The non-cell-autonomous function of ID1 promotes AML progression via ANGPTL7 from the microenvironment.

The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure. Here, we report that ID1 is highly expressed in the BMM of patients with AML, especially in BM mesenchymal stem cells, and that the high expression of ID1 in the AML BMM is induced by BMP6, secreted from AML cells. Knocking out ID1 in mesenchymal cells significantly suppresses the proliferation of cocultured AML cells. Loss of Id1 in the BMM results in impaired AML progression in AML mouse models. Mechanistically, we found that Id1 deficiency significantly reduces SP1 protein levels in mesenchymal cells cocultured with AML cells. Using ID1-interactome analysis, we found that ID1 interacts with RNF4, an E3 ubiquitin ligase, and causes a decrease in SP1 ubiquitination. Disrupting the ID1-RNF4 interaction via truncation in mesenchymal cells significantly reduces SP1 protein levels and delays AML cell proliferation. We identify that the target of Sp1, Angptl7, is the primary differentially expression protein factor in Id1-deficient BM supernatant fluid to regulate AML progression in mice. Our study highlights the critical role of ID1 in the AML BMM and aids the development of therapeutic strategies for AML.

Hydrogen-bonded organic frameworks in solution enables continuous and high-crystalline membranes.

Hydrogen-Bonded organic frameworks (HOFs) are a type of emerging porous materials. At present, little research has been conducted on their solution state. This work demonstrates that HOFs fragment into small particles while maintaining their original assemblies upon dispersing in solvents, as confirmed by Cryo-electron microscopy coupled with 3D electron diffraction technology. 1D and 2D-Nuclear Magnetic Resonance (NMR) and zeta potential analyses indicate the HOF-based colloid solution and the isolated molecular solution have significant differences in intermolecular interactions and aggregation behavior. Such unique solution processibility allows for fabricating diverse continuous HOF membranes with high crystallinity and porosity through solution-casting approach on various substrates. Among them, HOF-BTB@AAO membranes show high C3H6 permeance (1.979 × 10-7 mol·s-1·m-2·Pa-1) and excellent separation performance toward C3H6 and C3H8 (SF = 14). This continuous membrane presents a green, low-cost, and efficient separation technology with potential applications in petroleum cracking and purification.

Anchoring Single-Atomic Metal Sites in Metalloporphyrin-Based Covalent Organic Frameworks for Enhanced Photocatalytic Hydrogen Evolution.

A photoactive covalent organic framework (COF) was built from metalloporphyrin and bipyridine monomers and single-atomic Pt sites were subsequently installed. Integrating photosensitizing metalloporphyrin and substrate-activating Pt(bpy) moieties in a single solid facilitates multielectron transfer and accelerates photocatalytic hydrogen evolution with a maximum production rate of 80.4 mmol h-1 gPt -1 and turnover frequency (TOF) of 15.7 h-1 observed. This work demonstrates that incorporation of single-atomic metal sites with photoactive COFs greatly enhances photocatalytic activity and provides an effective strategy for the design and construction of novel photocatalysts.

Inhibition of USP1 reverses the chemotherapy resistance through destabilization of MAX in the relapsed/refractory B-cell lymphoma.

The patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL) have poor prognosis, and a novel and effective therapeutic strategy for these patients is urgently needed. Although ubiquitin-specific protease 1 (USP1) plays a key role in cancer, the carcinogenic effect of USP1 in B-cell lymphoma remains elusive. Here we found that USP1 is highly expressed in DLBCL patients, and high expression of USP1 predicts poor prognosis. Knocking down USP1 or a specific inhibitor of USP1, pimozide, induced cell growth inhibition, cell cycle arrest and autophagy in DLBCL cells. Targeting USP1 by shRNA or pimozide significantly reduced tumor burden of a mouse model established with engraftment of rituximab/chemotherapy resistant DLBCL cells. Pimozide significantly retarded the growth of lymphoma in a DLBCL patient-derived xenograft (PDX) model. USP1 directly interacted with MAX, a MYC binding protein, and maintained the stability of MAX through deubiquitination, which promoted the transcription of MYC target genes. Moreover, pimozide showed a synergetic effect with etoposide, a chemotherapy drug, in cell and mouse models of rituximab/chemotherapy resistant DLBCL. Our study highlights the critical role of USP1 in the rituximab/chemotherapy resistance of DLBCL through deubiquitylating MAX, and provides a novel therapeutic strategy for rituximab/chemotherapy resistant DLBCL.

