Single-Pore Nanofluidic Logic Memristor with Reconfigurable Synaptic Functions and Designable Combinations.

The biological neural network is a highly efficient in-memory computing system that integrates memory and logical computing functions within synapses. Moreover, reconfiguration by environmental chemical signals endows biological neural networks with dynamic multifunctions and enhanced efficiency. Nanofluidic memristors have emerged as promising candidates for mimicking synaptic functions, owing to their similarity to synapses in the underlying mechanisms of ion signaling in ion channels. However, realizing chemical signal-modulated logic functions in nanofluidic memristors, which is the basis for brain-like computing applications, remains unachieved. Here, we report a single-pore nanofluidic logic memristor with reconfigurable logic functions. Based on the different degrees of protonation and deprotonation of functional groups on the inner surface of the single pore, the modulation of the memristors and the reconfiguration of logic functions are realized. More noteworthy, this single-pore nanofluidic memristor can not only avoid the average effects in multipore but also act as a fundamental component in constructing complex neural networks through series and parallel circuits, which lays the groundwork for future artificial nanofluidic neural networks. The implementation of dynamic synaptic functions, modulation of logic gates by chemical signals, and diverse combinations in single-pore nanofluidic memristors opens up new possibilities for their applications in brain-inspired computing.

Clinical and genetic characteristics predict outcomes of acute myeloid leukemia patients with FLT3 mutations receiving venetoclax-based therapy.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous disease, and its heterogeneity is associated with treatment response. Despite the demonstrated success of venetoclax (VEN)-based therapy for AML, the effect of FLT3 mutations on the efficacy of the therapy is poorly understood. We aimed to compare the efficacy of VEN-based therapy between FLT3-mutated (FLT3mut ) and FLT3 wild-type (FLT3wt ) patients and identify the predictors of efficacy in FLT3mut patients. METHODS: A total of 266 AML patients (127 newly diagnosed [ND] and 139 refractory/relapsed [R/R]) receiving VEN-based regimens were enrolled in this study. A retrospective analysis was performed, and the treatment responses and overall survival (OS) of FLT3mut and FLT3wt patients were compared. Logistic regression and Cox proportional hazards model were applied to examine the clinical and genetic predictors of outcomes. RESULTS: With a median of two cycles of VEN-based therapy, for the ND AML cohort, the FLT3mut group had a comparable composite complete remission (CRc) rate with the FLT3wt group (79.3% vs. 61.2%, p = 0.072). For the R/R AML cohort, the FLT3mut group exhibited a lower CRc rate than the FLT3wt group. With a median follow-up of 8.6 months (95% confidence interval [CI], 8.0-10), the median OS observed in the FLT3mut and FLT3wt groups for both cohorts were close (14.0 vs. 19.9 months, p = 0.356; 10.0 vs. 11.9 months, p = 0.680). For the ND AML cohort, in FLT3mut patients, MRD-positive and RNA-splicing mutation predicted inferior survival (hazard ratio [HR], 10.3; 95% CI: 2.0-53.8; p = 0.006; HR 11.3; 95% CI: 1.2-109.3; p = 0.036, respectively). For the R/R AML cohort, in FLT3mut patients, adverse ELN risk was associated with an inferior response (odds ratio [OR], 0.2; 95% CI: 0.1-0.8; p = 0.025), whereas NPM1 co-mutation was associated with a superior response (57.1%; OR, 6.7; 95% CI: 1.5-30.1; p = 0.014). CR/CRi predicted a better survival (HR 0.2; 95% CI: 0.1-0.8; p = 0.029), while DNMT3A mutation predicted an inferior survival (HR, 4.6; 95% CI: 1.4-14.9; p = 0.011). CONCLUSIONS: FLT3 mutations may influence response to VEN-based therapy in R/R AML patients but not in ND AML patients. Furthermore, clinical and genetic characteristics could predict outcomes of FLT3mut patients receiving VEN-based therapy.

The Cd immobilization mechanisms in paddy soil through ureolysis-based microbial induced carbonate precipitation: Emphasis on the coexisting cations and metatranscriptome analysis.

