A chest CT-based nomogram for predicting survival in acute myeloid leukemia.

BACKGROUND: The identification of survival predictors is crucial for early intervention to improve outcome in acute myeloid leukemia (AML). This study aim to identify chest computed tomography (CT)-derived features to predict prognosis for acute myeloid leukemia (AML). METHODS: 952 patients with pathologically-confirmed AML were retrospectively enrolled between 2010 and 2020. CT-derived features (including body composition and subcutaneous fat features), were obtained from the initial chest CT images and were used to build models to predict the prognosis. A CT-derived MSF nomogram was constructed using multivariate Cox regression incorporating CT-based features. The performance of the prediction models was assessed with discrimination, calibration, decision curves and improvements. RESULTS: Three CT-derived features, including myosarcopenia, spleen_CTV, and SF_CTV (MSF) were identified as the independent predictors for prognosis in AML (P < 0.01). A CT-MSF nomogram showed a performance with AUCs of 0.717, 0.794, 0.796 and 0.792 for predicting the 1-, 2-, 3-, and 5-year overall survival (OS) probabilities in the validation cohort, which were significantly higher than the ELN risk model. Moreover, a new MSN stratification system (MSF nomogram plus ELN risk model) could stratify patients into new high, intermediate and low risk group. Patients with high MSN risk may benefit from intensive treatment (P = 0.0011). CONCLUSIONS: In summary, the chest CT-MSF nomogram, integrating myosarcopenia, spleen_CTV, and SF_CTV features, could be used to predict prognosis of AML.

Green preparation of CaO-based CO2 adsorbent by calcium-induced hydrogenation of shell wastes at room/moderate temperature.

Capturing CO2 using clamshell/eggshell-derived CaO adsorbent can not only reduce carbon emissions but also alleviate the impact of trash on the environment. However, organic acid was usually used, high-temperature calcination was often performed, and CO2 was inevitably released during preparing CaO adsorbents from shell wastes. In this work, CaO-based CO2 adsorbent was greenly prepared by calcium-induced hydrogenation of clamshell and eggshell wastes in one pot at room/moderate temperature. CO2 adsorption experiments were performed in a thermogravimetric analyzer (TGA). The adsorption performance of the adsorbents obtained from the mechanochemical reaction (BM-C/E-CaO) was superior to that of the adsorbents obtained from the thermochemical reaction (Cal-C/E-CaO). The CO2 adsorption capacity of BM-C-CaO at 650 °C is up to 36.82 wt%, but the adsorption decay rate of the sample after 20 carbonation/calcination cycles is only 30.17%. This study offers an alternative energy-saving method for greenly preparing CaO-based adsorbent from shell wastes.

Circular mRNA-based TCR-T offers a safe and effective therapeutic strategy for treatment of cytomegalovirus infection.

Circular mRNA (cmRNA) is particular useful due to its high resistance to degradation by exonucleases, resulting in greater stability and protein expression compared to linear mRNA. T cell receptor (TCR)-engineered T cells (TCR-T) represent a promising means of treating viral infections and cancer. This study aimed to evaluate the feasibility and efficacy of cmRNA in antigen-specific-TCR discovery and TCR-T therapy. Using human cytomegalovirus (CMV) pp65 antigen as a model, we found that the expansion of pp65-responsive T cells was induced more effectively by monocyte-derived dendritic cells transfected with pp65-encoding cmRNA compared with linear mRNA. Subsequently, we developed cmRNA-transduced pp65-TCR-T (cm-pp65-TCR-T) that specifically targets the CMV-pp65 epitope. Our results showed that pp65-TCR could be expressed on primary T cells for more than 7 days. Moreover, both in vitro killing and in vivo CDX models demonstrated that cm-pp65-TCR-T cells specifically and persistently kill pp65-and HLA-expressing tumor cells, significantly prolonging the survival of mice. Collectively, our results demonstrated that cmRNA can be used as a more effective technical approach for antigen-specific TCR isolation and identification, and cm-pp65-TCR-T may provide a safe, non-viral, non-integrated therapeutic approach for controlling CMV infection, particularly in patients who have undergone allogeneic hematopoietic stem cell transplantation.

