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Compared with young liver donors, aged liver donors are more susceptible to ischemia-reperfusion injury (IRI) following transplantation, which may be related to excessive inflammatory response and macrophage dysfunction, but the specific mechanism is unclear. Macrophage scavenger receptor 1 (MSR1) is a member of the scavenger receptor family, and plays an important regulatory role in inflammation response and macrophage function regulation. But its role in IRI following aged-donor liver transplantation is still unclear. This study demonstrates that MSR1 expression is decreased in macrophages from aged donor livers, inhibiting their efferocytosis and pro-resolving polarisation. Decreased MSR1 is responsible for the more severe IRI suffered by aged donor livers. Overexpression of MSR1 using F4/80-labelled AAV 9 improved intrahepatic macrophage efferocytosis and promoted pro-resolving polarisation, ultimately ameliorating IRI following aged-donor liver transplantation. In vitro co-culture experiments further showed that overexpression of MSR1 promoted an increase in calcium concentration, which further activated the PI3K-AKT-GSK3β pathway, and induced the upregulation of β-catenin. Overall, MSR1-dependent efferocytosis promoted the pro-resolving polarisation of macrophages through the PI3K-AKT-GSK3β pathway-induced up-regulating of β-catenin leading to improved IRI following aged-donor liver transplantation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To analyze the clinical characteristics and prognosis of patients with CD5 + diffuse large B-cell lymphoma (DLBCL)., Methods: The clinical data of 161 newly treated DLBCL patients in Gansu Provincial Hospital from January 2013 to January 2020 were retrospectively analyzed. According to CD5 expression, the patients were divided into CD5 + group and CD5 - group. The clinical characteristics and prognosis of the two groups were statistically analyzed., Results: The median age of patients in CD5 + group was 62 years, which was higher than 56 years in CD5 - group ( P =0.048). The proportion of women in CD5 + group was 62.96%, which was significantly higher than 41.79% in CD5 - group ( P =0.043). The proportion of patients with IPI score > 2 in CD5 + group was 62.96%, which was higher than 40.30% in CD5 - group ( P =0.031). Survival analysis showed that the median overall survival and progression-free survival time of patients in CD5 + group were 27(3-77) and 31(3-76) months, respectively, which were both shorter than 30(5-84) and 32.5(4-83) months in CD5 - group ( P =0.047, P =0.026). Univariate analysis showed that advanced age, positive CD5 expression, triple or double hit at initial diagnosis, high IPI score and no use of rituximab during chemotherapy were risk factors for the prognosis of DLBCL patients. Further Cox multivariate regression analysis showed that these factors were also independent risk factors except for advanced age., Conclusion: CD5 + DLBCL patients have a worse prognosis than CD5 - DLBCL patients. Such patients are more common in females, with advanced age and high IPI score, which is a special subtype of DLBCL.

Objective: To verify the consistency between the digital manufacturing simple intraoral Gothic arch-tracing device and the traditional intraoral Gothic arch-tracing device in determining the centric relation of complete dentures restoration., Methods: Ten outpatients with edentulous jaws were selec-ted, and the centric relation of the patients was determined by digital manufacturing of simple intraoral Gothic arch-tracing device (T1) and traditional intraoral Gothic arch-tracing device (T2); the difference of clinical operation time between the two methods was recorded; the upper and lower edentulous jaw plaster models were scanned with two kinds of centric relation, the Standard Triangle Language (STL) files imported into Geomagic studio software to apply the best fitting of multiple points of the both upper jaw models, the fitted STL files imported into the 3 shape viewer software, and the maximum position deviations of the vertical, labial (buccal) and lingual directions of the mandibular midline area and molar areas in T1 and T2 groups measured. During the clinical complete dentures try-in, we observed whether there was midline deviation in the mouth of T1 group and T2 group, and whether the occlusion of posterior teeth was stable or not., Results: The mean time spent on determining the centric relation of T1 and T2 groups was (41.90±2.64) min, (57.50±2.37) min respectively. Paired t test was conducted in the two groups, P < 0.01 with significant statistical difference; The mean maximum position deviation between T1 group and T2 group of the midline mandibular region in labial lingual direction was (0.32±0.14) mm, that was (0.40±0.23) mm in vertical direction; the mean maximum position deviation of molar area in buccal lingual direction was (0.35±0.23) mm and that was (0.33±0.20) mm in vertical direction. In the vertical and horizontal directions, the maximum position deviation of mandibles between group T1 and group T2 was controlled within 0.5 mm. In the process of clinical complete dentures try-in, there was no deviation from the center line of dentures. There was not warping, swinging and other poor stability phenomena in T1 and T2 groups., Conclusion: The digital manufacturing of simple intraoral Gothic arch-tracing device can be used to determine the centric relation of complete dentures, which can not only save time of clinical operation, but also ensure the accuracy of the centric relation.