Microbial induced carbonate precipitation (MICP) can immobilize metals and reduce their bioavailability. However, little is known about the immobilization mechanism of Cd in the presence of soil cations and the triggered gene expression and metabolic pathways in paddy soil. Thus, microcosmic experiments were conducted to study the fractionation transformation of Cd and metatranscriptome analysis. Results showed that bioavailable Cd decreased from 0.62 to 0.29 mg/kg after 330 d due to the MICP immobilization. This was ascribed to the increase in carbonate bound, Fe-Mn oxides bound, and residual Cd. The underlying immobilization mechanisms could be attributed to the formation of insoluble Cd-containing precipitates, the complexation and lattice substitution with carbonate and Fe, Mn and Al (hydr)oxides, and the adsorption on functional group on extracellular polymers of cell. During the MICP immobilization process, up-regulated differential expression urease genes were significantly enriched in the paddy soil, corresponding to the arginine biosynthesis, purine metabolism and atrazine degradation. The metabolic pathway of bacterial chemotaxis, flagellum assembly, and peptidoglycan biosynthesis and the expression of cadA gene related to Cd excretion enhanced Cd resistance of soil microbiome. Therefore, this study provided new insights into the immobilization mechanisms of Cd in paddy soils through ureolysis-based MICP process.

Sorafenib plus triplet therapy with venetoclax, azacitidine and homoharringtonine for refractory/relapsed acute myeloid leukemia with FLT3-ITD: A multicenter phase 2 study.

BACKGROUND: Patients with relapsed or refractory acute myeloid leukemia (R/R AML) and FLT3-internal tandem duplication (FLT3-ITD) respond infrequently to salvage chemotherapy. OBJECTIVE: To investigate the efficacy of sorafenib plus triplet therapy with venetoclax, azacitidine, and homoharringtonine (VAH) as a salvage therapy in this population. METHODS: This multicenter, single-arm, phase 2 study was conducted at 12 hospitals across China. Eligible patients had R/R AML with FLT3-ITD (aged 18-65 years) who were treated with VAH. The primary endpoint was composite complete remission (CRc) after two cycles. Secondary outcomes included the overall response rate (ORR), safety, and survival. RESULTS: Between July 9, 2020, and March 19, 2022, 58 patients were assessed for eligibility, 51 of whom were enrolled. The median patient age was 47 years (interquartile range [IQR] 31-57). CRc was 76.5% with ORR of 82.4%. At a median follow-up of 17.7 months (IQR, 8.7-24.7), the median duration of CRc was not reached (NR), overall survival was 18.1 months (95% confidence interval [CI], 11.8-NR) and event-free survival was 11.4 months (95% CI, 5.6-NR). Grade 3 or 4 adverse events occurring in ≥10% of patients included neutropenia in 47 (92.2%), thrombocytopenia in 41 (80.4%), anemia in 35 (68.6%), febrile neutropenia in 29 (56.9%), pneumonia in 13 (25.5%), and sepsis in 6 (11.8%) patients. Treatment-related death occurred in two (3.9%) patients. CONCLUSIONS: The sorafenib plus VAH regimen was well tolerated and highly active against R/R AML with FLT3-ITD. This regimen may be a suitable therapeutic option for this population, but larger population trials are needed to be explored. TRIAL REGISTRATION: Clinical Trials Registry: NCT04424147.

Transport Behavior of Cd2+ in Highly Weathered Acidic Soils and Shaping in Soil Microbial Community Structure.

The mining and smelting site soils in South China present excessive Cd pollution. However, the transport behavior of Cd in the highly weathered acidic soil layer at the lead-zinc smelting site remains unclear. Here, under different conditions of simulated infiltration, the migration behavior of Cd2+ in acid smelting site soils at different depths was examined. The remodeling effect of Cd2+ migration behavior on microbial community structure and the dominant microorganisms in lead-zinc sites soils was analyzed using high-throughput sequencing of 16S rRNA gene amplicons. The results revealed a specific flow rate in the range of 0.3-0.5 mL/min that the convection and dispersion have no obvious effect on Cd2+ migration. The variation of packing porosity could only influence the migration behavior by changing the average pore velocity, but cannot change the adsorption efficiency of soil particles. The Cd has stronger migration capacity under the reactivation of acidic seepage fluid. However, in the alkaline solution, the physical properties of soil, especially pores, intercept the Cd compounds, further affecting their migration capacity. The acid-site soil with high content of SOM, amorphous Fe oxides, crystalline Fe/Mn/Al oxides, goethite, and hematite has stronger ability to adsorb and retain Cd2+. However, higher content of kaolinite in acidic soil will increase the potential migration of Cd2+. Besides, the migration behavior of Cd2+ results in simplified soil microbial communities. Under Cd stress, Cd-tolerant genera (Bacteroides, Sphingomonas, Bradyrhizobium, and Corynebacterium) and bacteria with both acid-Cd tolerance (WCHB 1-84) were distinguished. The Ralstonia showed a high enrichment degree in alkaline Cd2+ infiltration solution (pH 10.0). Compared to the influence of Cd2+ stress, soil pH had a stronger ability to shape the microbial community in the soil during the process of Cd2+ migration.

Leaching Behavior of As and Pb in Lead-Zinc Mining Waste Rock under Mine Drainage and Rainwater.

