Efficacy and Safety of Children With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia After Anti-CD19 CAR T-Cell Therapy Without Bridging Transplantation.

BACKGROUND: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapies have demonstrated significant efficacy in achieving complete remission (CR) in pediatric patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). However, a considerable number of patients experience relapse within 1 year after CAR T-cell therapy, leading to an extremely poor prognosis, particularly in patients without bridging transplantation. MATERIALS AND METHODS: In our study, we investigated 42 children with R/R B-ALL who underwent anti-CD19 CAR T-cell therapy without bridging transplantation at our center. All patients were included in the response analysis and evaluated for survival and toxicity. RESULTS: The cohort that received the CAR T-cell infusion exhibited a 100% CR rate by day 28 (d28). The overall survival (OS) at 4 years was 61.3% ± 8.5%, and the event-free survival (EFS) was 55.9% ± 7.9%, with a median follow-up duration of 50.1 months. Minimal residual disease (MRD) ≥1% was associated with inferior outcomes, resulting in lower 4-year OS (P = .033) and EFS (P = .014) compared to MRD<1%. The incidences of grade ≥3 cytokine release syndrome (CRS) and neurotoxicity were 26.8% and 23.8%, respectively. Furthermore, MRD≥1% was identified as an independent factor associated with increased severity of CRS and occurrence of neurotoxicity. CONCLUSION: These findings suggest that reducing the pre-infusion MRD could serve as an effective treatment strategy to enhance the outcomes of CAR T-cell therapy.

CD19-specific CAR-T Cell Treatment of 115 Children and Young Adults with Acute B Lymphoblastic Leukemia: Long-Term Follow-up.

Purpose: Chemotherapy has been the primary treatment for patients with B-cell acute lymphoblastic leukemia (B-ALL). However, there are still patients who are not sensitive to chemotherapy, including those with refractory/relapse (R/R) disease and those experiencing minimal residual disease (MRD) re-emergence. Chimeric antigen receptor-T lymphocytes (CAR-T) therapy may provide a new treatment option for these patients. Materials and Methods: Oure institution conducted a single-arm prospective clinical trial (ChiCTR-OPN-17013507) using CAR-T-19 to treat R/R B-ALL and MRD re-emergent patients. One hundred and fifteen patients, aged 1-25 years (median age 8 years), were enrolled, including 67 R/R and 48 MRD re-emergent CD19-positive B-ALL patients. Results: All patients achieved morphologic CR, and within one month after infusion, 111 out of 115 (96.5%) patients achieved MRD-negative CR. With a median follow-up time of 48.4 months, the estimated 4-year leukemia-free survival (LFS) rate and overall survival (OS) rate were (68.7±4.5) % and (70.7±4.3) %, respectively. There were no significant differences in long-term efficacy observed among patients with different disease statuses before infusion (4-year OS: MRD re-emergence vs. R/R B-ALL, 70.6±6.6% vs. 66.5±6.1%, p=0.755; 4-year LFS: MRD re-emergence vs. R/R B-ALL, 67.3±7.0% vs. 63.8±6.2%, p=0.704). R/R B-ALL patients bridging to transplantation after CAR-T treatment had a superior OS and LFS compared to those who did not. However, for MRD re-emergent patients, there was no significant difference in OS and LFS, regardless of whether they underwent HSCT or not. Conclusion: CD19 CAR-T therapy effectively and safely cures both R/R B-ALL and MRD re-emergent patients.

Efficient production of xylooligosaccharides from Camellia oleifera shells pretreated by pyruvic acid at lower temperature.

XOS production from lignocellulose using organic carboxylic acids and alkyd acids has been widely reported. However, it still faces harsh challenges such as high energy consumption, high cost, and low purity. Pyruvic acid (PYA), a carbonyl acid with carbonyl and carboxyl groups, was used to produce XOS due to its stronger catalytic activity. In this work, XOS was efficiently prepared from COS in an autoclave under the condition of 0.21 M PYA-121 °C-35 min. The total yield of XOS reached 68.72 % without producing any toxic by-products, including furfural (FF) and 5-hydroxymethylfurfural (5-HMF). The yield of xylobiose (X2), xylotriose (X3), xylotetraose (X4), and xylopentaose (X5) were 20.58 %, 12.47 %, 15.74 %, and 10.05 %, respectively. Meanwhile, 89.05 % of lignin was retained in the solid residue, which provides a crucial functional group for synthesizing layered carbon materials (SRG-a). It achieves excellent electromagnetic shielding (EMS) performance through graphitization, reaching -30 dB at a thickness of 2.0 mm. The use of a PYA catalyst in the production of XOS has proven to be an efficient method due to lower temperature, lower acid consumption, and straightforward operation.

