Thiotepa-busulfan-fludarabine-based conditioning as a promising approach prior to allogeneic hematopoietic stem cell transplantation in patients with blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive myeloid malignancy associated with a poor prognosis. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) has emerged as a potential treatment strategy for BPDCN, standardized conditioning regimens remain lacking. In this manuscript, we present two cases of BPDCN that were treated with a thiotepa-busulfan-fludarabine (TBF)-based conditioning regimen prior to allo-HSCT. Both cases demonstrated complete remission post-transplantation, sustained donor chimerism, and remission maintenance, suggesting the potential efficacy of the TBF conditioning regimen for BPDCN transplantation. Given the small sample size in our study, we emphasize caution and advocate for larger studies to confirm the efficacy of TBF in the treatment of BPDCN.

Reexamining the Emergence and Stability of the Square Cylinder Phase in Block Copolymers.

Recently, a few AB-type multiblock copolymers have been successfully designed to form stable square cylinder phase based on self-consistent field theory (SCFT) calculations. The previous works only identify the stability region of the square phase but not analyzing its stability, which is closely related to the free-energy landscape. In this work, we have reexamined the stability of the square phase in B 1 A 1 B 2 A 2 B 3 ${{{\rm B}}_{1}{{\rm A}}_{1}{{\rm B}}_{2}{{\rm A}}_{2}{{\rm B}}_{3}}$ linear pentablock and ( B 1 A B 2 )​ 5 ${({{\rm B}}_{1}{\rm A}{{\rm B}}_{2}{)}_{5}}$ star triblock copolymers by drawing the free-energy landscape with respect to the two dimensions of a rectangular unit cell. Our results demonstrate that the square phase continuously transfers to the rectangular phase as the degree of packing frustration is gradually released. Moreover, the prolate contour lines of the free-energy landscape indicate the weak stability of the square phase in the B 1 A 1 B 2 A 2 B 3 ${{{\rm B}}_{1}{{\rm A}}_{1}{{\rm B}}_{2}{{\rm A}}_{2}{{\rm B}}_{3}}$ copolymer. In contrast, the stability of the square phase is notably improved in the ( B 1 A B 2 )​ 5 ${({{\rm B}}_{1}{\rm A}{{\rm B}}_{2}{)}_{5}}$ copolymer due to its enhanced concentration of bridging configurations. Our work sheds light on the understanding of the stability of the square cylinder phase in block copolymers. Accordingly, we propose some possible strategies for further designing new AB-type block copolymer systems to obtain more stable square phase.

CCDC50, an essential driver involved in tumorigenesis, is a potential severity marker of diffuse large B cell lymphoma.

Diffuse Large B Cell Lymphoma (DLBCL) is the most common form of blood cancer. Among the subtypes, the activated B-cell (ABC) subtype is typically more aggressive and associated with worse outcomes. However, the underlying mechanisms are not fully understood. In this study, we performed microarray analysis to identify potential ABC-DLBCL-associated genes. We employed Kaplan-Meier methods and cox univariate analysis to explore the prognostic value of the identified candidate gene Coiled-coil domain containing 50 (CCDC50). Additionally, we used DLBCL cell lines and mouse models to explore the functions and mechanisms of CCDC50. Finally, we isolated CCDC50-bearing exosomes from clinical patients to study the correlation between these exosomes and disease severity. Our results demonstrated that CCDC50 not only showed significantly positive correlations with ABC subtype, tumor stage and number of extranodal sites, but also suggested poor outcomes in DLBCL patients. We further found that CCDC50 promoted ABC-DLBCL proliferation in vitro and in vivo. Mechanistically, CCDC50 inhibited ubiquitination-mediated c-Myc degradation by stimulating the PI3K/AKT/GSK-3ß pathway. Moreover, CCDC50 expression was positively correlated with c-Myc at protein levels in DLBCL patients. Additionally, in two clinical cohorts, the plasma CCDC50-positive exosomes differentiated DLBCL subtypes robustly (AUC > 0.80) and predicted disease severity effectively (p < 0.05). Our findings suggest that CCDC50 likely drives disease progression in ABC-DLBCL patients, and the CCDC50-bearing exosome holds great potential as a non-invasive biomarker for subtype diagnosis and prognosis prediction of DLBCL patients.

Role of confinement in the shear banding and shear jamming in noncolloidal fiber suspensions.