At present, the pollution of arsenic (As) and lead (Pb) is becoming increasingly serious. The pollution caused by the release of As and Pb from lead-zinc mines has seriously affected the water and soil environment and threatened human health. It is necessary to reveal the release characteristics of As and Pb. The actual scene of mine drainage (MD) and rainwater (RW) leaching waste rocks is the one of the main reasons for the release of As and Pb. However, the leaching behavior of As and Pb in these waste rocks under MD and RW suffered from a lack of in-depth research. In this study, we investigated the occurrence of As and Pb in waste rocks (S1-S6) by using X-ray diffraction (XRD) and time-of-flight secondary ion mass spectrometry (TOF-SIMS), and then, the changes in As and Pb concentration and the hydrochemical parameter in leaching solution were systematically studied. Furthermore, the correlation between the release of As and Pb and mineral composition was also evaluated. Results showed that these waste rocks were mainly composed of carbonate and sulfide minerals. As and Pb were mainly bounded or associated with sulfide minerals such as arsenopyrite, pyrite, chalcopyrite, and galena in these waste rocks, and small parts of As and Pb were absorbed or encased by clay minerals such as kaolinite and chlorite. Under MD and RW leaching, the pH, redox potential (Eh), and electric conductivity (EC) of each waste rock tended to be consistent due to their buffering ability; the leachate pH of waste rocks with more carbonate minerals was higher than that of sulfide minerals. Both As and Pb were released most under MD leaching in comparison to RW, reaching 6.57 and 60.32 mg/kg, respectively, due to MD's low pH and high Eh value. However, As in waste rock released more under alkaline conditions because part of the arsenic was in the form of arsenate. As and Pb release were mainly positively correlated with the proportions of sulfide minerals in these waste rocks. MD leaching significantly promoted the release of As and Pb from waste rocks, which would cause a great threat to the surrounding environment, and control measures were imperative. This paper not only reveals the As and Pb pollution mechanism around the lead-zinc mining area but also provides a theoretical basis for the prevention and control of As and Pb pollution in the future.

Hypomethylating agents plus modified priming regimens compared with venetoclax-based regimens based on molecular characteristics for newly diagnosed patients with acute myeloid leukemia: a multi-center cohort study.

Venetoclax (VEN)-based regimens are the standard of care for elderly or unfit patients with newly diagnosed (ND) acute myeloid leukemia (AML). Some single-arm studies have implied that hypomethylating agents (HMAs) plus priming regimens may potentially provide an alternative therapeutic approach, owing to encouraging efficacy seen. However, no comparative data exists yet regarding these two treatment approaches. In this retrospective multi-center cohort study, we enrolled 294 ND AML patients, allocating 167 to the HMA + priming group and 127 to the VEN-based group. Treatment response and overall survival (OS) were compared between groups. Molecular subgroup analyses were also conducted. With a median of two cycles for HMA + priming group, the overall response (ORR) was 65.3%, including 55.1% complete remission (CR), 9.6% CR with incomplete hematologic recovery (CRi) and 0.6% morphologic leukemia-free state (MLFS). With a median of two cycles for VEN-based group, the ORR was 70.9%, including 46.5% CR, 18.9% CRi, and 5.5% MLFS. Response differences (ORR or CR/CRi) between groups were not significant (p > 0.05). With a median follow-up of 10.1 months, median OSs were similar between groups (20.9 vs 16.3 months, p = 0.41). However, VEN regimens demonstrated superior CR/CRi for patients with mutations in FLT3, IDH1/2, and NPM1 compared to HMA + priming (80.0% vs 35.0%, p = 0.01; 90.9% vs 65.5%, p = 0.02; 90.9% and 65.5%, p = 0.02, respectively). In conclusion, HMAs plus modified priming regimens might be a potential alternative therapeutic approach for patients with ND AML, but VEN-based regimens presented predominance in specific molecular subgroups. Molecular characteristics contribute to guiding choice of treatment.

Busulfan Plus Fludarabine Compared With Busulfan Plus Cyclophosphamide for AML Undergoing HLA-Haploidentical Hematopoietic Cell Transplantation: A Multicenter Randomized Phase III Trial.

