The tumor suppressor SALL2 opposes chemotherapeutic resistance in breast cancer.

Chemotherapy continues to be the primary treatment for certain types of breast cancer. However, despite an initial positive response to chemotherapeutic agents, the development of resistance is inevitable. The exact molecular mechanisms underlying this phenomenon remain unclear.

RNA-binding protein LSM7 facilitates breast cancer metastasis through mediating alternative splicing of CD44.

Aims: The RNA-binding protein LSM7 is essential for RNA splicing, acting as a key component of the spliceosome complex; however, its specific role in breast cancer (BC) has not been extensively investigated.

Materials And Methods: LSM7 expression in BC samples was evaluated through bioinformatics analysis and immunohistochemistry. The impact of LSM7 on promoting metastatic tumor characteristics was examined using transwell and wound healing assays, as well as an orthotopic xenograft model.

Nucleolar stress induces nucleolar stress body formation via the NOSR-1/NUMR-1 axis in Caenorhabditis elegans.

Environmental stimuli not only alter gene expression profiles but also induce structural changes in cells. How distinct nuclear bodies respond to cellular stress is poorly understood. Here, we identify a subnuclear organelle named the nucleolar stress body (NoSB), the formation of which is induced by the inhibition of rRNA transcription or inactivation of rRNA processing and maturation in C.

Germ granule compartments coordinate specialized small RNA production.

Germ granules are biomolecular condensates present in most animal germ cells. One function of germ granules is to help maintain germ cell totipotency by organizing mRNA regulatory machinery, including small RNA-based gene regulatory pathways. The C.

RANKL/RANK signaling recruits Tregs via the CCL20-CCR6 pathway and promotes stemness and metastasis in colorectal cancer.

TNF receptor superfamily member 11a (TNFRSF11a, RANK) and its ligand TNF superfamily member 11 (TNFRSF11, RANKL) are overexpressed in many malignancies. However, the clinical importance of RANKL/RANK in colorectal cancer (CRC) is mainly unknown. We examined CRC samples and found that RANKL/RANK was elevated in CRC tissues compared with nearby normal tissues.

USP7 promotes IgA class switching through stabilizing RUNX3 for germline transcription activation.

Class switch recombination (CSR) diversifies the effector functions of antibodies and involves complex regulation of transcription and DNA damage repair. Here, we show that the deubiquitinase USP7 promotes CSR to immunoglobulin A (IgA) and suppresses unscheduled IgG switching in mature B cells independent of its role in DNA damage repair, but through modulating switch region germline transcription. USP7 depletion impairs Sα transcription, leading to abnormal activation of Sγ germline transcription and increased interaction with the CSR center via loop extrusion for unscheduled IgG switching.

Insufficient phosphorylation of STAT5 in Tregs inhibits the expression of BLIMP-1 but not IRF4, reduction the proportion of Tregs in pediatric aplastic anemia.

Deficiency in regulatory T cells (Tregs) is an important mechanism underlying the pathogenesis of pediatric aplastic anemia, but its specific mechanism is unclear. In our study, we aimed to investigate whether IL-2/STAT5 can regulate the proliferation of Tregs in aplastic anemia (AA) by regulating their expression of B lymphocyte-induced mature protein-1 (BLIMP-1) or interferon regulatory factor 4 (IRF4). Through clinical research and animal experiments, we found that poor activation of the IL-2/STAT5 signaling pathway may leads to low expression of BLIMP-1 in Tregs of children with AA, which leads to defects in the differentiation and proliferation of Tregs in AA.

Enhancement of PRMT6 binding to a novel germline mutation associated with congenital anemia.

Mutations in the master hematopoietic transcription factor GATA1 are often associated with functional defects in erythropoiesis and megakaryopoiesis. In this study, we identified a novel GATA1 germline mutation (c.1162delGG, p.

Minimally invasive technique combined with external fixator in the treatment of pediatric flexion-type humeral supracondylar fractures.

Flexion-type pediatric humeral supracondylar fractures are rare, and the reduction technique remains contradictory. A minimally invasive technique using percutaneous leverage reduction combined with an external fixator was described to achieve satisfactory reduction and avoid the open reduction in this study. The operation and clinical results of patients treated with this technique were retrospectively compared with traditional closed reduction.

rRNA intermediates coordinate the formation of nucleolar vacuoles in C. elegans.

The nucleolus is the most prominent membraneless organelle within the nucleus. How the nucleolar structure is regulated is poorly understood. Here, we identified two types of nucleoli in C.

Immune desert in MMR-deficient tumors predicts poor responsiveness of immune checkpoint inhibition.

Background: Although many efforts have been devoted to identify biomarkers to predict the responsiveness of immune checkpoint inhibitors, including expression of programmed death-ligand 1 (PD-L1) and major histocompatibility complex (MHC) I, microsatellite instability (MSI), mismatch repair (MMR) defect, tumor mutation burden (TMB), tertiary lymphoid structures (TLSs), and several transcriptional signatures, the sensitivity of these indicators remains to be further improved.

Materials And Methods: Here, we integrated T-cell spatial distribution and intratumor transcriptional signals in predicting the response to immune checkpoint therapy in MMR-deficient tumors including tumors of Lynch syndrome (LS).

