Self-assembled patient-derived tumor-like cell clusters for personalized drug testing in diverse sarcomas.

Several patient-derived tumor models have emerged recently. However, soft tissue sarcomas (STSs) present a challenge in developing preclinical drug-testing models due to their non-epithelial and complex nature. Here, we report a model termed patient-derived tumor-like cell clusters (PTCs) derived from STS patients.

Multimodal targeting chimeras enable integrated immunotherapy leveraging tumor-immune microenvironment.

Although immunotherapy has revolutionized cancer treatment, its efficacy is affected by multiple factors, particularly those derived from the complexity and heterogeneity of the tumor-immune microenvironment (TIME). Strategies that simultaneously and synergistically engage multiple immune cells in TIME remain highly desirable but challenging. Herein, we report a multimodal and programmable platform that enables the integration of multiple therapeutic modules into single agents for tumor-targeted co-engagement of multiple immune cells within TIME.

Patient-derived tumor-like cell clusters for personalized chemo- and immunotherapies in non-small cell lung cancer.

Many patient-derived tumor models have emerged recently. However, their potential to guide personalized drug selection remains unclear. Here, we report patient-derived tumor-like cell clusters (PTCs) for non-small cell lung cancer (NSCLC), capable of conducting 100-5,000 drug tests within 10 days.

Comprehensive Detection of PD-L1 Protein and mRNA in Tumor Cells and Extracellular Vesicles through a Real-Time qPCR Assay.

A growing number of studies have shown that tumor cells secrete extracellular vesicles (EVs) containing programmed death-ligand 1 (PD-L1) protein. These vesicles can travel to lymph nodes and remotely inactivate T cells, thereby evading immune system attack. Therefore, the simultaneous detection of PD-L1 protein expression in cells and EVs is of great significance in guiding immunotherapy.

High-throughput screening of spike variants uncovers the key residues that alter the affinity and antigenicity of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has elicited a worldwide pandemic since late 2019. There has been ~675 million confirmed coronavirus disease 2019 (COVID-19) cases, leading to more than 6.8 million deaths as of March 1, 2023.

High-throughput saturation mutagenesis generates a high-affinity antibody against SARS-CoV-2 variants using protein surface display assay on a human cell.

As new mutations continue to emerge, the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus to evade the human immune system and neutralizing antibodies remains a huge challenge for vaccine development and antibody research. The majority of neutralizing antibodies have reduced or lost activity against SARS-CoV-2 variants. In this study, we reported a novel protein surface display system on a mammalian cell for obtaining a higher-affinity antibody in high-throughput manner.

ACE2 decoy receptor generated by high-throughput saturation mutagenesis efficiently neutralizes SARS-CoV-2 and its prevalent variants.

The recent global pandemic was a spillover from the SARS-CoV-2 virus. Viral entry involves the receptor binding domain (RBD) of the viral spike protein interacting with the protease domain (PD) of the cellular receptor, ACE2. We hereby present a comprehensive mutational landscape of the effects of ACE2-PD point mutations on RBD-ACE2 binding using a saturation mutagenesis approach based on microarray-based oligo synthesis and a single-cell screening assay.

Induction of functional neutrophils from mouse fibroblasts by thymidine through enhancement of Tet3 activity.

Neutrophils are derived from bone marrow hematopoietic stem cells (HSCs) and are the largest population among circulating white blood cells in humans, acting as the first line of defense against invading pathogens. Whether neutrophils can be generated by transdifferentiation strategies is unknown. Here, we show that thymidine induces the conversion of mouse fibroblasts to neutrophils.

Circular RNA circZbtb20 maintains ILC3 homeostasis and function via Alkbh5-dependent mA demethylation of Nr4a1 mRNA.

Group 3 innate lymphoid cells (ILC3s) play critical roles in innate immunity and gut homeostasis. However, how ILC3 homeostasis is regulated remains elusive. Here, we identified a novel circular RNA, circZbtb20, that is highly expressed in ILC3s and required for their maintenance and function.

Process simulation and comprehensive evaluation of a system of coal power plant coupled with waste incineration.

The technology of coal power plant coupled with waste incineration is considered as a promising technology for fossil fuel conservation and waste disposal. In this paper, a system of coal power plant coupled with waste incineration is simulated by Aspen Plus software, and a conventional coal power plant is also simulated for comparison. Comprehensive evaluation including thermodynamic, economic and environmental impact performances are analysed and compared.

An inducible circular RNA circKcnt2 inhibits ILC3 activation to facilitate colitis resolution.

Group 3 innate lymphoid cells (ILC3) are an important regulator for immunity, inflammation and tissue homeostasis in the intestine, but how ILC3 activation is regulated remains elusive. Here we identify a new circular RNA (circRNA) circKcnt2 that is induced in ILC3s during intestinal inflammation. Deletion of circKcnt2 causes gut ILC3 activation and severe colitis in mice.

Patient-derived tumor-like cell clusters for drug testing in cancer therapy.

Several patient-derived tumor models emerged recently as robust preclinical drug-testing platforms. However, their potential to guide clinical therapy remained unclear. Here, we report a model called patient-derived tumor-like cell clusters (PTCs).

The chromatin remodeler SRCAP promotes self-renewal of intestinal stem cells.

Lgr5 intestinal stem cells (ISCs) exhibit self-renewal and differentiation features under homeostatic conditions, but the mechanisms controlling Lgr5 + ISC self-renewal remain elusive. Here, we show that the chromatin remodeler SRCAP is highly expressed in mouse intestinal epithelium and ISCs. Srcap deletion impairs both self-renewal of ISCs and intestinal epithelial regeneration.

