalysts is effective in reducing the activity of a single titanium catalytic base agent. In addition, the glycol salts of titanium and silicon (Ti-EG and Si-EG) prepared in the present invention for use in the polyester catalytic process can avoid the introduction of other groups of impurities during the polyester catalytic process, which would lead to premature capping of the polyester in the process of polycondensation and chain building and make it difficult to increase the molecular weight, and thus affect the quality of the polyester. It has been verified that the ratio of Ti:Si is 1:1 (mol), and total amount added to the catalyst is 0.15% of the raw material amount, and the polycondensation temperature was 260-280 °C for 60 min. Compared with the single Ti-EG catalyst, the b* value of the synthesized PET was significantly reduced, and the molecular weight and other indexes did not change too much. In addition, at the end of catalysis, the catalyst was uniformly dispersed in the reaction system, which could be used as a matting agent for PET. . (PET) However addition TiEG Ti EG SiEG Si Si-EG TiSi 11 1 1: mol, mol , (mol) 015 0 15 0.15 260280 260 280 260-28 C 6 min b reduced much catalysis system (PET (mol 01 0.1 26028 26 28 260-2 0. 2602 2 260-

Abstract Fast calculations are widely required in the traditional applications and the emerging digital twin fields. For those considerations, a novel physics-based fast algorithm, namely generalized rotation-superposition method, is proposed for fast calculating linear elastic responses of generalized rotationally axisymmetric structures under arbitrary mechanical loads. This improved method breaks through the limitations of the previous basic rotation-superposition method in rotational similarity of load and structural axisymmetry, and greatly expands its application scope. In this paper, firstly, the basic theory of the rotation-superposition algorithm is introduced; secondly, the theoretical model of the generalized rotation-superposition method is established; thirdly, the effectiveness and accuracy are verified by using finite element simulations; finally, through a complex case study, the applicability of the generalized rotation-superposition method for complex engineering problems and its advantages in efficiently obtaining massive amounts of data are further illustrated. fields considerations physicsbased physics based rotationsuperposition rotation superposition loads axisymmetry scope paper firstly introduced secondly established thirdly simulations finally study illustrated

The overexpression of P-glycoprotein (P-gp/ABCB1) is a leading cause of multidrug resistance (MDR). Hence, it is crucial to discover effective pharmaceuticals that counteract ABCB1-mediated multidrug resistance. FRAX486 is a p21-activated kinase (PAK) inhibitor. The objective of this study was to investigate whether FRAX486 can reverse ABCB1-mediated multidrug resistance, while also exploring its mechanism of action. The CCK8 assay demonstrated that FRAX486 significantly reversed ABCB1-mediated multidrug resistance. Furthermore, western blotting and immunofluorescence experiments revealed that FRAX486 had no impact on expression level and intracellular localization of ABCB1. Notably, FRAX486 was found to enhance intracellular drug accumulation and reduce efflux, resulting in the reversal of multidrug resistance. Docking analysis also indicated a strong affinity between FRAX486 and ABCB1. This study highlights the ability of FRAX486 to reverse ABCB1-mediated multidrug resistance and provides valuable insights for its clinical application. Pglycoprotein P glycoprotein Pgp/ABCB1 PgpABCB1 PgpABCB gp/ABCB1 gp ABCB1 ABCB (P-gp/ABCB1 MDR. MDR . (MDR) Hence ABCB1mediated ABCBmediated mediated FRAX FRAX48 p21activated pactivated p21 activated p PAK (PAK inhibitor action CCK Furthermore Notably efflux application Pgp Pgp/ABCB gpABCB1 gpABCB gp/ABCB (P-gp/ABCB (MDR FRAX4 p2