Stroke is the second most common cause of death after cancer worldwide and a major cause of acquired disability in adults. Overwhelming majority of strokes are caused by cerebral ischemia and are classified as ischemic stroke. Microglia are the resident immune cells and play dual roles in response to ischemia injury in the central nervous system (CNS). On the one hand, microglia may contribute to tissue function recovery process by promoting inflammation resolution, cellular debris clearance, nerve regeneration and synapse remodeling. On the other hand, excessive activation of microglia aggravates nerve damage after ischemic injury. Here, we briefly describe the mechanism of microglia activation after stroke, and comprehensively review the dual role of microglia in neurodegeneration and regeneration after stroke. In-depth exploration of the cytotoxic and protective mechanisms of microglia will provide new targets and new strategies for stroke treatment.

In machine learning, we often face the situation where the event we are interested in has very few data points buried in a massive amount of data. This is typical in network monitoring, where data are streamed from sensing or measuring units continuously but most data are not for events. With imbalanced datasets, the classifiers tend to be biased in favor of the main class. Rare event detection has received much attention in machine learning, and yet it is still a challenging problem. In this paper, we propose a remedy for the standing problem. Weighting and sampling are two fundamental approaches to address the problem. We focus on the weighting method in this paper. We first propose a boosting-style algorithm to compute class weights, which is proved to have excellent theoretical property. Then we propose an adaptive algorithm, which is suitable for real-time applications. The adaptive nature of the two algorithms allows a controlled tradeoff between true positive rate and false positive rate and avoids excessive weight on the rare class, which leads to poor performance on the main class. Experiments on power grid data and some public datasets show that the proposed algorithms outperform the existing weighting and boosting methods, and that their superiority is more noticeable with noisy data., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 He and Cheng.)

Background: Currently, there is a lack of sepsis screening tools that can be widely used worldwide. Pulmonary sepsis can be of sufficient concern to physicians due to their noticeable symptoms, which usually rely less on screening tools., Aim: To investigate the efficiency of the international normalized ratio (INR) for the early rapid recognition of adult nonpulmonary infectious sepsis., Methods: This is a prospective observational study. A total of 108 sepsis patients and 106 nonsepsis patients were enrolled according to relevant inclusion and exclusion criteria. Commonly used clinical indicators, such as white blood cell, neutrophil count, lymphocyte count, neutrophil-lymphocyte count ratio (NLCR), platelets (PLT), prothrombin time, INR, activated partial thromboplastin time, and quick Sequential "Sepsis-related" Organ Failure Assessment (qSOFA) scores were recorded within 24 h after admission. The diagnostic performances of these clinical indicators were analyzed and compared through multivariate logistic regression analysis, Spearman correlation, and receiver operating characteristic curve analysis., Results: The INR value of the sepsis group was significantly higher than that of the nonsepsis group. INR has superior diagnostic efficacy for sepsis, with an area under the curve value of 0.918, when those preexisting diseases which significantly affect coagulation function were excluded. The diagnostic efficacy of the INR was more significant than that of NLCR, PLT, and qSOFA ( P < 0.05). Moreover, INR levels of 1.17, 1.20, and 1.22 could be used to categorize the relative risk of nonpulmonary infections sepsis into three categories: low, medium and high risk, respectively., Conclusion: The INR is a promising and easily available biomarker for diagnosis, and it can be used as one of the indicators for early screening of adult nonpulmonary infectious sepsis. When its value is higher than the optimal cutoff value (1.22), high vigilance is required for adult nonpulmonary infectious sepsis., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background and Aims: Tumor microenvironment plays an essential role in cancer development and progression. Cancer immunotherapy has become a promising approach for the treatment of hepatocellular carcinoma (HCC). We aimed to analyze the HCC immune microenvironment characteristics to identify immune-related genetic changes., Methods: Key immune-relevant genes (KIRGs) were obtained through integrating the differentially expressed genes of The Cancer Genome Atlas, immune genes from the Immunology Database and Analysis Portal, and immune differentially expressed genes determined by single-sample gene set enrichment analysis scores. Cox regression analysis was performed to mine therapeutic target genes. A regulatory network based on KIRGs, transcription factors, and immune-related long non-coding RNAs (IRLncRNAs) was also generated. The outcomes of risk score model were validated in a testing cohort and in clinical samples using tissue immunohistochemistry staining. Correlation analysis between risk score and immune checkpoint genes and immune cell infiltration were investigated., Results: In total, we identified 21 KIRGs, including programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), and found IKBKE, IL2RG, EDNRA, and IGHA1 may be equally important to PD-1 or CTLA4 . Meanwhile, KIRGs, various transcription factors, and IRLncRNAs were integrated to reveal that the NRF1-AC127024.5-IKBKE axis might be involved in tumor immunity regulation. Furthermore, the immune-related risk score model was established according to KIRGs and key IRLncRNAs, and verified more obvious discriminating power in the testing cohort. Correlation analysis indicated TNFSF4 , LGALS9 , KIAA1429 , IDO2 , and CD276 were closely related to the risk score, and CD4 T cells, macrophages, and neutrophils were the primary immune infiltration cell types., Conclusions: Our results highlight the importance of immune genes in the HCC microenvironment and further unravel the underlying molecular mechanisms in the development of HCC., Competing Interests: The authors have no conflict of interests related to this publication., (© 2021 Authors.)

