Diminished representation of vitamin-B12-producing bacteria in constipated elders with frailty.

Constipation and frailty are associated with intestinal dysbiosis. This study aims to identify intestinal microbial signatures that can differentiate between constipated elders accompanied by frailty and those without frailty. We collected stool samples from 61 participants and conducted 16S rRNA gene sequencing. Constipated patients with frailty (Constipation_F) exhibited reduced gut microbial diversities compared to constipated patients without frailty (Constipation_NF) and healthy individuals (C). From differential genera, random forest models identified 14, 8, and 5 biomarkers for distinguishing Constipation_F from Constipation_NF, Constipation_F from C, and Constipation_NF from C, respectively. Functional analysis revealed that pathways (P381-PWY and PWY-5507) related to vitamin B12 synthesis were reduced in Constipation_F, which aligns with the decreased abundances of vitamin-B12-producing Actinomyces and Akkermansia in this group. Our study unveils substantial differences in gut microbiota between constipated elders with frailty and those without, underscoring the diagnostic and therapeutic potential of genera involved in vitamin B12 synthesis.

IL-32 regulates trophoblast invasion through miR-205-NFκB-MMP2/9 axis contributing to the pregnancy-induced hypertension.

Interleukin-32 is a species-specific cytokine that plays an important role in inflammation, cancer, and other diseases; however, its role in reproductive and pregnancy-related diseases remains unknown. This study aimed to investigate the role of interleukin-32 in reproductive and pregnancy-related diseases. Placental tissues from patients with pregnancy-induced hypertension, healthy pregnant women, and trophoblast lines were analysed. Interleukin-32 expression was quantified via polymerase chain reaction and immunohistochemistry, and functional assays were performed after interleukin-32 modulation. Interleukin-32 was identified only in placental mammals, such as Carnivora, Cetartiodactyla, Chiroptera, Dermoptera, Lagomorpha, Perissodactyla, and Primates via bioinformatics. Immunohistochemistry and polymerase chain reaction revealed that interleukin-32 was highly expressed in human placental villi, poorly expressed in decidua and endometrial tissues, and was not detected in mouse tissues. Second, interleukin-32 upregulates miR-205 expression by increasing DROSHA expression, and miR-205 promotes interleukin-32 expression by targeting its promoter region. Interleukin-32 and miR-205 significantly enhanced the invasion ability of HTR8/SVneo cells (a trophoblast cell line) and the tube formation ability of human umbilical vein endothelial cells. Through quantitative reverse transcription polymerase chain reaction and western blotting, the interleukin-32/miR-205 loop increased MMP2 and MMP9 expression in HTR-8/SVneo cells via the nuclear factor kappa B signalling pathway. Finally, using quantitative reverse transcription polymerase chain reaction, interleukin-32 and miR-205 expression levels were significantly lower in the placentas of patients with pregnancy-induced hypertension than in women with normal pregnancies. In conclusion, interleukin-32 regulates trophoblast invasion through the miR-205-nuclear factor kappa B-MMP2/9 pathway, which is involved in pregnancy-induced hypertension.

Overexpression of RBM4 promotes acute myeloid leukemia cell differentiation by regulating alternative splicing of TFEB.

Alternative splicing is an efficient and ubiquitous transcriptional regulatory mechanism that expands the coding capacity of the genome and is associated with the occurrence and progression of cancer. The differentiation-promoting regimen is a potential therapeutic approach in cancer treatment. In this study, we screened NPMc-positive and NPMc-negative acute myeloid leukemia (AML) samples from the Cancer Genome Atlas, focusing on the splicing factor RNA-binding motif protein 4 (RBM4) and its splicing mechanism on the target gene transcription factor EB (TFEB), which are most relevant to the prognosis of AML. We also investigated the impact of the TFEB-dominant spliceosome on autophagy and differentiation of THP-1 and K562 cells. The results showed that RBM4 recognized the CU-rich sequence in intron 8 of TFEB, increasing the production of the TFEB-L spliceosome, which promoted autophagy. Overexpression of RBM4 increased autophagy and promoted cell differentiation. The combination of TFEB-L with the therapeutic drug rapamycin further promoted the differentiation of leukemia cell lines and primary leukemia cells in AML patients. This study suggested that overexpression of RBM4 could promote cell differentiation by promoting the production of the TFEB-dominant spliceosome, demonstrating the potential of the TFEB-dominant spliceosome combined with chemotherapy drugs to promote leukemia cell differentiation and improve patient prognosis.

