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Hang Xu,1,2,&ast; Tianhai Lin,1,2,&ast; Jianzhong Ai,1,2,&ast; Jiapeng Zhang,1,2 Shiyu Zhang,1,2 Yifan Li,1,2 Xiaonan Zheng,1,2 Peng Zhang,1,2 Qiang Wei,1,2 Ping Tan,1,2 Lu Yang1,2 1Department of Urology, West China Hospital, Sichuan University, Sichuan, People’s Republic of China; 2Institute of Urology, West China Hospital, Sichuan University, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping Tan; Lu Yang, Department of Urology, West China Hospital, Sichuan University, Sichuan, People’s Republic of China, Tel +86 18980606829 ; +86 15208212056, Email uro_tanping@163.com; wycleflue@scu.edu.cnPurpose: Previous studies have suggested that the preoperative lactate dehydrogenase-to-albumin ratio (LAR) is correlated with survival in several cancers except bladder cancer (BCa). This study aimed to determine the prognostic value of the LAR in patients with urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC).Patients and Methods: A total of 595 UCB patients with RC in West China Hospital from December 2010 to May 2020 were enrolled. A receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value of the LAR. Kaplan–Meier curves and Cox regression analyses were applied to evaluate the association of the LAR with overall survival (OS) and recurrence-free survival. Independent factors in multivariate analyses were selected to construct nomograms. Calibration curves, ROC curves, concordance index (C-index) and decision curve analyses were used to evaluate the performance of the nomograms.Results: The optimal cutoff value of the LAR was determined to be 3.8. Preoperative low LAR was associated with decreased OS (P < 0.001) and RFS (P < 0.001), especially in patients with ≥ pT2 disease. LAR was an independent factor for OS (hazard ratio [HR]: 1.719; P < 0.001) and RFS (HR: 1.429; P = 0.012). The addition of the LAR into nomograms could result in better prediction performance. The areas under the curves of the nomograms were 0.821 and 0.801 for the prediction of 3-year OS and RFS, respectively. The C-indexes of the nomograms were 0.760 and 0.741 for the prediction of OS and RFS, respectively.Conclusion: The preoperative LAR is a novel and reliable independent prognostic biomarker for survival in UCB after RC.Keywords: lactate dehydrogenase, albumin, lactate dehydrogenase to albumin ratio, bladder cancer, prognosis

Bordetella infection can be efficiently prevented through vaccination. The current study investigated the effects of an extract of Cochinchina momordica seed (ECMS) combined with oil on the immune responses to the inactivated Bordetella vaccine in mice. Serum IgG and IgG1 level was significantly increased in ECMS-oil group compared to any other group ( P < 0.05 ) 2 weeks after immunization, while groups ECMS200 μg/400 μg-oil had a markedly higher level of serum IgG2b and IgG3 than any other groups ( P < 0.05 ). Moreover, lipopolysaccharide/ConA-stimulated proliferation of splenocytes was significantly enhanced in ECMS 400 μg-oil immunized mice in comparison with mice in any other group ( P < 0.05 ). RT-PCR assay revealed that while ECMS800 μg-oil group had significantly higher levels of serum IL-4, IL-10, Toll-like receptor (TLR)2, and IL-1 beta than any other group ( P < 0.05 ), the levels of serum IL-2, IL-4, and IL-10 were markedly increased in ECMS 400 μg-oil group as compared to any other groups ( P < 0.05 ). Blood analysis showed that ECMS800 μg-oil and oil groups had a significantly higher number of immunocytes than any other groups ( P < 0.05 ). There were significant differences in the number of IgG+, IgG2b+, and IgA+ cells in the lung between ECMS800 μg-oil group and any other groups ( P < 0.05 ). Western blot analysis demonstrated that stimulation with ECMS 25 μg/mL or 50 ng/mL led to a significant increase in the expression of TLR2, MyD88, and NF-κB in Raw264.7 cells ( P < 0.05 ). Compared with any other group, the expression of MyD88 was markedly increased in the cells stimulated with ECMS 50 ng/mL, as indicated by the RT-PCR analysis ( P < 0.05 ). Overall, we observed that ECMS-oil efficiently enhanced the humoral or cellular immune responses against Bordetella and suggested that the mechanism of adjuvant activity of ECMS-oil might involve TLR2/MyD88/NF-κB signaling pathway.

