Poland Syndrome and Multimorbidity in a 79-Year-Old Male.

This case study highlights a 79-year-old man with chronic low back pain attributed to severe lumbar scoliosis. Physical examination revealed the unilateral absence of pectoral muscles and ipsilateral hand anomalies, indicative of Poland syndrome (PS). The patient also experienced depression due to chronic pain and PS-related anomalies. A multi-disciplinary approach proved effective in alleviating both pain and depression.

A Case Report of an Elderly Patient With Cushing's Disease and Multiple Chronic Conditions.

Cushing's disease (CD) is a rare and serious condition characterized by a persistent increase in cortisol levels, resulting in various complications across multiple bodily systems. Elderly individuals often face a multitude of chronic illnesses and geriatric syndromes, which can complicate the diagnosis and treatment of CD in this demographic. This case study details the presentation of an elderly patient with adrenocorticotropic hormone (ACTH)-dependent CD, who initially presented with an acute exacerbation of chronic obstructive pulmonary disease. The article delves into the unique onset characteristics and treatment strategies for CD in the elderly, providing valuable insights for the comprehensive management of similar clinical cases.

Neutrophil Heterogeneity Is Modified during Acute Lung Inflammation in Apoa1-/- Mice.

Neutrophils play important roles in inflammatory airway diseases. In this study, we assessed whether apolipoprotein A-I modifies neutrophil heterogeneity as part of the mechanism by which it attenuates acute airway inflammation. Neutrophilic airway inflammation was induced by daily intranasal administration of LPS plus house dust mite (LPS+HDM) to Apoa1-/- and Apoa1+/+ mice for 3 d. Single-cell RNA sequencing was performed on cells recovered from bronchoalveolar lavage fluid on day 4. Unsupervised profiling identified 10 clusters of neutrophils in bronchoalveolar lavage fluid from Apoa1-/- and Apoa1+/+ mice. LPS+HDM-challenged Apoa1-/- mice had an increased proportion of the Neu4 neutrophil cluster that expressed S100a8, S100a9, and Mmp8 and had high maturation, aggregation, and TLR4 binding scores. There was also an increase in the Neu6 cluster of immature neutrophils, whereas neutrophil clusters expressing IFN-stimulated genes were decreased. An unsupervised trajectory analysis showed that Neu4 represented a distinct lineage in Apoa1-/- mice. LPS+HDM-challenged Apoa1-/- mice also had an increased proportion of recruited airspace macrophages, which was associated with a reciprocal reduction in resident airspace macrophages. Increased expression of a common set of proinflammatory genes, S100a8, S100a9, and Lcn2, was present in all neutrophils and airspace macrophages from LPS+HDM-challenged Apoa1-/- mice. These findings show that Apoa1-/- mice have increases in specific neutrophil and macrophage clusters in the lung during acute inflammation mediated by LPS+HDM, as well as enhanced expression of a common set of proinflammatory genes. This suggests that modifications in neutrophil and macrophage heterogeneity contribute to the mechanism by which apolipoprotein A-I attenuates acute airway inflammation.

Mapping Knowledge Landscapes and Emerging Trends of Sarcopenic Obesity in Older Adults: A Bibliometric Analysis From 2004 to 2023.