Low-dose anti-thymocyte globulin plus low-dose post-transplant cyclophosphamide-based regimen for prevention of graft-versus-host disease after haploidentical peripheral blood stem cell transplants: a large sample, long-term follow-up retrospective study.

Introduction: The novel low-dose anti-thymocyte (ATG, 5 mg/kg) plus low-dose post-transplant cyclophosphamide (PTCy, 50 mg/kg) (low-dose ATG/PTCy)-based regimen had promising activity for prevention of graft-versus-host disease (GVHD) in haploidentical-peripheral blood stem cell transplantation (haplo-PBSCT), but its impacts on long-term outcomes remain to be defined. Methods: We performed a large sample, long-term follow-up retrospective study to evaluate its efficacy for GVHD prophylaxis. Results: The study enrolled 260 patients, including 162 with myeloid malignancies and 98 with lymphoid malignancies. The median follow-up time was 27.0 months. For the entire cohort, the cumulative incidences (CIs) of grade II-IV and III-IV acute GVHD (aGVHD) by 180 days were 13.46% (95% CI, 9.64%-17.92%) and 5.77% (95% CI, 3.37%-9.07%); while total and moderate/severe chronic GVHD (cGVHD) by 2 years were 30.97% (95% CI, 25.43%-36.66%) and 18.08% (95% CI, 13.68%-22.98%), respectively. The 2-year overall survival (OS), relapse-free survival (RFS), GVHD-free, relapse-free survival (GRFS), non-relapse mortality (NRM), and CIs of relapse were 60.7% (95% CI, 54.8%-67.10%), 58.1% (95% CI, 52.2%-64.5%), 50.6% (95% CI, 44.8-57.1%), 23.04% (95% CI, 18.06%-28.40%), and 18.09% (95% CI, 14.33%-23.97%, respectively. The 1-year CIs of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation were 43.46% (95% CI, 37.39%-49.37%) and 18.08% (95% CI, 13.68%-22.98%), respectively. In multivariate analysis, the disease status at transplantation was associated with inferior survivor outcomes for all patients and myeloid and lymphoid malignancies, while cGVHD had superior outcomes for all patients and myeloid malignancies, but not for lymphoid malignancies. Discussion: The results demonstrated that the novel regimen could effectively prevent the occurrence of aGVHD in haplo-PBSCT.

Exploring the role of sandwich-type polyoxometalates in {K10(PW9O34)2M4(H2O)2}@PCN-222 (M = Mn, Ni, Zn) for electroreduction of CO2 to CO.

To overcome the drawbacks of high solubility and instability of polyoxometalates (POMs) in aqueous solution and to expand their application in the electrocatalytic reduction of CO2 (ECR), we assemble sandwich-type POMs, K10[(PW9O34)2M4(H2O)2] (M = Mn, Ni, Zn, shortened as P2W18M4), into the hexagonal channel of a porphyrin-based metal-organic framework (MOF) PCN-222 to form P2W18M4@PCN-222 composites. Their ECR behavior displays polyoxoanion-dependent activity. P2W18Mn4@PCN-222 demonstrates a faradaic efficiency of 72.6% for the CO product (FECO), more than four times that of PCN-222 (FECO = 18.1%), and exhibits exceptional electrochemical stability over 36 h. P2W18Ni4@PCN-222 and P2W18Zn4@PCN-222 slightly increase (26.9%) and decrease (3.2%) in FECO, respectively. We combine the results with density functional theory (DFT) calculations to help understand the intrinsic reasons which reveals that the rate-determining step (RDS) reaction energy of P2W18Mn4@PCN-222 and P2W18Ni4@PCN-222 is significantly reduced compared to that of PCN-222. It is different in P2W18Zn4@PCN-222. Frontier molecular orbitals electron distribution results hint at directional electron transfer from P2W18Mn4/P2W18Ni4 to the porphyrin ring active center in PCN-222, promoting the electro-reduction of CO2 activity. By contrast, P2W18Zn4 may accumulate electrons from PCN-222, thus facilitating the hydrogen evolution reaction (HER). This work reveals the critical role of sandwich-type POMs in manipulating the electron transfer pathway during the electrocatalytic process. Our findings would broaden the scope of POM applications in electrochemical carbon dioxide reduction.

