An unappreciated cell survival-independent role for BAFF initiating chronic lymphocytic leukemia.

Background: Chronic Lymphocytic Leukemia (CLL) is characterized by the expansion of CD19+ CD5+ B cells but its origin remains debated. Mutated CLL may originate from post-germinal center B cells and unmutated CLL from CD5+ mature B cell precursors. Irrespective of precursor types, events initiating CLL remain unknown. The cytokines BAFF and APRIL each play a significant role in CLL cell survival and accumulation, but their involvement in disease initiation remains unclear. Methods: We generated novel CLL models lacking BAFF or APRIL. In vivo experiments were conducted to explore the impact of BAFF or APRIL loss on leukemia initiation, progression, and dissemination. Additionally, RNA-seq and quantitative real-time PCR were performed to unveil the transcriptomic signature influenced by BAFF in CLL. The direct role of BAFF in controlling the expression of tumor-promoting genes was further assessed in patient-derived primary CLL cells ex-vivo. Results: Our findings demonstrate a crucial role for BAFF, but not APRIL, in the initiation and dissemination of CLL cells. In the absence of BAFF or its receptor BAFF-R, the TCL1 transgene only increases CLL cell numbers in the peritoneal cavity, without dissemination into the periphery. While BAFF binding to BAFF-R is dispensable for peritoneal CLL cell survival, it is necessary to activate a tumor-promoting gene program, potentially linked to CLL initiation and progression. This direct role of BAFF in controlling the expression of tumor-promoting genes was confirmed in patient-derived primary CLL cells ex-vivo. Conclusions: Our study, involving both mouse and human CLL cells, suggests that BAFF might initiate CLL through mechanisms independent of cell survival. Combining current CLL therapies with BAFF inhibition could offer a dual benefit by reducing peripheral tumor burden and suppressing transformed CLL cell output.

A seven-immune-genes risk model predicts the survival and suitable treatments for patients with skin cutaneous melanoma.

Background: Skin cutaneous melanoma is characterized by high malignancy and prognostic heterogeneity. Immune cell networks are critical to the biological progression of melanoma through the tumor microenvironment. Thus, identifying effective biomarkers for skin cutaneous melanoma from the perspective of the tumor microenvironment may offer strategies for precise prognosis prediction and treatment selection. Methods: A total of 470 cases from The Cancer Genome Atlas and 214 from the Gene Expression Omnibus were systematically evaluated to construct an optimal independent immune cell risk model with predictive value using weighted gene co-expression network analysis, Cox regression, and least absolute shrinkage and selection operator assay. The predictive power of the developed model was estimated through receiver operating characteristic curves and Kaplan-Meier analysis. The association of the model with tumor microenvironment status, immune checkpoints, and mutation burden was assessed using multiple algorithms. Additionally, the sensitivity of immune and chemotherapeutics was evaluated using the ImmunophenScore and pRRophetic algorithm. Furthermore, the expression profiles of risk genes were validated using gene expression profiling interactive analysis and Human Protein Atlas resources. Results: The risk model integrated seven immune-related genes: ARNTL, N4BP2L1, PARP11, NUB1, GSDMD, HAPLN3, and IRX3. The model demonstrated considerable predictive ability and was positively associated with clinical and molecular characteristics. It can be utilized as a prognostic factor for skin cutaneous melanoma, where a high-risk score was linked to a poor prognosis and indicated an immunosuppressive microenvironment. Furthermore, the model revealed several potential target checkpoints and predicted the therapeutic benefits of multiple clinically used drugs. Conclusion: Our findings provide a comprehensive landscape of the tumor immune microenvironment in skin cutaneous melanoma and identify prognostic markers that may serve as efficient clinical diagnosis and treatment selection tools.

Complication Rates after Breast Surgery with the Motiva Smooth Silk Surface Silicone Gel Implants-A Systematic Review and Meta-Analysis.

BACKGROUND: In an era where textured devices are being phased out due to concerns about BIA-ALCL, the Motiva SilkSurface breast implants intend to alleviate historical prosthesis-related complications. However, its safety and feasibility remain unelucidated. METHODS: An analysis of Pubmed, Web of Science, Ovid, and Embase databases was performed. A total of 114 studies were identified initially, and 13 of these met the inclusion criteria and were assessed regarding postoperative parameters such as complication rate or follow-up period. RESULTS: In 4784 patients who underwent breast augmentation with Motiva SilkSurface breast implants, a total of 250 (5.2%) complications were observed. Short- and medium-term complication rates ranged from 2.8-14.4% and 0.32-16.67%, respectively. The most common complication was early seroma (n = 52, overall incidence = 1.08%), followed by early hematoma (n = 28, overall incidence = 0.54%). The incidence of capsule contracture was 0.54% and breast implant-associated-anaplastic large cell lymphoma was not observed. DISCUSSION: Although the majority of the studies in the current literature suggest the distinction of the Motiva SilkSurface breast implants in terms of postoperative complications and capsular contracture, its safety and feasibility need to be further elucidated with well-designed, large-scale, multicenter, prospective case-control studies. Other: No funding was received.