Results: In both cohorts, MMR-deficient tumors displayed personalized tumor immune signatures, including inflamed, immune excluded, and immune desert, which were not only individual-specific but also organ-specific.

LILRB1 immune cell infiltration identifies immunosuppressive microenvironment and dismal outcomes of patients with ovarian cancer.

Objective: Immune checkpoint inhibitors are commonly used in various types of cancer, but their efficacy in ovarian cancer (OC) is limited. Thus, identifying novel immune-related therapeutic targets is crucial. Leukocyte immunoglobulin-like receptor subfamily B1 (LILRB1), a key receptor of human leukocyte antigen G (HLA-G), is involved in immune tolerance, but its role in tumor immunity remains unclear.

Advances in immunology and immunotherapy for mesenchymal gastrointestinal cancers.

Mesenchymal gastrointestinal cancers are represented by the gastrointestinal stromal tumors (GISTs) which occur throughout the whole gastrointestinal tract, and affect human health and economy globally. Curative surgical resections and tyrosine kinase inhibitors (TKIs) are the main managements for localized GISTs and recurrent/metastatic GISTs, respectively. Despite multi-lines of TKIs treatments prolonged the survival time of recurrent/metastatic GISTs by delaying the relapse and metastasis of the tumor, drug resistance developed quickly and inevitably, and became the huge obstacle for stopping disease progression.

Corrigendum: Case report: Reconstruction of distal medial tibial epiphysis using iliac crest apophyseal autograft.

[This corrects the article DOI: 10.3389/fped.2022.

Systematic characterization of chromodomain proteins reveals an H3K9me1/2 reader regulating aging in C. elegans.

The chromatin organization modifier domain (chromodomain) is an evolutionally conserved motif across eukaryotic species. The chromodomain mainly functions as a histone methyl-lysine reader to modulate gene expression, chromatin spatial conformation and genome stability. Mutations or aberrant expression of chromodomain proteins can result in cancer and other human diseases.

Causal Inference of Central Nervous System-Regulated Hormones in COVID-19: A Bidirectional Two-Sample Mendelian Randomization Study.

We assessed the causal association of three COVID-19 phenotypes with insulin-like growth factor 1, estrogen, testosterone, dehydroepiandrosterone (DHEA), thyroid-stimulating hormone, thyrotropin-releasing hormone, luteinizing hormone (LH), and follicle-stimulating hormone. We used bidirectional two-sample univariate and multivariable Mendelian randomization (MR) analyses to evaluate the direction, specificity, and causality of the association between CNS-regulated hormones and COVID-19 phenotypes. Genetic instruments for CNS-regulated hormones were selected from the largest publicly available genome-wide association studies of the European population.

A ZTF-7/RPS-2 complex mediates the cold-warm response in C. elegans.

Temperature greatly affects numerous biological processes in all organisms. How multicellular organisms respond to and are impacted by hypothermic stress remains elusive. Here, we found that cold-warm stimuli induced depletion of the RNA exosome complex in the nucleoli but enriched it in the nucleoplasm.

Extra cup of tea intake associated with increased risk of Alzheimer's disease: Genetic insights from Mendelian randomization.

Background: Observational studies report inconclusive effects of tea consumption on the risk of Alzheimer's disease (AD), and the mechanisms are unclear. This study aims to investigate the effects of genetically predicted tea intake (cups of tea consumed per day) on AD, brain volume, and cerebral small vessel disease (CSVD) using the two-sample Mendelian randomization (MR) method.

Methods: Summary statistics of tea intake were obtained from UK Biobank ( = 447,485), and AD was from the International Genomics of Alzheimer's Project ( = 54,162).

BMAL1 collaborates with CLOCK to directly promote DNA double-strand break repair and tumor chemoresistance.

Accumulating evidence indicates a correlation between circadian dysfunction and genomic instability. However, whether the circadian machinery directly regulates DNA damage repair, especially in double-strand breaks (DSBs), remains poorly understood. Here, we report that in response to DSBs, BMAL1 is activated by ATM-mediated phosphorylation at S183.

Tyrosine kinase SRC-induced YAP1-KLF5 module regulates cancer stemness and metastasis in triple-negative breast cancer.

SRC is the first identified oncogene, and its aberrant activation has been implicated as a driving event in tumor initiation and progression. However, its role in cancer stemness regulation and the underlying regulatory mechanism are still elusive. Here, we identified a YAP1 tyrosine phosphorylation-dependent YAP1-KLF5 oncogenic module, as the key downstream mediator of SRC kinase regulating cancer stemness and metastasis in triple-negative breast cancer (TNBC).

SRC kinase-mediated signaling pathways and targeted therapies in breast cancer.

Breast cancer (BC) has been ranked the most common malignant tumor throughout the world and is also a leading cause of cancer-related deaths among women. SRC family kinases (SFKs) belong to the non-receptor tyrosine kinase (nRTK) family, which has eleven members sharing similar structure and function. Among them, SRC is the first identified proto-oncogene in mammalian cells.

Calcaneous interlocking nail treatment for calcaneous fracture: a multiple center retrospective study.

Background: Minimally invasive treatments for calcaneous fractures have the same outcomes and fewer complications. However, they are technically demanding, and there are a lack reduction tools. To overcome these problems, a calcaneous interlocking nail system was developed that can make reduction and fixation minimally invasive and effective.