MOF-derived transition metal-based catalysts for the electrochemical reduction of CO2 to CO: a mini review.

The excessive emission of CO2 derived from the consumption of fossil fuels has caused severe energy and environmental crises. The electrochemical reduction of CO2 into value-added products such as CO not only reduces the CO2 concentration in the atmosphere but also promotes sustainable development in chemical engineering. Thus, tremendous work has been devoted to developing highly efficient catalysts for the selective CO2 reduction reaction (CO2RR). Recently, MOF-derived transition metal-based catalysts have shown great potential for the CO2RR due to their various compositions, adjustable structures, competitive ability, and acceptable cost. Herein, based on our work, a mini-review is proposed for an MOF-derived transition metal-based catalyst for the electrochemical reduction of CO2 to CO. The catalytic mechanism of the CO2RR was first introduced, and then we summarized and analyzed the MOF-derived transition metal-based catalysts in terms of MOF-derived single atomic metal-based catalysts and MOF-derived metal nanoparticle-based catalysts. Finally, we present the challenges and perspectives for the subject topic. Hopefully, this review could be helpful and instructive for the design and application of MOF-derived transition metal-based catalysts for the selective CO2RR to CO.

Effect of leptin on the growth and expression of STAT3 in yak mammary epithelial cells.

Background and Aim: Leptin (LEP) is an autocrine and paracrine factor produced by the fat pad and acinar epithelial cells of the breast. This study aimed to investigate the effects of LEP on yak mammary epithelial cells (YMECs) and the expression of STAT3. In addition, we evaluated the possible effects of prolactin (PRL) on the function of LEP. Materials and Methods: The YMECs were treated with 0, 50, 100, 200, 400, and 800 ng/mL LEP for 48 h in the absence of PRL and the presence of 500 ng/mL PRL. The growth activity of YMECs was measured using the cell counting kit-8 assay. The changes in the lactation signaling pathway-related factor STAT3 were detected at the mRNA, protein, and protein phosphorylation levels using the reverse transcriptase-quantitative polymerase chain reaction and Western blotting. To explore whether LEP affects the activation of STAT3 through JAK2/JAK3 in YMECs, the JAK2/3 signaling pathway inhibitor AG490 was used at a fixed concentration of LEP. Results: Each concentration of LEP significantly promoted the expression of STAT3 mRNA (p < 0.05) in YMECs in the presence of PRL. In the absence of PRL, all concentrations of LEP were found to inhibit the expression of the STAT3 protein (p < 0.05). The expression of the STAT3 protein in YMECs was found to first increase followed by a decrease with an increase in the concentration of LEP. In addition, the phosphorylation level of STAT3 increased in all groups, except the 100 ng/mL concentration group. The STAT3 phosphorylation trend and protein expression were different, such that the level of protein phosphorylation was higher than that of the STAT3 protein (p < 0.05). The addition of AG490 reduced the expression of the STAT3 mRNA, STAT3 protein, and STAT3 phosphorylation in the LEP and LEP + PRL groups. Conclusion: Altogether, the results indicated that different concentrations of LEP exerted varying effects on the growth of YMECs and the expression of STAT3, and the activity of STAT3 was primarily activated by JAK2. The addition of LEP can effectively inhibit the downregulation of the JAK2/STAT3 signal pathway by AG490, mitigate its inhibitory effect on the proliferation of YMECs, and reduce apoptosis. We believe that these findings will provide a theoretical and experimental basis for future research in this field.

One-pot preparation of H2-mixed CH4 fuel and CaO-based CO2 sorbent by the hydrogenation of waste clamshell/eggshell at room temperature.

The preparation of clean fuel or CO2 adsorbents using industrial and domestic garbage is an alternative way of meeting global energy needs and alleviating environmental problems. Herein, H2-mixed CH4 fuel and CaO-based CO2 sorbent were first prepared in one pot by the mechanochemical reaction of pretreated clamshell or eggshell wastes (carbon and calcium source) with calcium hydride (hydrogen source) at room temperature. In the above reactions, CH4 was the sole hydrocarbon product, and its yield reached 78.23%. The H2/CH4 ratio of the produced H2-mixed CH4 fuel was tunable according to the need by changing the reaction conditions. It is inspiring that the simultaneously formed solid CaO/carbon products were efficient CaO-based sorbents, which possessed a higher CO2 adsorption capacity (49.81-58.74 wt.%) at 650 °C and could maintain good adsorption stability in 30 carbonation/calcination cycles (average activity loss per cycle of only 1.6%). The three achievements of the idea are that it can simultaneously eliminate clamshell or eggshell wastes, obtain valuable clean fuel, and acquire efficient CaO-based sorbents.

