Function analysis and characterisation of a novel chitinase, MdCht9, in Musca domestica.

Insect chitinases have been proposed as potential targets for pest control. In this work, a novel group IV chitinase gene, MdCht9, from Musca domestica was found to have multiple functions in the physiological activity, including chitin regulation, development and antifungal immunity. The MdCht9 gene was cloned and sequenced, its phylogeny was analysed and its expression was determined in normal and 20E treated larvae. Subsequently, RNA interference (RNAi)-mediated MdCht9 knockdown was performed, followed by biochemical assays, morphological observations and transcriptome analysis. Finally, the recombinant protein MdCht9 (rMdCht9) was purified and tested for anti-microbial activity and enzyme characteristics. The results showed that MdCht9 consists of three domains, highly expressed in a larval salivary gland. RNAi silencing of MdCht9 resulted in significant down-regulation of chitin content and expression of 15 chitin-binding protein (CBP) genes, implying a new insight that MdCht9 might regulate chitin content by influencing the expression of CBPs. In addition, more than half of the lethality and partial wing deformity appeared due to the dsMdCht9 treatment. In addition, the rMdCht9 exhibited anti-microbial activity towards Candida albicans (fungus) but not towards Escherichia coli (G-) or Staphylococcus aureus (G+). Our work expands on previous studies of chitinase while providing a potential target for pest management.

Application of CMV-IVIg as prophylaxis against cytomegalovirus reactivation in allogeneic hematopoietic stem cell transplantation patients.

Cytomegalovirus (CMV) reactivation remains one of the major and life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Yet, there is still a lack of safe and effective ways to prevent CMV reactivation in allo-HSCT patients. Here, we retrospectively analyzed a cohort of patients who underwent HSCT at our transplant center between 2018 and 2022 to evaluate the efficacy of prophylactic CMV-specific intravenous immunoglobulin (CMV-IVIg) against CMV reactivation. After Propensity Score Matching, the CMV reactivation rate was significantly decreased in the CMV-IVIg group (HR, 2.952; 95% CI,1.492-5.841; P = .002) compared with the control group. Additionally, the time duration of CMV reactivation (P = .001) and bacterial infection rate (P = .013) were significantly lower in the CMV-IVIg group. Moreover, prophylactic CMV-IVIg was more effective in CMV seropositive patients who received ATG as part of GVHD prevention (HR, 8.225; 95% CI,1.809-37.39; P = .006). In conclusion, CMV-IVIg is considered an effective and safe way to prevent CMV reactivation in HSCT recipients, which may be related to the acceleration of immune reconstitution in the early stage after transplantation.

A Novel Method for Remaining Useful Life Prediction of RF Circuits Based on the Gated Recurrent Unit-Convolutional Neural Network Model.

The remaining useful life (RUL) prediction of RF circuits is an important tool for circuit reliability. Data-driven-based approaches do not require knowledge of the failure mechanism and reduce the dependence on knowledge of complex circuits, and thus can effectively realize RUL prediction. This manuscript proposes a novel RUL prediction method based on a gated recurrent unit-convolutional neural network (GRU-CNN). Firstly, the data are normalized to improve the efficiency of the algorithm; secondly, the degradation of the circuit is evaluated using the hybrid health score based on the Euclidean and Manhattan distances; then, the life cycle of the RF circuits is segmented based on the hybrid health scores; and finally, an RUL prediction is carried out for the circuits at each stage using the GRU-CNN model. The results show that the RMSE of the GRU-CNN model in the normal operation stage is only 3/5 of that of the GRU and CNN models, while the prediction uncertainty is minimized.

CMV infection is a risk factor for hemorrhagic cystitis after hematopoietic stem cell transplantation.

