Single-cell analysis of a progressive Rosai-Dorfman disease affecting the cerebral parenchyma: a case report.

Neurologic Rosai-Dorfman disease (RDD) is a rare type of non-Langerhans cell histiocytosis that affects the central nervous system. Most neurologic RDDs grow like meningiomas, have clear boundaries, and can be completely resected. However, a few RDDs are invasive and aggressive, and no effective treatment options are available because the molecular mechanisms involved remain unknown. Here, we report a case of deadly and glucocorticoid-resistant neurologic RDD and explore its possible pathogenic mechanisms via single-cell RNA sequencing. First, we identified two distinct but evolutionarily related histiocyte subpopulations (the C1Q+ and SPP1+ histiocytes) that accumulated in the biopsy sample. The expression of genes in the KRAS signaling pathway was upregulated, indicating gain-of-function of KRAS mutations. The C1Q+ and SPP1+ histiocytes were highly differentiated and arrested in the G1 phase, excluding the idea that RDD is a lympho-histio-proliferative disorder. Second, although C1Q+ histiocytes were the primary RDD cell type, SPP1+ histiocytes highly expressed several severe inflammation-related and invasive factors, such as WNT5A, IL-6, and MMP12, suggesting that SPP1+ histiocytes plays a central role in driving the progression of this disease. Third, oligodendrocytes were found to be the prominent cell type that initiates RDD via MIF and may resist glucocorticoid treatment via the MDK and PTN signaling pathways. In summary, in this case, we report a rare presentation of neurologic RDD and provided new insight into the pathogenic mechanisms of progressive neurologic RDD. This study will also offer evidence for developing precision therapies targeting this complex disease.

Unlocking the potential: phenylboronic acid as a nuclear-targeting boron agent for neutron capture therapy.

It has been proposed that boron neutron capture therapy (BNCT) holds promise as a treatment modality for melanoma. However, the effectiveness of boron agents in delivery remains a critical issue to be addressed for BNCT. To this end, phenylboronic acid, which exhibits good water solubility and low cytotoxicity similar to BPA, has been investigated as a potential nuclear-targeting boron agent. The boron concentration of phenylboronic acid was found to be 74.47 ± 12.17 ng/106 B16F10 cells and 45.77 ± 5.64 ng/106 cells in the nuclei. Molecular docking experiments were conducted to investigate the binding of phenylboronic acid to importin proteins involved in nuclear transport. The potential of phenylboronic acid to serve as a desirable nucleus-delivery boron agent for neutron capture therapy in melanoma warrants further exploration.

In-depth human immune cellular profiling from newborn to frail.

Immune functional decline and remodeling accompany aging and frailty. It is still largely unknown how changes in the immune cellular composition differentiate healthy individuals from those become frail at a relatively early age. Our aim in this exploratory study was to investigate immunological changes from newborn to frailty, and the association between health statute and various immune cell subtypes. The participants analyzed in this study covered human cord blood cells and peripheral blood cells collected from young adults, healthy and frail old individuals. A total of 30 immune cell subsets was performed by flow cytometry based on the surface markers of immune cells. Furthermore, frailty was investigated for its relations with various leukocyte subpopulations. Frail individuals exhibited a higher CD4/CD8 ratio, a higher proportion of CD4+ central memory T (TCM) cells, CD8+ effector memory T cells, CD27- switched memory B (CD27-BSM) cells, CD27+ switched memory B cells, age-associated B cells (ABCs) and CD38-CD24- B cells, and a lower proportion of naïve CD8 + T cells and progenitor B cells. The Frailty index score was found to be associated with naïve T cells, CD4/CD8 ratio, ABCs, CD27-BSM cells, and CD4+ TCM cells. Our findings conducted a relatively comprehensive and extensive atlas of age- and frailty-related changes in peripheral leukocyte subpopulations from newborn to frailty. The immune phenotypes identified in this study can contribute to a deeper understanding of immunosenescence in frailty and may provide a rationale for future interventions and diagnosis.

Fludarabine Enhances Radiosensitivity by Promoting Ferroptosis in B-Cell Lymphoma.