The PARP1 Inhibitor Niraparib Represses DNA Damage Repair and Synergizes with Temozolomide for Antimyeloma Effects.

Purpose: Poly(ADP-ribose) polymerase 1 (PARP1) is necessary for single-strand break (SSB) repair by sensing DNA breaks and facilitating DNA repair through poly ADP-ribosylation of several DNA-binding and repair proteins. Inhibition of PARP1 results in collapsed DNA replication fork and double-strand breaks (DSBs). Accumulation of DSBs goes beyond the capacity of DNA repair response, ultimately resulting in cell death. This work is aimed at assessing the synergistic effects of the DNA-damaging agent temozolomide (TMZ) and the PARP inhibitor niraparib (Nira) in human multiple myeloma (MM) cells. Materials and Methods: MM RPMI8226 and NCI-H929 cells were administered TMZ and/or Nira for 48 hours. CCK-8 was utilized for cell viability assessment. Cell proliferation and apoptosis were detected flow-cytometrically. Immunofluorescence was performed for detecting γH2A.X expression. Soft-agar colony formation assay was applied to evaluate the antiproliferative effect. The amounts of related proteins were obtained by immunoblot. The combination index was calculated with the CompuSyn software. A human plasmacytoma xenograft model was established to assess the anti-MM effects in vivo. The anti-MM activities of TMZ and/or Nira were evaluated by H&E staining, IHC, and the TUNEL assay. Results: The results demonstrated that cotreatment with TMZ and Nira promoted DNA damage, cell cycle arrest, and apoptotic death in cultured cells but also reduced MM xenograft growth in nude mice, yielding highly synergistic effects. Immunoblot revealed that TMZ and Nira cotreatment markedly increased the expression of p-ATM, p-CHK2, RAD51, and γH2A.X, indicating the suppression of DNA damage response (DDR) and elevated DSB accumulation. Conclusion: Inhibition of PARP1 sensitizes genotoxic agents and represents an important therapeutic approach for MM. These findings provide preliminary evidence for combining PARP1 inhibitors with TMZ for MM treatment.

Atomically dispersed Fe-N-C catalyst displaying ultra-high stability and recyclability for efficient electroreduction of CO2 to CO.

To avoid the agglomeration of iron NPs and improve the dispersion of Fe SAs, we employed a mixed-ligand strategy to regulate the iron content in PCN-224(ZnxFey) and PCN-222(ZnxFey). Thanks to the sublimation of Zn and the Kirkendall effect, uniform dispersions of Fe SAs with 1.04-1.06 wt% were obtained in the pyrolysis products Zn0.5Fe0.5-N-C-224 and Zn0.5Fe0.5-N-C-222 with excellent CO2 → CO activity, super-stability, and recyclability.

New progress in the study of germline susceptibility genes of myeloid neoplasms.

In 2016, the World Health Organization incorporated 'myeloid neoplasms with germline predisposition' into its classification of tumors of hematopoietic and lymphoid tissues, revealing the important role of germline mutations in certain myeloid neoplasms, particularly myelodysplastic syndrome and acute myeloid leukemia. The awareness of germline susceptibility has increased, and some patients with myeloid neoplasms present with a preexisting disorder or organ dysfunction. In such cases, mutations in genes including CCAAT enhancer binding protein α (CEBPA), DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 (DDX41), RUNX family transcription factor 1 (RUNX1), GATA binding protein 2 (GATA2), Janus kinase 2 (JAK2) and ETS variant transcription factor 6 (ETV6) have been recognized. Moreover, with the application of advanced technologies and reports of more cases, additional germline mutations associated with myeloid neoplasms have been identified and provide insights into the formation, prognosis and therapy of myeloid neoplasms. The present review discusses the well-known CEBPA, DDX41, RUNX1, GATA2, JAK2 and ETV6 germline mutations, and other mutations including those of lymphocyte adapter protein/SH2B adapter protein 3 and duplications of autophagy related 2B, GSK3B interacting protein αnd RB binding protein 6, ubiquitin ligase, that remain to be confirmed or explored. Recommendations for the management of diseases associated with germline mutations are also provided.