[Clinical Significance of Minimal Residual Disease in Pediatric Patients with TCF3/PBX1+ B-cell Acute Lymphoblastic Leukemia].

OBJECTIVE: To explore the consistency of flow cytometry (FCM) method and polymerase chain reaction (PCR) technique in the detection of minimal residual disease (MRD) at different treatment stages in pediatric patients with TCF3/PBX1+ B-cell acute lymphoblastic leukemia (B-ALL) and the correlations between the detection results and prognosis. METHODS: The clinical data of 64 newly diagnosed pediatric patients with TCF3/PBX1+ B-ALL admitted to the Department of Pediatrics of Peking University People's Hospital from January 2005 to December 2017 were retrospectively analyzed. FCM and PCR methods were used to monitor the MRD level in bone marrow samples from 64 children during the same period of treatment on d33 and d90 respectively, and the detection results were analyzed. RESULTS: There were 37 males and 27 females in the 64 patients, with a median age of 8 years(range 0.8 to 16 years). The complete remission (CR) rate after the first cycle of induction chemotherapy was 98.4% (62/63), with overall CR rate of 100%. 12 patients experienced recurrence, with a median recurrence time of 16.9 (5.3-46.3) months. The median follow-up time of the 64 patients was 77.2 (1.0-184.8) months , and the 5-year overall survival (OS) rate and event-free survival (EFS) rate were 82.8%±4.7% and 75.0%±5.4%, respectively. On d90, the concordance rate of the MRD results from the two methods was 98.4%, and the related kappa value was 0.792 (P < 0.001), which were significantly higher than those on d33. After induction chemotherapy (d33), the 5-year EFS rate of MRD-FCM- group (79.3%±5.3%) was significantly better than that of MRD-FCM+ group (40.0%±21.9%) (P =0.028), there were no significant differences in the 5-year OS rate and EFS rate between MRD-PCR+ group and MRD-PCR- group, and the 5-year EFS rate of MRD-FCM-/PCR- group (85.4%±5.5%) was significantly better than that of MRD-FCM+/PCR+ group (40.0 %±21.9%) (P =0.026). CONCLUSION: In children with TCF3/PBX1+ B-ALL, the MRD results detected by FCM and PCR methods show good consistency, especially in consolidation therapy period (d90). The MRD level at the end of induction therapy (d33) is an important factor affecting the long-term prognosis, especially the MRD results detected by FCM method, which is significantly associated with prognosis.

Analysis of the benefit of gonadotropin-releasing hormone agonist treatment in premenopausal women undergoing hematopoietic cell transplantation.

Gonadotropin-releasing hormone agonist (GnRHa) appears to exhibit ovarian protection during chemotherapy for malignant tumors. The purpose of this study was to analyze the benefits of GnRHa in premenopausal women undergoing hematopoietic cell transplantation (HSCT). Candidates for myeloablative chemotherapy HSCT requiring fertility preservation in the Gynecological Endocrinology Clinic of Peking University People's Hospital from December 2011 to December 2021 were retrospectively analyzed. Patients who chose to receive GnRHa treatment were given at least 2 courses of a 3.75-mg dose of a GnRHa before myeloablative chemotherapy, and patients who chose not to receive GnRHa treatment were included in the control group. All patients were monitored for menstruation return and menopause-related symptoms, and ovarian function tests [follicle-stimulating hormone (FSH), luteinizing hormone, and estradiol] were performed 6-12 months after HSCT. In addition, we assessed the vaginal bleeding of patients in the laminar air-flow room (LAFR). A total of 234 cases were included in this study: 77 cases in the treatment group and 157 cases in the control group. The incidence of vaginal bleeding in the LAFR in the treatment group was significantly lower than that in the control group (24.68% vs. 79.62%, P < 0.001). The menopausal symptoms of the patients in the treatment group were reduced after transplantation (46.75% vs. 19.75%, P < 0.001). There was no difference in visible follicles by follow-up ultrasound in the two groups after HSCT (16.88% vs. 13.38%, P = 0.474). The level of FSH at 6-12 months after transplantation was lower (98.00 mIU/ml vs. 117.53 mIU/ml, P = 0.001). The proportion of patients with FSH < 40 mIU/ml did not differ between the two groups. One patient in the treatment group recovered spontaneous menstruation, while none recovered spontaneous menstruation in the control group (1.30% vs. 0%, P = 0.329). The use of GnRHa may relieve menopause-related symptoms and reduce vaginal bleeding in the LAFR and breakthrough bleeding after transplantation. GnRHa treatment can reduce the level of FSH after myeloablative chemotherapy, but it cannot reduce the incidence of premature ovarian failure in women of reproductive age following myeloablative HSCT.