Background The prevalence of obesity in combination with sarcopenia, the age-related loss of muscle mass and strength or physical function, is on the rise among adults aged 65 years and older. A significant portion of this demographic now falls under the classification of sarcopenic obesity, a high-risk geriatric syndrome predominantly seen in an aging population vulnerable to compounded complications from both sarcopenia and obesity. It is essential to promptly evaluate the impact of academic research in this field, taking into account factors such as geographical regions, authors, journals, and institutions. Furthermore, exploring current topics and identifying potential areas that could inspire future researchers to conduct additional studies is crucial for advancing overall health in this population. Methodology A search was conducted in the Web of Science Core Collection database to identify English language articles and reviews focusing on sarcopenic obesity in older adults, published between January 1, 2004, and December 31, 2023. Bibliometric analysis was performed using VOSviewer (v.1.6.18) and CiteSpace (v.6.1.R2). Results A total of 985 original English-language articles were collected, consisting of 783 articles and 202 reviews. The volume of research publications in this field has shown significant growth since 2012. The United States leads in contributions, with 239 articles (24.3% of the total) and the highest number of citations at 18,403, along with the highest total link strength. The University of Melbourne in Australia stands out with 25 published articles (2.5% of the total). University of Verona in Italy has the most citations at 9,405, and Monash University in Australia has the highest total link strength at 53. Among prolific authors, John A. Batsis from Duke University is the most productive with 24 articles (2.4% of the total). The journal "Nutrients" has the most articles on sarcopenic obesity in older adults, publishing 54 articles (5.5% of the total). Key topics in this area include sarcopenia, obesity, sarcopenic obesity, and elderly. Recent interventions focus on "nutrition" and "exercise" for sarcopenic obesity in older adults. Conclusions Research on sarcopenic obesity in older adults has seen significant growth on a global scale from 2004 to 2023, indicating a promising area for further study with potential benefits from current advancements. Although academic inquiries have shed light on various aspects of sarcopenic obesity in older adults, there remains a noticeable dearth of clinical research and evidence-based medicine on the effective management of this condition in elderly individuals. Future studies could focus on developing tailored interventions for older adults with sarcopenic obesity.

Mapping Knowledge Landscapes and Emerging Trends of the Links Between Frailty and Heart Failure: A Bibliometric Analysis From 2000 to 2023.

Background Frailty, within the context of heart failure (HF), is strongly linked to poor patient outcomes. Investigating the vulnerable condition of individuals with HF is crucial, not only for medical reasons but also as a significant public health challenge, especially among the elderly population where both HF and frailty are common. Therefore, it is essential to prioritize HF patients with frailty over those without such symptoms. To begin, promptly assessing the impact of academic research in this area is crucial, considering factors such as geographical regions, authors, journals, and institutions. Additionally, it is important to explore current topics and identify potential areas that could inspire future researchers to conduct further studies to advance public health. Methodology We conducted a search in the Web of Science Core Collection database to identify articles and reviews in the English language focusing on frailty and HF which were published from January 1, 2000, to December 31, 2023. To perform bibliometric analysis, VOSviewer (v.1.6.18) and CiteSpace (v.6.1.R2) were utilized. Results A total of 1,381 original English-language articles were gathered, comprising 1,162 articles and 219 reviews. The quantity of research publications in this area has experienced significant growth since 2013. Among all countries, the United States has contributed the largest number of publications, accounting for 409 articles (29.62% of the total). Additionally, the United States has received the highest number of citations, being cited a total of 13,329 times, as well as boasting the greatest total link strength. Duke University stands out as the institution with the highest number of research papers, having published 40 articles (2.90% of the total). It has also received the most citations, with a total of 2,455 times, and possesses the highest total link strength, which amounts to 212. Within the realm of prolific authors, Kentaro Kamiya from Kitasato University emerges as the most productive, having authored 28 articles (2.03% of the total). When considering scholarly journals, "Esc Heart Failure" contains the highest number of articles pertaining to frailty and HF, publishing a noteworthy 36 articles (2.61% of the total). Noteworthy keywords within this field encompass frailty, heart failure, elderly, mortality, and cardiovascular disease. Over the past five years, the most popular keywords have centered around "frailty syndrome," "sarcopenia," and "therapeutic interventions." Conclusions Research on frailty and HF at a global scale has experienced substantial growth between 2000 and 2023, demonstrating a prospective field for further exploration with potential advantages from ongoing progress. Prospective studies could prioritize the enhancement of cardiac rehabilitation for patients coping with HF and frailty while ensuring the preservation of their overall quality of life.

A Case of Pulmonary Actinomycosis With Concurrent Gastric Adenocarcinoma in an Older Adult.