Purpose. The current study was designed to investigate the impact of blood urea nitrogen (BUN), serum uric acid (UA), and cystatin (CysC) on the short-term outcomes and prognosis of colorectal cancer (CRC) patients undergoing radical surgery. Methods. CRC patients who underwent radical resection were included from Jan 2011 to Jan 2020 in a single clinical centre. The short-term outcomes, overall survival (OS), and disease-free survival (DFS) were compared in different groups. A Cox regression analysis was conducted to identify independent risk factors for OS and DFS. Results. A total of 2047 CRC patients who underwent radical resection were included in the current study. Patients in the abnormal BUN group had a longer hospital stay ( p = 0.002 ) and more overall complications ( p = 0.001 ) than that of the normal BUN group. The abnormal CysC group had longer hospital stay ( p < 0.01 ), more overall complications ( p = p < 0.01 ), and more major complications ( p = 0.001 ) than the normal CysC group. Abnormal CysC was associated with worse OS and DFS for CRC patients in tumor stage I ( p < 0.01 ). In Cox regression analysis, age ( p < 0.01 , HR = 1.041, 95% CI = 1.029–1.053), tumor stage ( p < 0.01 , HR = 2.134, 95% CI = 1.828–2.491), and overall complications ( p = 0.002 , HR = 1.499, 95% CI = 1.166–1.928) were independent risk factors for OS. Similarly, age ( p < 0.01 , HR = 1.026, 95% CI = 1.016–1.037), tumor stage ( p < 0.01 , HR = 2.053, 95% CI = 1.788–2.357), and overall complications ( p = 0.002 , HR = 1.440, 95% CI = 1.144–1.814) were independent risk factors for DFS. Conclusion. In conclusion, abnormal CysC was significantly associated with worse OS and DFS at TNM stage I, and abnormal CysC and BUN were related to more postoperative complications. However, preoperative BUN and UA in the serum might not affect OS and DFS for CRC patients who underwent radical resection.

Yuhao Zeng,1,&ast; Sha Zhu,1,&ast; Zilin Wang,1 Junru Chen,1 Jindong Dai,1 Zhenhua Liu,1 Guangxi Sun,1 Jiayu Liang,1 Xingming Zhang,1 Zhipeng Wang,1 Jinge Zhao,1 Yuchao Ni,1 Jiyu Yang,1 Minghao Wang,1 Qiang Wei,1 Xiang Li,1 Ni Chen,2 Zhiping Li,3 Xin Wang,3 Yali Shen,3 Jin Yao,4 Rui Huang,5 Jiyan Liu,6 Diming Cai,7 Hao Zeng,1 Pengfei Shen1 1Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 5Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 6Department of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 7Department of Medical Ultrasound, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengfei Shen; Hao Zeng, Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Email cdhx510@163.com; kucaizeng@163.comPurpose: Multidisciplinary team (MDT) discussion is a widely used model to manage patients diagnosed with cancer. However, there has been no direct evidence to prove its effect on the prognosis of metastatic renal cell carcinoma (mRCC) patients, so this study explored the impact of MDT discussion on mRCC patient survival.Methods: The clinical data of 269 mRCC patients were retrospectively collected from 2012 to 2021. The cases were grouped into the MDT and non-MDT groups, then subgroup analysis was performed according to different histology types, as well as exploring the role of MDT in patients who have undergone multiple-line therapy. Overall survival (OS) and progression free survival (PFS) were set as the study endpoint.Results: Approximately half (48.0%, 129/269) of the patients were in the MDT group, with univariable survival analyses showing these patients had remarkably longer median OS (MDT group: 73.7 months; non-MDT group: 33.2 months, hazard ratio (HR): 0.423 (0.288, 0.622), p< 0.001) and longer median PFS (MDT group: 16.9 months, non-MDT group: 12.7 months, HR: 0.722 (0.542, 0.962), p=0.026). Furthermore, MDT management resulted in longer survival for both ccRCC and non-ccRCC subgroups. Patients in the MDT group were more likely to receive multi-line therapy (MDT group: 79/129, 61.2% vs non-MDT group: 56/140, 40.0%, p< 0.001), and within this patient group, MDT management still resulted in longer OS (MDT group: 94.0 months; non-MDT group: 43.5 months, p=0.009).Conclusion: MDT is associated with prolonged overall survival in mRCC independent of histology, ensuring that patients receive better management and precise treatment.Keywords: mRCC, MDT, overall survival, prognosis, ccRCC, non-ccRCC, multi-line treatment