Oligodendrocyte Progenitor Cell Transplantation Ameliorates Preterm Infant Cerebral White Matter Injury in Rats Model.

Background: Cerebral white matter injury (WMI) is the most common brain injury in preterm infants, leading to motor and developmental deficits often accompanied by cognitive impairment. However, there is no effective treatment. One promising approach for treating preterm WMI is cell replacement therapy, in which lost cells can be replaced by exogenous oligodendrocyte progenitor cells (OPCs). Methods: This study developed a method to differentiate human neural stem cells (hNSCs) into human OPCs (hOPCs). The preterm WMI animal model was established in rats on postnatal day 3, and OLIG2+/NG2+/PDGFRα+/O4+ hOPCs were enriched and transplanted into the corpus callosum on postnatal day 10. Then, histological analysis and electron microscopy were used to detect lesion structure; behavioral assays were performed to detect cognitive function. Results: Transplanted hOPCs survived and migrated throughout the major white matter tracts. Morphological differentiation of transplanted hOPCs was observed. Histological analysis revealed structural repair of lesioned areas. Re-myelination of the axons in the corpus callosum was confirmed by electron microscopy. The Morris water maze test revealed cognitive function recovery. Conclusion: Our study showed that exogenous hOPCs could differentiate into CC1+ OLS in the brain of WMI rats, improving their cognitive functions.

Identification of apoptosis-related key genes and the associated regulation mechanism in thoracic aortic aneurysm.

BACKGROUND: This study investigated the role of apoptosis-related genes in thoracic aortic aneurysms (TAA) and provided more insights into TAA's pathogenesis and molecular mechanisms. MATERIAL/METHODS: Two gene expression datasets (GSE9106 and GSE26155) were retrieved from the Gene Expression Omnibus (GEO) database. Apoptosis-related genes were obtained from the KEGG apoptosis pathway (hsa04210). Differentially expressed apoptosis-related genes were identified by performing differential expression analysis using limma for TAA blood and tissue samples. GO and KEGG enrichment analysis of the differentially expressed apoptosis genes was performed using the Metascape web tool. The miRNA-mRNA regulatory network was reconstructed using the ENCORI and miRDB databases, and functional enrichment analysis was performed on the related miRNAs using the miEAA tool. The correlation between the expression levels of differentially expressed apoptosis-related genes and genes involved in immune infiltration in TAA was calculated using the CIBERSORT algorithm. The apoptosis modification patterns mediated by differentially expressed apoptosis-related genes were systematically assessed in TAA samples. RESULTS: A total of 9 differentially-expressed apoptosis-related genes were identified in TAA samples compared with normal samples. 150 miRNAs and 6 mRNAs regulatory networks were reconstructed using the ENCORI and miRDB databases. Immune infiltration analysis revealed that the GZMB had the strongest positive correlation with activated NK cells and the DFFA presented the strongest positive correlation with T cells follicular helper. 3 distinct apoptosis modification patterns mediated by 9 differentially-expressed apoptosis-related genes were identified. They differ in immune characteristics and drug sensitivity, and their biological functions in these subtypes were further studied. CONCLUSIONS: This study identified key apoptosis-related genes related to TAA and evaluated the modification patterns of key apoptosis genes in TAA, providing insights into potential targets and mechanisms of TAA pathogenesis and progression.

Homoharringtonine-Based Induction Regimen Improved the Remission Rate and Survival Rate in Chinese Childhood AML: A Report From the CCLG-AML 2015 Protocol Study.