The objective of this study is to investigate the impact of fludarabine, a signal transducer and activator of transcription-1 (STAT1) inhibitor, on the radiosensitivity of B-cell lymphoma (BCL) and to explore the underlying mechanisms. Radiotherapy is one of the primary treatments for BCL, and STAT1 plays a critical role in the transcription of cell proliferation-related genes, which are associated with radiotherapy and ferroptosis. This study aims to determine whether fludarabine can enhance the radiosensitivity of BCL and to elucidate the molecular pathways involved. Various in vitro methodologies, including CCK-8 assays, clonogenic formation assays, immunohistochemistry, immunofluorescence, flow cytometry, qRT-PCR, and Western blot analyses, were employed in B-cell lymphoma cell models to thoroughly investigate the effects of fludarabine on radiosensitivity. Subsequently, the obtained results were further validated through in vivo animal models and by examining human diffuse large B-cell lymphoma (DLBCL) cancer samples. Our findings demonstrate that the combination of fludarabine and irradiation synergistically inhibits cell viability and colony formation, while inducing apoptosis and ferroptosis in B-cell lymphoma cell lines Raji and Su-DHL-10. Moreover, fludarabine was found to enhance the ferroptosis induced by radiation, thereby synergistically impeding the growth of BCL. In vivo experiments confirmed these findings, revealing that the intraperitoneal injection of fludarabine significantly enhanced the inhibitory effects of radiation on Raji cell xenograft models, leading to an increased percentage of ferroptosis compared to models without fludarabine. Additionally, the administration of liproxstatin-1, a ferroptosis inhibitor, attenuated the inhibition of xenograft growth caused by the combination of fludarabine and irradiation. Furthermore, our analysis of clinical data revealed that increased co-expression of STAT1 and GPX4 is associated with poor overall survival in patients with diffuse large B-cell lymphoma. These results highlight the potential of fludarabine to enhance radiosensitivity and ferroptosis induction as a promising therapeutic strategy for BCL. Our results demonstrated that fludarabine promoted radiation-induced BCL death through the ferroptosis pathway. We have identified a previously unrecognized mechanism in the fludarabine and radiation combination, indicating that it is necessary to conduct prospective clinical trials to verify this new treatment regimen in BCL.

Hypoxia-induced factor-1α promotes radioresistance of esophageal cancer cells by transcriptionally activating LINC01116 and suppressing miR-3612 under hypoxia.

Esophageal cancer (EC) is a challenging tumor to treat with radiotherapy, often exhibiting resistance to this treatment modality. To explore the factors influencing radioresistance, we focused on the role of hypoxia-induced factor-1α (HIF-1α), and its interaction with the long noncoding RNA long intergenic nonprotein coding RNA 1116 (LINC01116). We analyzed the LINC01116 expression in EC and EC cell lines/human normal esophageal epithelial cell line (Het-1A). LINC01116 was silenced/overexpressed in EC109/KYSE30 cells under hypoxia, followed by radioresistance assessment. We measured HIF-1α levels in hypoxic EC cells and further validated the binding of HIF-1α with LINC01116, analyzing their interaction in EC cells. We then performed experiments in EC109 cells by transfection them with sh-HIF-1α/oe-LINC01116 to verify the effects. Additonally, we analyzed the localization of LINC01116 and its binding with miR-3612, followed by a combined experiment performed to validate the results. Our findings indicated that LINC01116 was highly expressed in EC and further elevated in hypoxic EC cells. LINC01116 was expressed at a high level in EC, which was further elevated in EC cells under hypoxic conditions. Knockdown of LINC01116 triggered EC cell apoptosis, thus suppressing radioresistance. Further investigation revealed that HIF-1α transcriptionally activated LINC01116 expression under hypoxia, and silencing HIF-1α lowered EC cell radioresistance by downregulating LINC01116. Under hypoxic conditions, LINC01116 could function as a sponge for miR-3612 and inhibit its expression. This interaction between LINC01116 and miR-3612 played a crucial role in mediating radioresistance in EC cells. Briefly, under hypoxic conditions, HIF-1α facilitates radioresistance of EC cells by transcriptionally activating LINC01116 expression and downregulating miR-3612.

Case report: Two case reports of cryptogenic brain abscess caused by Fusobacterium nucleatum and literature review.

