Clinical manifestations, prognostic factors, and outcomes of adenovirus pneumonia after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Severe pneumonia is one of the most important causes of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adenovirus (ADV) is a significant cause of severe viral pneumonia after allo-HSCT, and we aimed to identify the clinical manifestations, prognostic factors, and outcomes of ADV pneumonia after allo-HSCT. METHODS: Twenty-nine patients who underwent allo-HSCT at the Peking University Institute of Hematology and who experienced ADV pneumonia after allo-HSCT were enrolled in this study. The Kaplan-Meier method was used to estimate the probability of overall survival (OS). Potential prognostic factors for 100-day OS after ADV pneumonia were evaluated through univariate and multivariate Cox regression analyses. RESULTS: The incidence rate of ADV pneumonia after allo-HSCT was approximately 0.71%. The median time from allo-HSCT to the occurrence of ADV pneumonia was 99 days (range 17-609 days). The most common clinical manifestations were fever (86.2%), cough (34.5%) and dyspnea (31.0%). The 100-day probabilities of ADV-related mortality and OS were 40.4% (95% CI 21.1%-59.7%) and 40.5% (95% CI 25.2%-64.9%), respectively. Patients with low-level ADV DNAemia had lower ADV-related mortality and better OS than did those with high-level (≥ 106 copies/ml in plasma) ADV DNAemia. According to the multivariate analysis, high-level ADV DNAemia was the only risk factor for intensive care unit admission, invasive mechanical ventilation, ADV-related mortality, and OS after ADV pneumonia. CONCLUSIONS: We first reported the prognostic factors and confirmed the poor outcomes of patients with ADV pneumonia after allo-HSCT. Patients with high-level ADV DNAemia should receive immediate and intensive therapy.

Activation of PPARδ in bone marrow endothelial progenitor cells improves their hematopoiesis-supporting ability after myelosuppressive injury.

Dysfunctional bone marrow (BM) endothelial progenitor cells (EPCs) with high levels of reactive oxygen species (ROS) are responsible for defective hematopoiesis in poor graft function (PGF) patients with acute leukemia or myelodysplastic neoplasms post-allotransplant. However, the underlying mechanism by which BM EPCs regulate their intracellular ROS levels and the capacity to support hematopoiesis have not been well clarified. Herein, we demonstrated decreased levels of peroxisome proliferator-activated receptor delta (PPARδ), a lipid-activated nuclear receptor, in BM EPCs of PGF patients compared with those with good graft function (GGF). In vitro assays further identified that PPARδ knockdown contributed to reduced and dysfunctional BM EPCs, characterized by the impaired ability to support hematopoiesis, which were restored by PPARδ overexpression. Moreover, GW501516, an agonist of PPARδ, repaired the damaged BM EPCs triggered by 5-fluorouracil (5FU) in vitro and in vivo. Clinically, activation of PPARδ by GW501516 benefited the damaged BM EPCs from PGF patients or acute leukemia patients in complete remission (CR) post-chemotherapy. Mechanistically, we found that increased expression of NADPH oxidases (NOXs), the main ROS-generating enzymes, may lead to elevated ROS level in BM EPCs, and insufficient PPARδ may trigger BM EPC damage via ROS/p53 pathway. Collectively, we found that defective PPARδ contributes to BM EPC dysfunction, whereas activation of PPARδ in BM EPCs improves their hematopoiesis-supporting ability after myelosuppressive therapy, which may provide a potential therapeutic target not only for patients with leukemia but also for those with other cancers.

Biochemical risk factors and outcomes of acute promyelocytic leukemia patients with thrombotic events: a matched pair analysis.