PURPOSE: The busulfan plus fludarabine (BuFlu) conditioning regimen has lower transplant-related mortality (TRM) than busulfan plus cyclophosphamide (BuCy) in HLA-matched transplantation. We aimed to compare outcomes of the BuFlu regimen with those of the BuCy regimen in HLA-haploidentical hematopoietic cell transplantation (haplo-HCT). METHODS: We performed an open-label, randomized phase III trial at 12 hospitals in China. Eligible patients with AML (18-65 years) were randomly assigned 1:1 to receive BuFlu (busulfan 0.8 mg/kg four times per day on days -6 to -3; fludarabine 30 mg/m2 once daily on days -7 to -3) or BuCy (same dose of busulfan; cyclophosphamide 60 mg/kg once daily on days -3 and -2). The primary end point was 1-year TRM in the intention-to-treat population and safety in the per-protocol population. This trial is registered with ClinicalTrials.gov (identifier: NCT02487069) and is complete. RESULTS: From November 20, 2015, to September 30, 2019, 386 patients were randomly assigned to receive the BuFlu (n = 194) or BuCy (n = 192) regimen. The median follow-up was 55.0 (IQR, 46.5-69.0) months after random assignment. The 1-year TRM was 7.2% (95% CI, 4.1 to 11.4) and 14.1% (95% CI, 9.6 to 19.4; hazard ratio [HR], 0.51; 95% CI, 0.27 to 0.97; P = .041), the 5-year relapse was 17.9% (95% CI, 9.6 to 28.3) and 14.2% (95% CI, 9.1 to 20.5; HR, 1.12; 95% CI, 0.65 to 1.95; P = .670), and the 5-year overall survival was 72.5% (95% CI, 62.2 to 80.4) and 68.2% (95% CI, 58.9 to 75.9; HR, 0.84; 95% CI, 0.56 to 1.26; P = .465) in two groups, respectively. Grade 3 regimen-related toxicity (RRT) was reported for 0 of 191 patients following the BuFlu regimen and 9 (4.7%) of 190 patients following the BuCy regimen (P = .002). At least one type of grade 3-5 adverse event was reported for 130 (68.1%) of the 191 patients and 147 (77.4%) of the 190 patients in two groups, respectively (P = .041). CONCLUSION: The BuFlu regimen has a lower TRM and RRT and similar relapse for patients with AML undergoing haplo-HCT compared with the BuCy regimen.

Transcriptomics and metabolomics revealed the pulmonary protective mechanism of Xixin-Ganjiang Herb Pair for warming the lungs to dissolve phlegm in COPD rats.

Xixin-Ganjiang Herb Pair (XGHP), a classic combination treatment to warm the lungs and dissolve phlegm, is widely used in the treatment of various pulmonary diseases. Chronic obstructive pulmonary disease (COPD) refers to a group of chronic obstructive airway diseases that can seriously harm human health. However, the effective components, targets, and pathways that underlie XGHP in the treatment of COPD remain unclear. Therefore, this study initially identified the effective components of XGHP through the use of UPLC-MS/MS and pharmacologic methods of traditional Chinese medicine. Secondly, transcriptomic analysis of the lung tissues of rats revealed the pharmacodynamic transcripts of each group, and metabolomics analysis revealed the differential metabolites associated with XGHP treatment. Finally, molecular docking of effective components with transcriptome genes was performed and western blotting was performed in order to determine the expression of related proteins in rat lung tissue. Overall, 30 effective components of XGHP were identified, including L-asarinin, 6-gingerol, sesamin, kaempferol, and quercetin. Transcriptomic studies demonstrated that expression of 386 genes recovered after XGHP treatment, and that they were mainly enriched in the oxidative phosphorylation and AMPK signaling pathways. According to the metabolomics studies, expression of eight metabolites differed between the COPD and the XGHP groups. These metabolites were mainly involved the biosynthesis of unsaturated fatty acids. Finally, the transcriptomic and metabolomics data were integrated. FASN and SCD in AMPK signaling pathway were directly linked to certain metabolites, including linoleic acid, palmitic acid, and oleic acid. These results indicate that XGHP can inhibit pAMPK expression and negatively regulate FASN and SCD expression during treatment of COPD in order to enhance the biosynthesis of unsaturated fatty acids and maintain energy homeostasis.

Venetoclax Combined with Azacitidine and Homoharringtonine in Relapsed/Refractory AML: A Multicenter, Phase 2 Trial.