Brain abscess originates from a localized cerebritis area of brain parenchyma, remaining a refractory infectious disease in the central nervous system. Causative pathogens can be wide-ranging, including bacteria, fungi, or parasites; thus, precise pathogen identification and individualized antimicrobial therapy determine patients' outcomes. Here, we report two cases where both patients only presented with limb dysfunction, but without symptoms, signs, or biological evidence of infection. Samples were obtained through brain stereoscopic surgeries and microbial identifications were performed to confirm the infection of Fusobacterium nucleatum. Further appropriate treatments were given, and the patients recovered well. Patient 1 was a 73-year-old male with a 20-day history of left-sided limbs weakness. A brain MRI showed a space-occupying lesion with a heterogeneously ring-enhancement character in the right frontal lobe. This patient underwent puncture biopsy of the lesion with robot-assisted guidance to confirm a brain abscess. Empirical antibiotic therapy was immediately given until the pathogen was identified as Fusobacterium nucleatum; thus, he received specific antibiotic therapy with metronidazole and recovered well after treatment. Patient 2 was a 22-year-old female with heart disease history who complained of right-sided limb weakness for nine days. A brain MRI showed a circular enhanced lesion with a thin capsule wall and surrounding edema in the left frontal lobe. This patient underwent puncture drainage of the lesion with robot-assisted guidance and a brain abscess was confirmed. Empirical antibiotic therapy was given until the pathogen was identified as Fusobacterium nucleatum and then she also received metronidazole treatment. Her symptoms recovered and the lesion disappeared after 1 month. Hence, we reviewed the diagnosis and treatment of cryptogenic brain abscess caused by Fusobacterium nucleatum and highlight that precise neurosurgical interventions and identification of causative pathogens are crucial for the management of brain abscess.

Akkermansia muciniphila protects the intestine from irradiation-induced injury by secretion of propionic acid.

Intestinal dysbiosis frequently occurs in abdominal radiotherapy and contributes to irradiation (IR)-induced intestinal damage and inflammation. Akkermansia muciniphila (A. muciniphila) is a recently characterized probiotic, which is critical for maintaining the dynamics of the intestinal mucus layer and preserving intestinal microbiota homeostasis. However, the role of A. muciniphila in the alleviation of radiation enteritis remains unknown. In this study, we reported that the abundance of A. muciniphila was markedly reduced in the intestines of mice exposed to abdominal IR and in the feces of patients who received abdominal radiotherapy. Abundance of A. muciniphila in feces of radiotherapy patients was negatively correlated with the duration of diarrhea in patients. Administration of A. muciniphila substantially mitigated IR-induced intestinal damage and prevented mouse death. Analyzing the metabolic products of A. muciniphila revealed that propionic acid, a short-chain fatty acid secreted by the microbe, mediated the radioprotective effect. We further demonstrated that propionic acid bound to G-protein coupled receptor 43 (GRP43) on the surface of intestinal epithelia and increased histone acetylation and hence enhanced the expression of tight junction proteins occludin and ZO-1 and elevated the level of mucins, leading to enhanced integrity of intestinal epithelial barrier and reduced radiation-induced intestinal damage. Metformin, a first-line agent for the treatment of type II diabetes, promoted intestinal epithelial barrier integrity and reduced radiation intestinal damage through increasing the abundance of A. muciniphila. Together, our results demonstrated that A. muciniphila plays a critical role in the reduction of abdominal IR-induced intestinal damage. Application of probiotics or their regulators, such as metformin, could be an effective treatment for the protection of radiation exposure-damaged intestine.

Study on the Dynamic Changes in Non-Volatile Metabolites of Rizhao Green Tea Based on Metabolomics.

The processing of tea leaves plays a crucial role in the formation of the taste of the resulting tea. In order to study the compositions of and changes in taste-related substances during the processing of Rizhao green tea, non-targeted metabolomics was used, based on UHPLC-Q Exactive MS. Totals of 529, 349, and 206 non-volatile metabolites were identified using three different detection modes, of which 112 secondary metabolites were significantly changed. Significant variations in secondary metabolites were observed during processing, especially during the drying stage, and the conversion intensity levels of non-volatile metabolites were consistent with the law of "Drying > Fixation > Rolling". The DOT method was used to screen tea-quality-related compounds that contributed significantly to the taste of Rizhao green tea, including (-)-epicatechin gallate, (-)-epicatechin gallate, gallic acid, L-theanine, and L-leucine, which make important contributions to taste profiles, such as umami and bitterness. Metabolic pathway analysis revealed that purine metabolism, caffeine metabolism, and tyrosine metabolism perform key roles in the processing of Rizhao green tea in different processing stages. The results of this study provide a theoretical basis for tea processing and practical advice for the food industry.

