Identifying the atomic structures of porous materials in spatial and temporal dimensions by (scanning) transmission electron microscope ((S)TEM) is significant for their wide applications in ...catalysis, separation and energy storage. However, the sensitivity of materials to electron beams made it difficult to reduce the electron damage to specimens while maintaining the resolution and signal‐to‐noise ratio. It is therefore still challenging to capture multiple images of the same area in one crystal to image the temporal changes of lattices. Usings integrated differential phase contrast (iDPC) STEM, atomic‐resolution imaging of beam‐sensitive zeolite frameworks is achieved with an ultralow dose of 40 e− Å−2, 2–3 orders of magnitude lower than that of conventional STEM. Based on the iDPC technique, not only the atomic 3D architecture of ZSM‐5 crystals but also the changes of frameworks are observed during in situ experiments. Local structures and light‐element aromatics in ZSM‐5 crystals can also be revealed directly under iDPC‐STEM. These results provided not only an efficient tool to image beam‐sensitive materials with ultralow beam current but also a new strategy to observe and investigate the hydrocarbon pools in zeolite catalysts at the single‐molecule scale.
Atomic imaging of a ZSM‐5 framework by integrated differential phase contrast (iDPC) scanning transmission electron microscopy (STEM) is reported. The ZSM‐5 lattices are atomically resolved to reveal 3D frameworks and local structures of ZSM‐5 nanocrystals with a high resolution and signal‐to‐noise ratio. Light‐element aromatics adsorbed in ZSM‐5 and the structural changes of channels during the in situ heating process are also imaged.
Background
Mycobacterium tuberculosis
(MTB) is a relatively infrequent infection encountered during hematopoietic stem-cell transplantation (HSCT). The identification of MTB following HSCT remains a ...complex task, with delayed detection and misdiagnosis potentially resulting in unfavorable outcomes. Metagenomic next-generation sequencing (mNGS) represents a novel, highly sensitive, and rapid diagnostic tool in clinical settings for discerning intricate infections and detecting exceedingly rare pathogens
Methods
With the aid of mNGS, we diagnosed MTB in the lymph nodes and lungs of two patients with hematological diseases following allogeneic peripheral blood hematopoietic stem cell transplantation. Both patients presented with a fever, localized symptoms, and clinical signs. Following inconclusive results from routine tests, impractical biopsy procedures, and unsuccessful responses to empirical treatments, mNGS was employed as a final recourse, revealing DNA fragments of MTB in blood samples.
Results
The diagnoses were ultimately confirmed in conjunction with additional clinical evidence. The application of mNGS in MTB cases after allogeneic HSCT has rarely been reported. The mNGS technique can provide a prompt and highly sensitive indication leading to the definitive diagnosis of MTB in complex post-transplant scenarios.
Background
ZNF384
rearrangements are found in 5-10% of B-cell acute lymphoblastic leukemia (B-ALL) and 48% of B cell/myeloid mixed phenotype acute leukemia (B/M MPAL).
ZNF384
-rearranged B-ALL is ...prone to lineage conversion after chemotherapy.
TCF3
is the second most common rearrangement partner of
ZNF384
in B-ALL (27.5%) and the most common partner in B/M MPAL (53.3%).
TCF3-ZNF384
fusion is related to a poor steroid response and a high frequency of relapse. It is mostly reported in children and adolescents but rarely seen in adults.
Patients and Methods
Here, we report a rare case of adult common B-ALL with
TCF3-ZNF384
fusion in which the patient relapsed after one cycle of consolidation chemotherapy. Relapsed leukemia cells from the bone marrow were cultured for 72 hours ex vivo, and a panel of 156 kinds of cytotoxic drugs, targeted therapy drugs, combination chemotherapy drugs, etc., was used for sensitivity screening. The literature on
TCF3-ZNF384
fusion was reviewed, and reported cases with
TCF3-ZNF384
fusion were summarized. Clinical characteristics were compared between B-ALL and MPAL with
TCF3-ZNF384
fusion.
Results
The relapsed lymphoblasts showed moderate sensitivity to both acute myelocytic leukemia (AML) - and acute lymphoblastic leukemia (ALL)-directed combination chemotherapy schemes, as well as to multiple targeted therapeutic drugs. The hyper-CVAD (B) scheme showed synergistic effects with multiple targeted compounds and had the highest sensitivity. The patient chose the hyper-CVAD (B) scheme combined with sorafenib and achieved complete remission (CR), then consolidated with myeloid-directed homoharringtonine+cytarabine+daunorubicin (HAD) scheme and gained molecular CR. By reviewing the literature, we found that both the genomic landscapes and gene expression profiles of
ZNF384
-rearranged B-ALL and MPAL are similar and that both diseases have lineage plasticity. The gene expression profile in
TCF3-ZNF384
-positive patients shows enrichment of hematopoietic stem cell features. No significant differences in clinical characteristics were found between
TCF3-ZNF384
-positive ALL and MPAL.
