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Emerging evidence underscores the importance of CD8 + T cells in the pathogenesis of multiple sclerosis (MS), but the precise mechanisms remain ambiguous. This study intends to elucidate the involvement of a novel subset of follicular CD8 + T cells (CD8 + CXCR5 + T) in MS and an experimental autoimmune encephalomyelitis (EAE) murine model. The expansion of CD8 + CXCR5 + T cells was observed in both MS patients and EAE mice during the acute phase. In relapsing MS patients, higher frequencies of circulating CD8 + CXCR5 + T cells were positively correlated with new gadolinium-enhancement lesions in the central nervous system (CNS). In EAE mice, frequencies of CD8 + CXCR5 + T cells were also positively correlated with clinical scores. These cells were found to infiltrate into ectopic lymphoid-like structures in the spinal cords during the peak of the disease. Furthermore, CD8 + CXCR5 + T cells, exhibiting high expression levels of ICOS, CD40L, IL-21, and IL-6, were shown to facilitate B cell activation and differentiation through a synergistic interaction between CD40L and IL-21. Transferring CD8 + CXCR5 + T cells into naïve mice confirmed their ability to enhance the production of anti-MOG 35-55 antibodies and contribute to the disease progression. Consequently, CD8 + CXCR5 + T cells may play a role in CNS demyelination through heightening humoral immune responses., 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. Published by Elsevier B.V.)

Background: Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system, ranking third for morbidity and mortality worldwide. At present, no effective control method is available for this cancer type. In tumor cells, especially iron metabolization, is necessary for its growth and proliferation. High levels of iron are an important feature to maintain tumor growth; however, the overall mechanism remains unclear., Methods: We used western blotting, immunohistochemistry (IHC) and real-time quantitative PCR to analyze the expression of IGF2BP2 in cell lines and tissues. Further, RNA-sequencing, RNA immunoprecipitation and methylated RNA immunoprecipitation experiments explored the specific binding of target genes. Moreover, the RNA stability assay was performed to determine the half-life of genes downstream of IGF2BP2. In addition, the Cell Counting Kit-8, colony formation assay, 5-ethynyl-2'-deoxyuridine assay and flow cytometry were used to evaluate the effects of IGF2BP2 on proliferation and iron metabolism. Lastly, the role of IGF2BP2 in promoting CRC growth was demonstrated in animal models., Results: We observed that IGF2BP2 is associated with iron homeostasis and that TFRC is a downstream target of IGF2BP2. Further, overexpression of TFRC can rescue the growth of IGF2BP2-knockdown CRC cells. Mechanistically, we determined that IGF2BP2 regulates TFRC methylation via METTL4, thereby regulating iron metabolism and promoting CRC growth. Furthermore, using animal models, we observed that IGF2BP2 promotes CRC growth., Conclusion: IGF2BP2 regulates TFRC mRNA methylation via METTL4, thereby regulating iron metabolism and promoting CRC growth. Our study highlights the key roles of IGF2BP2 in CRC carcinogenesis and the iron transport pathways., (© 2023. The Author(s).)

We have successfully modified a series of pyrrolo[2,1- a ]isoquinolines via direct nitration under mild reaction conditions. Easily accessible nitrates including CAN, Cu(NO 3 ) 2 ·H 2 O, and Fe(NO 3 ) 3 ·9H 2 O all can serve as effective nitrating reagents for functionalizing pyrrolo[2,1- a ]isoquinolines. Various nitro-bearing pyrrolo[2,1- a ]isoquinolines have been efficiently prepared in acceptable to good yields.

Crimean-Congo hemorrhagic fever virus (CCHFV) can cause severe hemorrhagic fever in humans and is mainly transmitted by ticks. There is no effective vaccine for Crimean-Congo hemorrhagic fever (CCHF) at present. We developed three DNA vaccines encoding CCHFV nucleocapsid protein (NP), glycoprotein N-terminal (Gn) and C-terminal (Gc) fused with lysosome-associated membrane protein 1 (LAMP1) and assessed their immunogenicity and protective efficacy in a human MHC (HLA-A11/DR1) transgenic mouse model. The mice that were vaccinated three times with pVAX-LAMP1-CCHFV-NP induced balanced Th1 and Th2 responses and could most effectively protect mice from CCHFV transcription and entry-competent virus-like particles (tecVLPs) infection. The mice vaccinated with pVAX-LAMP1-CCHFV-Gc mainly elicited specific anti-Gc and neutralizing antibodies and provided a certain protection from CCHFV tecVLPs infection, but the protective efficacy was less than that of pVAX-LAMP1-CCHFV-NP. The mice vaccinated with pVAX-LAMP1-CCHFV-Gn only elicited specific anti-Gn antibodies and could not provide sufficient protection from CCHFV tecVLPs infection. These results suggest that pVAX-LAMP1-CCHFV-NP would be a potential and powerful candidate vaccine for CCHFV., 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 © 2023 Hu, Zhang, Liu, Ye, Zhao, Zhang, Qiang, Zhang, Lei, Jiang, Cheng and Zhang.)