EWELD: A Large-Scale Industrial and Commercial Load Dataset in Extreme Weather Events.

Load forecasting is crucial for the economic and secure operation of power systems. Extreme weather events, such as extreme heat and typhoons, can lead to more significant fluctuations in power consumption, making load forecasting more difficult. At present, due to the lack of relevant public data, the research on load forecasting under extreme weather events is still blank, so it is necessary to release a large-scale load dataset containing extreme weather events. The dataset includes electricity consumption data of industrial and commercial users under extreme weather events such as typhoons and extreme heat, which are collected at 15-minute intervals. The data is collected over six years from smart meters installed at the power entry points of users in southern China. The dataset consists of electricity consumption data from 386 industrial and commercial users in 17 industries, with more than 50 million records. During the recording period, extreme weather events such as typhoons and extreme heat are marked to form a total of 5,741 event records.

Cuproptosis-related genes signature and validation of differential expression and the potential targeting drugs in temporal lobe epilepsy.

Introduction: Temporal lobe epilepsy (TLE) is the most common subtype of epilepsy in adults and is characterized by neuronal loss, gliosis, and sprouting mossy fibers in the hippocampus. But the mechanism underlying neuronal loss has not been fully elucidated. A new programmed cell death, cuproptosis, has recently been discovered; however, its role in TLE is not clear. Methods: We first investigated the copper ion concentration in the hippocampus tissue. Then, using the Sample dataset and E-MTAB-3123 dataset, we analyzed the features of 12 cuproptosis-related genes in TLEs and controls using the bioinformatics tools. Then, the expression of the key cuproptosis genes were confirmed using real-time PCR and immunohistochemical staining (IHC). Finally, the Enrichr database was used to screen the small molecules and drugs targeting key cuproptosis genes in TLE. Results: The Sample dataset displayed four differentially expressed cuproptosis-related genes (DECRGs; LIPT1, GLS, PDHA1, and CDKN2A) while the E-MTAB-3123 dataset revealed seven DECRGs (LIPT1, DLD, FDX1, GLS, PDHB, PDHA1, and DLAT). Remarkably, only LIPT1 was uniformly upregulated in both datasets. Additionally, these DECRGs are implicated in the TCA cycle and pyruvate metabolism-both crucial for cell cuproptosis-as well as various immune cell infiltrations, especially macrophages and T cells, in the TLE hippocampus. Interestingly, DECRGs were linked to most infiltrating immune cells during TLE's acute phase, but this association considerably weakened in the latent phase. In the chronic phase, DECRGs were connected with several T-cell subclasses. Moreover, LIPT1, FDX1, DLD, and PDHB were related to TLE identification. PCR and IHC further confirmed LIPT1 and FDX1's upregulation in TLE compared to controls. Finally, using the Enrichr database, we found that chlorzoxazone and piperlongumine inhibited cell cuproptosis by targeting LIPT1, FDX1, DLD, and PDHB. Conclusion: Our findings suggest that cuproptosis is directly related to TLE. The signature of cuproptosis-related genes presents new clues for exploring the roles of neuronal death in TLE. Furthermore, LIPT1 and FDX1 appear as potential targets of neuronal cuproptosis for controlling TLE's seizures and progression.

HOXD-AS2-STAT3 feedback loop attenuates sensitivity to temozolomide in glioblastoma.