BACKGROUND: Relapsed or refractory acute myeloid leukemia (R/R AML) has a dismal prognosis. The aim of this study was to investigate the activity and tolerability of venetoclax combined with azacitidine plus homoharringtonine (VAH) regimen for R/R AML. METHODS: This phase 2 trial was done at ten hospitals in China. Eligible patients were R/R AML (aged 18-65 years) with an Eastern Cooperative Oncology Group performance status of 0-2. Patients received venetoclax (100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-14) and azacitidine (75 mg/m2 on days 1-7) and homoharringtonine (1 mg/m2 on days 1-7). The primary endpoint was composite complete remission rate [CRc, complete response (CR) plus complete response with incomplete blood count recovery (CRi)] after 2 cycles of treatment. The secondary endpoints include safety and survival. RESULTS: Between May 27, 2020, and June 16, 2021, we enrolled 96 patients with R/R AML, including 37 primary refractory AML and 59 relapsed AML (16 relapsed after chemotherapy and 43 after allo-HSCT). The CRc rate was 70.8% (95% CI 60.8-79.2). In the patients with CRc, measurable residual disease (MRD)-negative was attained in 58.8% of CRc patients. Accordingly, overall response rate (ORR, CRc plus partial remission (PR)) was 78.1% (95% CI 68.6-85.4). At a median follow-up of 14.7 months (95% CI 6.6-22.8) for all patients, median overall survival (OS) was 22.1 months (95% CI 12.7-Not estimated), and event-free survival (EFS) was 14.3 months (95% CI 7.0-Not estimated). The 1-year OS was 61.5% (95% CI 51.0-70.4), and EFS was 51.0% (95% CI 40.7-60.5). The most common grade 3-4 adverse events were febrile neutropenia (37.4%), sepsis (11.4%), and pneumonia (21.9%). CONCLUSIONS: VAH is a promising and well-tolerated regimen in R/R AML, with high CRc and encouraging survival. Further randomized studies are needed to be explored. Trial registration clinicaltrials.gov identifier: NCT04424147.

Co-occurrence network in core microorganisms driving the transformation of phosphorous fractionations during phosphorus recovery product used as soil fertilizer.

Phosphorus recovery from water and the subsequent reuse of its products can solve both water eutrophication and phosphorus resource waste issues. However, the potential use of the final recovered products as crop phosphorus fertilizers and the transformation of phosphorus fractions in soils have rarely been analyzed. In this study, the effects of a phosphorus recovery product (w-HC/CSH/P) obtained from our previous phosphorus recovery study on pepper growth were investigated. The association between soil phosphorus fraction transformation and the microbial co-occurrence network was investigated using high-throughput sequencing. The results showed that amendment with w-HC/CSH/P could promote the growth and chlorophyll content of pepper, which exhibited high phosphorus fertilizer efficiency. In addition, applying w-HC/CSH/P in soils could increase the microbial alpha-diversity during pepper cultivation and induce changes in the microbial community, leading to an increase in the relative abundance of Povalibacter, Lysobacter, and GP10 and a decrease in GP17. The proportion of Resin-P and NaHCO3-Po decreased, whereas that of NaOH-Po increased during pepper cultivation. psOTU331 (g_Latescibacteria), psOTU377 (g_Lysobacter), and psOTU461 (g_Pseudoxanthomonas) were the key microorganisms driving the transformation of phosphorus fractionation in the microbial co-occurrence network. Latescibacteria and Lysobacter were closely correlated with the transformation of NaHCO3-Po to NaOH-Po, and Pseudoxanthomonas was significantly correlated with a decrease in Resin-P. These observations highlight the potential of phosphorus recovery products as fertilizer for pepper and provide new insights into the transformation of phosphorus fractions corresponding to the microbiome in soils.

Case Report: CTC1 mutations in a patient with diffuse hepatic and splenic hemangiomatosis complicated by Kasabach-Merritt syndrome.

Diffuse hemangiomatosis of the liver and spleen is rare. Currently, few studies are available on diffuse hepatic and splenic hemangiomatosis accompanied by Kasabach-Merritt syndrome (KMS). The conserved telomere maintenance component 1 (CTC1) gene contributes to telomere maintenance and replication by forming the telomeric capping complex. Herein, we report a case of diffuse hemangiomatosis in the liver and spleen accompanied by KMS in a 59-year-old woman who carried two novel heterozygous CTC1 variants: c.435+9A>C and c.3074C>T (p.Ala1025Val). Using next-generation sequencing, we detected mutations in the CTC1 gene in our patient, who had chief complaints of fatigue and abdominal distension complicated by severe thrombocytopenia and consumptive coagulopathy. Clinical symptoms, laboratory tests, and imaging findings led to the diagnosis of diffuse hepatic and splenic hemangiomatosis accompanied by KMS. The patient was treated with prednisone, thalidomide, and sirolimus, and her general condition was ameliorated at the 4-month follow-up with improved platelet count and coagulation function. A CTC1 gene mutation may be involved in the pathological process of vascular diseases. A combination treatment regimen of prednisone, thalidomide, and sirolimus may be effective for KMS.

Genetic characteristics predict response to venetoclax plus hypomethylating agents in relapsed or refractory acute myeloid leukemia.