The jamming effect is critical in processing short fiber-reinforced thermoplastics (FRTs). Fiber jamming can induce discontinuous shear thickening (DST) in simple shear and result in fiber-matrix separation in more complex flows such as injection molding and compression molding of FRTs. The confinement effect commonly induces local jams and strongly enhances fiber jamming. However, the transient evolution of local fiber jams under confinement and its correlation with the tumbling of fibers are still elusive. In this study, we adopted rheo-PIV (particle image velocity) techniques to study this effect for glass fiber-reinforced thermoplastics (FRTs). The translational and tumbling motion of fiber were determined during rheological measurements, and the distribution of fiber orientation was determined by X-ray CT. Three shear banding regions appeared after the viscosity overshoot under high shear stress in suspensions with high fiber content, which was associated with the three regions of fiber orientation across the gap due to confinement. Shear banding was ascribed to the different tumbling speeds across the gap because of the different initial orientations and different wall confinements near and far from the wall. The local shear thickening and jamming behavior became most significant under intermediate confinement, and were affected by shear strain, shear stress, and fiber contents. 3D state diagrams were constructed to show the confinement effect on the evolution of shear banding and jamming.

The impact of intramolecular polydispersity on the self-assembly of ABn miktoarm star copolymers.

The self-assembly behaviors of ABn miktoarm star copolymers as one typical type of asymmetric architecture have been studied well in the past few decades due to their deflected phase boundaries. In particular, recently, they have attracted renewed theoretical interest due to their expanded spherical phase region that stabilizes complex Frank-Kasper spherical phases. However, previous theoretical studies have never considered ABn copolymers with unequal arm lengths, which is more or less the case for synthesized copolymers. In this work, we investigate the self-assembly behaviors of ABn miktoarm star copolymers with unequal B-arms using self-consistent field theory. We propose an intramolecular polydispersity index (iD) to quantify the distribution of unequal B-blocks. Accordingly, we further propose a simple quantity of an effective arm number nequ = n/iD for quantitatively comparing the phase boundaries between various ABn copolymer samples with different arm numbers or different distributions of B-blocks. Our results indicate that different ABn copolymers with equal nequ exhibit similar phase diagrams. On the other hand, we also found that the phase boundaries of two different samples with same nequ are not exactly overlapped. We speculate that the effect of spontaneous curvature may be mainly controlled by nequ, but the packing frustration of B-blocks may also be dependent on the other quantities that are closely related to the shape of the distribution of B-arms, such as higher order polydispersity indexes.

Distribution of an antioxidant in polypropylene/ethylene-octene copolymer blends studied by atomic force microscopy-infrared.

In this work, the microscopic distribution of antioxidant 1010 (AT1010) in blends of isotactic polypropylene (iPP) with an ethylene-octene copolymer (POE) was investigated in situ using the atomic force microscopy-infrared (AFM-IR) technique. Pellets of an iPP/POE blend containing AT1010 at a mass ratio of 79.5 : 20 : 0.5 were extruded at different screw speeds, and were then injection-molded into plates. The domain size of the POE disperse phase in the pellets was about 1 µm, regardless of the screw speed, and remained unchanged in the injection molding. AFM-IR analyses revealed that AT1010 preferred to stay in the POE disperse phase rather than in the iPP matrix, with a concentration ratio of ∼1.2 in the extruded pellets independent of the screw speed, which was further increased to ∼1.5 in the molded plates. The preferred concentration of AT1010 in the POE was in line with its higher solubility in rubber than in iPP, and the enhanced partition of AT1010 in the molded plates was attributed to a longer processing time in the molten state than that for the extruded pellets, which was verified by AFM-IR analyses of pellets extruded with different residence times.

In Situ Nitrogen Retention of Carbon Anode for Enhancing the Electrochemical Performance for Sodium-Ion Battery.

Retaining nitrogen for polyacrylonitrile (PAN) based carbon anode is a cost-effective way to make full use of the advantages of PAN for sodium-ion batteries (SIBs). Here, a simple strategy has been successfully adopted to retain N atoms in situ and increase production yield of a novel composite PAZ by mixing 3 wt % of zinc borate (ZB) with poly (acrylonitrile-co-itaconic acid) (PANIA). Among the prepared carbonised fibre (CF) samples, PAZ-CF-700 maintains the highest N content, retaining 90 % of the original N from PANIA. It represents the highest capacity storage contribution (80.55 %) and the lowest impedance Rct (117 Ω). Consequently, the specific capacity increases from 60 mAh g-1 of PANIA-CF-700 to 190 mAh g-1 of PAZ-CF-700 at a current density of 100 mA g-1 . At the same time, PAZ-CF-700 exhibits a good rate performance and excellent long-term cycling stability with a specific capacity of 94 mAh g-1 after 4000 cycles at 1.6 A g-1 .

MNK1 inhibitor CGP57380 overcomes mTOR inhibitor-induced activation of eIF4E: the mechanism of synergic killing of human T-ALL cells.