AIMS: Glioblastoma multiforme (GBM) is the deadliest glioma and its resistance to temozolomide (TMZ) remains intractable. Long non-coding RNAs (lncRNAs) play crucial roles in that and this study aimed to investigate underlying mechanism of HOXD-AS2-affected temozolomide sensitivity in glioblastoma. METHODS: We analyzed and validated the aberrant HOXD-AS2 expression in glioma specimens. Then we explored the function of HOXD-AS2 in vivo and in vitro and a clinical case was also reviewed to examine our findings. We further performed mechanistic experiments to investigate the mechanism of HOXD-AS2 in regulating TMZ sensitivity. RESULTS: Elevated HOXD-AS2 expression promoted progression and negatively correlated with prognosis of glioma; HOXD-AS2 attenuated temozolomide sensitivity in vitro and in vivo; The clinical case also showed that lower HOXD-AS2 sensitized glioblastoma to temozolomide; STAT3-induced HOXD-AS2 could interact with IGF2BP2 protein to form a complex and sequentially upregulate STAT3 signaling, thus forming a positive feedback loop regulating TMZ sensitivity in glioblastoma. CONCLUSION: Our study elucidated the crucial role of the HOXD-AS2-STAT3 positive feedback loop in regulating TMZ sensitivity, suggesting that this could be provided as a potential therapeutic candidate of glioblastoma.

Development and validation of nomograms to predict the survival probability and occurrence of a second primary malignancy of male breast cancer patients: a population-based analysis.

Background: Male breast cancer (MBC) is rare, which has restricted prospective research among MBC patients. With effective treatments, the prognosis of MBC patients has improved and developing a second primary malignancy (SPM) has become a life-threatening event for MBC survivors. However, few studies have focused on the prognosis of MBC patients and looked into the SPM issue in MBC survivors. Method: We reviewed MBC patients diagnosed between 1990 and 2016 from the latest Surveillance, Epidemiology, and End Results (SEER) Plus database. Competing risk models and nomograms were conducted for predicting the risk of cancer-specific death and SPM occurrence. C-indexes, calibration curves, ROC curves, and decision curve analysis (DCA) curves were applied for validation. Result: A total of 1,843 MBC patients with complete information were finally enrolled and 60 (3.26%) had developed an SPM. Prostate cancer (40%) was the most common SPM. The median OS of all the enrolled patients was 102.41 months, while the median latency from the initial MBC diagnosis to the subsequent diagnosis of SPM was 67.2 months. The patients who suffered from an SPM shared a longer OS than those patients with only one MBC (p = 0.027). The patients were randomly divided into the development cohort and the validation cohort (at a ratio of 7:3). The Fine and Gray competing risk model was used to identify the risk factors. Two nomograms were constructed and validated to predict the 5-year, 8-year, and 10-year survival probability of MBC patients, both of which had good performance in the C-index, ROC curves, calibration plots, and DCA curves, showing the ideal discrimination capability and predictive value clinically. Furthermore, we, for the first time, constructed a nomogram based on the competing risk model to predict the 5-year, 8-year, and 10-year probability of developing an SPM in MBC survivors, which also showed good discrimination, calibration, and clinical effectiveness. Conclusion: We, for the first time, included treatment information and clinical parameters to construct a nomogram to predict not only the survival probability of MBC patients but also the probability of developing an SPM in MBC survivors, which were helpful in individual risk estimation, patient follow-up, and counseling in MBC patients.

Ethanol extract of propolis regulates type 2 diabetes in mice via metabolism and gut microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Propolis is a traditional natural medicine with various activities such as antioxidant and anti-inflammatory, immunomodulatory, anti-tumour, gastroenteritis treatment and prevention, anti-microbial and parasitic, as well as glucose regulation and anti-diabetes, and is expected to be an anti-diabetic candidate with few side effects, but the mechanism of action of propolis on type 2 diabetes mellitus (T2DM) has not been fully elucidated. AIM OF THE STUDY: The purpose of this study was to investigate the mechanism of the effect of ethanol extract of propolis (EEP) on the regulation of blood glucose in T2DM mice. MATERIALS AND METHODS: We studied the possible mechanism of EEP on T2DM using an animal model of T2DM induced by a combination of a high-fat diet and intraperitoneal injection of streptozotocin (STZ). The experiment was divided into four groups, namely, the normal group (HC), model group (T2DM), EEP and metformin group (MET). Biochemical indexes and cytokines were measured, and the differences of metabolites in the serum were compared by 1H-NMR. In addition, the diversity of intestinal flora in feces was studied by 16S rDNA amplicon sequencing. RESULTS: The results showed that following treatment with EEP and MET, the weight-loss trend of mice was alleviated, and the fasting blood glucose, insulin secretion level, insulin resistance index, C peptide level and oral glucose tolerance level decreased, whereas the insulin sensitivity index increased, thereby EEP effectively alleviated the occurrence of T2DM and insulin resistance. Compared with the T2DM group, the concentrations of pro-inflammatory cytokines interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) decreased significantly in EEP and MET groups, whereas the concentrations of anti-inflammatory cytokine interleukin-10 (IL-10) increased significantly. Metabolomics results revealed that EEP and MET regulate carbohydrate metabolism and restore amino acid and lipid metabolism. Correlation analysis of intestinal flora in mouse feces showed that compared with the HC group, harmful bacteria such as Bilophila, Eubacterium_ventriosum_group, Mucispirillum and Desulfovibrio were found in the T2DM group, whereas the abundance of beneficial bacteria such as Lactobacillus was significantly reduced. Parabacteroides, Akkermansia, Leuconostoc, and Alloprevotella were abundantly present in the EEP group; however, the MET group showed an increase in the genus Parasutterella, which could regulate energy metabolism and insulin sensitivity. CONCLUSIONS: The results showed that EEP and MET reduce fasting blood glucose in T2DM mice, followed by alleviating insulin resistance, improving the inflammatory reaction of mice, regulating the metabolism of mice, and affecting the steady state of gut microbiota. However, the overall therapeutic effect of EEP is better than that of MET.