BACKGROUND: The heterogeneity of relapsed or refractory (R/R) acute myeloid leukemia (AML) leads to no response to venetoclax (VEN)-based therapy in more than half of the patients. Genetic characteristics are considered important predictors for response to treatment in adults with AML. However, the association of genetic characteristics with outcomes receiving VEN-based therapy is incompletely understood in R/R AML. OBJECTIVE: To evaluate the efficacy of VEN combined with hypomethylating agents (HMA) and identify the potential genetic predictors of response in R/R AML. METHODS: A total of 150 R/R AML patients treated with VEN combined with HMA were enrolled in this retrospective study. Outcomes of the response and overall survival (OS) were analyzed. The predictors of response and OS were analyzed by logistic regression or Cox proportional hazards model. RESULTS: With a median of two (range, 1-4) cycles of therapy, the overall response rate was 56.2%, including 22.0% complete remission (CR), 21.3% CR with incomplete hematologic recovery, 2.0% morphologic leukemia-free state, and 10.7% partial remission, in which 25 patients achieved measurable residual disease (MRD)-negative response. With a median follow-up of 11.2 [95% confidence interval (CI), 7.2-14.8] months, 1- and 2-year OS were 46.9% (95% CI, 37.8%-58.1%) and 38.9% (95% CI, 28.7%-52.9%), respectively. Adverse cytogenetics and European Leukemia Net (ELN) risk predicted inferior response to VEN-based therapy. Mutations in IDH1/2, NPM1, ASXL1, and chromatin-cohesin genes predicted superior response to VEN-based therapy, whereas mutations in active signaling genes such as FLT3-ITD and K/NRAS predicted inferior response. CONCLUSION: VEN combined with HMA was effective with R/R AML patients, and the response to treatment was associated with genetic characteristics.

A review on the bioleaching of toxic metal(loid)s from contaminated soil: Insight into the mechanism of action and the role of influencing factors.

The anthropogenic activities in agriculture, industrialization, mining, and metallurgy combined with the natural weathering of rocks, have led to severe contamination of soils by toxic metal(loid)s. In an attempt to remediate these polluted sites, a plethora of conventional approaches such as Solidification/Stabilization (S/S), soil washing, electrokinetic remediation, and chemical oxidation/reduction have been used for the immobilization and removal of toxic metal(loid)s in the soil. However, these conventional methods are associated with certain limitations. These limitations include high operational costs, high energy demands, post-waste disposal difficulties, and secondary pollution. Bioleaching has proven to be a promising alternative to these conventional approaches in removing toxic metal(loid)s from contaminated soil as it is cost-effective, environmentally friendly, and esthetically pleasing. The bioleaching process is influenced by factors including pH, temperature, oxygen, and carbon dioxide supply, as well as nutrients in the medium. It is crucial to monitor these parameters before and throughout the reaction since a change in any, for instance, pH during the reaction, can alter the microbial activity and, therefore, the rate of metal leaching. However, research on these influencing factors and recent innovations has brought significant progress in bioleaching over the years. This critical review, therefore, presents the current approaches to bioleaching and the mechanisms involved in removing toxic metal(loid)s from contaminated soil. We further examined and discussed the fundamental principles of various influencing factors that necessitate optimization in the bioleaching process. Additionally, the future perspectives on adding omics for bioleaching as an emerging technology are discussed.

Cloning and Bioinformatics Analysis of GhArfGAP in Cotton (Gossypium hirsutum) Boll Abscission Layer With Ethylene Treatment.

With the continuous growth of the human population, the demand for fiber is also rising sharply. As one of the main fiber plants available globally, cotton fiber yield (Gossypium hirsutum) is affected by boll abscission, which is related to the formation of the abscission layer. Therefore, we explored the formation of the abscission layer in cotton. The formation of the abscission layer in the cotton boll stalk was promoted by exogenous ethylene. It was found that both the number of the Golgi apparatus and the number of stacking layers increased in the dissociated cells. The GhArfGAP gene family in cotton was screened by the bioinformatics method, and the species and evolutionary relationship of the GhArfGAP gene family were analyzed. qRT-PCR showed that GhArfGAP13, GhArfGAP15, GhArfGAP25, and GhArfGAP34 in cotton had spatiotemporal-specific expression patterns. Subcellular localization suggested that GhArfGAP25 played a role in the Golgi apparatus. The expression of GhArfGAP25 in transgenic Arabidopsis thaliana is increased in the roots, stems, and leaves. Finally, we found that ethylene could induce the formation of the abscission layer in cotton. GhArfGAP13, GhArfGAP15, GhArfGAP25, and GhArfGAP34 might regulate the changes in the Golgi apparatus in the abscission layer. Taken together, the findings provide new ideas for the study of the formation of cotton abscission.

Prevention of acute graft-vs.-host disease by targeting glycolysis and mTOR pathways in activated T cells.