Purpose: Blood blister-like aneurysms (BBAs) have a high risk of early recurrence and postoperative rebleeding. This study compared the clinical outcomes and complications between endovascular intervention with low-profile visualized intraluminal support (LVIS) stent-assisted coiling and the surgical clipping in patients with BBAs., Methods: This retrospective study enrolled 39 patients with BBAs who underwent endovascular intervention with LVIS stent-assisted coiling (n = 21) or surgical clipping (n = 18) between January 2013 and July 2018. Primary outcomes were mortality and modified Rankin scale (mRS). Secondary outcomes were hospital stay, intensive care unit (ICU) stay and operation parameters. Complications were also retrospectively collated., Results: At baseline, the two groups were well balanced in patient characteristics. The hospital stays, ICU stays, operation time and intraoperative infusion volume were all significantly lower in LVIS group than that in clipping group (p < 0.05). A second operation was performed in 6 cases in the clipping group but none in the LVIS group (p = 0.006). The mean mRS score in the LVIS group was significantly lower than that of the clipping group both at hospital discharge and final follow-up (p < 0.001). Adverse outcomes occurred in 1 case in LVIS group and 7 in clipping group, with significant difference (p = 0.015). Complications were reported in 8 cases in LVIS group and 16 cases in clipping group, with significant difference (p < 0.001)., Conclusion: The endovascular intervention with LVIS stent-assisted coiling has better prognosis than surgical clipping. It decreased the risk of a second operation and procedure-related complications compared with surgical clipping.

Objective: To investigate the expression of CD56 in multiple myeloma (MM) cells and its relationship between extramedullary disease and extramedullary relapse., Methods: Clinical data of 99 patients with MM treated in our hospital from January 2015 to December 2019 was retrospectively analyzed. The patients were divided into positive group and negative group according to the expression of CD56. The relationship between CD56 and multiple myeloma extramedullary disease, extramedullary relapse was analyzed., Results: Among 99 newly diagnosed patients with MM, the positive rate of CD56 was 65%, and the incidence of extramedullary disease of patients in the CD56 positive group was lower than that in the CD56 negative group (17.19% vs 48.57%) (P<0.01). Meanwhile, the incidence of extramedullary relapse of patients in the CD56 positive group was lower than that in the CD56 negative group (1.56% vs 34.29%) (P<0.01)., Conclusion: CD56 is highly expressed in MM, and its low expression is associated with the occurrence of extramedullary disease and extramedullary relapse, which suggests that CD56 may be an important indicator for predicting the occurrence of extramedullary disease and extramedullary relapse.

Objective: The present study was to evaluate the anti-tumor effects of acidic RNA protein complex (FA-2-b-β) extracted from the wild edible Qinba mushroom in inducing of apoptosis and immunoregulation of tumor cell., Methods: Cell proliferation inducing rate of FA-2-b-β to K562 cell was measured using CCK-8. Apoptosis rate was detected by using flow cytometry. Chronic myeloid leukemia model was developed by tail vein injection/subcutaneous inoculation of K562 cells in NCG mice. The tumor burden of mice was observed. The general condition of the mice was monitored twice daily. The peripherivcal full blood counts of mice was tested daily. RT-qPCR and Western blot was FA-2-b-β performed to determine involvement of apoptotic-related gene and protenin, Immunofluorescence and immunohistochemistry was used to detected the expression of CD3, CD4 and CD8., Results: The proliferation and apoptosis of K562 cell could be inhibitied and induced by FA-2-b-β, there was 100% successful in the tumor formation in vivo, after treated by drug for 21 days there were significantly increased peripheral leucocytes, but decreased hemoglobin of mice treated by FA-2-b-β as compared with those in control group. The CD3, CD4 and CD8 showed positive in mice, and the propotation was imbalance, but it showed reserved after treated by FA-2-b-β., Conclusion: FA-2-b-β is strong anti-leukemia effect in vitro and in vivo, suggesting the traditional Chinese medicine maybe contribute to the anti-cancer and immunoregulation research.

Objective: To investigated the anti-tumor in vivo effect and mechanism of the acid RNA protein complex (FA-2-b-β) of Agaricus blazei Murrill extract., Methods: CCK-8 method was used to detected the inhibitory effect of FA-2-b-β on proliferation of primary CML cells from newly diagnosed CML patients, the CML mouse model was established by trail-venous injection of primary CML cells, and the survival time, blood cell count and body weight were observed, the immunoflouresence and immunehistochemistry analysis, RT-qPCR, Western bolt were used to detemine the expression of caspase-3 signal pathway-related apoptosis genes and proteins., Results: The experiments in vitro showed that the proliferative inhibitory rate in drug-treated group increased with concentration- and time-dependent manner (r 24 =0.9092, r 48 =0.9442, r 72 =0.9546), the inter group comparison showed the statistical difference of results. The experiments in vitro showed that the survival time prolonged, blood cell count increased and body weight recovered in FA-2-b-β-treated group and imatinib-treated group, despite the WBC count is still high. The RT-qPCR and Western blot showed that the expression of BAX and caspase-3 gene and protein were up-regulated, the expression of BCL-2, cytochroime C, caspase-8, caspase-9 and BCL-ABL gene and protein were down-regulated., Conclusion: The FA-2-b-β can induce apoptosis of primary CML cells and prolong the survival time of CML model mouse, which may be related with the caspase-3 signal pathway related genes and proteins.