The Study of SRSF1 Regulates Abnormal Alternative Splicing of BCL2L11 and the Role in Refractory Acute Myeloid Leukemia.

INTRODUCTION: Abnormalities in splicing factors, such as mutations or deregulated expression, can lead to aberrant splicing of target genes, potentially contributing to the pathogenesis of acute myeloid leukemia (AML). Despite this, the precise mechanism underlying the abnormal alternative splicing (AS) induced by SRSF1, a splicing factor associated with poor AML prognosis, remains elusive. METHODS: Using strict splicing criteria, we globally screened for AS events in NPMc-positive and NPMc-negative AML samples from TCGA. An AS network associated with AML prognosis was then established. Functional assays, including CCK-8, flow cytometry, and Western blot, were conducted on K562 and THP-1 cells overexpressing SRSF1. Cell viability following 72-h Omipalisib treatment was also assessed. To explore the mechanism of SRSF1-induced AS, we created a BCL2L11 miniGene with a site-specific mutation at its branch point. The AS patterns of both wild-type and mutant miniGenes were analyzed following SRSF1 overexpression in HEK-293T, along with the subcellular localization of different spliceosomes. RESULTS: SRSF1 was significantly associated with AML prognosis. Notably, its expression was markedly upregulated in refractory AML patients compared to those with a favorable chemotherapy response. Overexpression of SRSF1 promoted THP-1 cell proliferation, suppressed apoptosis, and reduced sensitivity to Omipalisib. Mechanistically, SRSF1 recognized an aberrant branch point within the BCL2L11 intron, promoting the inclusion of a cryptic exon 3, which in turn led to apoptosis arrest. CONCLUSION: Overexpression of SRSF1 and the resulting abnormal splicing of BCL2L11 are associated with drug resistance and poor prognosis in AML.

Kaempferol attenuates particle-induced osteogenic impairment by regulating ER stress via the IRE1α-XBP1s pathway.

Periprosthetic osteolysis and subsequent aseptic loosening are the primary causes of failure following total joint arthroplasty. Wear particle-induced osteogenic impairment is recognized as an important contributing factor in the development of osteolysis, with endoplasmic reticulum (ER) stress emerging as a pivotal underlying mechanism. Hence, searching for potential therapeutic targets and agents capable of modulating ER stress in osteoblasts is crucial for preventing aseptic loosening. Kaempferol (KAE), a natural flavonol compound, has shown promising osteoprotective effects and anti-ER stress properties in diverse diseases. However, the influence of KAE on ER stress-mediated osteogenic impairment induced by wear particles remains unclear. In this study, we observed that KAE effectively relieved TiAl6V4 particles-induced osteolysis by improving osteogenesis in a mouse calvarial model. Furthermore, we demonstrated that KAE could attenuate ER stress-mediated apoptosis in osteoblasts exposed to TiAl6V4 particles, both in vitro and in vivo. Mechanistically, our results revealed that KAE mitigated ER stress-mediated apoptosis by upregulating the IRE1α-XBP1s pathway while concurrently partially inhibiting the IRE1α-regulated RIDD and JNK activation. Collectively, our findings suggest that KAE is a prospective therapeutic agent for treating wear particle-induced osteolysis and highlight the IRE1α-XBP1s pathway as a potential therapeutic target for preventing aseptic loosening.

Correlation Between Hemoglobin Levels and Polycystic Ovary Syndrome Metabolic Disorder.