Actinomycosis is a chronic granulomatous disease that can affect various parts of the body, including the head and neck, lungs, abdominal and pelvic cavities, and wounds. It is caused by different actinomycetes like Actinomyces sherdii, Actinomyces glasii, Actinomyces cariosa, Actinomyces zurichensis, and Actinomyces europaea. Reported infections caused by actinomycetes include pulmonary actinomycosis, pelvic and abdominal infections, bone or artificial joint infections, endocarditis, complicated urinary tract infections, and soft tissue abscesses. The combination of pulmonary actinomycosis with gastric cancer is exceptionally rare in clinical practice, and the presence of actinomycetal infection alongside tumors in elderly patients poses significant challenges in treatment. This article presents the diagnosis and treatment process of an elderly patient with pulmonary actinomycosis and gastric adenocarcinoma.

Response of Phyllosphere and Rhizosphere Microbial Communities to Salt Stress of Tamarix chinensis.

As carriers of direct contact between plants and the atmospheric environment, the microbiomes of phyllosphere microorganisms are increasingly recognized as an important area of study. Salt secretion triggered by salt-secreting halophytes elicits changes in the community structure and functions of phyllosphere microorganisms, and often provides positive feedback to the individual plant/community environment. In this study, the contents of Na+ and K+ in the rhizosphere, plant and phyllosphere of Tamarix chinensis were increased under 200 mmol/L NaCl stress. The increase in electrical conductivity, Na+ and K+ in the phyllosphere not only decreased the diversity of bacterial and fungal communities, but also decreased the relative abundance of Actinobacteriota and Basidiomycota. Influenced by electrical conductivity and Na+, the bacteria-fungus co-occurrence network under salt stress has higher complexity. Changes in the structure of the phyllosphere microbial community further resulted in a significant increase in the relative abundance of the bacterial energy source and fungal pathotrophic groups. The relative abundance of Actinobacteriota and Acidobacteriota in rhizosphere showed a decreasing trend under salt stress, while the complexity of the rhizosphere co-occurrence network was higher than that of the control. In addition, the relative abundances of functional groups of rhizosphere bacteria in the carbon cycle and phosphorus cycle increased significantly under stress, and were significantly correlated with electrical conductivity and Na+. This study investigated the effects of salinity on the structure and physicochemical properties of phyllosphere and rhizosphere microbial communities of halophytes, and highlights the role of phyllosphere microbes as ecological indicators in plant responses to stressful environments.

Retrospective analysis of laboratory results in 18 cases of severe asthma treated with omalizumab.

OBJECTIVE: The aim of this study was to explore the laboratory results in severe as asthma patients with omalizumab therapy and provide evidence for estimating omalizumab efficacy. METHODS: Retrospective study of 18 patients with severe asthma received omalizumab therapy in Shanghai General Hospital from 2020 to 2022 was performed. The basic data of patients were collected. The absolute number and the percentage of basophil and eosinophil in peripheral blood, total IgE level in serum, and as pulmonary function were detected at the beginning of treatment and 4 months after treatment. Differences between two groups were analyzed using Paired T test. RESULTS: The most common allergens collected from patients with moderate to severe asthma were dust mite (positive ratio 55.56%), mixed mold (16.67%), cat and dog dander, and Aspergillus fumigatus (11.11%). There was no significant difference in eosinophil and basophil counts in peripheral blood between the two groups. However, serum total IgE levels increased from (437.55±279.35) KU/L to (1071.42±721.28) KU/L (P=0.004), and FEV1/FVC ratio increased from (65.53±14.15)% to (73.91±13.63)% (P=0.005) after 4 months of treatment. CONCLUSIONS: The existing laboratory indicators for evaluation of omalizumab efficacy are still very limited, and new biomarkers need to be further developed. Elevated serum IgE levels at four weeks of treatment and FEV1/FVC may be potential indicators for omalizumab monitoring.