Background: Although several risk factors of the multiple intracranial aneurysms (MIAs) formation has been reported, the results are controversial. We aimed to find out the risk factors of MIAs formation by analyzing our clinic data combined with a meta-analysis., Material and Methods: A retrospective review work of medical records for the patients with aneurysms was undertaken. Univariate analysis was used to examine all mentioned variables. Binary logistic regression analysis was used to identify the risk factors of MIAs formation., Results: In the retrospective review work, a total of 565 patients with aneurysm were included in this study. Of these 565 participants, 449 patients suffered SIAs and 116 patients suffered MIAs. Univariate analysis showed a significant difference in terms of female, cigarette smoking, family history of hypertension, and primary hypertension between the SIAs and MIAs group. The binary logistic regression analysis showed that the female (OR = 1.624), primary hypertension (OR = 1.563), and family history of hypertension (OR = 2.496) were independent risk factors of the formation of MIAs (for each P < 0.05). With regard to the meta-analysis results, it revealed that there was significant difference in the rates of female (P < 0.001), cigarette smoking (P < 0.001), primary hypertension (P = 0.001), and higher age (P = 0.011) among the MIAs patients., Conclusions: A higher rate of the formation of MIAs is closely associated with the elder and female. Patients with hypertension history, cigarette smoking, and family primary hypertension history also affected the formation of MIAs, these risk factors should be a guard against., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Young breast cancer survivors (YBCS) face unique challenges in coping with disease, distress, and relationship concerns. The purposes of this study were to understand the acceptability and feasibility of an online Mindfulness-Based Intervention (MBI) for YBCS and their partners (i.e., Couples Mindfulness-Based Intervention: C-MBI) and to compare the effectiveness of the C-MBI to a closely-matched control, an online MBI for individuals (I-MBI)., Methods: YBCS and their partners were recruited. Couples were randomly assigned to an 8-week C-MBI (couples = 41) or to I-MBI (couples = 36), which included one-hour video modules, a manual, and guided-meditation audios. Both couple members participated in the C-MBI; only the YBCS participated in the control I-MBI. Participants answered surveys about individual- and couple-level functioning at baseline and post-intervention., Results: Online delivery was shown to be feasible and acceptable. For YBCS and their partners, levels of perceived stress, anxiety, depression, and fatigue were lower after the intervention, in both conditions. Unexpectedly, however, participating in the C-MBI appeared to have detrimental effects on dyadic adjustment and relationship quality., Conclusion: Although YBCS and their partners reported online delivery was acceptable and benefited well-being, for couple-based MBIs to have benefits for relationship functioning, it may be necessary for couples to have the support of other couples and an instructor. Online delivery may be particularly acceptable and effective for clinical populations, including YBCS. Medical professionals may be more likely to recommend online-MBI programs to cancer survivors, because the programs are of little or no cost.

The specific roles of extracellular polymeric substances (EPS) and how factors influenced EPS's roles during U(VI) immobilization are still unclear. In this study, high content of U with the main form of nanoparticles was detected in EPS, accounting for 10-42% of total U(VI) removal. EPS might be utilized as energy source or even as electron donors when external carbon source was unavailable. The influencing degree of each experimental parameter to uranium (U) removal process was elucidated. The influential priority to U(IV)/U(VI) ratios in sludge was as follows: acetate, U(VI), and nitrate. The influential priority to total EPS contents was as follows: U(VI), nitrate and acetate. The complex interaction mechanism between U(VI) and EPS in the U immobilization process was proposed, which might involve three ways including biosorption, bioreduction and bioprecipitation. These results indicate important and various roles of EPS in U(VI) immobilization.

An unreported ruthenium(ii) complex containing bisoxazoline ligands has been synthesized and characterized. To test the catalytic ability of the ruthenium complex, the synthesis of anilines from nitro compounds in the presence of a mild reducing agent sodium borohydride and visible light has been developed. Mechanistic studies involving the experiment and DFT calculations suggest that the reaction could involve a radical pathway with the assistance of a photoredox catalyst.

Papillary thyroid cancer (PTC) has inflicted huge threats to the health of mankind. Metal pollution could be a potential risk factor of PTC occurrence, but existing relevant epidemiological researches are limited. The current case-control study was designed to evaluate the relationships between exposure to multiple metals and the risk of PTC. A total of 262 histologically confirmed PTC cases were recruited. Age- and gender-matched controls were enrolled at the same time. Urine samples were used as biomarkers to reflect the levels of environmental exposure to 13 metals. Conditional logistic regression models were adopted to assess the potential association. Single-metal and multi-metal models were separately conducted to evaluate the impacts of single and co-exposure to 13 metals. The increased concentration of urinary Cd, Cu, Fe, and Pb quartiles was found significant correlated with PTC risk. We also found the decreased trends of urinary Se, Zn, and Mn quartiles with the ORs for PTC. These dose-response associations between Pb and PTC were observed in the single-metal model and remained significant in the multi-metal model (OR 25-50th =1.39, OR 50-75th =3.32, OR >75th =7.62, p for trend <0.001). Our study suggested that PTC was positively associated with urinary levels of Cd, Cu, Fe, Pb, and inversely associated with Se, Zn, and Mn. Targeted public health policies should be made to improve the environment and the recognition of potential risk factors. These findings need additional studies to confirm in other population.