Glutamylation of deubiquitinase BAP1 controls self-renewal of hematopoietic stem cells and hematopoiesis.

All hematopoietic lineages are derived from a limited pool of hematopoietic stem cells (HSCs). Although the mechanisms underlying HSC self-renewal have been extensively studied, little is known about the role of protein glutamylation and deglutamylation in hematopoiesis. Here, we show that carboxypeptidase CCP3 is most highly expressed in BM cells among CCP members.

SPRY4 is responsible for pathogenesis of adolescent idiopathic scoliosis by contributing to osteogenic differentiation and melatonin response of bone marrow-derived mesenchymal stem cells.

Adolescent idiopathic scoliosis (AIS) is a complex, three-dimensional deformity of the spine that commonly occurs in pubescent girls. Decreased osteogenic differentiation and aberrant melatonin signalling have been demonstrated in mesenchymal stem cells (MSCs) from AIS patients and are implicated in the pathogenesis of AIS. However, the molecular mechanisms underlying these abnormal cellular features remain largely unknown.

Combustion of single particles from sewage sludge/pine sawdust and sewage sludge/bituminous coal under oxy-fuel conditions with steam addition.

Co-pelletization of sewage sludge (SS) and conventional fuels for combustion is considered to be a feasible SS disposal method. Oxy-fuel combustion is recognized as a promising technology to reduce the emission of CO. In practical applications, the combustion atmosphere in oxy-fuel boiler is O/CO/HO, which is different from that in the conventional boiler (O/N).

A higher-order configuration of the heterodimeric DOT1L-AF10 coiled-coil domains potentiates their leukemogenenic activity.

Chromosomal translocations of (Mixed Lineage Leukemia 1) yield oncogenic chimeric proteins containing the N-terminal portion of MLL1 fused with distinct partners. The MLL1-AF10 fusion causes leukemia through recruiting the H3K79 histone methyltransferase DOT1L via AF10's octapeptide and leucine zipper (OM-LZ) motifs. Yet, the precise interaction sites in DOT1L, detailed interaction modes between AF10 and DOT1L, and the functional configuration of MLL1-AF10 in leukeomogenesis remain unknown.

Yeats4 drives ILC lineage commitment via activation of transcription.

Innate lymphoid cells (ILCs) play critical roles in defending infections and maintaining mucosal homeostasis. All ILCs arise from common lymphoid progenitors (CLPs) in bone marrow. However, how CLPs stratify and differentiate into ILC lineages remains elusive.

LncRNA HAND2-AS1 promotes liver cancer stem cell self-renewal via BMP signaling.

Hepatocellular carcinoma (HCC) is the most prevalent liver cancer, characterized by a high rate of recurrence and heterogeneity. Liver cancer stem cells (CSCs) may well contribute to both of these pathological properties, but the mechanism underlying their self-renewal maintenance is poorly understood. Here, we identified a long noncoding RNA (lncRNA) termed HAND2-AS1 that is highly expressed in liver CSCs.

IL-13 secreted by ILC2s promotes the self-renewal of intestinal stem cells through circular RNA circPan3.

Intestinal stem cells (ISCs) are maintained by stemness signaling for precise modulation of self-renewal and differentiation under homeostasis. However, the way in which intestinal immune cells regulate the self-renewal of ISCs remains elusive. Here we found that mouse and human Lgr5 ISCs showed high expression of the immune cell-associated circular RNA circPan3 (originating from the Pan3 gene transcript).

The long non-coding RNA LncHDAC2 drives the self-renewal of liver cancer stem cells via activation of Hedgehog signaling.

Background & Aims: Liver cancer is the second leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults. The aim of this study was to define the role of the long non-coding RNA lncHDAC2 in the tumorigenesis of HCC.

Long noncoding RNA lncAIS downregulation in mesenchymal stem cells is implicated in the pathogenesis of adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a complex, three dimensional deformity of the spine that commonly occurs in pubescent girls. Abnormal osteogenic differentiation of mesenchymal stem cells (MSCs) is implicated in the pathogenesis of AIS. However, the biological roles of long noncoding RNAs (lncRNAs) in the regulation of osteogenic differentiation of MSCs are unknown.

LncGata6 maintains stemness of intestinal stem cells and promotes intestinal tumorigenesis.

The intestinal epithelium harbours remarkable self-renewal capacity that is driven by Lgr5 intestinal stem cells (ISCs) at the crypt base. However, the molecular mechanism controlling Lgr5 ISC stemness is incompletely understood. We show that a Gata6 long noncoding RNA (lncGata6) is highly expressed in ISCs.

Long noncoding RNA lncHand2 promotes liver repopulation via c-Met signaling.

Background & Aims: Long noncoding RNAs (lncRNAs) play important roles in various biological processes, regulating gene expression by diverse mechanisms. However, how lncRNAs regulate liver repopulation is unknown. Herein, we aimed to identify lncRNAs that regulate liver repopulation and elucidate the signaling pathways involved.

A Circular RNA Protects Dormant Hematopoietic Stem Cells from DNA Sensor cGAS-Mediated Exhaustion.

Disrupting the balance between self-renewal and differentiation of hematopoietic stem cells (HSCs) leads to bone marrow failure or hematologic malignancy. However, how HSCs sustain their quiescent state and avoid type I interferon (IFN)-mediated exhaustion remains elusive. Here we defined a circular RNA that we named cia-cGAS that was highly expressed in the nucleus of long-term (LT)-HSCs.