PURPOSE: Homoharringtonine (HHT) is commonly used for the treatment of Chinese adult AML, and all-trans retinoic acid (ATRA) has been verified in acute promyelocytic leukemia (APL). However, the efficacy and safety of HHT-based induction therapy have not been confirmed for childhood AML, and ATRA-based treatment has not been evaluated among patients with non-APL AML. PATIENTS AND METHODS: This open-label, multicenter, randomized Chinese Children's Leukemia Group-AML 2015 study was performed across 35 centers in China. Patients with newly diagnosed childhood AML were first randomly assigned to receive an HHT-based (H arm) or etoposide-based (E arm) induction regimen and then randomly allocated to receive cytarabine-based (AC arm) or ATRA-based (AT arm) maintenance therapy. The primary end points were the complete remission (CR) rate after induction therapy, and the secondary end points were the overall survival (OS) and event-free survival (EFS) at 3 years. RESULTS: We enrolled 1,258 patients, of whom 1,253 were included in the intent-to-treat analysis. The overall CR rate was significantly higher in the H arm than in the E arm (79.9% v 73.9%, P = .014). According to the intention-to-treat analysis, the 3-year OS was 69.2% (95% CI, 65.1 to 72.9) in the H arm and 62.8% (95% CI, 58.7 to 66.6) in the E arm (P = .025); the 3-year EFS was 61.1% (95% CI, 56.8 to 65.0) in the H arm and 53.4% (95% CI, 49.2 to 57.3) in the E arm (P = .022). Among the per-protocol population, who received maintenance therapy, the 3-year EFS did not differ significantly across the four arms (H + AT arm: 70.7%, 95% CI, 61.1 to 78.3; H + AC arm: 74.8%, 95% CI, 67.0 to 81.0, P = .933; E + AC arm: 72.9%, 95% CI, 65.1 to 79.2, P = .789; E + AT arm: 66.2%, 95% CI, 56.8 to 74.0, P = .336). CONCLUSION: HHT is an alternative combination regimen for childhood AML. The effects of ATRA-based maintenance are comparable with those of cytarabine-based maintenance therapy.

Efficient co-production of xylo-oligosaccharides and fermentable sugars from sugarcane bagasse by glutamic acid pretreatment.

In the production of xylo-oligosaccharides (XOS) by organic acid pretreatment, it is often difficult to isolate organic acids from XOS. Here, an acidic amino acid, glutamic acid (GA), was used to pretreat sugarcane bagasse (SCB) to prepare XOS and fermentable sugars. The effects of GA concentration, hydrolysis temperature, and pretreatment time on the yield and polymerization distribution of XOS were investigated. After hydrolysis by 0.2 M GA at 140 °C for 30 min, the maximum yield of X2-5 was 53.3%, and the concentrations of xylose and furfural were 1.8 g/L and 0.1 g/L, respectively. Meanwhile, GA increased the pore size and porosity of SCB as well as the number of functional groups of amino acid residues, which improved the enzymatic efficiency and the maximum yield of glucose was 95.3%. Thus, GA pretreatment provides a more economical, environmentally friendly and sustainable method for the co-production of XOS and glucose from SCB.

Coproduction of xylooligosaccharides, glucose, and less-condensed lignin from sugarcane bagasse using syringic acid pretreatment.

Current strategies for the production of xylooligosaccharides (XOS) from biomass through non-enzymatic catalysis often led to a certain degree of lignin condensation, which severely restrains subsequent enzyme hydrolysis of cellulose. Herein, syringic acid (SA) pretreatment was investigated to coproduce XOS, glucose, and less-condensed lignin from sugarcane bagasse. SA acted as a catalyst and lignin condensation inhibitor during the pretreatment. The highest XOS yield of 58.7% (27.7% xylobiose and 24.7% xylotriose) was obtained at 180 °C - 20 min - 9% SA, and the corresponding xylose/XOS ratio was only 0.42. Compared with the pretreatment at 180 °C - 20 min - 0% SA, the addition of 9% SA increased the glucose yield from 85.7% to 92.4% and decreased the degree of lignin condensation from 0.55 to 0.42. Moreover, 26.7% of SA could be easily recovered. This work presents a pretreatment strategy in which the efficient production of XOS and the suppression of lignin condensation are achieved simultaneously.