Knockdown of LAMB3 suppressed radioresistance in nasopharyngeal carcinoma via deactivating NRF2 signaling pathway.

Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia and Southern China. Laminin subunit beta-3 (LAMB3) has been validated to participate in diverse cancers. Nevertheless, the role and mechanism of LAMB3 in NPC remain unclear. In this study, LAMB3 expression is upregulated in NPC cells and tissues. Interestingly, knockdown of LAMB3 promoted apoptosis and reduced the radioresistance of NPC cells. Besides, shLAMB3 enhanced X-ray-induced reactive oxygen species (ROS) accumulation. Mechanically, knockdown of LAMB3 deactivated nuclear factor erythroid-2-related factor 2 (NRF2) signaling pathway via enhancing forkhead box 3 (FOXO3) expression. In rescue experiments, suppression of NRF2 signaling pathway abrogated shLAMB3-induced NPC cell apoptosis and ROS accumulation under X-ray treatment. Similarly, LAMB3 knockdown restrains NPC tumor growth and reduces radioresistance in vivo. Thus, these findings concluded that knockdown of LAMB3 enhanced apoptosis and ROS accumulation, and suppressed radioresistance in NPC via enhancing FOXO3 expression and deactivating NRF2 signaling pathway, facilitating the development of novel strategies for NPC radioresistance.

Case Report: An Intracranial Aspergillus Infection with Cyst Formation.

Intracranial fungal infection is a rare condition that often requires surgical intervention. In this study, we present a case of intracranial fungal infection with a space-occupying effect and a long medical history of five years. We comprehensively evaluated the medical history, symptoms, imaging manifestations, and pathological examinations of the patient to confirm this rare case of fungal infection with cyst formation. Moreover, we reviewed the literature on intracranial fungal infection, hoping to draw awareness and attention to this rare disease.

Atf7ip and Setdb1 interaction orchestrates the hematopoietic stem and progenitor cell state with diverse lineage differentiation.

Hematopoietic stem and progenitor cells (HSPCs) are a heterogeneous group of cells with expansion, differentiation, and repopulation capacities. How HSPCs orchestrate the stemness state with diverse lineage differentiation at steady condition or acute stress remains largely unknown. Here, we show that zebrafish mutants that are deficient in an epigenetic regulator Atf7ip or Setdb1 methyltransferase undergo excessive myeloid differentiation with impaired HSPC expansion, manifesting a decline in T cells and erythroid lineage. We find that Atf7ip regulates hematopoiesis through Setdb1-mediated H3K9me3 modification and chromatin remodeling. During hematopoiesis, the interaction of Atf7ip and Setdb1 triggers H3K9me3 depositions in hematopoietic regulatory genes including cebpß and cdkn1a, preventing HSPCs from loss of expansion and premature differentiation into myeloid lineage. Concomitantly, loss of Atf7ip or Setdb1 derepresses retrotransposons that instigate the viral sensor Mda5/Rig-I like receptor (RLR) signaling, leading to stress-driven myelopoiesis and inflammation. We find that ATF7IP or SETDB1 depletion represses human leukemic cell growth and induces myeloid differentiation with retrotransposon-triggered inflammation. These findings establish that Atf7ip/Setdb1-mediated H3K9me3 deposition constitutes a genome-wide checkpoint that impedes the myeloid potential and maintains HSPC stemness for diverse blood cell production, providing unique insights into potential intervention in hematological malignancy.