Acute promyelocytic leukemia (APL) stands out as a distinctive form of acute leukemia, exhibiting a higher occurrence of thrombotic events when contrasted with other leukemia subtypes. Since thrombosis is a relatively rare but unfavorable condition with poor prognostic implications, it is crucial to determine the risk factors for thrombotic events in APL(thrombosis in large venous or arterial from onset to differentiation therapy in 30d). We performed a retrospective study involving 950 APL patients between January 2000 and October 2022, from which 123 were excluded by younger than 16 years of age, 95 were excluded by incomplete data, and 6 were excluded by thrombosis related to CVC or PICC. A total of 23 APL patients with thrombosis for inclusion in our analysis were performed a 1:5 ratio matching based on sex (perfect match) and age (within 5 years) to patients without thrombosis. These patients were continuously monitored in the outpatient department over a period of 5 years. We meticulously examined clinical and laboratory data to pinpoint the risk factors related to thrombotic events in APL. Our primary clinical endpoints were all-cause mortality and achieving complete remission, while secondary clinical outcomes included APL relapse. Thrombotic events were observed in 2.4% (23/950) of APL patients. Compared to patients without thrombosis, patients with thrombosis had higher lactate dehydrogenase (LDH) [313 (223, 486) vs. 233 (188, 367) U/L, p = 0.020], higher indirect bilirubin [11.2 (7.4, 18.6) vs.8.3 (6.0, 10.7) umol/L, p = 0.004], higher creatinine [72 (62, 85) vs. 63 (54, 74) umol/L, p = 0.026], higher CD2 expression (65.2 vs. 15.2%, p < 0.001), higher CD15 expression (60.9 vs. 24.3%, p = 0.001), and PML/RARαisoforms (p < 0.001). Multivariate-logistic-regression analysis revealed several factors that were markedly related to thrombosis, including LDH (OR≈1.003, CIs≈1.000-1.006, p = 0.021), indirect bilirubin (OR≈1.084, CIs≈1.000-1.188, p = 0.043), CD2 expression positive (OR≈16.629, CIs≈4.001-62.832, p < 0.001), and CD15 expression positive (OR≈7.747, CIs≈2.005-29.941, p = 0.003). The S-type (OR≈0.012, CIs≈0.000-0.310, p = 0.008) and L-type (OR≈0.033, CIs≈0.002-0.609, p = 0.022) PML/RARα isoforms were negatively associated with thrombosis. Kaplan-Meier curves indicated that the survival rates were remarkably varied between APL patients with and without thrombosis (HR:21.34, p < 0.001). LDH and indirect bilirubin are variables significantly associated with thrombosis in APL, S-type and L-type PML/RARαisoforms exhibit a negative association with thrombotic events. The thrombotic events of APL can predict the subsequent survival of thrombosis. The findings of our study have the potential to facilitate early detection of thrombosis and enhance the prognosis for individuals with APL who develop thrombosis. Further validation of our findings will be essential through future prospective or multicenter studies.

Dissolved organic matter, calcium ion and extracellular polymeric substances on living associated bacteria of Microcystis colony are crucial for unicellular Microcystis to efficiently form colonies.

Microcystis typically forms colonies under natural conditions, which contributes to occurrence and prevalence of algal blooms. The colonies consist of Microcystis and associated bacteria (AB), embedded in extracellular polymeric substances (EPS). Previous studies indicate that AB can induce Microcystis to form colonies, however the efficiency is generally low and results in a uniform morphotype. In this study, by using filtrated natural water, several AB strains induced unicellular M. aeruginosa to form colonies resembling several Microcystis morphotypes. The mechanisms were investigated with Methylobacterium sp. Z5. Ca2+ was necessary for Z5 to induce Microcystis to form colonies, while dissolved organic matters (DOM) facilitated AB to agglomerate Microcystis to form large colonies. EPS of living Z5, mainly the aromatic protein components, played a key role in colony induction. Z5 initially aggregated Microcystis via the bridging effects of Ca2+ and DOM, followed by the induction of EPS synthesis and secretion in Microcystis. In this process, the colony forming mode shifted from cell adhesion to a combination of cell adhesion and cell division. Intriguingly, Z5 drove the genomic rearrangement of Microcystis by upregulating some transposase genes. This study unveiled a novel mechanism about Microcystis colony formation and identified a new driver of Microcystis genomic evolution.

Bioaccumulation, trophic transfer and risk assessment of polycyclic musk in marine food webs of the Bohai Sea.