Diagnostic Value and Prognosis Significance of Cerebrospinal Fluid Examination by Flow Cytometry in Pediatric Acute Lymphoblastic Leukemia.

Purpose: To explore the diagnostic value and the prognostic significance of cerebrospinal fluid (CSF) examination by flow cytometry (FC) in children with central nervous system leukemia (CNSL). Method: This is a retrospective observational study. We select 986 pediatric patients with newly diagnosed acute lymphoblastic leukemia from January 2012 to December 2018 as the research objects and analyze the sensitivity and specificity of different methods for diagnosing CNSL. The recurrence rate and survival rate of CNSL in different groups were compared. Results: Among the 986 cases, 31 cases (positive rate of 3.14%) were positive by FC, and the cytospin-based cytomorphology (CC) test was positive in 6 cases (positive rate of 0.61%). CC combined with FC might improve the diagnostic sensitivity (from 30% to 65%, 𝑥2 value was 5.143, P = .016). The 2-year event-free survival (EFS) of 31 FC + children was 59.5% ± 9.2%, and that of 955 FC - children was 74.1% ± 1.8% (P = .004). The 2-year overall survival (OS) of the 2 groups were 63.6% ± 9.7% and 80.2% ± 1.5%, respectively (P = .004). In order to exclude the influence of CNSL, we divided the patients into 3 groups: CNSL group and non-CNSL group with CSF FC + , FC - group. There was no significant difference in EFS between FC - group and non-CNSL group with FC + (2-year EFS were 74.1% ± 1.8% and 68.7% ± 9.8%, respectively, P = .142), and there was a significant difference in OS (2-year OS were 80.2% ± 1.5% and 67.5% ± 10.3%, respectively, P = .029). Conclusion: The test of FC combined with CC may improve the diagnostic sensitivity of CNSL. The EFS and OS of children with FC + are worse than those of children with FC -. However, for those patients with non-CNSL, but only FC + at the initial diagnosis, the EFS is not significantly affected by strengthening systemic chemotherapy and increasing the number of intrathecal injections.

Prognostic Significance of CD20 Expression in Children with Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia.

INTRODUCTION: The prognostic significance of CD20 in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains unclear. Therefore, in this study, we evaluated the prognostic value of CD20 expression in leukemia blasts in pediatric BCP-ALL at our institute. METHODS: Between 2005 and 2017, 796 children with newly diagnosed Philadelphia-negative BCP-ALL were enrolled consecutively; clinical characteristics and treatment outcomes were analyzed and compared between CD20-positive and CD20-negative groups. RESULTS: CD20 positivity was observed in 22.7% of enrolled patients. The analysis of overall and event-free survival showed that white blood cell count ≥50 × 109/L, no ETV6-RUNX1, day 33 minimal residual disease (MRD) ≥0.1%, and week 12 MRD ≥0.01% were independent risk factors. Meanwhile, in the CD20-positive group, week 12 MRD ≥0.01% was the only factor associated with long-term survival. Moreover, subgroup analysis revealed that in patients with extramedullary involvement (p = 0.047), MRD ≥0.1% on day 33 (p = 0.032), or MRD ≥0.01% at week 12 (p = 0.004), CD20 expression led to a poorer outcome compared to those without CD20 expression. CONCLUSIONS: Pediatric BCP-ALL with CD20 expression had unique clinicopathological characteristics, and MRD remained the major prognostic factor. CD20 expression had no prognostic value in pediatric BCP-ALL.

Clinical Analysis of Pediatric T-Cell Acute Lymphoblastic Leukemia Using the MRD-Oriented Strategy System.

Pediatric T-cell acute lymphoblastic leukemia (T-ALL) has historically been associated with a poor prognosis. However, prognostic indicators and methods of treatment used for T-ALL remain controversial. A total of 136 children newly diagnosed with T-ALL between 2005 and 2018 were consecutively enrolled in this study. We assessed the effect of different prognostic factors, such as clinical characteristics, minimal residual disease (MRD), and the role of transplantation in postremission treatment, as the outcomes. Compared with B-ALL patients, patients with T-ALL are generally older, more likely to be male and have a higher white blood cell count. The complete remission (CR) rate was 95.6%, while the 5-year overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse (CIR) were 74.3 ± 3.7%, 71.3 ± 3.9%, and 24.4 ± 3.8%, respectively. In the multivariate analysis, day 33 MRD ≥0.1% and hyperleukocytosis were associated with a significantly worse prognosis in the whole group. Transplantation resulted in a significant survival advantage, compared with chemotherapy, for high-risk (HR) patients (5-year CIR: 15.6 ± 10.2% vs. 55.6 ± 11.7%, P = .029). The prognosis of children with T-ALL was poor, and the MRD on day 33 was found to be an important predictive factor of clinical outcome at our center.