Comparison of Survival Between Autologous and Allogeneic Stem Cell Transplantation in Patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma: A Meta-Analysis.

This study aimed to compare the efficacy of allogeneic stem cell transplantation (allo-SCT) versus autologous SCT (auto-SCT) in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL). Medline, CENTRAL, and EMBASE databases through December 31, 2019 were searched. The primary endpoints were overall survival (OS) and progression-free survival (PFS) rates. The secondary outcomes include transplant-related mortality (TRM), event-free survival, relapse/or progression, and nonrelapse mortality (NRM). The 18 retrospective studies enrolled 8,058 B-NHL patients (allo-SCT = 1,204; auto-SCT = 6,854). The OS was significantly higher in patients receiving auto-SCT than allo-SCT (pooled odds ratio [OR]: 1.69, 95% confidence interval [CI]: 1.29 to 2.22, P < 0.001), but no significant difference was found in PFS (pooled OR: 0.98, 95% CI: 0.69 to 1.38, P = 0.891). Auto-SCT patients also had lower TRM and NRM (TRM: OR = 0.23, P < 0.001; NRM: OR = 0.16, P < 0.001), but higher relapse or progression rate (OR = 2.37, P < 0.001) than allo-SCT patients. Subgroup analysis performed for different grades and subtypes of B-NHL showed higher OS in auto-SCT patients with high-grade B-NHL and diffused large B-cell lymphoma (DLBCL). There was, nevertheless, higher PFS in allo-SCT patients with low-grade B-NHL and follicular lymphoma (FL), and lower PFS in allo-SCT patients with DLBCL than their auto-SCT counterparts. In conclusion, the meta-analysis demonstrated that relapsed or refractory B-NHL patients who received auto-SCT have improved OS than those treated with allo-SCT, especially among those with DLBCL, but lower PFS among those with FL. However, the study is limited by a lack of randomized trials, patients' heterogeneity, and possible selection bias.

Revealing the structure-activity relationship of two Cu-porphyrin-based metal-organic frameworks for the electrochemical CO2-to-HCOOH transformation.

The eCO2RR activity is correlated to the internal structural character of the catalyst. We employed two types of structural models of porphyrin-based MOFs of PCN-222(Cu) and PCN-224(Cu) into heterogeneous catalysis to illustrate the effect of structural factors on the eCO2RR performance. The composite catalyst PCN-222(Cu)/C displays better activity and selectivity (η = 450 mV, FEHCOOH = 44.3%, j = 3.2 mA cm-2) than PCN-224(Cu)/C (η = 450 mV, FEHCOOH = 34.1%, j = 2.4 mA cm-2) for the CO2 reduction to HCOOH in the range of -0.7--0.9 V (vs. RHE) due to its higher BET surface area, CO2 uptake, and a larger pore diameter. It is interesting that PCN-224(Cu)/C displays better performance in the range of -0.4--0.6 V (vs. RHE) due to its greater heat of adsorption, Qst and a higher affinity for CO2 molecule, which could promote the capture of CO2 onto the exposed active sites. As a result, PCN-224(Cu)/C exhibits better stability for the long-term electrolysis.

Polyoxometalate-Based Compounds for Photo- and Electrocatalytic Applications.

Photo/electrocatalysis of water (H2 O) splitting and CO2 reduction reactions is a promising strategy to alleviate the energy crisis and excessive CO2 emissions. For the hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and CO2 reduction reaction (CO2 RR) involved, the development of effective photo/electrocatalysts is critical to reduce the activation energy and accelerate the sluggish dynamics. Polyoxometalate (POM)-based compounds with tunable compositions and diverse structures are emerging as unique photo/electrocatalysts for these reactions as they offer unparalleled advantages such as outstanding solution and redox stability, quasi-semiconductor behaviour, etc. This Minireview provides a basic introduction related to photo/electrocatalytic HER, OER and CO2 RR, followed by the classification of pristine POM-based compounds toward different catalytic reactions. Recent breakthroughs in engineering POM-based compounds as efficient photo/electrocatalysts are highlighted. Finally, the advantages, challenges, strategies and outlooks of POM-based compounds on improving photo/electrocatalytic performance are discussed.