Objective: The purpose of this study was to explore the relationship between hemoglobin levels and metabolic disorders in patients with PCOS. Methods: A total of 573 patients were selected, based on the hemoglobin level; 342 patients with PCOS were divided into two groups as follows: Group A (normal Hb group, n = 269) and Group B (high Hb group, n = 73); 231 non-PCOS patients were divided into two groups as follows: Group C (normal Hb group, n = 199), and Group D (high Hb group, n = 32). The general information, glucose and lipid metabolism indicators, and uric acid levels of all patients were compiled for data analysis. Results: (1) Hb, HGB concentration in mean red blood cells and RDW in PCOS patients were higher than those in non-PCOS patients, and MCV was lower than that in non-PCOS patients (P < 0.05); (2) Compared with Group A, patients in Group B had higher BMI, Hb, 2-hPG, FINS, 2-hINS, HOMA-IR, LDL-C, and uric acid levels while the QUICKI was lower; in Group C, the age, FSH, HDL-C, and LDL-C were higher, and AMH, BMI, T, TG, and uric acid level were lower (P<0.05); compared with Group D, AMH, BMI, FINS, HOMA-IR, TG, uric acid level increased, while age, FSH, and QUICKI decreased in Group B; and Hb and T decreased in Group C (P<0.05); (3) Pearson's correlation analysis indicated that Hb in PCOS patients was positively correlated with BMI, FPG, 2-hPG, FINS, 2-hINS, and HOMA-IR, and negatively correlated with the QUICKI (P<0.05); (4) Multi-factor logistic regression analysis suggested that the high Hb level in PCOS patients was an independent risk factor of IR (P<0.05). Conclusion: Hb level in patients with PCOS was associated with BMI and glucose metabolism indicators; a high Hb level may be an independent risk factor for IR.

Bibliometric and visual analysis of Kawasaki disease in children from 2012 to 2022.

Background: In recent years, the incidence of Kawasaki disease among the pediatric population has experienced a significant increase. With complications mainly affecting the cardiovascular system, Kawasaki disease has received widespread attention from scholars worldwide. Numerous articles on Kawasaki disease in children have been published far. However, there is a lack of studies that use visualization methods to perform a bibliometric analysis of the relevant literature. This study aims to obtain overall information on the output characteristics of publications on childhood Kawasaki disease between 2012 and 2022 through bibliometric analysis, identify research hotspots and frontiers, and provide new ideas and references for future clinical and scientific research. Methods: Literature meeting the inclusion criteria was screened from the Web of Science Core Collection, PubMed, and Scopus databases. Visual analysis of the literature by country, institution, journal, author, keywords, and references was performed using Citespace (6.1.R6), VOSviewer (1.6.18), and the online bibliometric website (https://bibliometric.com/). Results: A total of 4,867 eligible publications were included. The number of annual publications is generally rising, rapidly increasing since 2019. Among countries and institutions, China and KAOHSIUNG CHANG GUNG MEMORIAL HOSPITAL have the highest output of articles. With 104 publications, Ho-Chang Kuo has a high impact in the field of KD. The most cited author is Jane W. Newburger. The most prolific journal is FRONTIERS IN PEDIATRICS. CIRCULATION is the most frequently co-cited journal. The most popular keyword in frequency and centrality is "immunoglobulin". The reference with the highest burst intensity was Verdoni L, LANCET, 2020. Conclusion: Kawasaki disease in children remains a hot topic among pediatricians worldwide and is receiving increasing attention. We innovated the "national-institutional-journal" model, which promotes further international cooperation in this field. The hot topics in the field of pediatric KD are "KD pathogenesis", "immunoglobulin resistance and complementary therapy", and "cardiovascular complications". Frontiers include disease-related ("multisystem inflammatory syndrome", "coronavirus disease 2019", "hypotension"), treatment-related ("procalcitonin", " anakinra"), and pathogenesis ("polymerase chain reaction").

Change point detection for high dimensional data via kernel measure with application to human aging brain data.