Hemorrhagic cystitis (HC) is a common complication after transplantation. The purpose of this study was to examine the incidence and risk factors for HC after hematopoietic stem cell transplantation (HSCT). The records of patients who underwent allogenic HSCT from January 2012 to December 2018 at our institution were retrospectively reviewed. Cox proportional regression and Kaplan-Meier analyses were performed to determine independent risk factors for HC. The statistical analysis was performed in May 2020. A total of 173 patients underwent HSCT, and 53 (30.6%) developed grade 2 or 3 HC cystitis at a median of 37 days (range - 5 to 98 days) after transplantation. Thirty-two patients developed moderate (grade 2) cystitis and 21 severe (grade 3) cystitis. Of the 173 patients, 61 developed acute graft-versus-host disease (GVHD) (median onset day 24) and 79 experienced cytomegalovirus (CMV) reactivation (median onset day 35). The relative risk (RR) of developing a CMV infection for patients with acute GVHD was 2.77 times that of patients without acute GVHD (P < 0.001). CMV infection was the only independent variable significantly associated with HC in both univariate and multivariate analyses. The estimated hazard ratio (HR) of CMV infection for the development of HC was 5.57 (95% confidence interval [CI]: 2.52 to 12.33, P < 0.001). CMV infection is an independent risk factor for the development of HC after HSCT, and acute GVHD is a risk factor for CMV reactivation. Decreasing the frequency of GVHD after HSCT may result in a lower frequency of HC.

The Application and Efficacy of Second Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia.

BACKGROUND: We retrospectively analyzed the application and clinical efficacy of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia patients who relapsed or had primary graft failure (PGF) after first transplantation. METHODS: From 2007 to 2021, eight patients with acute leukemia who received second allo-HSCT in our hospital were collected, including 6 relapsed patients and 2 patients with PGF after the first HSCT. RESULTS: All the patients received complete donor implantation after second transplantation. The median time of neutrophils and platelet implantation were 12 days (10 days - 13 days) and 23 days (12 days - 123 days). Two cases (25.0%) developed grade II aGVHD, and 4 cases (50.0%) developed cGVHD. Leukemia-free survival (LFS) and overall survival (OS) at 1 year both were 71.4% and at 3 years both were 28.6%. After a median follow-up of 1,556 days (range, 257 - 5,252 days), 3 of the patients (37.5%) survived and 5 (62.5%) died. One patient with NR before second transplantation, treated with a conditioning regime of CLAG-M bridging BuCy, has survived for more than 5 years (61 months). Relapse was the main death reason. CONCLUSIONS: Second allo-HSCT is an effective means to treat acute leukemia patients with relapsed and PGF after first transplantation.

[Toxicity attenuation processing technology and mechanism of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction].

This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 ℃ for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.

[Gender differences in antidepressant effect of raw Rehmanniae Radix].

For the first time, this study evaluated the gender differences and mechanisms of the antidepressant effects of raw Rehmanniae Radix(RRR) based on the classic depression model with traditional Chinese medicine syndrome of Yin deficiency and internal heat. The depression model with Yin deficiency and internal heat was established by the widely recognized and applied method of thyroxine induction of the classic depression model with Yin deficiency and internal heat(chronic unpredictable mild stress). Male and female mice were simultaneously treated with RRR. The study analyzed indicators of nourishing Yin and clearing heat, conventional antidepressant efficacy test indicators, and important biomolecules reflecting the pathogenesis and prevention and treatment mechanisms of depression, and conducted a correlation analysis of antidepressant efficacy, Yin-nourishing and heat-clearing efficacy, and biological mechanism in different genders, thereby comprehensively assessing the antidepressant effects of RRR on depression of Yin deficiency and internal heat, as well as its gender differences and mechanisms. RRR exhibited antidepressant effects in both male and female mouse models, and its antidepressant efficacy showed gender differences, with a superior effect observed in females. Moreover, the effects of RRR on enhancing or improving hippocampal neuronal pathology, nucleus-positive areas, postsynaptic dense area protein 95, and synaptophysin protein expression were more significant in females than in males. In addition, RRR significantly reversed the abnormal upregulation of nuclear factor(NF)-κB/cyclooxygenase 2(COX2)/NOD-like receptor thermal protein domain associated protein 3(NLRP3) pathway proteins in the hippocampus of both male and female mouse models. The antidepressant effects of RRR were more pronounced in depression female mice with Yin deficiency and internal heat syndrome, possibly due to the improvement of neuronal damage and enhancement of neuroplasticity. The antidepressant mechanisms of RRR for depression with Yin deficiency and internal heat syndrome may be associated with the downregulation of the NF-κB/COX2/NLRP3 pathway to reduce neuronal damage and enhance neuroplasticity.

A novel intensive conditioning regimen for allogeneic hematopoietic stem cell transplantation in the treatment of relapsed/refractory acute myeloid leukemia.