Background: Vascular endothelial growth factor receptor-3 (VEGFR-3) / vascular endothelial growth factor -c (VEGF-C) signaling is reported to negatively regulate TLR4-triggered inflammation of macrophages. This study aims to clarify whether the VEGFR-3/VEGF-C signaling can suppress Kupffer cells (KCs) activation and attenuate hepatic ischemia-reperfusion injury (IRI) after liver transplantation., Methods: A rat model of liver transplantation was performed. Donor livers were perfused with VEGF-C injection via portal vein during cold preservation, and controls were perfused with UW solution. Serum levels of alanine transaminase (ALT), total bilirubin (TBIL) and inflammatory cytokines, as well as histology were analyzed after 24 h. KCs were isolated from grafts, RT-PCR and immunofluorescence were used to evaluate polarization-specific marker genes, western bolt was employed to assess the expression of suppressor of cytokine signaling 1(SOCS1) and phosphorylated glycogen synthase kinase 3β (p-GSK3β), and EMSA was utilized to quantify the NF-κB transcriptional activity., Results: Compared with controls, VEGF-C perfusion reduced ALT and TBIL levels and alleviated liver damage. Furthermore, VEGF-C perfusion suppressed serum proinflammatory cytokines secretion and increased IL-10.In addition, the VEGFR-3 mRNA of KCs was increased after reperfusion. VEGF-C perfusion suppressed NF-κB activity and up-regulated the expression of SOCS1 and p-GSK3β in KCs, and shifted the M1/M2 balance toward an anti-inflammatory profile., Conclusion: Exogenous VEGF-C protects liver graft from IRI by regulating the inflammatory response and modifying polarization of KCs., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose : Suppression of the Toll like receptor 4 (TLR4)-nuclear factor-κB (NF-κB) signaling was critical in protection against liver IRI. Previous studies revealed that Liver X receptors (LXRs) activation could antagonize TLR4-NF-κB signaling. The purpose of this study is to determine whether LXRs agonist GW3965 can suppress the TLR4-NF-κB signaling during liver transplantation and protect ischemia-reperfusion injury (IRI). Materials and Methods : Sprague Dawley (SD) rats were used to perform orthotropic liver transplantation. Donors were pretreatment with GW3965 (0.3 mg/kg) through caudal vein injection 30 min before the surgery. The followings were analyzed after transplantation: alanine aminotransferase (ALT), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) level in serum, ATP binding cassette transporter A1 (Abca1) expression, NF-κB transcriptional activity, apoptosis and histological injury. Results : GW3965 pretreatment significantly ameliorated the degree of IRI associated with the effects of upregulating Abca1 expression, inhibiting NF-κB transcriptional activity, and downregulating TNF-α and IL-6 level. Conclusion : LXRs activation attenuated hepatic IRI by preventing TLR4-NF-κB signaling.

Background: High-grade serous ovarian cancer (HGSOC) is the most lethal of all gynecological malignancies. Patients often suffer from chemoresistance. Several studies have reported that Fn14 could regulate migration, invasion, and angiogenesis in cancer cells. However, its functional role in chemoresistance of HGSOC is still unknown., Methods: The expression of Fn14 in tissue specimens was detected by IHC. CCK-8 assay was performed to determine changes in cell viability. Apoptosis was measured by flow cytometry. The potential molecular mechanism of Fn14-regulated cisplatin resistance in HGSOC was investigated using qRT-PCR, western blotting, and Co-IP assays. The role of Fn14 in HGSOC was also investigated in a xenograft mouse model., Results: In this study, we found that Fn14 was significantly downregulated in patients with cisplatin resistance. Patients with low Fn14 expression were associated with shorter progression-free survival and overall survival. Overexpression of Fn14 suppressed cisplatin resistance in OVCAR-3 cells, whereas knockdown of Fn14 did not affect cisplatin resistance in SKOV-3 cells. Interestingly, Fn14 could exert anti-chemoresistance effect only in OVCAR-3 cells harboring a p53-R248Q mutation, but not in SKOV-3 cells with a p53-null mutation. We isolated and identified primary cells from two patients with the p53-R248Q mutation from HGSOC patients and the anti-chemoresistance effect of Fn14 was observed in both primary cells. Mechanistic studies demonstrated that overexpression of Fn14 could reduce the formation of a Mdm2-p53-R248Q-Hsp90 complex by downregulating Hsp90 expression, indicating that degradation of p53-R248Q was accelerated via Mdm2-mediated ubiquitin-proteasomal pathway., Conclusion: Our findings demonstrate for the first time that Fn14 overcomes cisplatin resistance through modulation of the degradation of p53-R248Q and restoration of Fn14 expression might be a novel strategy for the treatment of HGSOC.