Abstract Background Myocardial fibrosis (MF) occurs throughout the onset and progression of cardiovascular disease, and early diagnosis of MF is beneficial for improving cardiac function, but there is a lack of research on early biomarkers of MF. Objectives Utilizing bioinformatics techniques, we identified potential biomarkers for MF. Methods Datasets related to MF were sourced from the GEO database. After processing the data, differentially expressed genes were screened. Differentially expressed genes were enriched, and subsequently, protein-protein interaction (PPI) was performed to analyze the differential genes. The associated miRNAs and transcription factors were predicted for these core genes. Finally, ROC validation was performed on the core genes to determine their specificity and sensitivity as potential biomarkers. The level of significance adopted was 5% (p < 0.05). Results A total of 91 differentially expressed genes were identified, and PPI analysis yielded 31 central genes. Enrichment analysis showed that apoptosis, collagen, extracellular matrix, cell adhesion, and inflammation were involved in MF. One hundred and forty-two potential miRNAs were identified. the transcription factors JUN, NF-κB1, SP1, RELA, serum response factor (SRF), and STAT3 were enriched in most of the core targets. Ultimately, IL11, GADD45B, GDF5, NOX4, IGFBP3, ACTC1, MYOZ2, and ITGB8 had higher diagnostic accuracy and sensitivity in predicting MF based on ROC curve analysis. Conclusion Eight genes, IL11, GADD45B, GDF5, NOX4, IGFBP3, ACTC1, MYOZ2, and ITGB8, can serve as candidate biomarkers for MF. Processes such as cellular apoptosis, collagen protein synthesis, extracellular matrix formation, cellular adhesion, and inflammation are implicated in the development of MF. (MF disease function techniques database data screened subsequently proteinprotein (PPI Finally 5 p 0.05. 005 0.05 . 0 05 0.05) 9 3 apoptosis adhesion fortytwo forty two JUN NFκB1, NFκB1 NFκB NF κB1, κB1 κB NF-κB1 SP1 SP RELA SRF, SRF , (SRF) STAT targets Ultimately IL11 IL GADD45B GADDB GADD B GDF5 GDF NOX4 NOX IGFBP3 IGFBP ACTC1 ACTC MYOZ2 MYOZ ITGB synthesis formation 00 0.0 NF-κB (SRF IL1 0.

Resumo Fundamento A fibrose miocárdica (FM) ocorre durante o início e a progressão da doença cardiovascular, e o diagnóstico precoce da FM é benéfico para melhorar a função cardíaca, mas há uma falta de pesquisa sobre biomarcadores precoces da FM. Objetivos Utilizando técnicas de bioinformática, identificamos potenciais biomarcadores para FM. Métodos Os conjuntos de dados relacionados à FM foram obtidos do banco de dados Gene Expression Omnibus (GEO). Após o processamento dos dados, genes diferencialmente expressos foram rastreados. Genes diferencialmente expressos foram enriquecidos e, subsequentemente, interação proteína-proteína (PPI) foi realizado para analisar os genes diferenciais. Os miRNAs associados e fatores de transcrição foram previstos para esses genes centrais. Finalmente, a validação ROC foi realizada nos genes centrais para determinar sua especificidade e sensibilidade como potenciais biomarcadores. O nível de significância adotado foi de 5% (p < 0,05). Resultados Um total de 91 genes diferencialmente expressos foram identificados, e a análise PPI produziu 31 genes centrais. A análise de enriquecimento mostrou que apoptose, colágeno, matriz extracelular, adesão celular e inflamação estavam envolvidos na FM. Cento e quarenta e dois miRNAs potenciais foram identificados. Os fatores de transcrição JUN, NF-κB1, SP1, RELA, SRF e STAT3 foram enriquecidos na maioria dos alvos principais. Por fim, IL11, GADD45B, GDF5, NOX4, IGFBP3, ACTC1, MYOZ2 e ITGB8 tiveram maior precisão diagnóstica e sensibilidade na predição de FM com base na análise da curva ROC. Conclusão Oito genes, IL11, GADD45B, GDF5, NOX4, IGFBP3, ACTC1, MYOZ2 e ITGB8, podem servir como biomarcadores candidatos para FM. Processos como apoptose celular, síntese de proteína de colágeno, formação de matriz extracelular, adesão celular e inflamação estão implicados no desenvolvimento da FM. (FM cardiovascular cardíaca bioinformática GEO. GEO . (GEO) rastreados subsequentemente proteínaproteína (PPI diferenciais Finalmente 5 p 0,05. 005 0,05 0 05 0,05) 9 identificados 3 colágeno extracelular JUN NFκB1, NFκB1 NFκB NF κB1, κB1 κB NF-κB1 SP1 SP RELA STAT principais fim IL11 IL GADD45B GADDB GADD B GDF5 GDF NOX4 NOX IGFBP3 IGFBP ACTC1 ACTC MYOZ ITGB (GEO 00 0,0 NF-κB IL1 0,

Abstract Introduction: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. Methods: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5’end or 3’end of TERC was detected. We recruited 100 patients of elective surgery. Results: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5’ end or 3’ end of TERC was not found. Conclusions: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications. Introduction aging (TL trait disease (TERC operation elderly Methods leukocytes (BIS analyses 5end 5 3end 3 detected 10 surgery Results r 078 0 78 0.78 0.001, 0001 0.001 , 001 0.001) 084 84 0.84 0.004, 0004 0.004 004 0.004) 083 83 0.83 085 85 0.85 0.029. 0029 0.029 . 029 0.029) 0.58, 058 58 (0.58 021 21 0.21 019 19 0.19 0.12 012 12 variables However Conclusions complications 1 07 7 0.7 000 0.00 00 08 8 0.8 002 0.02 02 0.58 05 (0.5 2 0.2 01 0.1 0. 0.0 0.5 (0. (0 (