A series of Re modified NiMo/Al2O3 hydrodesulfurization (HDS) catalysts with different contents of Re2O7 were successfully synthesized by stepwise impregnation method and co-impregnation method respectively. The effects of Re modification and impregnation methods on the physical-chemical properties of the prepared catalysts were determined by the characterization techniques such as XRD, N2 physical adsorption-desorption, NH3-TPD, Py-FTIR and HRTEM. Finally, the effects of the Re modification and the impregnation methods on the catalytic activity and the HDS reaction route selectivity were evaluated using 4,6-dimethyldibenzothiophene (4,6-DMDBT) as a probe. The results show that the crystal morphologies and pore structures of the synthesized catalysts varied with the contents of Re2O7 and the impregnation methods and the amounts of acid sites can be modulated by the incorporation of Re2O7 and the impregnation methods. Moreover, Re modification was conducive to the formation of the “type II” Ni-Mo-S active phase by changing the morphology of the Ni promoted MoS2 slabs. The HDS evaluation of 4,6-DMDBT results show that Re modification can effectively improve the 4,6-DMDBT conversions, DDS route selectivity and even 3,3′-dimethylcyclohexanebenzene (3,3′-DMCHB) selectivity in varying degrees, and compared with that of co-impregnation method, the Re modification by stepwise impregnation method exhibited a more prominent effect. In general, 1 wt% Re2O7 content was the most favorable to the HDS reaction since excessive Re2O7 content has very little promoting effect.

Annulus fibrosus (AF) repair remains a challenge because of its limited self-healing ability. Endogenous repair strategies combining scaffolds and growth factors show great promise in AF repair. Although the unique and beneficial characteristics of decellularized extracellular matrix (ECM) in tissue repair have been demonstrated, the poor mechanical property of ECM hydrogels largely hinders their applications in tissue regeneration. In the present study, we combined polyethylene glycol diacrylate (PEGDA) and decellularized annulus fibrosus matrix (DAFM) to develop an injectable, photocurable hydrogel for AF repair. We found that the addition of PEGDA markedly improved the mechanical strength of DAFM hydrogels while maintaining their porous structure. Transforming growth factor-β1 (TGF-β1) was further incorporated into PEGDA/DAFM hydrogels, and it could be continuously released from the hydrogel. The

Identification of network vulnerability is one of the important means of cyberspace operation, management and security. As a typical case of network vulnerability, network cascading failures are often found in infrastructure networks such as the power grid system, communication network and road traffic, where the failure of a few nodes may cause devastating disasters to the whole complex system. Therefore, it is very important to identify the critical nodes in the network cascading failure and understand the internal laws of cascading failure in complex systems so as to fully grasp the vulnerability of complex systems and develop a network management strategy. The existing models for cascading failure analysis mainly evaluate the criticality of nodes by quantifying their importance in the network structure. However, they ignore the important load, node capacity and other attributes in the cascading failure model. In order to address those limitations, this paper proposes a novel critical node identification method in the load network from the perspective of a network adversarial attack. On the basis of obtaining a relatively complete topology, first, the network attack can be modeled as a cascading failure problem for the load network. Then, the concept of load percolation is proposed according to the percolation theory, which is used to construct the load percolation model in the cascading failure problem. After that, the identification method of critical nodes is developed based on the load percolation, which accurately identifies the vulnerable nodes. The experimental results show that the load percolation parameter can discover the affected nodes more accurately, and the final effect is better than those of the existing methods.

All biological functions evolve by fixing beneficial mutations and removing deleterious ones. Therefore, continuously fixing and removing the same essential function to separately diverge monophyletic gene families sounds improbable. Yet, here we report that brassinosteroid insensitive1 kinase inhibitor1 (BKI1)/membrane-associated kinase regulators (MAKRs) regulating a diverse function evolved into BKI1 and MAKR families from a common ancestor by respectively enhancing and losing ability to bind brassinosteroid receptor brassinosteroid insensitive1 (BRI1). The BKI1 family includes BKI1, MAKR1/BKI1-like (BKL) 1, and BKL2, while the MAKR family contains MAKR2-6. Seedless plants contain only BKL2. In seed plants, MAKR1/BKL1 and MAKR3, duplicates of BKL2, gained and lost the ability to bind BRI1, respectively. In angiosperms, BKL2 lost the ability to bind BRI1 to generate MAKR2, while BKI1 and MAKR6 were duplicates of MAKR1/BKL1 and MAKR3, respectively. In dicots, MAKR4 and MAKR5 were duplicates of MAKR3 and MAKR2, respectively. Importantly, BKI1 localized in the plasma membrane, but BKL2 localized to the nuclei while MAKR1/BKL1 localized throughout the whole cell. Importantly, BKI1 strongly and MAKR1/BKL1 weakly inhibited plant growth, but BKL2 and the MAKR family did not inhibit plant growth. Functional study of the chimeras of their N- and C-termini showed that only the BKI1 family was partially reconstructable, supporting stepwise evolution by a seesaw mechanism between their C- and N-termini to alternately gain an ability to bind and inhibit BRI1, respectively. Nevertheless, the C-terminal BRI1-interacting motif best defines the divergence of BKI1/MAKRs. Therefore, BKI1 and MAKR families evolved by gradually gaining and losing the same function, respectively, extremizing divergent evolution and adding insights into gene (BKI1/MAKR) duplication and divergence.