Acquiring an effective CaO-based CO2 sorbent and achieving selective methanation of CO2.

CO2 capture, utilization, and storage are promising strategies to solving the problems of superfluous CO2 or energy shortage. Here, mechanochemical reduction of CO2 by a MgH2/CaH2 mixture was first performed, by which we achieve selective methanation of CO2 and acquire an effective CaO-based CO2 sorbent, simultaneously. The selectivity of methanation is near 100% and the yield of CH4 reaches 30%. Four MgO and carbon-doped CaO-based CO2 sorbents (MgO/CaO/C, MgO/2CaO/C, MgO/4CaO/C, and MgO/8CaO/C) were formed as solid products in these reactions. Among them, the MgO/4CaO/C sorbent shows high initial adsorption amount of 59.3 wt% and low average activity loss of 1.6% after 30 cycles. This work provides a novel, well-scalable, and sustainable approach to prepare an efficient inert additive-including CaO-based CO2 sorbent and selectively convert CO2 to CH4 at the same time.

Self-Assembly of a Phosphate-Centered Polyoxo-Titanium Cluster: Discovery of the Heteroatom Keggin Family.

Over the past 200 years, the most famous and important heteroatom Keggin architecture in polyoxometalates has only been synthesized with Mo, W, V, or Nb. Now, the self-assembly of two phosphate (PO4 3- )-centered polyoxo-titanium clusters (PTCs) is presented, PTi16 and PTi12 , which display classic heteroatom Keggin and its trivacant structures, respectively. Because TiIV has lower oxidate state and larger ionic radius than MoVI , WVI , VV , and NbV , additional TiIV centres in these PTCs are used to stabilize the resultant heteroatom Keggin structures, as demonstrated by the cooresponding theoretical calculation results. These photoactive PTCs can be utilized as efficient photocatalysts for highly selective CO2 -to-HCOOH conversion. This new discovery indicates that the classic heteroatom Keggin family can be assembled with Ti, thus opening a research avenue for the development of PTC chemistry.

An adjustable dual-emission fluorescent metal-organic framework: Effective detection of multiple metal ions, nitro-based molecules and DMA.

A novel multifunctional Pb(II)-based MOF, [Pb1.5(DBPT)]2·(DMA)3(H2O)4 (1), with excellent chemical stability, was successfully assembled by connecting {Pb2O10} unit with a multi-topic polycarboxylate ligand of 3-(3,5-dicarboxylphenyl)-5-(4-carboxylphenyl)-1-H-1,2,4-triazole (H3DBPT). It exhibits dual fluorescence emissions at 380 nm (λex = 280 nm) and 540 nm (λex = 380 nm), respectively. Through the adjustable dual fluorescence emissions, it could act as a turn-off and turn-on switch for detecting N,N-dimethylacetamide (DMA) molecule. Moreover, Fe3+ ions exert luminescence quenching role on compound 1 at both excitation lengths in water, among which the quenching at λex = 280 nm is of high sensitivity (KSV = 1.2 × 105), and the quenching at λex = 380 nm is of wide-range. The sensing for metal ions of In3+, Zr4+, and Al3+ is also effective at λex = 280 nm, with the KSV constants of 1.6 × 105, 1.6 × 105, and 4.3 × 104, respectively. More importantly, a series of nitroaromatic compounds (TNP, 2,4,6-trinitrophenol; 4-NA, 4-nitroaniline; NB, nitrobenzene) and nitro-based drugs (MNZ, metronidazole; DMZ, dimetridazole) could be detected at both excitation lengths, demonstrating the advantage of broad range response of fluorescence sensing. Thanks to the excellent chemical stability and unusual dual emission luminescence properties for chemical detection of various metal ions, nitro-based molecules and DMA solvent, the Pb-based MOF reported in this work is, therefore, a very promising multi-response sensor.