We conducted a prospective study to evaluate the efficacy and safety of cladribine, cytarabine, mitoxantrone, and granulocyte colony-stimulating factor (CLAG-M) regimen combined with busulfan and cyclophosphamide (BuCy) as new intensive conditioning before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed/refractory acute myeloid leukemia (AML). 24 patients were enrolled. The median follow-up was 15.2 months (range 1.9-67.0 months). Except for one patient who died before graft infusion, the evaluable 23 patients (96%) achieved complete remission (CR). The two-year overall survival (OS) rate and leukemia-free survival (LFS) rate were 61.4% and 59.4%, respectively. The non-relapse mortality (NRM) was 9.1%. Univariate analysis revealed that the myeloid blast phase of chronic myelomonocytic leukemia (CMML), an EVI1 mutated, blood blasts ≥20% at transplant, and extramedullary disease were risk factors for LFS.

Vitamin C-dependent lysine demethylase 6 (KDM6)-mediated demethylation promotes a chromatin state that supports the endothelial-to-hematopoietic transition.

Hematopoietic stem cells (HSCs)/progenitor cells (HPCs) are generated from hemogenic endothelial cells (HECs) during the endothelial-to-hematopoietic transition (EHT); however, the underlying mechanism remains poorly understood. Here, using an array of approaches, including CRSPR/Cas9 gene knockouts, RNA-Seq, ChIP-Seq, ATAC-Seq etc., we report that vitamin C (Vc) is essential in HPC generation during human pluripotent stem cell (hPSC) differentiation in defined culture conditions. Mechanistically, we found that the endothelial cells generated in the absence of Vc fail to undergo the EHT because of an apparent failure in opening up genomic loci essential for hematopoiesis. Under Vc deficiency, these loci exhibited abnormal accumulation of histone H3 trimethylation at Lys-27 (H3K27me3), a repressive histone modification that arose because of lower activities of demethylases that target H3K27me3. Consistently, deletion of the two H3K27me3 demethylases, Jumonji domain-containing 3 (JMJD3 or KDM6B) and histone demethylase UTX (UTX or KDM6A), impaired HPC generation even in the presence of Vc. Furthermore, we noted that Vc and jmjd3 are also important for HSC generation during zebrafish development. Together, our findings reveal an essential role for Vc in the EHT for hematopoiesis, and identify KDM6-mediated chromatin demethylation as an important regulatory mechanism in hematopoietic cell differentiation.

Postmortem interval determination using mRNA markers and DNA normalization.

Postmortem interval (PMI) determination is an important part of criminal investigations, but it is still subject to uncertainty. Degradation of mRNA in PMI determination has been studied in decays; however, some studies have reported no correlation between PMI and RNA degradation. Thus, we aimed to determine whether RNA quantity was correlated with PMI. Heart and brain tissues were separated from a mouse model of a 0-48 h PMI with 29 time points. We then coextracted the DNA and RNA in one tube with Bioteke coextraction kits and selected some mRNA markers associated with cell oxygen deprivation and apoptosis as target genes, such as hypoxia-associated factor (HAF), apoptosis-inducing factor (AIF), hypoxia-inducible factor 2 alpha (HIF2a), and factor inhibiting HIF (FIH). We measured the quantity of these markers using real-time quantitative PCR (qPCR), and Caspase-3 DNA and 18S were each used for normalization. The results showed that in the heart tissue, the degradation of HIF2a, AIF, and FIH was correlated with PMI, as was the degradation of HIF2a, FIH, and AIF in brain tissue when normalized with Caspase-3 DNA. However, when normalized with 18S, only the degradation of HIF2a in brain tissue was correlated with PMI. Interestingly, the quantity of HAF in brain tissue was found to increase after death with either 18S or Caspase-3 DNA normalization, and it was significantly correlated with 0-48 h PMI. These results indicated that mRNA quantity can be used to determine PMI and that Caspase-3 DNA is feasible for PMI estimation. In summary, we established mathematical models for PMI determination using multiple mRNA markers and multiple tissues and further studies are needed to validate and investigate these markers and mathematical models in human tissues.Duo Peng and Meili Lv contributed equally to this work.

Reactivation of resolved hepatitis B virus infection combined with nephrotic syndrome in a patient after allogeneic haematopoietic stem cell transplantation.