Although the treatment of adult T-cell acute lymphoblastic leukemia (T-ALL) has been significantly improved, the heterogeneous genetic landscape of the disease often causes relapse. Aberrant activation of mammalian target of rapamycin (mTOR) pathway in T-ALL is responsible for treatment failure and relapse, suggesting that mTOR inhibition may represents a new therapeutic strategy. In this study, we investigated whether the mTOR complex 1 (mTORC1) inhibitor everolimus could be used as a therapeutic agent against human T-ALL. We showed that rapamycin and its analog RAD001 (everolimus) exerted only mild inhibition on the viability of Jurkat, CEM and Molt-4 cell lines (for everolimus the maximum inhibition was <40% at 100 nM), but greatly enhanced the phosphorylation of eIF4E, a downstream substrate of MAPK-interacting kinase (MNK) that was involved in promoting cell survival. Furthermore, we demonstrated in Jurkat cells that mTOR inhibitor-induced eIF4E phosphorylation was independent of insulin-like growth factor-1/insulin-like growth factor-1 receptor axis, but was secondary to mTOR inhibition. Then we examined the antileukemia effects of CGP57380, a MNK1 inhibitor, and we found that CGP57380 (4-16 µM) dose-dependently suppressed the expression of both phosphor-MNK1 and phosphor-eIF4E, thereby inhibiting downstream targets such as c-Myc and survivin in T-ALL cells. Importantly, CGP57380 produced a synergistic growth inhibitory effect with everolimus in T-ALL cells, and treatment with this targeted therapy overcame everolimus-induced eIF4E phosphorylation. In conclusion, our results suggest that dual-targeting of mTOR and MNK1/eIF4E signaling pathways may represent a novel therapeutic strategy for the treatment of human T-ALL.

ERG11 Gene Mutations and MDR1 Upregulation Confer Pan-Azole Resistance in Candida tropicalis Causing Disseminated Candidiasis in an Acute Lymphoblastic Leukemia Patient on Posaconazole Prophylaxis.

In this study, we present a rare case of fatal breakthrough Candida tropicalis infection in a patient with acute lymphoblastic leukemia (ALL) while on posaconazole prophylaxis. Then, we explore the mechanisms underlying azole resistance by focusing on enhanced efflux pumps and changes in the azole target enzyme Erg11p, which was encoded by the ERG11 gene. Our study demonstrates that Y132C substitution of Erg11p combined with MDR1 overexpression may be the pan-azole resistance mechanisms in Candida tropicalis.

Investigation of Dual Network Construction for Toughening in Bio-Based Polyamide Composites.

This study investigated the role of constructing a dual network in toughening bio-based long-chain polyamide 610 (PA610) composites. Rheological studies were conducted to reveal the effects of toughening agent type and content on the material properties. According to the variation trend of mechanical properties and the appearance of a rheological low-frequency plateau of the materials, the percolation network concentration ϕc of the toughening agent in the PA610 matrix was determined to be 13.5 vol.%. The interfacial interaction of the composite was evaluated through the percolation theory, and the scaling value v = 1.36 for both indicated the good affinity between PA610 and the toughening agent. Rheology results found that the combination of ethylene terpolymer (PTW) and maleic anhydride-g-styrene-b-(ethylene-butylene)-b-styrene (MAH-SEBS) could achieve an optimal balance between the mechanical properties and fluidity of the composites. Furthermore, the addition of ultra-high-molecular-weight polytetrafluoroethylene (PTFE), in conjunction with the toughening agent, facilitated the construction of a dual semi-interpenetrating network. The strengthened intermolecular interactions restricted the relative slippage and mobility of the polymer chains and therefore enhanced the strength and toughness of the material. This study provides new possibilities and approaches for optimizing the comprehensive properties of bio-based polyamide materials.

Extensional Flow-Induced Concentration Gradient in Entangled Polymer Solutions with Chemically Identical Species.

Entangled polymer solutions show different rheological behavior from melts in fast extensional flow. This discrepancy is not expected according to the classic tube model and is an urgent issue to be solved in polymer physics. While in the tube model the polymer concentration is considered to be homogeneous, we show that extensional flow-induced concentration gradient may happen in polymer solutions even with chemically identical solutes and solvents. Through labeling an aggregation-induced emission (AIE) probe on oligomeric solvents, the flow-induced concentration gradient is visualized by combining extensional rheology and ex situ fluorescence microscopy. Microdomains of oligomeric solvents with a length scale of tens of micrometers are observed, and their influence on rheological behavior cannot be ignored.

Effective management of a rare case of primary renal intravascular large B-cell lymphoma with modified R-CHOP regimen: A case report.