Conclusion
TCF3-ZNF384
-positive leukemia may be a distinct subtype of leukemia regardless of immunophenotype. Considering the frequent lineage switches and sensitivity to both ALL- and AML-directed schemes, a uniform strategy directed at both lymphoid and myeloid lineages or at hematopoietic stem cells may be better for
TCF3-ZNF384
-positive leukemia. Small molecule targeted therapies may be promising treatment options and deserve further investigation.
Follicular lymphoma (FL), a common indolent B-cell lymphoma, has the potential to transform into an aggressive lymphoma, such as diffuse large B-cell lymphoma (DLBCL). The outcome of patients with ...transformed follicular lymphoma (tFL) is poor, especially in patients with transformed lymphoma after chemotherapy and patients with progression within 24 months (POD24). Chimeric antigen receptor (CAR) T-cell therapy combined with autologous stem cell transplantation (ASCT) has promising antitumor efficacy.
Here, we described a 39-year-old male patient who was initially diagnosed with FL that transformed into DLBCL with POD24, CD20 negativity,
mutation, and a bulky mass after 3 lines of therapy, all of which were adverse prognostic factors. We applied a combination approach: CD19 CAR T-cell infusion following ASCT. Ibrutinib was administered continuously to enhance efficacy, DHAP was administered as a salvage chemotherapy, and ICE was administered as a bridging regimen. The patient underwent BEAM conditioning on days -7~ -1, a total of 3.8 × 10
kg CD34
stem cells were infused on days 01~02, and a total of 10
CAR T cells (relmacabtagene autoleucel, relma-cel, JWCAR029) were infused on day 03. The patient experienced grade 2 cytokine release syndrome (CRS), manifesting as fever and hypotension according to institutional standards. There was no immune effector cell-associated neurotoxicity syndrome (ICANS) after CAR T-cell infusion. Finally, the patient achieved CMR at +1 month, which has been maintained without any other adverse effects.
This case highlights the amazing efficacy of CD19 CAR T-cell therapy following ASCT for R/R tFL, thus providing new insight on therapeutic strategies for the future.
Here we report the direct atomic scale observation of ZSM-5 pores and the influence of extra-framework Al on methanol to aromatic (MTA). We synthesized a nano sized ZSM-5 catalyst with a short
b
...-axis, and fully opened straight channels. A 98% ultrahigh aromatic selectivity, more than 300 hours long life time and high anti-hydrothermal ability can be achieved in the MTA process.
Genomic loss of mismatched human leukocyte antigen (HLA loss) is one of the most vital immune escape mechanisms of leukemic cells after allogeneic hematopoietic stem cell transplantation (allo-HSCT). ...However, the methods currently used for HLA loss analysis have some shortcomings. Limited literature has been published, especially in lymphoid malignancies. This study aims to evaluate the incidences, risk factors of HLA loss, and clinical outcomes of HLA loss patients. In all, 160 patients undergoing partially mismatched related donor (MMRD) transplantation from 18 centers in China were selected for HLA loss analysis with the next-generation sequencing (NGS)-based method, which was validated by HLA-KMR. Variables of the prognostic risk factors for HLA loss or HLA loss–related relapse were identified with the logistic regression or the Fine and Gray regression model. An HLA loss detection system, HLA-CLN HLA chimerism for loss of heterozygosity (LOH) analysis by NGS, was successfully developed. Forty (25.0%) patients with HLA loss were reported, including 27 with myeloid and 13 with lymphoid malignancies. Surprisingly, 6 of those 40 patients did not relapse. The 2-year cumulative incidences of HLA loss (22.7% vs 22.0%, P = 0.731) and HLA loss–related relapse (18.4% vs 20.0%, P = 0.616) were similar between patients with myeloid and lymphoid malignancies. The number of HLA mismatches (5/10 vs <5/10) was significantly associated with HLA loss in the whole cohort odds ratio (OR): 3.15, P = 0.021 and patients with myeloid malignancies (OR: 3.94, P = 0.021). A higher refined-disease risk index (OR: 6.91, P = 0.033) and donor–recipient ABO incompatibility (OR: 4.58, P = 0.057) contributed to HLA loss in lymphoid malignancies. To sum up, HLA-CLN could overcome the limitations of HLA-KMR and achieve a better HLA coverage for more patients. The clinical characteristics and outcomes were similar in patients with HLA loss between myeloid and lymphoid malignancies. In addition, the results suggested that a patient with HLA loss might not always relapse.