Heparan sulfate regulates IL-21 bioavailability and signal strength that control germinal center B cell selection and differentiation.

In antibody responses, mutated germinal center B (BGC) cells are positively selected for reentry or differentiation. As the products from GCs, memory B cells and antibody-secreting cells (ASCs) support high-affinity and long-lasting immunity. Positive selection of BGC cells is controlled by signals received through the B cell receptor (BCR) and follicular helper T (TFH) cell-derived signals, in particular costimulation through CD40. Here, we demonstrate that the TFH cell effector cytokine interleukin-21 (IL-21) joins BCR and CD40 in supporting BGC selection and reveal that strong IL-21 signaling prioritizes ASC differentiation in vivo. BGC cells, compared with non-BGC cells, show significantly reduced IL-21 binding and attenuated signaling, which is mediated by low cellular heparan sulfate (HS) sulfation. Mechanistically, N-deacetylase and N-sulfotransferase 1 (Ndst1)-mediated N-sulfation of HS in B cells promotes IL-21 binding and signal strength. Ndst1 is down-regulated in BGC cells and up-regulated in ASC precursors, suggesting selective desensitization to IL-21 in BGC cells. Thus, specialized biochemical regulation of IL-21 bioavailability and signal strength sets a balance between the stringency and efficiency of GC selection.

Research on the Governance Relationship among Stakeholders of Construction Waste Recycling Based on ANP-SNA.

A method based on Analytic Network Process and Social Network Analysis (ANP-SNA) was proposed in this paper to determine and better clarify the governance relationship among various stakeholders involved. Firstly, fourteen stakeholders of construction waste recycling were identified using the snowball sampling method, and the governance relationships of these stakeholders were summarized into four aspects with eight indicators. Secondly, the weights of the stakeholder governance relationship indicators were determined based on Analytic Network Process (ANP). Thirdly, the Social Network Analysis (SNA) method was used to model the governance relationship network of the stakeholders, and the governance relationships among different stakeholders in the network were described by quantitative analysis of network cohesion, network centrality, structural holes, and other indicators. Finally, key points for optimizing the governance relationships among stakeholders of construction waste recycling were proposed in this paper, so as to provide a new solution for the collaborative governance of stakeholders.

Chances and challenges-analysis of trends in breast reconstruction.

INTRODUCTION: While breast reconstruction has become more and more important within the past decade, research focus areas as well as trends are in constant change. METHOD: The publications from 2012 to 2021 were retrieved from the Web of Science Core Collection database. CiteSpace visualization analysis software was used to analyze the institutions, countries, regions, categories, and keywords on breast reconstruction research. RESULT: A total of 3092 articles were selected. The number of articles published in the last 10 years showed an upward trend year by year. The journal "Plastic and Reconstructive Surgery" had the largest number of publications and citations, representing the core journal. The USA had the largest number of publications and the most extensive cooperation with other countries. The research highlights mainly focused on the improvement of surgical techniques, enhancing postoperative recovery, and oncological safety. CONCLUSION: Over the past decade, research on breast reconstruction has developed steadily, and considerable achievements in the field of surgical techniques, postoperative recovery, and oncological safety were reached. Plastic surgeons should continue to strive for a higher level of evidence study designs, while also recognizing the importance of international and multiple-center cooperation.

Breast Reconstruction- Developing a Volumetric Outcome Algorithm.

Postoperative loss of breast volume represents a significant parameter for outcome evaluation of breast reconstruction. Breast volume broadly varies- depending of reconstruction method as well as surgical differences. A structural pattern of breast volume loss provides an essential parameter for preoperative design, helps to reduce postoperative breast asymmetry rate and thereby the need for reoperation. Therefore we hereby compare volume change of the three main reconstruction techniques: autologous flap-based, prosthesis-based and autologous fat transplantation breast reconstruction. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Levels of Coenzyme Q10 and Several COQ Proteins in Human Astrocytoma Tissues Are Inversely Correlated with Malignancy.