Abstract Objective: To investigate the optimal timing of initial intravenous immunoglobulin (IVIG) treatment in Kawasaki disease (KD) patients. Methods: KD patients were classified as the early group (day 1-4), conventional group (day 5-7), conventional group (day 8-10), and late group (after day 10). Differences among the groups were analyzed by ANOVA and Chi-square analysis. Predictors of IVIG resistance and the optimal cut-off value were determined by multiple logistic regression analyses and receiver operating characteristic (ROC) curve analysis. Results: There were no significant differences in IVIG resistance among the 4 groups (p = 0.335). The sensitivity analysis also confirmed no difference in the IVIG resistance between those who started the initial IVIG ≤ day 7 of illness and those who received IVIG >day 7 of illness (p = 0.761). In addition, patients who received IVIG administration more than 7 days from the onset had a higher proportion of coronary artery abnormalities (p = 0.034) and longer length of hospitalization (p = 0.033) than those who started IVIG administration less than 7 days. The optimal cut-off value of initial IVIG administration time for predicting IVIG resistance was >7 days, with a sensitivity of 75.25% and specificity of 82.41%. Conclusions: IVIG therapy within 7 days of illness is found to be more effective for reducing the risk of coronary artery abnormalities than those who received IVIG >day 7 of illness. IVIG treatment within the 7 days of illness seems to be the optimal therapeutic window of IVIG. However, further prospective studies with long-term follow-up are required. Objective (IVIG (KD Methods 14, 14 1 , 1-4) 57, 57 5 5-7) 810, 810 8 10 8-10) after 10. . 10) Chisquare Chi square cutoff cut off ROC (ROC Results p 0.335. 0335 0.335 0 335 0.335) 0.761. 0761 0.761 761 0.761) addition 0.034 0034 034 0.033 0033 033 > 7525 75 25 75.25 8241 82 41 82.41% Conclusions However longterm long term followup follow up required 1-4 5-7 81 8-10 0.33 33 076 0.76 76 0.03 003 03 752 2 75.2 824 82.41 1- 5- 8-1 0.3 3 07 0.7 0.0 00 75. 82.4 8- 0. 82.

ABSTRACT Purpose: To investigate the role of puerarin on renal fibrosis and the underlying mechanism in renal ischemia and reperfusion (I/R) model. Methods: Rats were intraperitoneally injected with puerarin (50 or 100 mg/kg) per day for one week before renal I/R. The level of renal collagen deposition and interstitial fibrosis were observed by hematoxylin and eosin and Sirius Red staining, and the expression of α-smooth muscle actin (α-SMA) was examined by immunohistochemical staining. The ferroptosis related factors and TLR4/Nox4-pathway-associated proteins were detected by Western blotting. Results: Puerarin was observed to alleviate renal collagen deposition, interstitial fibrosis and the α-SMA expression induced by I/R. Superoxide dismutase (SOD) activities and glutathione (GSH) level were decreased in I/R and hypoxia/reoxygenation (H/R), whereas malondialdehyde (MDA) and Fe2+ level increased. However, puerarin reversed SOD, MDA, GSH and Fe2+ level changes induced by I/R and H/R. Besides, Western blot indicated that puerarin inhibited the expression of ferroptosis related factors in a dose-dependent manner, which further demonstrated that puerarin had the effect to attenuate ferroptosis. Moreover, the increased expression of TLR/Nox4-pathway-associated proteins were observed in I/R and H/R group, but puerarin alleviated the elevated TLR/Nox4 expression. Conclusions: Our results suggested that puerarin inhibited oxidative stress and ferroptosis induced by I/R and, thus, delayed the progression of renal fibrosis, providing a new target for the treatment of renal fibrosis. Purpose IR I R (I/R model Methods 50 (5 10 mg/kg mgkg mg kg staining αsmooth α smooth αSMA SMA (α-SMA TLR4/Nox4pathwayassociated TLR4Nox4pathwayassociated TLRNoxpathwayassociated TLR4/Nox4 pathway associated TLR4 Nox4 TLR Nox blotting Results SOD (SOD (GSH hypoxiareoxygenation hypoxia reoxygenation H/R, HR , H (H/R) MDA (MDA Fe2 Fe However Besides dosedependent dose dependent manner Moreover TLR/Nox4pathwayassociated TLRNox4pathwayassociated group TLRNox4 TLRNox TLR/Nox Conclusions thus 5 ( 1 Nox4pathwayassociated pathwayassociated TLR4Nox4 TLR4/Nox (H/R Noxpathwayassociated TLR4Nox