Identifying the existence and locations of change points has been a broadly encountered task in many statistical application areas. The existing change point detection methods may produce unsatisfactory results for high-dimensional data since certain distributional assumptions are made on data, which are hard to verify in practice. Moreover, some parameters (such as the number of change points) need to be estimated beforehand for some methods, making their powers sensitive to these values. Here, we propose a kernel-based U $$ U $$ -statistic to identify change points (KUCP) for high dimensional data, which is free of distributional assumptions and sup-parameter estimations. Specifically, we employ a kernel function to describe similarities among the subjects and construct a U $$ U $$ -statistic to test the existence of change point for a given location. The asymptotic properties of the U $$ U $$ -statistic are deduced. We also develop a procedure to locate the change points sequentially via a dichotomy algorithm. Extensive simulations demonstrate that KUCP has higher sensitivity in identifying existence of change points and higher accuracy in locating these change points than its counterparts. We further illustrate its practical utility by analyzing a gene expression data of human brain to detect the time point when gene expression profiles begin to change, which has been reported to be closely related with aging brain.

Association of Serum Vitamin D With Periodontal Disease.

OBJECTIVE: There are conflicting reports on the relationship between vitamin D and periodontal disease. Our research is intended to further analyse the association between serum 25(OH)D3, a vitamin D precursor and periodontal disease based on a large national survey sample in Japan. METHODS: We downloaded the 2009-2018 National Health and Nutrition Examination Survey (NHANES) cycle, which included a total of 23,324 samples. Logistic regression of factors influencing perioral disease including periodntal disease, and subgroup logistic regression were performed to analyse the relationship between serum vitamin D and perioral disease, using WTMEC2YR as weights for regression analysis. Then machine learning model-based prediction of perioral disease onset was performed, and the machine learning algorithms used included boost tree, artificial neural network, AdaBoost, and random forest. RESULTS: We evaluated the vitamin D, age, sex, race, education, marriage, body mass index, ratio of family income to poverty (PIR), smoking, alcohol consumption, diabetes, and hypertension as variables in the included samples. Vitamin D was negatively associated with perioral disease; compared with Q1, the odds ratios and 95% CI were 0.8 (0.67-0.96) for Q2, 0.84 (0.71-1.00) for Q3, and 0.74 (0.6-0.92) for Q4 (P for trend <.05), respectively. The results of the subgroup analysis showed that the effect of 25(OH)D3 on periodontal disease was more pronounced in women younger than 60 years. Based on the accuracy and receiver operating characteristic curve, we concluded that a boost tree was a relatively good model to predict periodontal disease. CONCLUSIONS: Vitamin D might be a protective factor for periodontal disease, and boost tree analysis we emplyed was a relatively good model to predict perioral disease.

Worldwide Bronchiolitis obliterans research: A bibliometric analysis of the published literature between 2002 and 2022.

Bronchiolitis obliterans (BO) is a rare and irreversible chronic respiratory disease. The diagnosis of BO is challenging, and there still needs to be specific therapies and uniform treatment guidelines available. Research on BO has grown steadily over the past 20 years, and with the continued interest of researchers in this area, a bibliometric study of BO becomes necessary. This topic aims to assess the current state of research in BO over the last 2 decades and to identify research hotspots and emerging directions. Information on BO-related articles were obtained from the Science Citation Index Expand of the Web of Science Core Collection (WOSCC [SCI-E]) database. Citespace (6.1.R6), VOSviewer (1.6.18), and the online bibliometrics website (https://bibliometric.com/) were used for bibliometric analysis mainly to include country/region, institution, author, journal, keywords, and references and to construct visual knowledge network diagrams. A total of 4153 publications from the WOSCC [SCI-E] database were included in this study. Most publications come from the United States, Japan, and Germany, which collaborate relatively more frequently. Research institutions in the United States, especially the University of Washington, published the largest number of BO-related articles. Regarding authors, Vos, R is the most productive author, while Verleden, GM is the most influential in BO. In addition, JOURNAL OF HEART AND LUNG TRANSPLANTATION is the journal with the most published articles. The most cited article is Estenne M, 2002. Based on the clustering analysis of keywords and references, the diagnosis of bronchiolitis obliterans syndrome (BOS), treatment of BOS, and risk factors of BO are the current research hotspots and future research trends. We analyzed the publication trends in BO by bibliometrics and mapped the knowledge network of major contributing countries/regions, institutions, authors, and journals. Current research hotspots were found based on the main keywords and references. The outcome may help researchers identify potential collaborators, collaborating institutions, and hot fronts in BO to enhance collaboration on critical issues and improve the diagnosis and treatment of BO.