BACKGROUND: After allogeneic haematopoietic stem cell transplantation (allo-HSCT), Hepatitis B virus reactivation (HBVr) can be observed in patients with previous resolved Hepatitis B virus (HBV) infections. Nephrotic syndrome (NS) is the main clinical manifestation of HBsAg-positive glomerulonephritis. However, the development of HBVr combined with NS after allo-HSCT is uncommon. CASE PRESENTATION: We presented a case of a 47-year-old female with acute myelogenous leukemia who underwent HLA-identical sibling allo-HSCT and achieved leukemia free survival. She had pretransplant serological markers of a resolved HBV infection (HBsAg-negative, anti-HBc and anti-HBs positive). However, she developed HBVr combined with nephrotic syndrome (NS) 16 months after HSCT. Her histological renal lesion was mesangial proliferative glomerulonephritis. IgA+, IgM+, and C1q deposits but not HBV antigens (HBsAg and HBcAg) were identified in her renal biopsy material. Long-term entecavir and immunosuppression resulted in decrease of HBV virus replication, amelioration of proteinuria and stabilisation of renal function. CONCLUSIONS: Entecavir combined with immunosuppression has efficacy in the treatment of HBVr combined with NS after allo-HSCT, but long course of treatment is needed. Closely monitoring and antiviral prophylaxis might be necessary for allo-HSCT recipients to prevent reactivation of resolved HBV infection and its related complications.

Diffuse Large B Cell Lymphoma Coexistent with Follicular Cell Lymphoma.

BACKGROUND: Diffuse large B cell lymphoma (DLBCL) and follicular cell lymphoma (FL) synchronously occurring in the same individual is unusual. The authors describe a rare case of DLBCL coexisting with FL at diagnosis in a male patient, with intestinal and lymph node involvement. METHODS: Hematologic investigation, intestinal tumor biopsy, bone marrow examination, cytogenetic analysis, and PCR were performed. RESULTS: The patient received three courses of R-CHOP regimen chemotherapy, the mesentery lymph nodes were reduced to 2.7 x 1.4 cm compared to 5.4 x 5.0 cm at diagnosis. However, the mesentery lymph nodes were increased to 4.7 x 3.5 cm after four additional courses R-CHOP treatment. Unfortunately, the patient refused chemotherapy treatment or hematopoietic stem cell transplantation (HSCT) and was lost to follow-up. CONCLUSIONS: The presence of DLBCL coexisting with FL at diagnosis is rare and has generally been the subject of isolated case reports. Further studies are required to better understand the biological insights of the disease and to propose an optimal management strategy for this type of lymphoma.

Identification of a Novel Gene Mutation in a Chinese Pedigree with X-linked Thrombocytopenia.

BACKGROUND: X-linked thrombocytopenia (XLT) is a milder form of Wiskott-Aldrich syndrome (WAS), characterized predominantly by thrombocytopenia with small-sized platelets. Mutations in the WAS gene are responsible for the disease. We herein detected a new mutation in the WAS gene responsible for XLT in a 3-generation Chinese pedigree. METHODS: Peripheral blood samples were collected from 7 members in the family. WAS gene was amplified from genomic DNA isolated from leucocytes, and then direct sequencing was performed. RESULTS: Three male members of this family (the proband, his younger brother and maternal uncle) had thrombocytopenia and decreased mean platelet volume. A homozygous mutation (T>C) was found at nucleotide position 319 in exon 3, causing the amino acid Tyr (T) to be abnormally changed to His (H) at position 107. Two female members (the proband's mother and grandmother) were carriers of the mutation. CONCLUSIONS: XLT is easy to misdiagnose as immune thrombocytopenic purpura (ITP). The diagnosis of XLT should be considered in any male with congenital microthrombocytopenia or early onset of microthrombocytope-nia (< 7 fL). This article adds to the growing number of known mutations associated with XLT.

Surface Energy and Surface Stability of Ag Nanocrystals at Elevated Temperatures and Their Dominance in Sublimation-Induced Shape Evolution.