ABSTRACT Purpose: To determine the predictive value of maternal White Blood Cells (WBC), neutrophils, and C-Reactive Protein (CRP) for diagnosing Histological Chorioamnionitis (HCA) among women with Preterm Premature Rupture of Membranes (PPROM) who underwent cervical cerclage. Methods: A retrospective cross-sectional study was conducted among women with singleton pregnancy and PPROM, who underwent cervical cerclage during 2018-2020. Results: A total of 55 eligible women were included in the final analysis, including 36 (61.02%) cases with HCA and 19 (38.98%) without HCA. Women with HCA had higher WBC count (12.31 ± 2.80) × 109/L and neutrophil count (9.67 ± 2.90)×109/L than those without HCA (10.35 ± 2.53) × 109/L and 7.82 ± 2.82 × 109/L, respectively) (both p < 0.05). The cut-off value of WBC count at 10.15×109/L was found to be the most effective in identifying HCA, with an Area Under Curve (AUC) of 0.707 (95% CI: 0.56-0.86; p = 0.012), sensitivity of 86.11%, specificity of 57.90%, Positive Predictive Value (PPV) of 79.49%, Negative Predictive Value (NPV) of 68.75%, and Youden index of 0.44. The combination of WBC + neutrophil had a slightly higher (AUC = 0.711, 95% CI: 0.57–0.86; p = 0.011), specificity (68.42%), and PPV (81.25%), but lower sensitivity (72.22%), than the WBC count alone. A cut-off value of neutrophil at 7.46 × 109/L was effective in identifying HCA, with an AUC of 0.689 (95% CI: 0.53-0.84; p = 0.022). Discussion: Combination use of WBC+neutrophil was found to be the most accurate predictor of HCA among women with PPROM after surgery of cervical cerclage. Purpose WBC, , (WBC) neutrophils CReactive C Reactive CRP (CRP (HCA (PPROM Methods crosssectional cross sectional 20182020. 20182020 2018 2020. 2020 2018-2020 Results 5 analysis 3 61.02% 6102 61 02 (61.02% 1 38.98% 3898 38 98 (38.98% 12.31 1231 12 31 (12.3 2.80 280 2 80 109L L 109 9.67 967 9 67 (9.6 2.90×109/L 290109L 2.90 ×109/L 90 10.35 1035 10 35 (10.3 2.53 253 53 782 7 82 7.8 282 2.8 respectively both 0.05. 005 0.05 . 0 05 0.05) cutoff cut off 1015109L 15 0707 707 0.70 95 (95 CI 0.560.86 056086 0.56 0.86 56 86 0.56-0.86 0.012, 0012 0.012 012 0.012) 8611 11 86.11% 5790 57 57.90% (PPV 7949 79 49 79.49% NPV (NPV 6875 68 75 68.75% 044 44 0.44 0711 711 0.711 0.57–0.86 057086 0.011, 0011 0.011 011 0.011) 68.42%, 6842 68.42% 42 (68.42%) 81.25%, 8125 81.25% 81 25 (81.25%) 72.22%, 7222 72.22% 72 22 (72.22%) alone 746 46 7.4 0689 689 0.68 0.530.84 053084 0.53 0.84 84 0.53-0.84 0.022. 0022 0.022 022 0.022) Discussion WBCneutrophil (WBC 2018202 201 202 2018-202 61.02 610 6 (61.02 38.98 389 (38.98 12.3 123 (12. 28 8 9.6 96 (9. 290 2.9 10.3 103 (10. 2.5 78 7. 2. 00 0.0 070 70 0.7 (9 560 0.560.8 05608 056 0.5 086 0.8 0.56-0.8 001 0.01 01 861 86.11 579 57.90 794 4 79.49 687 68.75 04 0.4 071 71 0.71 0.57–0.8 05708 684 68.42 (68.42% 812 81.25 (81.25% 722 72.22 (72.22% 74 068 0.6 530 0.530.8 05308 053 084 0.53-0.8 002 0.02 201820 20 2018-20 61.0 (61.0 38.9 (38.9 12. (12 9. 29 10. (10 0. 07 ( 0.560. 0560 08 0.56-0. 86.1 57.9 79.4 68.7 0.57–0. 0570 68.4 (68.42 81.2 (81.25 72.2 (72.22 06 0.530. 0530 0.53-0. 20182 2018-2 61. (61. 38. (38. (1 0.560 0.56-0 86. 57. 79. 68. 0.57–0 057 (68.4 81. (81.2 72. (72.2 0.530 0.53-0 2018- (61 (38 0.56- 0.57– (68. (81. (72. 0.53- (6 (3 0.57 (68 (81 (72 (8 (7