Towards targeting transposable elements for cancer therapy.

Transposable elements (TEs) represent almost half of the human genome. Historically deemed 'junk DNA', recent technological advancements have stimulated a wave of research into the functional impact of TEs on gene-regulatory networks in evolution and development, as well as in diseases including cancer. The genetic and epigenetic evolution of cancer involves the exploitation of TEs, whereby TEs contribute directly to cancer-specific gene activities. This Review provides a perspective on the role of TEs in cancer as being a 'double-edged sword', both promoting cancer evolution and representing a vulnerability that could be exploited in cancer therapy. We discuss how TEs affect transcriptome regulation and other cellular processes in cancer. We highlight the potential of TEs as therapeutic targets for cancer. We also summarize technical hurdles in the characterization of TEs with genomic assays. Last, we outline open questions and exciting future research avenues.

Asthmatic patients with high serum amyloid A have proinflammatory HDL: Implications for augmented systemic and airway inflammation.

RATIONALE: Serum amyloid A (SAA) is bound to high-density lipoproteins (HDL) in blood. Although SAA is increased in the blood of patients with asthma, it is not known whether this modifies asthma severity. OBJECTIVE: We sought to define the clinical characteristics of patients with asthma who have high SAA levels and assess whether HDL from SAA-high patients with asthma is proinflammatory. METHODS: SAA levels in serum from subjects with and without asthma were quantified by ELISA. HDLs isolated from subjects with asthma and high SAA levels were used to stimulate human monocytes and were intravenously administered to BALB/c mice. RESULTS: An SAA level greater than or equal to 108.8 µg/mL was defined as the threshold to identify 11% of an asthmatic cohort (n = 146) as being SAA-high. SAA-high patients with asthma were characterized by increased serum C-reactive protein, IL-6, and TNF-α; older age; and an increased prevalence of obesity and severe asthma. HDL isolated from SAA-high patients with asthma (SAA-high HDL) had an increased content of SAA as compared with HDL from SAA-low patients with asthma and induced the secretion of IL-6, IL-1ß, and TNF-α from human monocytes via a formyl peptide receptor 2/ATP/P2X purinoceptor 7 axis. Intravenous administration to mice of SAA-high HDL, but not normal HDL, induced systemic inflammation and amplified allergen-induced neutrophilic airway inflammation and goblet cell metaplasia. CONCLUSIONS: SAA-high patients with asthma are characterized by systemic inflammation, older age, and an increased prevalence of obesity and severe asthma. HDL from SAA-high patients with asthma is proinflammatory and, when intravenously administered to mice, induces systemic inflammation, and amplifies allergen-induced neutrophilic airway inflammation. This suggests that systemic inflammation induced by SAA-high HDL may augment disease severity in asthma.

Immunotherapy-Induced Hypophysitis Following Treatment With Tislelizumab in an Elderly Patient With Bladder Cancer and Prostate Cancer: A Case Report.

Immune checkpoint inhibitors represent a hopeful and emerging group of medications employed in the regulation of the immune response against cancer, displaying tremendous potential in cancer treatment. However, the administration of these drugs has been linked to the occurrence of adverse events, among which hypophysitis appears to be a prevailing complication affecting a substantial number of patients. Given the potential gravity of this condition, it is strongly recommended to actively monitor hormone levels throughout the treatment process, allowing for the prompt detection and provision of appropriate therapeutic measures. The present study showcases a case involving a 72-year-old individual afflicted with both bladder cancer and prostate cancer, who subsequently developed autoimmune hypophysitis and secondary adrenocortical insufficiency following the administration of programmed death protein 1 (PD-1) inhibitors.

BCR-ABL triggers a glucose-dependent survival program during leukemogenesis through the suppression of TXNIP.