Preparation of ultrafine and highly loaded silver nanoparticle composites and their highly efficient applications as reductive catalysts and antibacterial agents.

The size of silver nanoparticles (Ag NPs) and loading amount of Ag NPs onto their substrate/carrier are two key factors for their efficient applications. Herein, we present a facile method for in situ synthesizing ultrafine and highly loaded Ag NPs on the surface of tannin-coated catechol-formaldehyde resin (TA-CFR) nanospheres. TA-CFR nanospheres act as green and highly efficient reducing agents for converting silver ions (Ag+) into Ag NPs, and the size of resultant Ag NPs is only âˆ¼ 7.5 nm, and the Ag NPs loading capacity of TA-CFR is as high as 61.5 wt%, both of which contribute to the very high specific surface area of Ag NPs. Consequently, the as-synthesized TA-CFR@Ag composites show high catalytic performance, and the catalytic rate for the reduction of 4-nitrophenol is almost 10 times higher than that of the control. Meanwhile, TA-CFR@Ag composites also possess high antibacterial activity, efficiently inhibiting the growth of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Furthermore, tannin coating (thickness: ∼ 15 nm) minimizes the aggregation of Ag NPs, and enhances the reusability and stability of resultant Ag NPs, because of their high surface charges (the zeta potential is up to -65.5 ± 1.9 mV) and strong coordination capability with Ag NPs. This work provides a new frontier to develop multifunctional nanomaterials focusing on the green catalyst synthesis and environmental-remedy applications.

Prognostic significance and immune landscape of a fatty acid metabolism-related gene signature in colon adenocarcinoma.

Background: Fatty acid metabolism (FAM), as a hallmark of caner, plays important roles in tumor initiation and carcinogenesis. However, the significance of fatty acid metabolism-related genes in colon adenocarcinoma (COAD) are largely unknown. Methods: RNA sequencing data and clinical information were downloaded from the Cancer Genome Atlas (TCGA) cohort. Univariate and multivariate Cox regression analyses were utilized to construct a fatty acid metabolism-related gene signature. Kaplan-Meier survival and receiver operating characteristic (ROC) analyses were used to verify the performance of this signature. GEO datasets were applied to validate the signature. Maftools package was utilized to analyze the mutation profiles of this signature. Correlation between the risk signature and stemness scores was compared by RNA stemness score (RNAss). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set variation analysis (GSVA) were performed to explore the potential functions and signaling pathways. Immune landscape of the signature was explored by analyzing different immune cells infiltration, immune functions and microsatellite instability. A nomogram was constructed by combining the risk signature and multiple clinical factors. Expression levels and prognostic values of the risk genes were revealed in the cancer genome atlas and GEO databases. Moreover, the expression the risk genes were measured in cell lines using real time quantitative PCR (qRT-PCR). Results: Eight fatty acid metabolism-related genes (CD36, ENO3, MORC2, PTGR1, SUCLG2, ELOVL3, ELOVL6 and CPT2) were used to construct a risk signature. This signature demonstrated better prognostic value than other clinicopathological parameters, with AUC value was 0.734 according to the cancer genome atlas database. There was negative correlation between the riskscore and RNA stemness score. The patients in the high-risk group demonstrated higher infiltration of M0 macrophages, and less infiltration of activated CD4 memory T cells and Eosinophils. There were more MSI patients in the high-risk group than those in the low-risk group (38% vs. 30%). The risk scores of patients in the MSI group were slightly higher than those in the microsatellite stability group. Gene ontology, kyoto encyclopedia of genes and genomes and gene set variation analysis enrichment analyses showed that several metabolism-related functions and signaling pathways were enriched. A nomogram showed good predictive capability of the signature. Moreover, qRT-PCR revealed upregulated expression of ENO3, MORC2, SUCLG2 and ELOVL6, and downregulated expression of CPT2 in all examined colon adenocarcinoma cell lines. Conclusion: This study provided novel insights into a fatty acid metabolism-related signature in the prognosis an immune landscape of colon adenocarcinoma patients.