Abstract Adaptation of photoperiod-sensitive japonica rice varieties from long-day (LD) to short-day (SD) conditions is impeded by their extremely early flowering in response to photoperiod change, but the genetic factor underlying this is still elusive. We detected mutations in Hd1 in Zhenjing2400 through gene mapping and sequencing analysis. Genome resequencing of the varieties Zhenjing2400 and Jiahe218 identified single nucleotide polymorphisms (SNPs) in the other flowering-related genes Ehd1, SDG725, OsCOL15, DTH2, and DTH7. We constructed recombinant inbred lines (RILs) derived from a cross between Zhenjing2400 and Jiahe218, and selected homozygous lines with these six genes. We established that photoperiod insensitivity is caused by a defective Hd1 gene. In addition, the effect of Hd1 and Ehd1 on heading date was stronger than that of the other four genes. Measurements of agronomic traits and quality traits in homozygous lines demonstrated the superiority of the hd1 ehd1 genotype for eating quality and photoperiod-insensitive high yield. photoperiodsensitive sensitive longday long day LD (LD shortday short SD (SD change elusive Hd Zhenjing Zhenjing240 analysis Jiahe Jiahe21 SNPs (SNPs floweringrelated related Ehd SDG725 SDG OsCOL15 OsCOL DTH2 DTH DTH7 RILs (RILs addition hd ehd photoperiodinsensitive insensitive yield Zhenjing24 Jiahe2 SDG72 OsCOL1 Zhenjing2 SDG7

Abstract Objective Abnormal complement activation is associated with periodontitis. W54011 is a novel non-peptide C5aR antagonist (C5aRA) that exhibits favorable anti-inflammatory effects in various inflammatory models. However, whether W54011 inhibits periodontitis has not yet been fully elucidated. To address this, we have investigated the probable anti-inflammatory mechanism of W54011 in LPS-treated inflammation in human gingival fibroblasts (HGFs). Methodology HGFs were isolated from healthy gingival tissue samples using the tissue block method and were identified with immunofluorescence staining. The CCK8 assay and reverse transcription-PCR (RT-PCR) were used to select the optimal induction conditions for Lipopolysaccharide (LPS) and C5aRA (according to supplementary data S1, S2 and S3). The levels of inflammatory cytokines, C5aR, and the activation of NF-κB/MAPK signaling pathways were determined by RT-quantitative PCR (RT-qPCR) and Western blotting. Results Immunofluorescence results showed that vimentin and FSP-1 were positive in HGFs and Keratin was negative in HGFs. Immunofluorescence staining demonstrated that C5aRA inhibited LPS-stimulated nuclear translocation of p-p65. RT-qPCR and Western blotting showed that C5aRA reduced the expression of IL-1β, IL-6, TNF-α, C5aR, p-p65, p-IκBα, p-JNK, p-c-JUN, and TLR4 in LPS-induced HGFs. Conclusion These findings suggested that C5aRA attenuated the release of inflammatory cytokines in LPS-induced HGFs by blocking the activation of the NF-κB and MAPK signaling pathways. W W5401 nonpeptide non peptide CaR C aR CaRA aRA (C5aRA antiinflammatory anti models However elucidated this LPStreated LPS treated . (HGFs) CCK transcriptionPCR transcription RTPCR RT (RT-PCR (LPS according S1 S S3. S3 S3) NFκB/MAPK NFκBMAPK NF κB/MAPK κB RTquantitative quantitative RTqPCR qPCR (RT-qPCR FSP1 FSP 1 FSP- LPSstimulated stimulated pp65. pp65 pp p p65. p65 p-p65 IL1β, IL1β ILβ IL 1β, 1β β IL-1β IL6, IL6 6, 6 IL-6 TNFα, TNFα TNF α, α TNF-α pp65, p65, pIκBα, pIκBα IκBα, IκBα p-IκBα pJNK, pJNK JNK, JNK p-JNK pcJUN, pcJUN c JUN, JUN p-c-JUN TLR LPSinduced induced NFκB W540 (HGFs κBMAPK pp6 p6 p-p6 IL- W54 p-p W5