Imatinib is highly effective in the treatment of chronic myelogenous leukemia (CML), but the primary and acquired imatinib resistance remains the big hurdle. Molecular mechanisms for CML resistance to tyrosine kinase inhibitors, beyond point mutations in BCR-ABL kinase domain, still need to be addressed. Here, we demonstrated that thioredoxin-interacting protein (TXNIP) is a novel BCR-ABL target gene. Suppression of TXNIP was responsible for BCR-ABL triggered glucose metabolic reprogramming and mitochondrial homeostasis. Mechanistically, Miz-1/P300 complex transactivates TXNIP through the recognition of TXNIP core promoter region, responding to the c-Myc suppression by either imatinib or BCR-ABL knockdown. TXNIP restoration sensitizes CML cells to imatinib treatment and compromises imatinib resistant CML cell survival, predominantly through the blockage of both glycolysis and glucose oxidation which results in the mitochondrial dysfunction and ATP production. In particular, TXNIP suppresses expressions of the key glycolytic enzyme, hexokinase 2 (HK2), and lactate dehydrogenase A (LDHA), potentially through Fbw7-dependent c-Myc degradation. In accordance, BCR-ABL suppression of TXNIP provided a novel survival pathway for the transformation of mouse bone marrow cells. Knockout of TXNIP accelerated BCR-ABL transformation, whereas TXNIP overexpression suppressed this transformation. Combination of drug inducing TXNIP expression with imatinib synergistically kills CML cells from patients and further extends the survival of CML mice. Thus, the activation of TXNIP represents an effective strategy for CML treatment to overcome resistance.

Pan-cancer analysis identifies tumor-specific antigens derived from transposable elements.

Cryptic promoters within transposable elements (TEs) can be transcriptionally reactivated in tumors to create new TE-chimeric transcripts, which can produce immunogenic antigens. We performed a comprehensive screen for these TE exaptation events in 33 TCGA tumor types, 30 GTEx adult tissues and 675 cancer cell lines, and identified 1,068 TE-exapted candidates with the potential to generate shared tumor-specific TE-chimeric antigens (TS-TEAs). Whole-lysate and HLA-pulldown mass spectrometry data confirmed that TS-TEAs are presented on the surface of cancer cells. In addition, we highlight tumor-specific membrane proteins transcribed from TE promoters that constitute aberrant epitopes on the extracellular surface of cancer cells. Altogether, we showcase the high pan-cancer prevalence of TS-TEAs and atypical membrane proteins that could potentially be therapeutically exploited and targeted.

[Practice of Palliative Care Consultation Proposed by the Emergency Department in Peking Union Medical College Hospital].

Objective To summarize the palliative care consultations proposed by the Emergency Department of Peking Union Medical College Hospital. Methods A retrospective study was conducted on 22 palliative care consultations in the Emergency Department of Peking Union Medical College Hospital from January 2017 to June 2020. Results A total of 18 patients (6 males and 12 females) received palliative care consultations in the Emergency Department,with the average age of (65±8) years (36-88 years).Specifically,10 and 6 patients received once and twice consultations,respectively,and 2 patients did not complete the consultation.Of the patients receiving palliative care consultations,15 had malignant tumors and 3 had non-neoplastic diseases.The reasons for palliative care consultations included communication (61.1%,11/18) and pain relief (61.1%,11/18).In terms of the place of death,8 patients died in the hospital and 6 patients in other medical institutions. Conclusion There is a clear demand for palliative care consultation in the Emergency Department of Peking Union Medical College Hospital,and the consultation can bring help to both emergency doctors and patients.

[Feasibility and Efficacy of Training Program for Aromatherapy in Palliative Care].