Overcoming imatinib mesylate (IM) resistance and disease persistence in patients with chronic myeloid leukemia (CML) is of considerable importance to the issue of potential cure. Here we asked ...whether autocrine signaling contributes to survival of BCR/ABL+ cells in the presence of IM and nilotinib (NI; AMN107), a novel, more selective Abl inhibitor. Conditioned media (CM) of IM-resistant LAMA84 cell clones (R-CM) was found to substantially protect IM-naive LAMA cells and primary CML progenitors from IM- or NI-induced cell death. This was due to an increased secretion of the granulocyte-macrophage colony-stimulating factor (GM-CSF), which was identified as the causative factor mediating IM resistance in R-CM. GM-CSF elicited IM and NI drug resistance via a BCR/ABL-independent activation of the janus kinases 2 (JAK-2)/signal transducer and activator of transcription 5 (STAT-5) signaling pathway in GM-CSF receptor α receptor (CD116)–expressing cells, including primary CD34+/CD116+ GM progenitors (GMPs). Elevated mRNA and protein levels of GM-CSF were detected in IM-resistant patient samples, suggesting a contribution of GM-CSF secretion for IM and NI resistance in vivo. Importantly, inhibition of JAK-2 with AG490 abrogated GM-CSF–mediated STAT-5 phosphorylation and NI resistance in vitro. Together, adaptive autocrine secretion of GM-CSF mediates BCR/ABL-independent IM and NI resistance via activation of the antiapoptotic JAK-2/STAT-5 pathway. Inhibition of JAK-2 overcomes GM-CSF–induced IM and NI progenitor cell resistance, providing a rationale for the application of JAK-2 inhibitors to eradicate residual disease in CML.
Drug-resistant cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT) often leads to morbidity and mortality. Several studies have shown that CMV-cytotoxic T lymphocytes ...(CTLs) can overcome drug-resistant CMV infection, but still many questions remain unanswered. Here, we present a case of refractory CMV infection after allogeneic HSCT (allo-HSCT). Donor-derived CMV-CTLs failed to eliminate the virus in unique peripheral blood on the first application, when 70 mg methylprednisolone (MP) was taken per day. After a second attempt with a combination of 8 mg MP with leflunomide, a complete and persisting clearance of all involved sites, including peripheral blood, urinary system, leptomeninges, and retina, was achieved. To summarize, intravenous infusion of CTLs can eliminate CMV in the oculi and central nervous system (CNS), and a low dosage of 8 mg MP has no interaction with CMV-CTLs.
Carbon nanotubes (CNTs) are one of the strongest known materials. When assembled into fibres, however, their strength becomes impaired by defects, impurities, random orientations and discontinuous ...lengths. Fabricating CNT fibres with strength reaching that of a single CNT has been an enduring challenge. Here, we demonstrate the fabrication of CNT bundles (CNTBs) that are centimetres long with tensile strength over 80 GPa using ultralong defect-free CNTs. The tensile strength of CNTBs is controlled by the Daniels effect owing to the non-uniformity of the initial strains in the components. We propose a synchronous tightening and relaxing strategy to release these non-uniform initial strains. The fabricated CNTBs, consisting of a large number of components with parallel alignment, defect-free structures, continuous lengths and uniform initial strains, exhibit a tensile strength of 80 GPa (corresponding to an engineering tensile strength of 43 GPa), which is far higher than that of any other strong fibre.
•Techno-economic analysis of the synthetic route of syngas to aromatics is reported.•Systematic models for direct and indirect route are built based on the Aspen Plus.•Energy consumption and economic ...aspects are both seriously CO-conversion dependent.•Product selectivity exhibits insignificant effect on the total installation cost and heat utility.•Direct STA route shows advantages at the conversion of CO above 66%–72%, without considering the formation of CO2.
Direct conversion of syngas-to-aromatics (STA) is an increasing vital catalytic field that still contains much uncertainty. For the first time, we report the process simulation of STA via direct routes and indirect STA (syngas first to produce methanol, then methanol being converted into aromatics). The conversion of CO was selected as the sensitivity indicator for the evaluation of energy consumption and economic aspects. A low conversion of CO resulted in a low yield (and low partial pressure) of aromatics and an increasing difficulty in separating them from unreacted syngas and light hydrocarbons. The associated increased investment and operational costs were analyzed quantitatively. Direct STA shows obvious advantages in operational cost savings and in construction costs when the conversion of CO was higher than 66–72% when compared with the indirect STA route. The simulation results provide new insights into the upper limits of the process of developing catalysts.
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