Resumo Fundamento A estratificação de risco precoce com biomarcadores simples é essencial em pacientes com infarto do miocárdio sem supradesnivelamento do segmento ST (IAMSSST). Objetivo Este estudo tem o objetivo de avaliar a associação entre nível de big endotelina-1 plasmática (ET-1) e o escore SYNTAX (SS) em pacientes com IAMSSST. Métodos Foram recrutados 766 pacientes com IAMSSST que passaram por angiografia coronária. Os pacientes foram divididos em três grupos: SS baixo (≤22), SS intermediário (23-32), e SS alto (>32). A correlação de Spearman, o ajuste de curva suave, a regressão logística, e a análise de curva característica de operação do receptor (ROC) foram realizados para avaliar a associação entre o nível de big ET-1 plasmática e o SS. Um p-valor <0.05 foi considerado estatisticamente significativo. Resultados Foi identificada uma correlação significativa entre a big ET-1 e o SS (r=0,378, p<0,001). A curva suavizada indicou uma correlação positiva entre o nível de big ET-1 plasmática e o SS. A análise de curva ROC demonstrou que a área sob a curva foi de 0,695 (0,661-0,727) e o ponto de corte ideal do nível de big ET-1 plasmática foi de 0,35 pmol/l. A regressão logística demonstrou que a big ET-1 elevada era um preditor independente de SS intermediário a alto em pacientes com IAMSSST, seja como variável contínua [RC (IC 95%: 1,110 (1,053-1,170), p<0,001] ou como variável categórica [RC (IC 95%: 2,962 (2,073-4,233), p<0,001]. Conclusão Em pacientes com IAMSSST, o nível de big ET-1 plasmática estava significativamente correlacionado ao SS. O nível de big ET-1 plasmática elevado foi um preditor independente para SS intermediário a alto. . (IAMSSST) endotelina1 endotelina 1 endotelina- ET1 ET (ET-1 (SS 76 coronária grupos ≤22, 22 ≤22 , (≤22) 2332, 2332 23 32 (23-32) >32. >32 (>32) Spearman suave (ROC ET- pvalor p valor 005 0 05 <0.0 significativo r=0,378, r0378 r 378 (r=0,378 p<0,001. p0001 p<0,001 001 p<0,001) 0695 695 0,69 0,6610,727 06610727 0,661 0,727 661 727 (0,661-0,727 035 35 0,3 pmoll pmol l pmol/l RC IC 95% 95 1110 110 1,11 1,0531,170, 10531170 1,053 1,170 053 170 (1,053-1,170) 2962 2 962 2,96 2,0734,233, 20734233 2,073 4,233 073 4 233 (2,073-4,233) (IAMSSST (ET- 7 ≤2 (≤22 3 (23-32 >3 (>32 00 <0. r=0,378 r037 37 (r=0,37 p000 p<0,00 069 69 0,6 6610 0,6610,72 0661072 0661 0,66 0727 0,72 66 72 (0,661-0,72 03 0, 9 111 11 1,1 0531 1,0531,170 1053117 1053 1,05 1170 1,17 17 (1,053-1,170 296 96 2,9 0734 2,0734,233 2073423 2073 2,07 4233 4,23 07 (2,073-4,233 (ET ≤ (≤2 (23-3 > (>3 <0 r=0,37 r03 (r=0,3 p00 p<0,0 06 6 0,6610,7 066107 066 072 0,7 (0,661-0,7 1, 1,0531,17 105311 105 1,0 117 (1,053-1,17 29 2, 2,0734,23 207342 207 2,0 423 4,2 (2,073-4,23 (≤ (23- (> < r=0,3 r0 (r=0, p0 p<0, 0,6610, 06610 (0,661-0, 1,0531,1 10531 10 (1,053-1,1 2,0734,2 20734 20 42 4, (2,073-4,2 ( (23 r=0, (r=0 p<0 0,6610 (0,661-0 1,0531, (1,053-1, 2,0734, (2,073-4, (2 r=0 (r= p< (0,661- 1,0531 (1,053-1 2,0734 (2,073-4 r= (r (0,661 (1,053- (2,073- (0,66 (1,053 (2,073 (0,6 (1,05 (2,07 (0, (1,0 (2,0 (0 (1, (2, (1