The surface energy and surface stability of Ag nanocrystals (NCs) are under debate because the measurable values of the surface energy are very inconsistent, and the indices of the observed thermally stable surfaces are apparently in conflict. To clarify this issue, a transmission electron microscope is used to investigate these problems in situ with elaborately designed carbon-shell-capsulated Ag NCs. It is demonstrated that the {111} surfaces are still thermally stable at elevated temperatures, and the victory of the formation of {110} surfaces over {111} surfaces on the Ag NCs during sublimation is due to the special crystal geometry. It is found that the Ag NCs behave as quasiliquids during sublimation, and the cubic NCs represent a featured shape evolution, which is codetermined by both the wetting equilibrium at the Ag-C interface and the relaxation of the system surface energy. Small Ag NCs (≈10 nm) no longer maintain the wetting equilibrium observed in larger Ag NCs, and the crystal orientations of ultrafine Ag NCs (≈6 nm) can rotate to achieve further shape relaxation. Using sublimation kinetics, the mean surface energy of Ag NCs at 1073 K is calculated to be 1.1-1.3 J m-2 .

A Case of Cutaneous Involvement in T Lymphoblastic Lymphoma Leukemia.

BACKGROUND: Cutaneous involvement is more prevalent in B lymphoblastic lymphoma (B-LBL) than T lymphoblastic lymphoma (T-LBL). The authors describe a rare case of cutaneous involvement in a 25-year-old woman with T lymphoblastic lymphoma leukemia. METHODS: Hematologic investigation, bone marrow aspirate and biopsy, cytogenetic analysis and cutaneous lesion biopsy were performed. RESULTS: The patient achieved complete remission after induction therapy with the regimen of CHOEP + P, then received another CHOEP + P regimen. Unfortunately, the patient refused further treatment and was lost to follow-up. CONCLUSIONS: Skin biopsy, immunohistochemistry of the skin lesions, bone marrow aspirate, and biopsy are important to confirm a diagnosis of T-LBL. Cutaneous involvement in T-LBL as a prognostic factor needs further studies.

Targeting GLI1 Suppresses Cell Growth and Enhances Chemosensitivity in CD34+ Enriched Acute Myeloid Leukemia Progenitor Cells.

BACKGROUND/AIMS: Resistance of leukemia stem cells (LSCs) to chemotherapy in patients with acute myeloid leukemia (AML) causes relapse of disease. Hedgehog (Hh) signaling plays a critical role in the maintenance and differentiation of cancer stem cells. Yet its role in AML remains controversial. The purpose of the present study is to investigate the role of GLI1, the transcriptional activator of Hh signaling, in AML progenitor cells and to explore the anti-AML effects of GLI small-molecule inhibitor GANT61. METHODS: The expression of GLI1 mRNA and protein were examined in AML progenitor cells and normal cells. The proliferation, colony formation, apoptosis and differentiation of AML progenitor cells were also analyzed in the presence of GANT61. RESULTS: Kasumi-1 and KG1a cells, containing more CD34+ cells, expressed higher level of GLI1 compared to U937 and NB4 cells with fewer CD34+ cells. Consistently, a positive correlation between the protein levels of GLI1 and CD34 was validated in the bone marrow mononuclear cells (BMMC) of AML patients tested. GANT61 inhibited the proliferation and colony formation in AML cell lines. Importantly, GANT61 induced apoptosis in CD34+ enriched Kasumi-1 and KG1a cells, whereas it induced differentiation in U937 and NB4 cells. Furthermore, GANT61 enhanced the cytotoxicity of cytarabine (Ara-c) in primary CD34+ AML cells, indicating that inhibition of GLI1 could be a promising strategy to enhance chemosensitivity. CONCLUSIONS: The present findings suggested that Hh signaling was activated in AML progenitor cells. GLI1 acted as a potential target for AML therapy.

Renovascular morphological changes in a rabbit model of hydronephrosis.