Objective To explore the feasibility and efficacy of the training program for aromatherapy in palliative care. Methods Data from four aromatherapy training programs held at Peking Union Medical College Hospital from 2016 to 2019 was collected.The feasibility and efficacy of the training were measured based on the self-reported questionnaires from 120 trainees. Results A total of 56 valid questionnaires were collected.The total score of the programs was 8.09.Trainees reported that the program enriched theoretical knowledge and enhanced practical confidence.After the training,79.6% of the trainees carried out aromatherapy in practice,while those who failed to practice were mainly due to the lack of appropriate opportunities.Some trainees suggested adding more practice hours and hoped to get follow-up guidance on a case-by-case basis. Conclusions It is feasible to carry out the short-term training program of aromatherapy in palliative care,which can enrich trainees' theoretical knowledge and enhance the practical confidence.It is necessary to provide continuous guidance after training to increase the proportion of trainees adopting aromatherapy in palliative care practice.

Genomic and transcriptomic determinants of response to neoadjuvant therapy in rectal cancer.

The incidence of rectal cancer is increasing in patients younger than 50 years. Locally advanced rectal cancer is still treated with neoadjuvant radiation, chemotherapy and surgery, but recent evidence suggests that patients with a complete response can avoid surgery permanently. To define correlates of response to neoadjuvant therapy, we analyzed genomic and transcriptomic profiles of 738 untreated rectal cancers. APC mutations were less frequent in the lower than in the middle and upper rectum, which could explain the more aggressive behavior of distal tumors. No somatic alterations had significant associations with response to neoadjuvant therapy in a treatment-agnostic manner, but KRAS mutations were associated with faster relapse in patients treated with neoadjuvant chemoradiation followed by consolidative chemotherapy. Overexpression of IGF2 and L1CAM was associated with decreased response to neoadjuvant therapy. RNA-sequencing estimates of immune infiltration identified a subset of microsatellite-stable immune hot tumors with increased response and prolonged disease-free survival.

Application of Big Data Clustering and Visual Communication in Business Website Interface Design.

The interface design of commercial websites is used in this paper to demonstrate the application of big data clustering and visual communication technologies. This paper presents the new requirements of user integration, emotion, and personalization by analyzing the broad influence of big data clustering technology and visual communication on the design concept and design method of commercial website interface design. Then, focusing on the information of visual graphic elements in web interface design and discussing how structures, images, words, emotions, and other elements can convey information more effectively through graphic means, the information in the web interface is creatively divided into two types: implicit and explicit. The database for the interface interaction system is built as part of this paper, which also uses fuzzy clustering to organize the data from the interface retrieval database and the hierarchical structure design method of process constraints to carry out interface information interaction and big data fusion processing. According to experiments, this algorithm's accuracy can reach 95.75%, which is about 11% higher than that of other approaches. This study can offer a workable design strategy for a business website's user interface.

KRAS Mutants Upregulate Integrin ß4 to Promote Invasion and Metastasis in Colorectal Cancer.

KRAS mutation in colorectal cancer is associated with aggressive tumor behavior through increased invasiveness and higher rates of lung metastases, but the biological mechanisms behind these features are not fully understood. In this study, we show that KRAS-mutant colorectal cancer upregulates integrin α6ß4 through ERK/MEK signaling. Knocking-out integrin ß4 (ITGB4) specifically depleted the expression of integrin α6ß4 and this resulted in a reduction in the invasion and migration ability of the cancer cells. We also observed a reduction in the number and area of lung metastatic foci in mice that were injected with ITGB4 knockout KRAS-mutant colorectal cancer cells compared with the mice injected with ITGB4 wild-type KRAS-mutant colorectal cancer cells, while no difference was observed in liver metastases. Inhibiting integrin α6ß4 in KRAS-mutant colorectal cancer could be a potential therapeutic target to diminish the KRAS-invasive phenotype and associated pulmonary metastasis rate. IMPLICATIONS: Knocking-out ITGB4, which is overexpressed in KRAS-mutant colorectal cancer and promotes tumor aggressiveness, diminishes local invasiveness and rates of pulmonary metastasis.

Identifying Diagnostic MicroRNAs and Investigating Their Biological Implications in Rectal Cancer.