ROBO1 deficiency impairs HSPC homeostasis and erythropoiesis via CDC42 and predicts poor prognosis in MDS.

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic neoplasms originating from hematopoietic stem progenitor cells (HSPCs). We previously identified frequent roundabout guidance receptor 1 (ROBO1) mutations in patients with MDS, while the exact role of ROBO1 in hematopoiesis remains poorly delineated. Here, we report that ROBO1 deficiency confers MDS-like disease with anemia and multilineage dysplasia in mice and predicts poor prognosis in patients with MDS. More specifically, Robo1 deficiency impairs HSPC homeostasis and disrupts HSPC pool, especially the reduction of megakaryocyte erythroid progenitors, which causes a blockage in the early stages of erythropoiesis in mice. Mechanistically, transcriptional profiling indicates that Cdc42, a member of the Rho-guanosine triphosphatase family, acts as a downstream target gene for Robo1 in HSPCs. Overexpression of Cdc42 partially restores the self-renewal and erythropoiesis of HSPCs in Robo1-deficient mice. Collectively, our result implicates the essential role of ROBO1 in maintaining HSPC homeostasis and erythropoiesis via CDC42.

Retromer subunit, CfVps35 is required for growth development and pathogenicity of Colletotrichum fructicola.

BACKGROUND: Tea oil is widely used as edible oil in China, which extracted from the seeds of Camellia oleifera. In China, the national oil-tea camellia planting area reached 4.533 million hectares, the output of oil-tea camellia seed oil was 627 000 tons, and the total output value reached 18.3 billion dollars. Anthracnose is the common disease of Ca. oleifera, which affected the production and brought huge economic losses. Colletotrichum fructicola is the dominant pathogen causing anthracnose in Ca. oleifera. The retromer complex participates in the intracellular retrograde transport of cargos from the endosome to the trans-Golgi network in eukaryotes. Vacuolar protein sorting 35 is a core part of the retromer complex. This study aimed to investigate the role of CfVps35 in C. fructicola. RESULTS: The CfVPS35 gene was deleted, resulting in reduced mycelial growth, conidiation, and response to cell wall stresses. Further analysis revealed that CfVps35 was required for C. fructicola virulence on tea oil leaves. In addition, the ΔCfvps35 mutant was defective in glycogen metabolism and turgor during appressorium development. CONCLUSION: This study illustrated that the crucial functions of CfVps35 in growth, development, and pathogenicity.

Screening of gene detection of monogenic inherited disorder in an infertile population in Henan Province: an autosomal recessive disorder carried by maple syrup urine disease.

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Primary renal small cell carcinoma: A case report.

BACKGROUND: Small cell carcinoma (SCC) is a malignant tumour that is frequently accompanied by extensive metastasis. Primary renal SCC has typical characteristics related to SCC and is extremely rare, with no uniform treatment standard. Clinical treatment is mainly based on the literature. Here we report the diagnosis and treatment of an interesting case of primary renal SCC. CASE SUMMARY: We report a tortuous course of treatment for a 68-year-old man. Four years before diagnosis, the patient developed continuous gross haematuria, during which he underwent several ureteral biopsies, ureteral stricture relief, and urine exfoliated cell examinations; however, SCC was not confirmed. One month before radical resection of the renal pelvic carcinoma, the severe haematuria recurred. Computed tomography revealed transitional cell carcinoma in the right kidney and right upper ureter. A preoperative examination exluded the possibility of a pulmonary origin of the tumour, and primary renal SCC was diagnosed. The postoperative pathology findings were suggestive of SCC. The patient was treated with combined chemotherapy but died of tumour progression at 7 mo postoperative. CONCLUSION: Our patient's disease onset in the context of a succession of regular testing and the fact that it occurred so quickly with perirenal encroachment immediately after diagnosis reveals the cruel and unforgiving side of the disease. Furthermore, patients with poor comprehensive treatment results require new treatment regimens.