Galaxolide (HHCB) and tonalide (AHTN) are dominant musks added to personal care products. However, the accumulate and trophic transfer of SMs through the marine food chain are unclear. In this study, organisms were collected from three bays in Bohai Sea to investigate the bioaccumulation, trophic transfer, and health risk of SMs. The HHCB and AHTN concentrations in the muscles range from 2.75 to 365.40 µg/g lw and 1.04-4.94 µg/g lw, respectively. The median HHCB concentrations in muscles were the highest in Bohai Bay, followed by Laizhou Bay and Liaodong Bay, consistent with the HHCB concentrations in sediments. The different fish tissues from Bohai Bay were analyzed, and the HHCB and AHTN concentrations followed the heart > liver > gill > muscles. The trophic magnification factors (TMF) were lower than 1 and the health risk assessment showed no adverse health effects. The results provide insights into the bioaccumulation and trophic transfer behavior of SMs in marine environments.

Surface-active agent enhanced FRET effect Cu-doped NH2-MIL-88(Fe) for highly sensitive detection of 3-nitro-L-tyrosine.

In this study, Cu-doped NH2-MIL-88(Fe) metal-organic frameworks (MOF) were synthesized via a one-step method. Characterization techniques such as XPS, XRD and FTIR confirmed the successful incorporation of Cu2+ into NH2-MIL-88(Fe), naming this MOF as NH2-MIL-88(Fe)@Cu2+. This MOF was employed to develop a highly sensitive fluorescence sensing platform for detecting 3-nitro-L-tyrosine(3-NT). The potential for fluorescence resonance energy transfer (FRET) was suggested by the spectral overlap between NH2-MIL-88(Fe)@Cu2+'s emission and 3-NT's UV absorption. To augment this effect, cationic surfactant hexadecyltrimethylammonium bromide (CTAB), which self-assembled into nanostructured microspheres above its critical micelle concentration, was utilized. The charged surface of these microspheres, formed by the self-assembly of CTAB, is bound to the MOF surface through electrostatic force and simultaneously attracts 3-NT. Adjusting the solution's pH strengthened the interaction between NH2-MIL-88(Fe)@Cu2+ and 3-NT, thereby enhancing their mutual FRET interaction. Experimental results indicated that CTAB's introduction markedly improved the FRET effects, potentially converting a weak FRET into a strong one and enhancing detection sensitivity and accuracy. Under optimal conditions, NH2-MIL-88(Fe)@Cu2+ detected 3-NT within 0-30 µM range, with a limit of detection (LOD, S/N = 3) of 41.1 nM. Finally, the applicability of the sensor is tested by calibrating measurements in fetal bovine serum samples, achieving good performance in terms of sensitivity, selectivity and reproducibility. This research provides a method for efficient and highly sensitive 3-NT detection and insights into the FRET effect between MOF and target molecules, likely advancing related fields and inspiring future fluorescence sensor designs.

Enhanced bovine genome annotation through integration of transcriptomics and epi-transcriptomics datasets facilitates genomic biology.

BACKGROUND: The accurate identification of the functional elements in the bovine genome is a fundamental requirement for high-quality analysis of data informing both genome biology and genomic selection. Functional annotation of the bovine genome was performed to identify a more complete catalog of transcript isoforms across bovine tissues. RESULTS: A total of 160,820 unique transcripts (50% protein coding) representing 34,882 unique genes (60% protein coding) were identified across tissues. Among them, 118,563 transcripts (73% of the total) were structurally validated by independent datasets (PacBio isoform sequencing data, Oxford Nanopore Technologies sequencing data, de novo assembled transcripts from RNA sequencing data) and comparison with Ensembl and NCBI gene sets. In addition, all transcripts were supported by extensive data from different technologies such as whole transcriptome termini site sequencing, RNA Annotation and Mapping of Promoters for the Analysis of Gene Expression, chromatin immunoprecipitation sequencing, and assay for transposase-accessible chromatin using sequencing. A large proportion of identified transcripts (69%) were unannotated, of which 86% were produced by annotated genes and 14% by unannotated genes. A median of two 5' untranslated regions were expressed per gene. Around 50% of protein-coding genes in each tissue were bifunctional and transcribed both coding and noncoding isoforms. Furthermore, we identified 3,744 genes that functioned as noncoding genes in fetal tissues but as protein-coding genes in adult tissues. Our new bovine genome annotation extended more than 11,000 annotated gene borders compared to Ensembl or NCBI annotations. The resulting bovine transcriptome was integrated with publicly available quantitative trait loci data to study tissue-tissue interconnection involved in different traits and construct the first bovine trait similarity network. CONCLUSIONS: These validated results show significant improvement over current bovine genome annotations.