Obstructive nephropathy ultimately leads to end-stage renal failure. Renovascular lesions are involved in various nephropathies, and most renal diseases have an ischemic component that underlies the resulting renal fibrosis. The aim of this study was to investigate whether morphological changes occur in the renal vasculature in hydronephrosis and the possible mechanisms involved. A model of complete unilateral ureteral obstruction (CUUO) was used. Experimental animals were divided into five groups: a normal control group (N) and groups of animals at 1st week (O1), 2nd week (O2), 4th week (O4) and 8th week (O8) after CUUO. Blood pressure was measured, renal arterial trees and glomeruli were assessed quantitatively, and renovascular three-dimensional reconstruction was performed on all groups. Glomerular ultrastructural changes were examined by transmission electron microscopy. The results showed that the systolic blood pressure was significantly increased in the obstructed groups (O1, O2, O4 and O8). Three-dimensional reconstruction showed sparse arterial trees in the O8 group, and a tortuous and sometimes ruptured glomerular basement membrane was found in the O4 and O8 groups. Furthermore, epithelial media thickness and media/lumen ratio were increased, lumen diameters were decreased, and the cross-sectional area of the media was unaltered in the segmental renal artery, interlobar artery and afferent arterioles, respectively. In conclusion, renal arterial trees and glomeruli were dramatically altered following CUUO and the changes may be partially ascribed to vascular remodeling. Elucidation of the molecular mechanisms of renovascular morphological alterations will enable the development of potential therapeutic approaches for hydronephrosis.

Coordination recognition of differential template units of lanthanide chiral chain.

Coordination-driven self-assembly processes often produce remarkable structures. In particular, self-assembly processes mediated by chiral template units have provided research ideas for analyzing the formation of chiral macromolecules in living organisms. In this study, by regulating the proportion of reaction raw materials in the "one-pot" synthesis of lanthanide complexes, we constructed chiral template units with different coordination orientations. As a result, lanthanide chiral chains connected to different structures were obtained through the self-assembly process of coordination recognition. In particular, driven by coordination, chiral template units with codirectional coordination points (called cis configuration) coordinate solely with cis template units during the self-assembly process to obtain a one-dimensional (1D) chain R-1/S-1 with an "S"-shaped distribution. Moreover, chiral template units with reversed coordination sites (called trans configuration) and twisted chiral template units are connected solely to templates with the same configuration to form a 1D chain R-2/S-2 with an axial helix. A circular dichroism spectrum shows that R-1/S-1 and R-2/S-2 are two pairs of enantiomers. The controllable construction of these two differential 1D chains is of great significance for studying coordination recognition at the molecular level. To the best of our knowledge, this is the first study to construct a 1D lanthanide chain through the self-assembly process of coordination recognition. The assembly process of nucleotides to form a hierarchical structure is simulated. This work provides a vivid example of the controllable synthesis of lanthanide complexes with precise structures and offers a new perspective on the formation process of chiral macromolecules that simulates natural processes.

Autophagy is essential for human myelopoiesis.

Emergency myelopoiesis (EM) is essential in immune defense against pathogens for rapid replenishing of mature myeloid cells. During the EM process, a rapid cell-cycle switch from the quiescent hematopoietic stem cells (HSCs) to highly proliferative myeloid progenitors (MPs) is critical. How the rapid proliferation of MPs during EM is regulated remains poorly understood. Here, we reveal that ATG7, a critical autophagy factor, is essential for the rapid proliferation of MPs during human myelopoiesis. Peripheral blood (PB)-mobilized hematopoietic stem/progenitor cells (HSPCs) with ATG7 knockdown or HSPCs derived from ATG7-/- human embryonic stem cells (hESCs) exhibit severe defect in proliferation during fate transition from HSPCs to MPs. Mechanistically, we show that ATG7 deficiency reduces p53 localization in lysosome for a potential autophagy-mediated degradation. Together, we reveal a previously unrecognized role of autophagy to regulate p53 for a rapid proliferation of MPs in human myelopoiesis.

Super-enhancer-associated gene CAPG promotes AML progression.

Acute myeloid leukemia is the most common acute leukemia in adults, the barrier of refractory and drug resistance has yet to be conquered in the clinical. Abnormal gene expression and epigenetic changes play an important role in pathogenesis and treatment. A super-enhancer is an epigenetic modifier that promotes pro-tumor genes and drug resistance by activating oncogene transcription. Multi-omics integrative analysis identifies the super-enhancer-associated gene CAPG and its high expression level was correlated with poor prognosis in AML. CAPG is a cytoskeleton protein but has an unclear function in AML. Here we show the molecular function of CAPG in regulating NF-κB signaling pathway by proteomic and epigenomic analysis. Knockdown of Capg in the AML murine model resulted in exhausted AML cells and prolonged survival of AML mice. In conclusion, SEs-associated gene CAPG can contributes to AML progression through NF-κB.