Intravascular large B-cell lymphoma, known for its diverse organ involvement, presents significant diagnostic challenges, particularly when it affects the kidneys. This report highlights a rare case of primary renal intravascular large B-cell lymphoma in a 60-year-old male patient, who presented with persistent fever and renal dysfunction. The case underscores the intricacy of diagnosis and the efficacy of personalized treatment. Following the identification of primary renal intravascular large B-cell lymphoma, a modified R-CHOP regimen was administered, resulting in notable amelioration of symptoms and renal function following the initial treatment cycle. The patient achieved sustained complete remission without any complications after completing five subsequent R-CHOP cycles and two additional cycles of rituximab monotherapy, as confirmed by recent assessments. He is currently under regular follow-up for ongoing monitoring and improvement. This case adds to the limited yet expanding pool of knowledge concerning intravascular large B-cell lymphoma, emphasizing the necessity for personalized therapeutic strategies in atypical presentations. It also highlights the importance of early detection and customized intervention in managing rare lymphoma subtypes with unique organ involvement.

Spontaneous movement of a retrotransposon generated genic dominant male sterility providing a useful tool for rice breeding.

Male sterility in plants provides valuable breeding tools in germplasm innovation and hybrid crop production. However, genetic resources for dominant genic male sterility, which hold great promise to facilitate breeding processes, are extremely rare in natural germplasm. Here we characterized the Sanming Dominant Genic Male Sterility in rice and identified the gene SDGMS using a map-based cloning approach. We found that spontaneous movement of a 1978-bp long terminal repeat (LTR) retrotransposon into the promoter region of the SDGMS gene activates its expression in anther tapetum, which causes abnormal programmed cell death of tapetal cells resulting in dominant male sterility. SDGMS encodes a ribosome inactivating protein showing N-glycosidase activity. The activation of SDGMS triggers transcription reprogramming of genes responsive to biotic stress leading to a hypersensitive response which causes sterility. The results demonstrate that an ectopic gene activation by transposon movement can give birth to a novel trait which enriches phenotypic diversity with practical utility.

Dyslipidemia in diffuse large B-cell lymphoma based on the genetic subtypes: a single-center study of 259 Chinese patients.

Background: Diffuse large B-cell lymphoma (DLBCL) is a kind of highly heterogeneous non-Hodgkin lymphoma, both in clinical and genetic terms. DLBCL is admittedly categorized into six subtypes by genetics, which contain MCD, BN2, EZB, N1, ST2, and A53. Dyslipidemia is relevant to a multitude of solid tumors and has recently been reported to be associated with hematologic malignancies. We aim to present a retrospective study investigating dyslipidemia in DLBCL based on the molecular subtypes. Results: This study concluded that 259 patients with newly diagnosed DLBCL and their biopsy specimens were available for molecular typing. Results show that the incidence of dyslipidemia (87.0%, p <0.001) is higher in the EZB subtype than in others, especially hypertriglyceridemia (78.3%, p = 0.001) in the EZB subtype. Based on the pathological gene-sequencing, patients with BCL2 gene fusion mutation are significantly correlative with hyperlipidemia (76.5%, p = 0.006) and hypertriglyceridemia (88.2%, p = 0.002). Nevertheless, the occurrence of dyslipidemia has no remarkable influence on prognosis. Conclusion: In summary, dyslipidemia correlates with genetic heterogeneity in DLBCL without having a significant influence on survival. This research first connects lipids and genetic subtypes in DLBCL.

[Mapping of Sanming dominant genic male sterility gene in rice].

The mutant of "Sanming Dominant Genic Male Sterile Rice" was found from an F2 population of cross "SE2lS/Basmati370" by Sanming Institute of Agricultural Science in 2001. It has proven that the male sterility of this mutant is controlled by a dominant gene (named as SMS). By multiple backcrosses, this dominant male sterile allele was introduced into the genetic background of an indica rice cultivar Jiafuzhan (which was known as Jiabuyu). In order to map SMS, a mapping population was constructed by crossing Jiabuyu with a japonica cultivar Nipponbare and further crossing the F1 with Jiafuzhan. By bulked segregant analysis and linkage analysis using SSR and INDEL markers, SMS was mapped to a 99 kb interval between INDEL markers ZM30 and ZM9 on chromosome 8. This result will facilitate cloning of SMS.

A novel ferroptosis-related gene signature can predict prognosis and influence immune microenvironment in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a highly heterogeneous hematopoietic malignancy that strongly correlates with poor clinical outcomes. Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death which plays an important role in various human cancers. Nevertheless, the prognostic significance and functions of ferroptosis-related genes (FRGs) in AML have not received sufficient attention. The aim of this article was to evaluate the association between FRGs levels and AML prognosis using publicly available RNA-sequencing datasets. The univariate Cox regression analysis identified 20 FRGs that correlate with patient overall survival. The LASSO Cox regression model was used to construct a prognostic 12-gene risk model using a TCGA cohort, and internal and external validation proved the signature efficient. The 12-FRGs signature was then used to assign patients into high- and low-risk groups, with the former exhibiting markedly reduced overall survival, compared to the low-risk group. ROC curve analysis verified the predictive ability of the risk model. Functional analysis showed that immune status and drug sensitivity differed between the 2 risk groups. In summary, FRGs is a promising candidate biomarker and therapeutic target for AML.