A global study for acute myeloid leukemia with RARG rearrangement.

Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and 26.5% of the cases, respectively. Immunophenotyping showed the following characteristics: positive for CD33, CD13, and MPO but negative for CD38, CD11b, CD34, and HLA-DR. Cytogenetics showed normal karyotype in 38% and t(11;12) in 26% of patients. The partner genes of RARG were diverse and included CPSF6, NUP98, HNRNPc, HNRNPm, PML, and NPM1. WT1- and NRAS/KRAS-mutations were common comutations. None of the 34 patients responded to ATRA and/or ATO. Death within 45 days from diagnosis occurred in 10 patients (∼29%). At the last follow-up, 23 patients had died, and the estimated 2-year cumulative incidence of relapse, event-free survival, and overall survival were 68.7%, 26.7%, and 33.5%, respectively. Unsupervised hierarchical clustering using RNA sequencing data from 201 patients with AML showed that 81.8% of the RARG fusion samples clustered together, suggesting a new molecular subtype. RARG rearrangement is a novel entity of AML that confers a poor prognosis. This study is registered with the Chinese Clinical Trial Registry (ChiCTR2200055810).

Denitrification performance and bacterial ecological network of a reactor using biodegradable poly(3-hydroxybutyrate-co-3-hydroxyvalerate) as an electron donor for nitrate removal from aquaculture wastewater.

Nitrate accumulation is a common phenomenon in aquaculture that can lead to eutrophication of surrounding water bodies. This study used poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) as a carbon source and substrate and performed a microbial co-occurrence network ecological analysis to elucidate the denitrification processes in two packed-bed reactors with different salinities. The denitrification rate reached maximum values of 0.438 and 0.446 kg m-3 d-1 in reactor I (salinity 0 ‰) and reactor II (salinity 20 ‰), respectively. Although ammonia was formed in both systems based on dissimilation nitrate reduction to ammonia (DNRA), the concentration was very low (2.47 ± 1.99 and 2.84 ± 1.79 mg L-1); moreover, the nitrite content was average (1.01 ± 0.87 and 0.96 ± 0.86 mg L-1). These results suggested that denitrification dominated in both reactors. PHBV generally presented a stable release of DOC, although a sharp increase was observed in the start-up period of reactor II. 16S rRNA results showed that reactor I had richer microbial diversity than reactor II. Among the top ten taxa, Betaproteobacteria was the dominant class in reactor I while Gammaproteobacteria was the dominant class in reactor II. In the stable period, Thauera and Denitromonas was the most abundant genera in reactor I and reactor II, respectively. In addition, the bacterial co-occurrence network showed that reactor I had a more complex node and edge network and faster start-up time compared to reactor II; however, reactor II had a more stable nitrogen removal capacity. Higher expression of NorB and NosZ genes in reactor II indicated higher efficient denitrification in seawater system. The SEM and FTIR showed bacterial development and materials surface erosion. These findings verified the denitrification performance and niche differences between freshwater and seawater environments.

Prognostic significance of Wilms' tumor gene 1 expression in children with B-cell precursor acute lymphoblastic leukemia.