Importance: Accurate clinical staging is important in rectal cancer because it determines the appropriate treatment and prognosis. Despite the use of multiple diagnostic imaging tools, it is sometimes difficult to clinically distinguish stage I tumors from stage II or III locally advanced disease. Identification of differentiating microRNAs (miRNAs) between these 2 groups may improve the clinical diagnostic power and provide insight into the biology of tumor progression. Objectives: To investigate differences in the expression of miRNAs in stage I vs stage II or III rectal cancers and integrate matched mRNA profiling data to identify possible functional roles of these miRNAs. Design, Setting, and Participants: The primary tumor specimens from patients who were enrolled in 2 prospective clinical trials between March 24, 2004, and November 16, 2012 (American College of Surgeons Oncology Group [ACOSOG] Z6041 and Timing of Rectal Cancer Response to Chemoradiation [TIMING]) were sequenced to arrive at a set of 127 cases (41 stage I and 86 stage II or III tumors) with matched miRNA and messenger RNA (mRNA) profiling data. These findings were also evaluated in an independent cohort of 127 patient specimens (29 stage I and 98 stage II or III tumors) from The Cancer Genome Atlas Rectum Adenocarcinoma (TCGA-READ) that also had matched miRNA and mRNA data. Data analysis was performed from September 1, 2019, to September 1, 2020. Main Outcomes and Measures: Alterations in miRNA expression between stage I and stage II or III tumors and their potential gene targets. Results: A total of 254 pretreatment rectal adenocarcinoma specimens were analyzed in this study as 2 distinct cohorts: 127 samples in the ACOSOG/TIMING (stage I group: 27 [66%] male; mean [SD] age, 64.4 [10.8] years; stage II or III group: 47 [55%] male; mean [SD] age, 57.0 [11.4] years), and another 127 samples from TCGA-READ (stage I group: 17 [59%] male; mean [SD] age, 63.6 [12.0] years; stage II or III group: 48 [49%] male; mean [SD] age, 64.5 [11.4] years). A total of 19 miRNAs were overexpressed in stage II or III vs stage I tumors in both cohorts. This miRNA signature had an excellent discriminative value for distinguishing stage II or III from stage I rectal tumors (area under the curve, 0.88; 95% CI, 0.83-0.94 in ACOSOG/TIMING cohort and area under the curve, 0.84; 95% CI, 0.77-0.91 in the TCGA-READ cohort). Integrative analysis revealed 3 miRNA-mRNA pairs that exhibited significant correlations in both cohorts: miR-31-5p-SATB2, miR-143-3p-KLF5, and miR-204-5p-EZR. Conclusions and Relevance: This diagnostic study found that many of the dysregulated miRNAs in stage II or III vs stage I rectal cancers have biological implications for tumor progression. The results of this study suggest that these miRNAs could assist as diagnostic biomarkers to better identify patients with locally advanced rectal cancer.

Competitive binding of E3 ligases TRIM26 and WWP2 controls SOX2 in glioblastoma.

The pluripotency transcription factor SOX2 is essential for the maintenance of glioblastoma stem cells (GSC), which are thought to underlie tumor growth, treatment resistance, and recurrence. To understand how SOX2 is regulated in GSCs, we utilized a proteomic approach and identified the E3 ubiquitin ligase TRIM26 as a direct SOX2-interacting protein. Unexpectedly, we found TRIM26 depletion decreased SOX2 protein levels and increased SOX2 polyubiquitination in patient-derived GSCs, suggesting TRIM26 promotes SOX2 protein stability. Accordingly, TRIM26 knockdown disrupted the SOX2 gene network and inhibited both self-renewal capacity as well as in vivo tumorigenicity in multiple GSC lines. Mechanistically, we found TRIM26, via its C-terminal PRYSPRY domain, but independent of its RING domain, stabilizes SOX2 protein by directly inhibiting the interaction of SOX2 with WWP2, which we identify as a bona fide SOX2 E3 ligase in GSCs. Our work identifies E3 ligase competition as a critical mechanism of SOX2 regulation, with functional consequences for GSC identity and maintenance.