Objective: The α-ketoglutarate (αKG), a metabolite of glutaminolysis, is reported to orchestrate macrophages activation. This study aims to clarify whether the αKG / glutaminolysis metabolism can suppress Kupffer cells (KCs) activation during liver transplantation and attenuate hepatic ischemia-reperfusion injury (IRI)., Methods: Donor livers were perfused with DM-αKG (a cell-permeable analog of αKG) or BPTES (an inhibitor of glutaminase 1) via portal vein during cold preservation, and controls were perfused with UW solution. Then, a rat model of liver transplantation was performed. Serum levels of alanine transaminase (ALT), total bilirubin (TBIL) and inflammatory cytokines, as well as histology, were analyzed after 24 h. KCs were isolated from grafts. RT-PCR and immunofluorescence were used to evaluate polarization-specific marker genes. Western bolt was employed to assess the expression of phosphorylation of glycogen synthase kinase 3β (p-GSK3β) and suppressor of cytokine signaling 1 (SOCS1). EMSA was utilized to quantify the NF-κB transcriptional activity., Results: Compared with controls, DM-αKG perfusion decreased ALT and TBIL levels, alleviated liver damage, and reduced apoptosis, while BPTES group showed higher ALT and TBIL levels, severe damage and more apoptosis. Furthermore, DM-αKG perfusion suppressed NF-κB activity, up-regulated the expression of p-GSK3β and SOCS1 in KCs, and shifted the M1/M2 balance toward an anti-inflammatory profile. Besides, DM-αKG suppressed serum pro-inflammatory cytokines secretion and increased IL-10., Conclusions: αKG produced by glutaminolysis protects liver graft from IRI by regulating the inflammatory response and modifying the polarization of KCs., (Copyright © 2018. Published by Elsevier Masson SAS.)

Objective: To evaluate the wear intensity and surface roughness of occlusal veneers on premolars made of microhybrid composite resin or two kinds of ceramics in vitro after the thermocycling and cyclic mechanical loading tests., Methods: In the study,24 fresh extracted human premolars without root canal treatment were prepared (cusps reduction of 1.5 mm in thickness to simulate middle to severe tooth wear, the inclinations of cusps were 20°). The prepared teeth were restored with occlusal veneers made of three different materials: microhybrid composite, heat-pressed lithium disilicate ceramic and computer-aided design/computer-aided manufacturing (CAD/CAM) lithium disilicate ceramic in the thickness of 1.5 mm. The occlusal veneers were cemented with resin cement. The specimens were fatigued using the thermocycling and cyclic mechanical loading tests after being stored in water for 72 h. The wear of specimens was measured using gypsum replicas and 3D laser scanner before and after the thermocycling and cyclic mechanical loading tests and the mean lost distance (mm) was used to indicate the level of wear. The surfaces of occlusal contact area were observed and the surface roughness was recorded using 3D laser scanning confocal microscope before and after the fatigue test. Differences between the groups were compared using ONE-way ANOVA(P<0.05)., Results: All the specimens successfully survived after the thermocycling and cyclic mechanical loading tests. The mean wear of microhybrid composite group, heat-pressed lithium disilicate ceramic group, and CAD/CAM lithium disilicate ceramic group was (-0.13±0.03) mm, (-0.05±0.01) mm and (-0.05±0.01) mm, the wear of microhybrid composite was significantly higher than the two ceramic groups(P<0.001).The mean surface roughness(Ra)before the fatigue test was(1.24±0.20) μm, (0.75±0.09) μm, (0.73±0.14) μm and it became (1.81±0.24) μm, (1.53±0.26) μm and (1.77±0.23) μm after the test . Before the fatigue test, the surface roughness of microhybrid composite was significantly higher than the two ceramic groups(P<0.001) and after the test, the surface roughness of heat-pressed lithium disilicate ceramic was significantly lower than microhybrid composite(P=0.005) and CAD/CAM lithium disilicate ceramic (P=0.010)., Conclusion: From the view of wear speed, microhybrid composite was significantly higher than the two kinds of ceramics, but it was similar to enamel when the opposing tooth was natural. The surface roughness before the themocycling and cyclic mechanical loading test of microhybrid composite was significantly higher than that of the two ceramic groups. After the test, the surface roughness of heat-pressed ceramic was significantly lower than that of the other two groups. From the view of surface roughness, heat-pressed ceramic has more advantage.