CAR-T Therapy Followed by Hematopoietic Stem Cell Transplantation Can Improve Survival in Children Relapsed/Refractory Philadelphia Chromosome-positive B-cell Acute Lymphoblastic Leukemia.

BACKGROUND: Philadelphia chromosome (Ph)-positive B-cell acute lymphoblastic leukemia (ALL) has a high complete remission (CR) rate, but relapse and prolonged measurable residual disease remain serious problems. We sought to describe the CR rate measurable residual disease negative rate and address the results and safety of pediatric patients who underwent after receiving chimeric antigen receptor (CAR) specific for CD19 (CAR-19) followed by hematopoietic stem cell transplantation (HSCT) for the treatment of Ph-positive ALL. METHODS: A descriptive study was conducted at Peking University People's Hospital from September 2013 to January 2021. 13 patients with relapsed/refractory Ph-positive B-ALL who received CAR-T therapy followed by allo-HSCT were included. We concentrated on the overall patient survival and CR rate. RESULTS: The median time between CAR-T therapy and allo-HSCT was 58 days. Among all the patients, the CR rate was 100%, the flow cytometry negativity rate was 84.62%, and the BCR-ABL negativity rate was 53.85% at 1 month after CAR-T infusion. All the patients achieved a major molecular response in 6 months after HSCT. After a median follow-up of 45 months, the 3-year OS rate was 66.7%, and the 3-year DFS rate was 61.5%. The 3-year OS rate of patients with BCR-ABL-positive pre-HSCT was significantly lower than that in the BCR-ABL-negative group (40.0% vs. 85.7%, P=0.042). Also, the same trend was observed for the 3-year DFS rate but did not differ significantly (40.0% vs. 75.0%, P=0.233). CONCLUSIONS: CAR-T therapy followed by allo-HSCT can be a safe and effective treatment for Ph-positive B-ALL pediatric patients.

High dimensional proteomic mapping of bone marrow immune characteristics in immune thrombocytopenia.

To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia (ITP), this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight (CyTOF). Thirty-six patients with ITP and nine healthy volunteers were enrolled in the study. As soluble immunomodulatory molecules, more sCD25 and sGalectin-9 were detected in ITP patients. On the cell surface, co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T cells. In contrast, co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell subsets. Taking a platelet count of 30×109 L-1 as the cutoff value, ITP patients with high and low platelet counts showed different T cell immune profiles. Antigen-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions, respectively, and participate in the pathogenesis of ITP. In conclusion, the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of ITP. They may offer novel targets to develop personalized immunotherapies.

[Genetic background of lily germplasm resources based on SSR markers].

To study the genetic background of lily (Lilium spp.) germplasm resources, and accurately evaluate and select excellent germplasm for genetic improvement of lily, we analyzed the genetic background of 62 lily germplasm accessions from 11 provinces of China by using simple sequence repeat (SSR) molecular markers. The results showed that 15 out of 83 pairs of lily SSR primers were polymorphic. A total of 157 allelic loci were amplified, with the number of alleles per locus ranging from 5 to 19 and the average number of effective alleles per locus being 4.162 8. The average observed heterozygosity and expected heterozygosity were 0.228 2 and 0.694 1, respectively. The average polymorphic information content was 0.678 8. The average Nei's diversity index and Shannon's information index were 0.694 1 and 1.594 9, respectively, indicating that the tested lily germplasm had high genetic diversity. The 62 germplasm accessions were classified into 5 groups by the unweighted pair group method with arithmetic mean (UPGMA) and into 3 groups by the principal component analysis. The two analyses revealed a geographic correlation among different groups. The majority of lily germplasm accessions from the same source tended to cluster together. The population structure analysis classified the lily accessions into 4 populations and 1 mixed population. The above results provide a theoretical basis and genetic resources for the precise identification and breeding of lily germplasm resources.