In situ repair or reconstruction of the abdominal aorta-iliac artery by autologous fascia-peritoneum with posterior rectus sheath for the treatment of the infected abdominal aortic and iliac artery aneurysms: A case series and literature review.

Background: Infected abdominal aortic and iliac artery aneurysms are considered acute and severe diseases with insidious onset, rapid development, and high mortality in vascular surgery. Currently, there is no better treatment, either anatomic or extra-anatomical repair. Case presentation: From February 2018 to April 2022, 7 patients with infected abdominal aortic and iliac artery aneurysms did not have sufficient autologous venous material for repair. With the consent of the Ethics Committee of the hospital, it uses the autologous peritoneal fascial tissue with rectus sheath to repair or reconstruct the infected vessels in situ. There were 5 cases of infected abdominal aortic aneurysm, 1 case of an infected common iliac aneurysm, and 1 case of the infected internal iliac aneurysm. Aortoduodenal fistula was found in 3 cases, all of them were given duodenal fistula repair and gastrojejunostomy and cholecystostomy. Three cases of infected abdominal aortic aneurysms were repaired with the autologous peritoneal fascial tissue patch, and 2 cases of infected abdominal aortic aneurysms were reconstructed by the autologous peritoneal fascial tissue suture to bifurcate graft in situ, the autologous peritoneal fascial tissue suture reconstructed the rest 2 cases of infected iliac aneurysm to tubular graft in situ. It was essential that Careful debridement of all infected tissue and adequate postoperative irrigation and drainage. Antibiotics were administered perioperatively, and all patients were subsequently treated with long-term antibiotics based on bacterial culture and susceptibility results of infected tissues and blood. All 7 patients had underwent surgery successfully. But there were 2 cases died of anastomotic infection or massive hemorrhage after the operation, the other 5 cases survived. The follow-up time was 2-19 months. The enhanced CT of postoperation showed that the reconstructed arteries were smooth without obvious stenosis or expansion, and no abdominal wall hernia occurred. Conclusion: In situ repair or reconstruction with autologous peritoneal fascial tissue with rectus sheath is a feasible treatment for the infected aneurysm patients without adequate autologous venous substitute, but it still needs long-term follow-up and a large sample to be further confirmed.

Metformin alleviates irradiation-induced intestinal injury by activation of FXR in intestinal epithelia.

Abdominal irradiation (IR) destroys the intestinal mucosal barrier, leading to severe intestinal infection. There is an urgent need to find safe and effective treatments to reduce IR-induced intestinal injury. In this study, we reported that metformin protected mice from abdominal IR-induced intestinal injury by improving the composition and diversity of intestinal flora. The elimination of intestinal microbiota (Abx) abrogated the protective effects of metformin on irradiated mice. We further characterized that treatment of metformin increased the murine intestinal abundance of Lactobacillus, which mediated the radioprotective effect. The administration of Lactobacillus or fecal microbiota transplantation (FMT) into Abx mice considerably lessened IR-induced intestinal damage and restored the radioprotective function of metformin in Abx mice. In addition, applying the murine intestinal organoid model, we demonstrated that IR inhibited the formation of intestinal organoids, and metformin alone bore no protective effect on organoids after IR. However, a combination of metformin and Lactobacillus or Lactobacillus alone displayed a strong radioprotection on the organoid formation. We demonstrated that metformin/Lactobacillus activated the farnesoid X receptor (FXR) signaling in intestinal epithelial cells and hence upregulated tight junction proteins and mucins in intestinal epithelia, increased the number of goblet cells, and augmented the mucus layer thickness to maintain the integrity of intestinal epithelial barrier, which eventually contributed to reduced radiation intestinal injury. In addition, we found that Lactobacillus abundance was significantly increased in the intestine of patients receiving metformin while undergoing abdominal radiotherapy and the abundance was negatively correlated with the diarrhea duration of patients. In conclusion, our results demonstrate that metformin possesses a protective effect on IR-induced intestinal injury by upregulating the abundance of Lactobacillus in the intestine.