We aim to compare the long-term oncologic outcomes, including overall survival (OS), cancer-specific survival (CSS), and bladder cancer recurrence (BCR) among patients with ureter carcinoma who received nephroureterectomy (RNU) or partial ureterectomy (PU).We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results database between 2004 and 2015 of patients with ureter carcinoma who underwent RNU or PU. Propensity score matching (PSM) was applied to balance the baseline data. The Kaplan-Meier method with subgroup analysis was conducted to verify the effect of the two surgery types. Fine-Gray competing risk regression estimated the cumulative incidence of BCR.A total of 2509 patients were involved; 665 (26.5%) patients underwent PU, and 1844 (73.5%) patients underwent RNU. Patients who underwent PU experienced a similar OS and CSS compared with those who underwent RNU in both PSM cohorts (HR [hazard ratio], 1.07 (0.93-1.23); P = 0.37; HR, 1.10 (0.91-1.31); P = 0.32, respectively), adjust model (HR, 0.99 (0.88-1.11); P = 0.87; HR, 1.05 (0.90-1.20); P = 0.55, respectively), and the subgroup analysis. For BCR, the patients who underwent PU were associated with a similar risk of developing BCR compared with those that received RNU, according to the univariate competing risk model (P = 0.47), adjust model (HR, 1.00 (0.73-1.37); P = 1), and subgroup analysis.RNU did not confer a distinct survival advantage compared with PU, which supports the role of PU in treating patients with ureter carcinomas.

The shortage of donor liver restricts liver transplantation (LT). Nowadays, donor liver with ABO blood group incompatibility between donor and recipient has become an option to expand the source of donor liver. Although it is now possible to perform ABO-incompatible (ABO-I) LT, antibody-mediated rejection (AMR) has been recognized as the primary cause of desperate outcomes after ABO-I LT. Anti-A/B antibody is the trigger of immune response to ABO-I LT graft injury. Therapeutic plasma exchange (TPE) can quickly reduce the titer of plasma antibodies and effectively inhibit humoral immunity.We searched PubMed and CNKI databases using search terms "therapeutic plasma exchange", "ABO-incompatible liver transplantation", "ABO-I LT", "liver transplantation", "LT", "antibody-mediated rejection", and "AMR". Additional publications were identified by a manual search of references from key articles. The relevant publications published before September 30, 2020 were included in this review.Different centers have made different attempts on whether to use TPE, when to use TPE and how often to use TPE. However, the control standard of lectin revision level is always controversial, the target titer varies significantly from center to center, and the standard target titer has not yet been established. TPE has several schemes to reduce antibody titers, but there is a lack of clinical trials that provide standardized procedures.TPE is essential for ABO-I LT. Hence, further research and clinical trials should be conducted to determine the best regimen for TPE to remove ABO antibodies and prevent AMR.

The oxidation-reduction (redox) status of the cell influences or regulates transcription factors and enzymes involved in epigenetic changes, such as DNA methylation, histone protein modifications, and chromatin structure and remodeling. These changes are crucial regulators of chromatin architecture, leading to differential gene expression in eukaryotes. But the cell's redox homeostasis is difficult to sustain since the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) is not equal in plants at different developmental stages and under abiotic stress conditions. Exceeding optimum ROS and RNS levels leads to oxidative stress and thus alters the redox status of the cell. Consequently, this alteration modulates intracellular epigenetic modifications that either mitigate or mediate the plant growth and stress response.Recent studies suggest that the altered redox status of the cell reform the cellular functions and epigenetic changes. Recent high-throughput techniques have also greatly advanced redox-mediated gene expression discovery, but the integrated view of the redox status, and its associations with epigenetic changes and subsequent gene expression in plants are still scarce. In this review, we accordingly focus on how the redox status of the cell affects epigenetic modifications in plants under abiotic stress conditions and during developmental processes. This is a first comprehensive review on the redox status of the cell covering the redox components and signaling, redox status alters the post-translational modification of proteins, intracellular epigenetic modifications, redox interplay during DNA methylation, redox regulation of histone acetylation and methylation, redox regulation of miRNA biogenesis, redox regulation of chromatin structure and remodeling and conclusion, future perspectives and biotechnological opportunities for the future development of the plants.The interaction of redox mediators such as ROS, RNS and antioxidants regulates redox homeostasis and redox-mediated epigenetic changes. We discuss how redox mediators modulate epigenetic changes and show the opportunities for smart use of the redox status of the cell in plant development and abiotic stress adaptation. However, how a redox mediator triggers epigenetic modification without activating other redox mediators remains yet unknown.