Objective: To make more accurate occlusal quantitative analysis of three-dimensional (3D) virtual dental models and to compare the occlusal contact obtained by intraoral and dental cast scan., Methods: In this study, 5 subjects were intraoral scanned using laser scanner (3 shapes, Germany) to obtain the 3D virtual models of one tooth (the first molar), two teeth (the second premolar and the first molar), three teeth (the premolars and the first molar) and their opposite teeth, respectively. The silicone impressions were made and dental stone models were poured for each of them. The dental casts were scanned and then they were fixed to the maximum intercuspal position with a special locating jig for a rescanning of occlusal position. The virtual models taken intraorally and obtained with dental cast scan were introduced to a 3D quantitative analysis system, and some criteria regarding to occlusal contact were calculated and analyzed. The occlusal criteria were mean values of occlusal clearance space between the upper and lower occlusal surface (clearance), occlusal contact area (area), and cusp inclination (angle) of the mandibular first molar. Paired t tests were used to evaluate differences of occlusal criteria between the virtual models obtained with the intraoral scan and dental cast scan (α=0.05)., Results: The mean values of occlusal clearance of one to three teeth obtained by way of intraoral scan were smaller than those obtained by way of cast scan by 0.134 mm, 0.177 mm, and 0.207 mm, respectively. While the occlusal contact areas were greater than the cast scan by 8.65 mm 2 , 10.28 mm 2 , and 11.46 mm 2 . No statistically significant differences were found between the cusps inclinations obtained with the two scanning methods, and the interclass correlations were high., Conclusion: Occlusal clearance obtained by intraoral scan was less than that by cast scan while the occlusal contact area was greater than the latter, indicating that intraoral occlusal contact was closer. The difference of the standard deviations of occlusal clearance measured by the two methods were small and that of occlusal contact area was influenced by the number of teeth scanned intraorally. There was no statistical difference in cusp inclination between the two methods.

A Rh/Ni-catalyzed cascade sequence of allylamine isomerization and hydrophosphonylation to synthesize α-aminophosphonates has been disclosed. The reaction, which not only allows the generation of widespread valuable α-aminophosphonates under simple systems and mild conditions, but also enriches the process of olefin isomerization-addition both in catalytic systems and various reaction types.

A new class of chiral atropoisomeric (P, N) ligand precursors has been obtained with excellent diastereoselectivities and high yields through diastereoselective metal-free intramolecular radical oxidative C-H amination with chiral phosphamide as the auxiliary group. This method provides a concise and highly valuable pathway for the synthesis of enantiopure aminophosphine ligands in large-scale.

Brown planthopper (BPH) is the most destructive pest of rice in Asia. To date 29 BPH resistance genes have been identified, but only a few genes are being used in breeding due to inefficient markers for marker-assisted selection (MAS) and little knowledge of the real effects of the genes. In this study we individually transferred 13 genes or QTLs (Bph14, QBph3, QBph4, Bph17, Bph15, Bph20, Bph24, Bph6, Bph3, Bph9, Bph10, Bph18 and Bph21) into cultivar 9311 by marker assisted backcross breeding (MABB). Through positive and negative selection we narrowed the segments from donors containing Bph14, Bph15, Bph6 and Bph9 to 100-400 kb. Whole-genome background selection based on a high resolution SNP array was performed to maximize reconstitution of the recurrent parent genome (RPG 99.2-99.9%). All genes reduced BPH growth and development and showed antibiotic responses in seedlings. Based on genetic effects and amino acid sequences of genes in three clusters we inferred that Bph10 and Bph21 might be identical to Bph26, whereas Bph9 and Bph18 were different. Bph15 might be same with Bph17, but QBph4, Bph20 and Bph24 might be different. We believe that these NILs will be useful in rice BPH resistance research and breeding.

A new strategy for the synthesis of chiral α-amino phosphonates by enantioselective C-H phosphonylation of allylamine with phosphite in the presence of a chiral Brønsted acid catalyst has been developed. This protocol successfully integrates direct C-H oxidation with asymmetric phosphonylation and exhibits high enantioselectivity.

Brown planthopper (BPH) is the most destructive pest of rice in Asia. The BPH resistance in the introgression line IR65482-17-511-5-7 (IR65482-17) is derived from the wild rice species Oryza australiensis. An F2:3 population from a cross between Zhenshan 97 (ZS97) and IR65482-17 was used to map three quantitative trait loci (QTLs) for seedling resistance and feeding rate to BPH. The loci were distributed on chromosomes 2, 4 and 12. The QTL qBph4.2 on chromosome 4 had the largest effect, and contributed 36-44% of the phenotypic variance with a LOD score of 19-29. To validate the effect of qBph4.2, two near-isogenic lines (NILs) containing the qBph4.2 locus in the backgrounds of ZS97 and 9311 were developed by marker-assisted backcrossing (MABC). BPH bioassays showed that lines homozygous for the IR65482-17 allele (NIL+) of qBph4.2 tented to have significantly higher seedling resistance to BPH than those homozygous for the ZS97 or 9311 alleles (NIL-). Resistance was associated with a lower feeding rate by the insect. qBph4.2 was delimited to a ~300 kb (0.04 cM) region flanked by markers RM261 and S1, and co-segregating with XC4-27. This study will facilitate map-based cloning and marker-assisted selection of the gene, and permits further studies of gene function and resistance mechanisms in rice: BPH interaction., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The first Cu-catalyzed cascade sp(3) C-H bond oxidative functionalization of the 2-ethylazaarenes has been developed. The two different sp(3) C-H bonds in 2-ethylazaarenes are selectively oxidized and four new types of bonds (C=O, C=N, C-C, C-O) are constructed in one operation. Starting from the simple substrates and cheap nitro source, this reaction provides an efficient approach to produce new kinds of isoxazolines.