Introduction: The prognostic role of Wilms' tumor 1 (WT1) gene expression at diagnosis in children with B cell precursor acute lymphoblastic leukemia (BCP-ALL) is still controversial. Methods: We detected the WT1 transcript levels of 533 de novo pediatric BCP-ALL patients using TaqMan-based real-time quantitative PCR and analyzed their clinical features. Results: The WT1 transcript levels differed among the distinct molecularly defined groups, with the highest levels in the KMT2A rearrangements (KMT2A-r) group. According to the results of the X-tile software, all patients were divided into two groups: WT1/ABL ≥ 0.24% (group A) and <0.24% (group B). The proportions of patients whose age was ≥10 years old, with immunophenotype of Pro-B, belonging in high-risk group, or with minimal residual disease (MRD) ≥ 0.01% at week 12 were significantly higher in group A than in group B. In the B-other group, WT1 overexpression was an independent risk factor of overall survival (OS) rate (P = 0.042), and higher MRD ≥ 0.01% at week 12 was associated with lower OS rate (P<0.001) and event-free survival rate (P<0.001). Moreover, the subgroup analysis revealed that, in patients with initial WBC<50 × 109/L or MRD<0.1% at day 33 or MRD<0.01% at week 12 or in the standard-risk group, WT1 overexpression led to a poorer outcome in comparison with those with WT1 downexpression (P<0.05). Discussion: Therefore, pediatric BCP-ALL with WT1 overexpression had unique clinico-pathological characteristics and poor treatment response. In B-other patients, WT1 overexpression at diagnosis predicted an inferior prognosis. The WT1 gene may serve as a biomarker for monitoring residual disease in the B-other population, especially in children in the standard-risk group.

Dual-Responsive Hydrogels with Three-Stage Optical Modulation for Smart Windows.

Since room temperature management consumes a large amount of building energy, thermochromic smart windows have been extensively used for temperature regulation and energy management. However, the development of the smart window is still limited by its simple thermochromic performance, unreasonable thermochromic temperature, and the lack of additional stimulation conditions. In this work, a dual-responsive hydrogel was developed by introducing sodium dodecyl sulfate (SDS) and sodium chloride into the cross-linking network of poly(N-isopropylacrylamide) (PNIPAM) and polyacrylamide (PAM) for energy-saving and privacy protection. By controlling the temperature from low (<15 °C) to medium (15-28 °C) to high (>28 °C), the dual-responsive hydrogel achieved a reversible three-stage transition of opaque-transparent-translucent. The hydrogel exhibited a satisfactory solar modulation ability (Tlum = 80.3%, ΔTsol,15-18°C = 72.9%, ΔTsol,18-35°C = 42.7%) and effective IR and UV shielding at high (or low) temperatures. Moreover, compared with traditional windows, smart windows made of dual-responsive hydrogels could offer better thermal insulation and heat preservation. The electrochromic properties of the dual-responsive hydrogel presented a facile strategy to meet the needs of different situations. The dual-responsive hydrogel features energy-saving, privacy protection, three-stage optical modulation, and multistimulus responsiveness, making it an ideal smart window candidate.

Outcomes of allogeneic haematopoietic stem cell transplantation for paediatric patients with MLL-rearranged acute myeloid leukaemia.

BACKGROUND: The presence of mixed-lineage leukaemia rearrangement (MLL-r) in paediatric patients with acute myeloid leukaemia (AML) is a poor prognostic predictor. Whether allogeneic haematopoietic stem cell transplantation (allo-HSCT) is beneficial in such cases remains unclear. METHODS: We evaluated the outcomes and prognostic factors of allo-HSCT in 44 paediatric patients with MLL-r AML in the first complete remission (CR1) between 2014 and 2019 at our institution. RESULTS: For all the 44 patients, the 3-year overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse (CIR) were 74.5%, 64.1%, and 29.1%, respectively. Among them, 37 (84.1%) patients received haploidentical (haplo)-HSCT, and the 3-year OS, EFS, and CIR were 73.0%, 65.6%, and 26.4%, respectively. The 100-day cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) post-transplantation was 27.3%, and that of grade III-IV aGVHD was 15.9%. The overall 3-year cumulative incidence of chronic graft-versus-host disease (cGVHD) post-transplantation was 40.8%, and that of extensive cGVHD was 16.7%. Minimal residual disease (MRD)-positive (MRD +) status pre-HSCT was significantly associated with lower survival and higher risk of relapse. The 3-year OS, EFS, and CIR differed significantly between patients with MRD + pre-HSCT (n = 15; 48.5%, 34.3% and 59%) and those with MRD-pre-HSCT (n = 29; 89.7%, 81.4% and 11.7%). Pre-HSCT MRD + status was an independent risk factor in multivariate analysis. CONCLUSIONS: Allo-HSCT (especially haplo-HSCT) can be a viable strategy in these patients, and pre-HSCT MRD status significantly affected the outcomes.