Evaluating the Clinical Utility of Semi-Quantitative Luciferase Immunosorbent Assay Using Treponema pallidum Antigens in Syphilis Diagnosis and Treatment Monitoring.

OBJECTIVE: To assess the clinical applicability of a semi-quantitative luciferase immunosorbent assay (LISA) for detecting antibodies against Treponema pallidum antigens TP0171 (TP15), TP0435 (TP17), and TP0574 (TP47) in diagnosing and monitoring syphilis. METHOD: LISA for detection of anti-TP15, TP17, and TP47 antibodies was developed and evaluated for syphilis diagnosis using 261 serum samples (161 syphilis, 100 non-syphilis). 90 serial serum samples from six syphilis rabbit models (three treated, three untreated) and 110 paired serum samples from 55 syphilis patients were used to assess treatment effects by utilizing TRUST as reference. RESULTS: Compared to TPPA, LISA-TP15, LISA-TP17, and LISA-TP47 showed sensitivity of 91.9%, 96.9%, and 98.8%, specificity of 99%, 99%, and 98%, and AUC of 0.971, 0.992, and 0.995, respectively, in diagnosing syphilis. Strong correlations (rs = 0.89-0.93) with TPPA were observed. In serial serum samples from rabbit models, significant difference in the relative light unit (RLU) were observed between the treatment and control group for LISA-TP17 (days 31-51) and LISA-TP47 (days 41). In paired serum samples form syphilis patients, TRUST titers and the RLU of LISA-TP15, LISA-TP17, and LISA-TP47 decreased post treatment (P < 0.001). When TRUST titers decreased by 0, 2, 4, or ≥8-folds, the RLU decreased by 17.53%, 31.34%, 48.62%, and 72.79% for LISA-TP15; 8.84%, 17.00%, 28.37%, and 50.57% for LISA-TP17; 22.25%, 29.79%, 51.75%, and 70.28% for LISA-TP47, respectively. CONCLUSION: Semi-quantitative LISA performs well for syphilis diagnosis while LISA-TP17 is more effective for monitoring syphilis treatment in rabbit models and clinical patients.

Coherent beam combining of femtosecond third-harmonic generators: towards high-power, high-beam-quality UV light generation.

Coherent beam combining (CBC) of two femtosecond third-harmonic (TH) generators is proposed and demonstrated. By applying phase modulation to one of the fundamental laser pulses, the feedback loop effectively eliminates both phase and pointing errors between the two TH femtosecond laser beams. The system delivers 345-nm femtosecond laser pulses with 22-W average power at 1-MHz repetition rate. The average combining efficiency is 91.5% over approximately 1 h of testing. The beam quality of the combined ultraviolet (UV) laser beam is near-diffraction-limited with M2 factors of M X2=1.36, M Y2=1.24, which are similar to those of the individual channels. This scheme exhibits promising potential for increasing high-beam-quality UV laser power.

The impact of low-velocity shock waves on the dynamic behaviour characteristics of nanobubbles.

Low-velocity shock wave-induced contraction and expansion of nanobubbles can be applied to biocarriers and microfluidic systems. Although experiments have been conducted to study the application effects, the dynamic behavior characteristics of nanobubbles remain unexplored. In this work, we utilize molecular dynamics (MD) simulations to investigate the dynamic behavior characteristics of nanobubbles influenced by low-velocity shock waves in a liquid argon system. The DBSCAN (Density-Based Spatial Clustering of Applications with Noise) machine learning method is used to calculate the equivalent radius of nanobubbles. Two statistical methods are then utilized to predict the time series changes in the equivalent radius of nanobubbles without rebound shock waves. The piston velocity is analyzed using the bisection method to obtain the critical impact states of the nanobubble. The results show that at the low velocity shock wave (piston velocity of 0.1 km s-1), the shock wave pressure is small, the non-vacuum nanobubbles contract and expand in a circular shape, and the gas particles inside the bubble are not dispersed. In contrast, the vacuum nanobubbles collapse directly. As the shock wave rebounds upon impact, it triggers periodic contraction and expansion of the nanobubbles. The predictions indicate that the equivalent radius will vary within a small range according to the pre-predicted values in the absence of the rebound shock wave. Nanobubbles are present in four critical impact states: dispersed gaps, multiple smaller bubbles, two split bubbles, and a concave bubble.