Abstract Background Early risk stratification with simple biomarkers is essential in patients with non-ST segment-elevation myocardial infarction (NSTEMI). Objective This study aimed to evaluate the association between plasma big endothelin-1 (ET-1) level and the SYNTAX score (SS) in patients with NSTEMI. Methods A total of 766 patients with NSTEMI undergoing coronary angiography were recruited. Patients were divided into three groups: low SS (≤22), intermediate SS (23-32), and high SS (>32). Spearman correlation, smooth curve fitting, logistic regression, and receiver operating characteristic (ROC) curve analysis were performed to evaluate the association between plasma big ET-1 level and the SS. A p-value <0.05 was considered statistically significant. Results There was a significant correlation between the big ET-1 and the SS (r=0.378, p<0.001). The smoothing curve indicated a positive correlation between the plasma big ET-1 level and the SS. The ROC curve analysis showed that the area under the curve was 0.695 (0.661-0.727) and the optimal cutoff of plasma big ET-1 level was 0.35pmol/l. Logistic regression showed that elevated big ET-1 was an independent predictor of intermediate-high SS in patients with NSTEMI, whether entered as a continuous variable [OR (95% CI): 1.110 (1.053-1.170), p<0.001] or as a categorical variable [OR (95% CI): 2.962 (2.073-4.233), p<0.001]. Conclusion In patients with NSTEMI, the plasma big ET-1 level was significantly correlated with the SS. Elevated plasma big ET-1 level was an independent predictor for intermediate-high SS. nonST non ST segmentelevation segment elevation . (NSTEMI) endothelin1 endothelin 1 endothelin- ET1 ET (ET-1 (SS 76 recruited groups ≤22, 22 ≤22 , (≤22) 2332, 2332 23 32 (23-32) >32. >32 (>32) fitting (ROC ET- pvalue p value 005 0 05 <0.0 r=0.378, r0378 r 378 (r=0.378 p<0.001. p0001 p<0.001 001 p<0.001) 0695 695 0.69 0.6610.727 06610727 0.661 0.727 661 727 (0.661-0.727 035pmoll pmoll 35pmol l pmol 0.35pmol/l intermediatehigh OR 95% 95 (95 CI CI) 1110 110 1.11 1.0531.170, 10531170 1.053 1.170 053 170 (1.053-1.170) 2962 2 962 2.96 2.0734.233, 20734233 2.073 4.233 073 4 233 (2.073-4.233) (NSTEMI (ET- 7 ≤2 (≤22 3 (23-32 >3 (>32 00 <0. r=0.378 r037 37 (r=0.37 p000 p<0.00 069 69 0.6 6610 0.6610.72 0661072 0661 0.66 0727 0.72 66 72 (0.661-0.72 9 (9 111 11 1.1 0531 1.0531.170 1053117 1053 1.05 1170 1.17 17 (1.053-1.170 296 96 2.9 0734 2.0734.233 2073423 2073 2.07 4233 4.23 07 (2.073-4.233 (ET ≤ (≤2 (23-3 > (>3 <0 r=0.37 r03 (r=0.3 p00 p<0.0 06 6 0. 0.6610.7 066107 066 072 0.7 (0.661-0.7 ( 1. 1.0531.17 105311 105 1.0 117 (1.053-1.17 29 2. 2.0734.23 207342 207 2.0 423 4.2 (2.073-4.23 (≤ (23- (> < r=0.3 r0 (r=0. p0 p<0. 0.6610. 06610 (0.661-0. 1.0531.1 10531 10 (1.053-1.1 2.0734.2 20734 20 42 4. (2.073-4.2 (23 r=0. (r=0 p<0 0.6610 (0.661-0 1.0531. (1.053-1. 2.0734. (2.073-4. (2 r=0 (r= p< (0.661- 1.0531 (1.053-1 2.0734 (2.073-4 r= (r (0.661 (1.053- (2.073- (0.66 (1.053 (2.073 (0.6 (1.05 (2.07 (0. (1.0 (2.0 (0 (1. (2. (1

RESUMO Introdução A corrida pode promover a saúde, prevenir a obesidade, doenças cardiovasculares e cerebrovasculares entre outras doenças crônicas. Muitas pesquisas relatam os benefícios desse exercício de resistência aeróbica, mas pouco conhecimento há sobre os impactos da corrida na osteoartrite do joelho. Objetivo Observar e estudar o efeito clínico da corrida na melhora da dor e da função em pacientes com osteoartrite de joelho. Métodos Setenta casos que preencheram os critérios de inclusão foram selecionados e divididos aleatoriamente em grupos controle e observação. Os pacientes do grupo de observação receberam 8 semanas de exercício neuromuscular (NEMEX) e 8 semanas de treinamento de força muscular do quadríceps enquanto o grupo controle foi sujeitado a um protocolo de corrida. Os pacientes foram avaliados usando a Escala de Dor e o Índice de Osteoartrite das Universidades Western Ontario and McMaster (WOMAC) após 1, 2, 4 e 8 semanas de tratamento. Resultados Após 1, 2, 4 e 8 semanas de tratamento, os escores de função WOMAC dos dois grupos melhoraram significativamente comparados ao encontrado antes do tratamento (P <0,05). Não houve diferença entre os dois grupos antes do tratamento e após 1, 2 semanas de tratamento. Após 4 e 8 semanas de tratamento, a função do grupo de observação foi melhor que a do grupo controle, a diferença foi estatisticamente significativa (t= -4,287, -6,355, P<0,05). Conclusões Ambos os métodos de treinamento NEMEX e o treinamento de força muscular do quadríceps podem efetivamente melhorar o nível funcional dos pacientes, e o NEMEX melhora mais significativamente do que o treinamento de força muscular do quadríceps. Nível de evidência II; Estudos terapêuticos - Investigação de resultados.