Graft-versus-host disease (GvHD) is a common life-threatening complication that can occur following allogeneic hematopoietic stem cell transplantation. This occurs if donor T cells recognize the host as foreign. During acute GvHD (aGVHD), activated T cells utilize glycolysis as the main source of energy generation. Therefore, inhibition of T cell glycolysis is a potential treatment strategy for aGVHD. In the present study, the effects of the combination of the glycolysis inhibitor 3-bromopyruvate (3-BrPA) and the mTOR inhibitor rapamycin (RAPA) on a mode of aGVHD were explored. In vitro mixed lymphocyte culture model was established by using splenocytes from C57BL/6 (H-2b) mice as responder and inactivated splenocytes from BALB/c (H-2d) mice as stimulator. In this model, 3-BrPA treatment (0-100 µmol/l) was found to suppress cell viability, increase cell apoptosis and reduce IFN-γ secretion, in a concentration-dependent manner. 3-BrPA treatment (0-100 µmol/l) was found to suppress cell viability, increase cell apoptosis and reduce IFN-γ secretion, in a concentration-dependent manner. In addition, combined treatment with 3-BrPA (0-100 µmol/l) alongside RAPA (20 µmol/l) exhibited synergistic effects on inhibiting cell viability and IFN-γ production, compared with those following either treatment alone. An aGVHD model was established by injection of bone marrow cells and spleen cells from the donor-C57BL/6(H-2b) mice to the receptor-BALB/c(H-2d) mice which were underwent total body irradiation first. In the aGVHD model, 3-BrPA (10 mg/kg/day), RAPA (2.5 and 5 mg/kg/day) and both in combination (5 and 2.5 mg/kg/day for 3-BrPA and RAPA, respectively) were all found to alleviate the damage caused by aGVHD, in addition to prolonging the survival time of mice with acute GvHD. In particular, the combined 3-BrPA and RAPA treatment resulted in the highest median survival time among all groups tested. In addition, the effects induced by combined 3-BrPA and RAPA treatment were found to be comparable to those in the 5 mg/kg/day RAPA group but superior to the 3-BrPA group with regards to the cumulative survival profile, GvHD score and lung histological score. The 3-BrPA and RAPA combination group also exhibited the lowest IFN-γ levels among all groups. Therefore, the combination of inhibiting both glycolysis and mTOR activity is a promising strategy for acute GvHD prevention.

Cadmium, lead and arsenic contamination in an abandoned nonferrous metal smelting site in southern China: Chemical speciation and mobility.

The investigation of chemical speciation of primary toxic metal(loid)s (Cd, Pb, and As) in soil profile in nonferrous metal smelting site is a key to the assessment of their mobility characteristics and formulation of subsequent remediation strategy. In this study, 74 soil samples were collected at 12 different soil profiles; soil physio-chemical properties and total content of Cd, Pb and As and corresponding chemical speciation were also determined. The results showed that the mean total concentration followed the order of Pb > As > Cd. A large proportion of Pb, Cd and As were accumulated in upper soil profiles (depth < 3 m). Heavy pollution of Pb, Cd and As were observed in the whole soil profile at the area of fuel oil storage tank (ZY6) and lead smelting area (ZY8). The dominant fraction of Cd was exchangeable fraction (F1); Pb was dominant in Fe/Mn oxides-bound fraction (F3) in most cases; Crystallized Fe/Al hydrous oxides bound fraction (F4) generally accounted for a large proportion of As. Mobility factor (MF) followed the order Cd > As > Pb, indicating that Cd was the most mobile element in soil profiles. Pearson correlation analysis found that MFCd was significantly positively correlated to soil silt; the F4 fraction percentage of As was significantly positively correlated to soil redox potential (Eh). Additionally, MFCd/Pb was found to be positively correlated to crystalline iron (Fec), while negatively correlated to amorphous iron (Feo). The findings reported in this study, on the basis of distribution characteristics of chemical speciation could provide a new solution for future soil remediation at the site. Long-term solutions to metal(loid)s pollution might be offered by microbial-assisted soil washing technique that promotes the transformation of Fe/Mn oxides-bound fraction and organic/sulfide-bound fraction.

Dynamic assessment of measurable residual disease in favorable-risk acute myeloid leukemia in first remission, treatment, and outcomes.