In a previous study, we reported the alterations of primary antioxidant enzymes and decreased citrate synthase (CS) activities in different grades of human astrocytoma tissues. Here, we further investigated coenzyme Q10 (CoQ10) levels and protein levels of polyprenyl diphosphate synthase subunit (PDSS2) and several COQ proteins required for CoQ10 biosynthesis in these tissues. We found that the level of endogenous CoQ10, but not of exogenous α-tocopherol, was higher in nontumor controls than in all grades of astrocytoma tissues. The levels of COQ3, COQ5, COQ6, COQ7, COQ8A, and COQ9, but not of COQ4, were lower in Grade IV astrocytoma tissues than in controls or low-grade (Grades I and II) astrocytomas, but PDSS2 levels were higher in astrocytoma tissues than in controls. Correlation analysis revealed that the levels of CoQ10 and COQ proteins were negatively correlated with malignancy degree and positively correlated with CS activity, whereas PDSS2 level was positively correlated with malignancy. Moreover, lower level of mitochondrial DNA-encoded cytochrome c oxidase subunit 2 was not only associated with a higher malignancy degree but also with lower level of all COQ proteins detected. The results revealed that mitochondrial abnormalities are associated with impaired CoQ10 maintenance in human astrocytoma progression.

Volumetry in Breast Reconstruction: Always New, Always Better?

Although breast surgeries for aesthetic or reconstructive purposes are regularly performed, no focus has been laid on establishing an adequate and reliable volumetry method. While CT and MRI scan represent methods that are already in clinical use, the 3D scan  is a novel and promising tool, easy to use with the possibility to measure the anatomic breast volume in an upright position. Nevertheless, its reliability is broadly underinvestigated. LEVEL OF EVIDENCE V : This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Understanding Breast Implant Illness: Etiology is the Key.

Because breast augmentation is one of the most popular cosmetic procedures, the issue of implant-related complications has been widely debated ever since the FDA approved the use of implants in 1962. Although decades have passed, breast implant illness (BII) still represents a poorly defined and controversial complication. With ongoing nonscientific discussion in the mainstream media and on social media, revealing the etiology of BII is urgent because knowledge of this subject ultimately influences patients' decisions. Little or no scientific research is currently available on BII and no final conclusions regarding its etiology, clinical manifestations, diagnostic criteria, or treatment have been made. This review aims to give an overview of the hypotheses on the etiology of BII and seeks inspiration to improve the conditions of BII patients.

Starch physicochemical properties of double recessive sweet-waxy maize.

Sweet-waxy is a new type of maize with waxy and sugary double recessive genes. This study aims to clarify starch structural and functional properties of this maize type. Grains with sweet-waxy and waxy phenotypes were separated from an ear using the two sweet-waxy maize hybrids of ATN and NKY as materials. Compared with waxy maize starch, the sweet-waxy maize starch mainly comprises small-sized round granules despite the typical waxy character of both starches. Mw, Mn, and relative crystallinity of sweet-waxy starch were higher than those of waxy starch in both hybrids. The average chain length of waxy starch was higher in ATN but lower in NKY compared with that of sweet-waxy starch. However, polydispersity (Mw/Mn) and F1 fraction were high in sweet-waxy and waxy starches in ATN and NKY, respectively. Breakdown viscosity, gelatinization enthalpy and temperatures of both hybrids were low in sweet-waxy starch. Peak viscosity was higher in waxy starch in NKY and similar between sweet-waxy and waxy starches in ATN. Retrogradation percentage was high and low for sweet-waxy starches in ATN and NKY, respectively.

Characterization of human mitochondrial PDSS and COQ proteins and their roles in maintaining coenzyme Q10 levels and each other's stability.

Mutations of many PDSS and COQ genes are associated with primary coenzyme Q10 (CoQ10) deficiency, whereas mitochondrial DNA (mtDNA) mutations might cause secondary CoQ10 deficiency. Previously, we found that COQ5 and COQ9 proteins are present in different protein complexes in the mitochondria in human 143B cells and demonstrated that COQ5 and COQ9 knockdown suppresses CoQ10 levels. In the present study, we characterized other PDSS and COQ proteins and examined possible crosstalk among various PDSS and COQ proteins. Specific antibodies and mitochondrial localization of mature proteins for these proteins, except PDSS1 and COQ2, were identified. Multiple isoforms of PDSS2 and COQ3 were observed. Moreover, PDSS1, PDSS2, and COQ3 played more important roles in maintaining the stability of the other proteins. Protein complexes containing PDSS2, COQ3, COQ4, COQ6, or COQ7 protein in the mitochondria were detected. Two distinct PDSS2-containing protein complexes could be identified. Transient knockdown of these genes, except COQ6 and COQ8, decreased CoQ10 levels, but only COQ7 knockdown hampered mitochondrial respiration and caused increased ubiquinol:ubiquinone ratios and accumulation of a putative biosynthetic intermediate with reversible redox property as CoQ10. Furthermore, suppressed levels of PDSS2 and various COQ proteins (except COQ3 and COQ8A) were found in cybrids containing the pathogenic mtDNA A8344G mutation or in FCCP-treated 143B cells, which was similar to our previous findings for COQ5. These novel findings may prompt the elucidation of the putative CoQ synthome in human cells and the understanding of these PDSS and COQ protein under physiological and pathological conditions.