The roles of long non-coding RNA TDRG1 have been revealed in several tumors, especially its roles in CSC progression have been recently elucidated; However, its effects in lung CSC progression have not been revealed. In the present study, we collected 3D non-adherent spheres as the CSC model to measure lncRNA TDRG1 level in lung CSC and the parental lung cancer cells, and found that TDRG1 level was significantly upregulated in lung CSCs compared to that of parental lung cancer cells. Then we constructed the lung CSCs with or without TDRG1 stable knockdown and lung cancer cells with or without TDRG1 stable overexpression. It was found that TDRG1 positively regulated lung cancer stemness. Mechanistically, we identified that TDRG1 directly bound to Sox2 mRNA, which is a critical stemness regulator, enhanced its mRNA stability, and thus increased Sox2 expression. Indeed, we demonstrated that TDRG1 aggravated lung cancer stemness dependent on Sox2 expression. Thus, this study suggests that TDRG1 is a critical stemness promoter of lung cancer cells by acting as a stabilizer for Sox2 mRNA.

We briefly discuss that the similarity of LTR retrotransposons to retroviruses is a great opportunity for the development of a genetic engineering tool that exploits intragenic elements in the plant genome for plant genetic improvement. Long terminal repeat (LTR) retrotransposons are very similar to retroviruses but do not have the property of being infectious. While spreading between its host cells, a retrovirus inserts a DNA copy of its genome into the cells. The ability of retroviruses to cause infection with genome integration allows genes to be delivered to cells and tissues. Retrovirus vectors are, however, only specific to animals and insects, and, thus, are not relevant to plant genetic engineering. However, the similarity of LTR retrotransposons to retroviruses is an opportunity to explore the former as a tool for genetic engineering. Although recent long-read sequencing technologies have advanced the knowledge about transposable elements (TEs), the integration of TEs is still unable either to control them or to direct them to specific genomic locations. The use of existing intragenic elements to achieve the desired genome composition is better than using artificial constructs like vectors, but it is not yet clear how to control the process. Moreover, most LTR retrotransposons are inactive and unable to produce complete proteins. They are also highly mutable. In addition, it is impossible to find a full active copy of a LTR retrotransposon out of thousands of its own copies. Theoretically, if these elements were directly controlled and turned on or off using certain epigenetic mechanisms (inducing by stress or infection), LTR retrotransposons could be a great opportunity to develop a genetic engineering tool using intragenic elements in the plant genome. In this review, the recent developments in uncovering the nature of LTR retrotransposons and the possibility of using these intragenic elements as a tool for plant genetic engineering are briefly discussed.

The ATP-binding cassette subfamily B (ABCB) is an important transporter family, and many members are well known for their auxin transport function. However, reports on the function of the ABCB genes during Moso bamboo development are few. In this study, we identified and characterized 37 PhABCB genes in Moso bamboo and classified them into five subgroups, Ⅰ–Ⅴ. We further observed gene family expansion and gene loss events during the evolution of the PhABCB gene family. It was found that the expansion of the PhABCB family was mainly attributed to the whole-genome duplication and DNA-transposed duplication models. Gene co-expression analysis and quantitative real-time PCR revealed that several PhABCB genes may be involved in the development of the secondary cell wall (SCW) during the rapid growth of Moso bamboo. Through examining their expression in different parts of the bamboo internode where the cell walls exhibited different developmental stages, the roles of eight candidate PhABCBs in the SCW development were further characterized. Of the eight PhABCB genes, PhABCB7, PhABCB11, PhABCB14, and PhABCB21 may be involved in the SCW biogenesis in Moso bamboo. This study provides the basis for discovering the potential role of PhABCB genes in Moso bamboo cell wall development; further studies are needed to elucidate how these PhABCBs function in SCW development by regulating the polar transport of auxin.