Thyroid follicular renal cell carcinoma excluding thyroid metastases: A case report.

BACKGROUND: Thyroid follicular renal cell carcinoma is a special type of renal cell carcinoma newly recognized in recent years. It has attracted attention because of its unique histology, immunophenotype, and clinical characteristics. It has a very low incidence, and the number of case reports available for review is limited. Moreover, a thyroid mass with type of tumour is rare. CASE SUMMARY: We report a case of a renal mass with a bilateral thyroid mass that was accidentally discovered in a 60-year-old man during physical examination. B-mode ultrasound showed a hypoechoic mass in the middle and lower parenchyma of the right kidney, and computed tomography showed an iso-density shadow tumour in the right kidney. Contrast agents had a significant continuous enhancement effect on the tumour, and the enhancement was not uniform. After partial nephrectomy, pathological analysis was performed to rule out the possibility that the renal tumour was caused by thyroid tumour metastasis. Needle biopsy of the thyroid tumour confirmed that the renal cell carcinoma was not related to the thyroid tumour. The patient was alive at the last postoperative follow-up. CONCLUSION: This is the third published case in which thyroid tumour biopsy was performed to confirm that thyroid follicular renal cell carcinoma is not thyroid related.

Civil war hinders crop production and threatens food security in Syria.

Assessing the impact of violent conflict on Syrian agriculture is challenging given data limitations and attributability issues. Using satellite data at 30 m spatial resolution, we found that the extent of productive cropland showed greater interannual variability and spatial heterogeneity after the start of the civil war in 2011. Using changes in satellite-based night-time light as a proxy for war impact intensity, we also found that cropland close to severely impacted urban settlements faced greater disruption. Fixed-effects models revealed the relationship between productive cropland and precipitation for the pre-war period, whereas a counterfactual scenario constructed for the period 2012-2019 showed substantial variation at the regional level. While the ongoing conflict promoted cropland cultivation in safer zones, cropland reduction took place in the country's northwest and southeast regions. Our study demonstrated the combined utility of daytime and night-time satellite data to assess food insecurity in extreme environments and can help guide distribution of food and aid in Syria.

Chidamide triggers BTG1-mediated autophagy and reverses the chemotherapy resistance in the relapsed/refractory B-cell lymphoma.

Rituximab/chemotherapy relapsed and refractory B cell lymphoma patients have a poor overall prognosis, and it is urgent to develop novel drugs for improving the therapy outcomes. Here, we examined the therapeutic effects of chidamide, a new histone deacetylase (HDAC) inhibitor, on the cell and mouse models of rituximab/chemotherapy resistant B-cell lymphoma. In Raji-4RH/RL-4RH cells, the rituximab/chemotherapy resistant B-cell lymphoma cell lines (RRCL), chidamide treatment induced growth inhibition and G0/G1 cell cycle arrest. The primary B-cell lymphoma cells from Rituximab/chemotherapy relapsed patients were sensitive to chidamide. Interestingly, chidamide triggered the cell death with the activation of autophagy in RRCLs, likely due to the lack of the pro-apoptotic proteins. Based on the RNA-seq and chromatin immunoprecipitation (ChIP) analysis, we identified BTG1 and FOXO1 as chidamide target genes, which control the autophagy and the cell cycle, respectively. Moreover, the combination of chidamide with the chemotherapy drug cisplatin increased growth inhibition on the RRCL in a synergistic manner, and significantly reduced the tumor burden of a mouse lymphoma model established with engraftment of RRCL. Taken together, these results provide a theoretic and mechanistic basis for further evaluation of the chidamide-based treatment in rituximab/chemotherapy relapsed and refractory B-cell lymphoma patients.