ABSTRACT Introduction Running can promote health prevent obesity, cardiovascular, and cerebrovascular diseases, among other chronic diseases. Much research reports the benefits of this aerobic resistance exercise, but little is known about the impacts of running on knee osteoarthritis. Objective To observe and study the clinical effect of running on pain and function improvement in patients with knee osteoarthritis. Methods Seventy cases that met the inclusion criteria were selected and randomly divided into control and observation groups. Patients in the observation group received eight weeks of neuromuscular exercise (NEMEX) and eight weeks of quadriceps muscle strength training while the control group was subjected to a running protocol. Patients were assessed using the Western Ontario and McMaster Universities Pain Scale and Osteoarthritis Index (WOMAC) after 1, 2, 4 and 8 weeks of treatment. Results After 1, 2, 4, and 8 weeks of treatment, the WOMAC function scores of the two groups significantly improved compared to that found before treatment (P < 0.05); There was no difference between the two groups before treatment and after 1, 2 weeks of treatment. After 4 and 8 weeks of treatment, the function of the observation group was better than that of the control group; the difference was statistically significant (t= -4.287, -6.355, P<0.05). Conclusions NEMEX training methods and quadriceps muscle strength training can effectively improve patients’ functional level, but NEMEX improves more significantly than quadriceps muscle strength training. Evidence level II; Therapeutic Studies - Investigating the results.

RESUMEN Introducción La corrida puede promover la salud, prevenir la obesidad, enfermedades cardiovasculares y cerebrovasculares, entre otras enfermedades crónicas. Muchas investigaciones informan los beneficios de este ejercicio de resistencia aeróbica, pero se sabe poco sobre los impactos de correr en la osteoartritis de rodilla. Objetivo Observar y estudiar el efecto clínico de la corrida sobre el dolor y la mejora funcional en pacientes con artrosis de rodilla. Métodos Setenta casos que cumplieron con los criterios de inclusión fueron seleccionados y divididos aleatoriamente en grupos de control y observación. Los pacientes del grupo de observación recibieron 8 semanas de ejercicio neuromuscular (NEMEX) y 8 semanas de entrenamiento de fuerza de los cuádriceps, mientras que el grupo de control se sometió a un protocolo de corrida. Los pacientes fueron evaluados utilizando la escala de dolor y el índice de osteoartritis de las universidades de Western Ontario y McMaster (WOMAC) después de 1, 2, 4 y 8 semanas de tratamiento. Resultados Después de 1, 2, 4 y 8 semanas de tratamiento, las puntuaciones de función WOMAC de los dos grupos mejoraron significativamente en comparación con las encontradas antes del tratamiento (P < 0,05). No hubo diferencia entre los dos grupos antes del tratamiento y después de 1, 2 semanas de tratamiento. Después de 4 y 8 semanas de tratamiento, la función del grupo de observación fue mejor que la del grupo control, la diferencia fue estadísticamente significativa (t= -4.287, -6.355, P<0.05). Conclusiones Tanto los métodos de entrenamiento NEMEX como el entrenamiento de la fuerza muscular del cuádriceps pueden mejorar eficazmente el nivel funcional de los pacientes, y NEMEX mejora de forma más significativa que el entrenamiento de la fuerza muscular del cuádriceps. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

ABSTRACT As a common problem in rice (Oryza sativa L.) production, lodging will not only increase harvest costs and reduce rice production, but also affect rice taste seriously and reduce its commercial value. There is still a lack of systematic research on the effect of lodging resistance of rice after returning wheat (Triticum aestivum L.) straw to the field. The study evaluated the effects of continuous straw returning and different fertilizer input levels on the lodging resistance of rice stalks based on years of experiments, using a split zone design with two factors including full return of straw to the field and straw removal, and three fertilization levels (conventional fertilization, 50% of conventional fertilization and no fertilization) under each factor, for a total of six treatments. Results suggested that under the same level of chemical fertilizer application, treatments of straw returning significantly increased stalk flexural resistance up to 33.74% as well as decreased the lodging index by a maximum of 33.86% compared with straw removal. Decrease of chemical fertilizer application increased significantly stalk flexural resistance, while decreased significantly lodging index. Rice plant height, center of gravity height, internode length, stem wall thickness and internode dry weight were main factors that influence rice lodging resistance. Compared with straw removal, straw returning combined with chemical fertilizers applying could significantly increase rice yield up to 19.62%. The increase in rice yield increased the risk of rice lodging. The continuous return of straw to the field combined with the application of chemical fertilizers reduced the risk of rice lodging to a certain extent, and meanwhile it achieved successive annual increase in rice production, which has a good promotion prospect.