Salvage haploidentical transplantation for graft failure after first haploidentical allogeneic stem cell transplantation: an updated experience.

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. However, there are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). Herein, we report updated outcomes in 30 patients using this method. The median time of the second transplantation was 96.5 (33-215) days after the first transplantation. Except for one patient who died at +19d and before engraftment, neutrophil engraftments were achieved in all patients at 11 (8-24) days, while platelet engraftments were achieved in 22 (75.8%) patients at 17.5 (9-140) days. The 1-year OS and DFS were 60% and 53.3%, and CIR and TRM was 6.7% and 33.3%, respectively. Compared with the historical group, neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were better in the novel regimen group, and OS was also improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using the novel regimen represents a promising option to rescue patients with graft failure after the first haploidentical transplantation.

A simple mitochondria-immobilized fluorescent probe for the detection of hydrogen peroxide.

Hydrogen peroxide (H2O2), as one of reactive oxygen species (ROS) widely present in the human body, is involved in a variety of physiological activities. Many human diseases are associated with abnormal levels of H2O2 in the body. Mitochondria are the main organelles producing H2O2 in the human body, and monitoring the level of H2O2 in mitochondria can help to deepen the understanding of the detailed functions of H2O2 in physiological activities. However, due to the highly dynamic nature of the cells, real-time quantitative monitoring of H2O2 levels in mitochondria remains an ongoing challenge. Herein, a novel highly immobilized mitochondria-targeting fluorescent probe (QHCl) for detection of H2O2 was reasonably constructed based on quinolinium dye containing benzyl chloride moiety. Spectral experimental results demonstrated QHCl possessed outstanding selectivity toward H2O2 (λex/em = 380/513 nm). In addition, QHCl can quantitatively detect H2O2 in the concentration range of 0-20 µM with excellent sensitivity (LOD = 0.58 µM) under the PBS buffer solution (10 mM, pH = 7.4). Finally, bioimaging experiments demonstrated that the probe QHCl was able to be used for accurately detecting both endogenous and exogenous H2O2 in the mitochondria of living cells and zebrafish by its unique mitochondrial immobilization.

Characterization of the Dynamic Behavior of Multinanobubble System under Shock Wave Influence.

Shockwave-induced changes in nanobubbles cause cavitation erosion and membrane damage but can also be applied to biocarrier transport. Currently, research focuses on single nanobubbles; however, in reality, nanobubbles usually appear as a multibubble system. Therefore, this study proposes a method based on cutting and replicating to construct a multibubble model. This method can be widely applied to molecular dynamics (MD) models and enhance the customization capabilities of MD models. The dynamic behavior of a multinanobubble system with different numbers and arrangements of nanobubbles is investigated with the MD method under the influence of shock waves in a liquid argon system. The study also explores the range of influence between nanobubbles. The results show that in the case of two nanobubbles, when the distance between the bubbles is constant, the smaller the angle between the direction of the shock wave and the line connecting the bubbles, the greater is the influence between nanobubbles, and the moment of collapse of the nanobubbles farther away from the shock wave is slower. When three nanobubbles are arranged with a right offset, after the first bubble collapses, the effect on the other two bubbles is similar to the changes in bubbles when the angle of arrangement is 30° or 60°. Under a different arrangement, the change of shock wave velocity on the nanobubble size only affects its collapse time and contraction collapse rate. When the shock wave with a radian of about 2.87 or greater than 2.87 touches the bubbles, the collapse of the second nanobubble will not be affected.

Study on the Melt Rheological Characterization of Micro-Tube Gas-Assisted Extrusion Based on the Cross-Scale Viscoelastic Model.