Background: Minimal research has been performed regarding total arch replacement through partial upper sternotomy in patients with acute type A aortic dissection who are obese, and the safety and feasibility of this procedure need to be further investigated. The present study investigated the potential clinical advantages of using a partial upper sternotomy versus a conventional full sternotomy for total arch replacement in patients who were obese., Methods: This was a retrospective study. From January 2017 to January 2020, a total of 65 acute type A aortic dissection patients who were obese underwent total arch replacement with triple-branched stent graft. Among them, 35 patients underwent traditional full sternotomy, and 30 patients underwent partial upper sternotomy. The perioperative clinical data and postoperative follow-up results of the two groups were collected, and the feasibility and clinical effect of partial upper sternotomy in total arch replacement were summarized., Results: The in-hospital mortality rates of the two groups were similar. The total operative time, cardiopulmonary bypass, aortic cross-clamp, cerebral perfusion, and deep hypothermic circulatory arrest times were also similar in both groups. The thoracic drainage and postoperative red blood cell transfusion volumes in the partial upper sternotomy group were significantly lower than those in the full sternotomy group. Mechanical ventilation time was shorter in the partial upper sternotomy group than that in the full sternotomy group. Additionally, the incidences of pulmonary infection, hypoxemia, and sternal diaphoresis were lower in the partial upper sternotomy group than those in the full sternotomy group., Conclusion: This study showed that total arch replacement surgery through a partial upper sternotomy in patients with acute type A aortic dissection who are obese is safe, effective, and superior to full sternotomy in terms of blood loss, postoperative blood transfusion, and respiratory complications., 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 © 2023 Xie, He, Wu, Qiu, Jiang, Gao and Chen.)

Background: Partial upper sternotomy (mini-ER) can be used in some adult cardiac surgeries but is seldom performed in the treatment of acute type A aortic dissection (AAAD). This study aimed to assess the feasibility and short-term outcomes of complete stent-graft replacement of the arch with triple-branched stent graft for AAAD through a mini-ER., Methods: From 2015 to 2018, 254 patients with AAAD underwent complete stent-graft replacement of the arch with a triple-branched stent graft. Replacement was performed with conventional full sternotomy (con-ER) in 142 patients and with mini-ER in the other 112 patients. Using propensity score matching, the clinical data were compared between 100 patients in the mini-ER group and 100 patients in the con-ER group., Results: After propensity score matching, there were no significant between-group differences in aortic cross-clamp time, cardiopulmonary bypass time, or total operative time. The amount of mediastinal drainage and number of red blood cell units were significantly lower in the mini-ER group compared with the con-ER group (P < .001). The intubation time was significantly shorter in the mini-ER group (P < .001). The treatment costs were also lower in the mini-ER group (P < .001). There were no significant between-group differences in 30-day mortality (9% vs 8%; P > .99) or postoperative complications., Conclusions: This study shows that extensive repair of AAAD through a mini-ER is feasible. It was superior to con-ER in terms of blood loss, postoperative ventilation time, and treatment costs., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Controversial opinions exist for aortic valve replacement (AVR) through partial upper sternotomy in obese patients. Moreover, this study sought to investigate the potential clinical advantage of partial upper sternotomy aortic valve replacement (mini-AVR) over conventional full sternotomy aortic valve replacement (con-AVR) in obese patients., Methods: This was a retrospective and observational study. From January 2015 to December 2020, a total of 184 obese [body mass index (BMI) ≥ 30 kg  m 2 ] patients undergoing isolated primary AVR were included: 98 patients underwent conventional full sternotomy, and 86 patients underwent partial upper sternotomy. Propensity score (PS) matching was applied to eliminate the bassline imbalances in the mini-AVR and the con-AVR groups., Results: After one-to-one propensity score matching, two groups of 60 patients were obtained. No in-hospital death occurred in the two groups. In addition, cardiopulmonary bypass time and total operative time were similar across the 2 groups, but the aortic cross-clamp time was significantly shorter in the con-AVR group (P = .0.022). The amount of mediastinal drainage at 48 h after surgery (P =  0.018) and postoperative blood transfusions (P =  0.014) were significantly lower in the mini-AVR group. There was no difference in ventilation time (P = .0.145), but a shorter intensive care unit stay time (P =  0.021) in the mini-AVR group., Conclusion: This study demonstrates that aortic valve replacement through a mini-AVR in obese patients is a safe and effective procedure. It outperformed con-AVR in terms of blood loss, blood product transfusion, and ICU stay., (© 2022. The Author(s).)