Background: NBD (NEMO binding domain) peptides could selectively inhibit the inflammation induced NF-κB activity, while sparing the protective functions of basal NF-κB activity. The aim of this study was to determine whether NBD peptides inhibited the transcriptional activity of nuclear factor-κB (NF-κB) during liver transplant ischemia-reperfusion injury (IRI), without affecting its basal function., Materials and Methods: Sprague Dawley (SD) rats were performed orthotropic liver transplantation according to the Kamada technique. Donors were given NBD peptides (8 mg/kg, intraperitoneal) 2 h before surgery (n = 24) and the controls were treated with the same volume of physiologic saline (n = 24). An additional 16 animals in normal condition (did not undergo any surgery) were also divided into two groups and given the same treatment as above to assess the effect of NBD peptides on basal function. We analyzed levels of alanine aminotransferase (ALT), tumor necrosis factor (TNF-α), IKK (IκB kinase) complex phosphorylation, IκBα degradation, NF-κB transcriptional activity, apoptosis, and performed a morphologic study of liver tissues at 3, 6, and 24 h after portal vein reperfusion and in normal condition (n = 8)., Results: Pretreatment with NBD peptides significantly improved liver function, attenuating liver parenchymal cell damage, apoptosis by down-regulating TNF-α level, inhibiting IKK complex phosphorylation, IκBα degradation, and NF-κB transcriptional activity, but had no effect in normal condition., Conclusion: NBD peptides attenuated hepatic IRI by preventing NF-κB activation, without affecting basal NF-κB activity., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Raman spectroscopy can be used in situ real-time measurement because it's rapid, and it is helpful to real-time online monitoring of process control. With the complexity of the environment and the characteristics of Raman signal, it is hard to avoid some overlapping spectrum peaks. Based on the advantage of immune algorithm, an immune algorithm (IA) was applied to the overlapping Raman signals of aromatics. With extraction of each single Raman spectrum peak signal from the mixture signals for resolution, Results show that the method is effective to identify the overlapped Raman signal for its fast resolution and accurate quantitative determination with the relative error less than 1%. For the overlapping Raman signals with fluorescence background disturbance, we proposed an adaptive immune algorithm, which is combined with independent component analysis. It can effectively resolve the fluorescence background signal, and it provides a new way for Raman spectra analysis of complex samples.

Aim: The aim of this study was to determine whether Astragaloside IV (AST-IV) inhibited the transcriptional activity of nuclear factor-κB (NF-κB), attenuating liver transplant ischemia-reperfusion injury (IRI)., Methods: Sprague Dawley (SD) rats were randomly divided into 2 groups: donors given AST-IV (1.5 mL; 100 μg/mL, intravenous [IV]) 1 hour before surgery (n = 32), versus controls treated with 1.5 mL physiological saline (n = 32). Orthotropic liver transplantation was performed according to the Kamada technique. Eight animals in each group were followed for seven days after surgery to assess survival. The remaining hosts in each group were divided into 3 subgroups (n = 8) to be examined at 3, 6, and 24 hours after portal vein reperfusion. We analyzed levels of alanine aminotransferase (ALT), tumor necrosis factor (TNF)-α, and NF-κB transcriptional activity and performed a morphological study of liver tissues, NF-κB, and glucocorticoid receptor (GR) expression in Kupffer cells (KCs)., Results: Pretreatment with AST-IV significantly improved survival rates and liver function, attenuating liver parenchymal cell damage by down-regulating TNF-α levels and NF-κB expressions, inhibiting NF-κB transcriptional activity, up-regulating GR expression., Conclusion: AST-IV attenuated hepatic IRI by inhibiting NF-κB transcriptional activity. The mechanism may relate to up-regulation of GR expression., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To promote the nasal absorption of recombinant hirudin-2, the preparation and physicochemical properties of recombinant hirudin-2 liposomes, as well as its pharmacokinetic characteristics and bioavailability in rats after nasal administration were investigated., Method: Recombinant hirudin-2 liposomes were prepared by reversal phase evaporation; the test of physicochemical properties including encapsulation efficiency, particle size and stability of liposome suspensions were determined by HPLC; Recombinant hirudin-2 concentration in plasma was determined by chromogenic substrate method and the relative bioavailability and pharmacokinetic parameters were also calculated using software program 3p87., Result: The encapsulation efficiency of recombinant hirudin-2 liposome reached greater than 76.95%, with an average particle size of about 168.3 nm, size distribution ranging from 24 to 286 nm, relative peak width of +/- 0.47, and a good stability., Conclusion: Compared with recombinant hirudin-2 solution, liposome preparation enhanced the nasal absorption of recombinant hirudin-2.

DNA computation is to use DNA molecules for information storing and processing. The task is accomplished by encoding and interpreting DNA molecules in suspended solutions before and after the complementary binding reactions. DNA computation is attractive, due to its fast parallel information processing, remarkable energy efficiency, and high storing capacity. Challenges currently faced by DNA computation are: 1) lack of theoretical computational models for applications and 2) high error rate for implementation. This paper attempts to address these problems from mathematical modeling and genetic coding aspects. The first part of this paper presents a mathematical formulation of DNA computation. The model may serve as a theoretical framework for DNA computation. In the second part, a genetic code based DNA computation approach is presented to reduce error rate for implementation, which has been a major concern for DNA computation. The method provides a promising alternative to reduce error rate for DNA computation.