In the micro-tube gas-assisted extrusion process, flow theories ignoring cross-scale viscoelastic variations fail to effectively characterize the rheological state of the melt. To investigate the impact of cross-scale viscoelastic variation on the quality of the micro-tube gas-assisted extrusion, a 3D multiphase flow extrusion model incorporating a double gas-assisted layer was developed. Subsequently, we modified the DCPP constitutive equations based on the cross-scale factor model. Both the traditional and gas-assisted extrusions were simulated under macroscale and cross-scale models using the Ansys Polyflow. Finally, using the established gas-assisted extrusion platform, extrusion experiments were conducted. The results indicate that, owing to the reduced melt viscosity under the cross-scale model, the deformation behavior of the melt is more pronounced than in the macroscale model. The cross-scale model's numerical results more closely match the experimental outcomes under the same parameters, thereby confirming the feasibility of the theoretical analysis and numerical simulation. Moreover, the predictive capability of the cross-scale model for the micro-tube gas-assisted extrusion is further validated through numerical and experimental analyses with varying parameters. It is demonstrated that the cross-scale viscoelastic variation is a critical factor that cannot be overlooked in the gas-assisted extrusion.

Deep-learning-based image super-resolution of an end-expandable optical fiber probe for application in esophageal cancer diagnostics.

Significance: Endoscopic screening for esophageal cancer (EC) may enable early cancer diagnosis and treatment. While optical microendoscopic technology has shown promise in improving specificity, the limited field of view (<1 mm) significantly reduces the ability to survey large areas efficiently in EC screening. Aim: To improve the efficiency of endoscopic screening, we propose a novel concept of end-expandable endoscopic optical fiber probe for larger field of visualization and for the first time evaluate a deep-learning-based image super-resolution (DL-SR) method to overcome the issue of limited sampling capability. Approach: To demonstrate feasibility of the end-expandable optical fiber probe, DL-SR was applied on simulated low-resolution microendoscopic images to generate super-resolved (SR) ones. Varying the degradation model of image data acquisition, we identified the optimal parameters for optical fiber probe prototyping. The proposed screening method was validated with a human pathology reading study. Results: For various degradation parameters considered, the DL-SR method demonstrated different levels of improvement of traditional measures of image quality. The endoscopists' interpretations of the SR images were comparable to those performed on the high-resolution ones. Conclusions: This work suggests avenues for development of DL-SR-enabled sparse image reconstruction to improve high-yield EC screening and similar clinical applications.

Haploidentical hematopoietic stem cell transplantation with busulfan, cyclophosphamide, and fludarabine conditioning for X-linked adrenal cerebral leukodystrophy.

OBJECTIVE: We investigated the safety and efficacy of haploidentical stem cell transplantation (SCT) in pediatric patients with X-linked adrenoleukodystrophy (ALD). METHODS: A retrospective analysis of transplantation data from 29 cases of ALD, treated between December 2014 and April 2022, was conducted. Neurologic function scores (NFS) were assessed. The conditioning regimen was busulfan 9.6 mg/kg, cyclophosphamide 200 mg/kg, and fludarabine 90 mg/m2 (BFC). Graft-versus-host disease prophylaxis consisted of anti-human thymocyte globulin, cyclosporine A, mycophenolate mofetil, and short course of methotrexate. RESULTS: Among the 29 cases, 14 cases (NFS = 0) were asymptomatic, and 15 (NFS ≥ 1) were symptomatic. The median age at SCT was 8 years (range: 4-16 years); the median follow-up time was 1058 days (range: 398-3092 days); 28 cases were father donors and 1 case was a grandfather donor. Hematopoietic reconstitution was successful in all patients, and all of them achieved complete donor chimerism at the time of engraftment. The leading cause of death was still primary disease progression (n = 4). Survival free of major functional disabilities was 100% in asymptomatic patients versus 66.67% in the symptomatic group (p = .018). CONCLUSION: BFC regimen used in haploidentical SCT was administered safely without major transplant-related complications even in symptomatic patients, and neurological symptoms were stabilized after SCT.