Malignancies of alimentary tract include esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), colon adenocarcinoma (COAD), and rectum adenocarcinoma (READ). Despite of their similarities in cancer development and progression, there are numerous researches concentrating on single tumor but relatively little on their common mechanisms. Our study explored the transcriptomic data of digestive tract cancers from The Cancer Genome Atlas database, yielding their common differentially expressed genes including 1,700 mRNAs, 29 miRNAs, and 362 long non-coding RNAs (lncRNAs). There were 12 mRNAs, 5 miRNAs, and 16 lncRNAs in the core competitive endogenous RNAs network by RNA-RNA interactions, highlighting the prognostic nodes of SERPINE1, hsa-mir-145, and SNHG1. In addition, the weighted gene co-expression network analysis (WGCNA) illustrated 20 gene modules associated with clinical traits. By taking intersections of modules related to the same trait, we got 67 common genes shared by ESCA and READ and screened 5 hub genes, including ADCY6, CXCL3, NPBWR1, TAS2R38, and PTGDR2. In conclusion, the present study found that SERPINE1/has-mir-145/SNHG1 axis acted as promising targets and the hub genes reasoned the similarity between ESCA and READ, which revealed the homogeneous tumorigenicity of digestive tract cancers at the transcriptome level and led to further comprehension and therapeutics for digestive tract cancers., 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 Lu, Shi, Zhang, Zhou, Zhou, Feng, Lu, Yang, Zhang, Liu, Li, Sun, Zheng, Jiang and Yang.)

BACKGROUND To observe and demonstrate therapeutic effects and side effects of two selective COX-2 inhibitors, imrecoxib and celecoxib, on patients with axial spondyloarthritis (axSpA) and observe the correlation between imaging scores and serum DKK-1 levels. MATERIAL AND METHODS Sixty patients with axSpA were randomly assigned to receive 200 mg imrecoxib or 200 mg celecoxib twice daily. Fifty-one patients who completed follow-up were included in the study. At baseline, week 4, and week 12, the clinical parameters, inflammatory markers (ESR, CRP), and adverse reactions were recorded. Serum DKK-1 levels were investigated by enzyme-linked immunosorbent assay. Radiographic scores were calculated by sacroiliac joint SPARCC (Spondyloarthritis Research Consortium of Canada) score method at baseline serum DKK-1 levels and week 12. RESULTS Patients in the imrecoxib group (n=25) and patients in the celecoxib group (n=26) were improved at week 4. At week 12, all clinical parameters and inflammatory markers were improved in the two groups and the differences was not statistically significant. Serum DKK-1 levels were decreased and the differences were not statistically significant. Serum DKK-1 levels in patients in the imrecoxib group at baseline were negatively correlated with all study parameters, while those in the celecoxib group had correlations with BASFI (r=-0.048, p=0.027) and Schober test (r=0.437, p=0.048), without any correlation with other clinical parameters or inflammatory markers. CONCLUSIONS Patients experienced significant improvement in disease activity, functional parameters, and inflammatory markers when treated with selective COX-2 inhibitors for 12 weeks, and the efficacy of imrecoxib was not inferior to celecoxib. Selective COX-2 inhibitors imrecoxib and celecoxib had no obvious effects on serum DKK-1 levels.

Aim: To evaluate the efficacies of six derivatives of Compound 2, a novel YycG histidine kinase inhibitor with the thiazolidione core structure in the treatment of medical device-related biofilm infections., Methods: The minimal inhibitory concentration (MIC) of the derivatives was determined using the macrodilution broth method, and the minimal bactericidal concentration (MBC) was obtained via sub-culturing 100 μL from each negative tube from the MIC assay onto drug-free Mueller-Hinton agar plates. Biofilm-killing effect for immature (6 h-old) biofilms was examined using a semiquantitative plate assay, and the effect on mature (24 h-old) biofilms was observed under a confocal laser scanning microscope (CLSM)., Results: The derivatives potently suppressed the growth of Staphylococcus epidermidis. The MIC values of the derivatives H2-10, H2-12, H2-20, H2-29, H2-27, and H2-28 on S epidermidis ATCC 35984 were 24.3, 6.5, 6.2, 3.3, 3.1, and 1.5 μg/mL, respectively. The MBC values of these derivatives were 48.6, 52.2, 12.4, 52.6, 12.4, and 6.2 μg/mL, respectively. The derivatives killed all bacteria in immature (6 h-old) biofilms and eliminated the biofilm proliferation. The derivatives also displayed strong bactericidal activities toward cells in mature (24 h-old) biofilms, whereas they showed low cytotoxicity and hemolytic activity toward Vero cells and human erythrocytes., Conclusion: The bactericidal and biofilm-killing activities of the new anti-YycG compounds were significantly better than the parent Compound 2.