We aimed to investigate outcomes of different post-remission treatment (PRT) choices based on dynamic measurable residual disease (MRD) by multiparameter flow cytometry in favorable-risk AML (FR-AML). Four hundred and three younger patients with FR-AML in first complete remission (CR1) were enrolled in this registry-based cohort study, including 173 who received chemotherapy (CMT), 92 autologous stem cell transplantation (auto-SCT), and 138 allogeneic SCT (allo-SCT). The primary endpoint was the 5-year overall survival (OS). Subgroup analyses were performed based on dynamic MRD after the 1st, 2nd, and 3rd courses of chemotherapy. In subgroups of patients with negative MRD after 1 or 2 course of chemotherapy, comparable OS was observed among the CMT, auto-SCT, and allo-SCT groups (p = 0.340; p = 0.627, respectively). But CMT and auto-SCT had better graft-versus-host-disease-free, relapse-free survival (GRFS) than allo-SCT in both subgroups. For patients with negative MRD after three courses of chemotherapy, allo-SCT had better disease-free-survival than CMT (p = 0.009). However, OS was comparable among the three groups (p = 0.656). For patients with persistently positive MRD after 3 courses of chemotherapy or recurrent MRD, allo-SCT had better OS than CMT and auto-SCT (p = 0.011; p = 0.029, respectively). Dynamic MRD might improve therapy stratification and optimize PRT selection for FR-AML in CR1.

Vertical distribution of the toxic metal(loid)s chemical fraction and microbial community in waste heap at a nonferrous metal mining site.

Over the past few decades, nonferrous mining has produced numerous waste rock and part of the waste that has not been properly treated was generally dumped at roadsides and hill slopes. However, the vertical distributions of toxic metal(loid)s and composition of microbial communities in waste heap and the under-laid pristine soil are rarely studied. In this work, the fraction-related distributions of toxic metal(loid)s were investigated at a waste heap profile and the indigenous microbial assemblages were also analyzed by Illumina sequencing of 16 s rRNA genes. Results showed that compared to the under-laid pristine soil, content of toxic metal(loid)s, especially Cd, As and Pb, in waste rock layer were higher. Most of As in subsoil existed as non-specifically sorbed and specifically-sorbed fractions, which could be ascribed to the migration from the upper layer. The mobility was significantly correlated with Eh, EC, clay content, CEC and the total content of metal(loid)s. Phyla Proteobacteria, Acidobacteria and Firmicutes dominated the microbial communities. The microbial community compositions at the genus level were similar, but their relative abundances were mainly influenced by pH, CEC, Eh, SOM, and bioavailability content of toxic metal(loid)s. Besides, microbial functions of elements (S, Fe, Mn and As) oxidation/reduction and metabolites (siderophore, biosurfactant, organic acid, phosphatase and urease) potentially were used for pollutants bioremediation.

Association Between Measurable Residual Disease in Patients With Intermediate-Risk Acute Myeloid Leukemia and First Remission, Treatment, and Outcomes.

Importance: Measurable residual disease (MRD) is widely used as a therapy-stratification factor for acute myeloid leukemia (AML), but the association of dynamic MRD with postremission treatment (PRT) in patients with intermediate-risk AML (IR-AML) has not been well investigated. Objective: To investigate PRT choices based on dynamic MRD in patients with IR-AML. Design, Setting, and Participants: This cohort study examined 549 younger patients with de novo IR-AML in the South China Hematology Alliance database during the period from January 1, 2012, to June 30, 2016, including 154 who received chemotherapy, 116 who received an autologous stem cell transplant (auto-SCT), and 279 who received an allogeneic SCT (allo-SCT). Subgroup analyses were performed according to dynamic MRD after the first, second, and third courses of chemotherapy. The end point of the last follow-up was August 31, 2020. Statistical analysis was performed from December 1, 2019, to September 30, 2020. Exposures: Receipt of chemotherapy, auto-SCT, or allo-SCT. Main Outcomes and Measures: The primary end points were 5-year cumulative incidence of relapse and leukemia-free survival. Results: Subgroup analyses were performed for 549 participants (314 male participants [57.2%]; median age, 37 years [range, 14-60 years]) according to the dynamics of MRD after 1, 2, or 3 courses of chemotherapy. Comparable cumulative incidences of relapse, leukemia-free survival, and overall survival were observed among participants who had no MRD after 1, 2, or 3 courses of chemotherapy. Participants who underwent chemotherapy and those who underwent auto-SCT had better graft-vs-host disease-free, relapse-free survival (GRFS) than those who underwent allo-SCT (chemotherapy: hazard ratio [HR], 0.35 [95% CI, 0.14-0.90]; P = .03; auto-SCT: HR, 0.07 [95% CI, 0.01-0.58]; P = .01). Among participants with MRD after 1 course of chemotherapy but no MRD after 2 or 3 courses, those who underwent auto-SCT and allo-SCT showed lower cumulative incidence of relapse (auto-SCT: HR, 0.25 [95% CI, 0.08-0.78]; P = .01; allo-SCT: HR, 0.08 [95% CI, 0.02-0.24]; P < .001), better leukemia-free survival (auto-SCT: HR, 0.26 [95% CI, 0.10-0.64]; P = .004; allo-SCT: HR, 0.21 [95% CI, 0.09-0.46]; P < .001), and overall survival (auto-SCT: HR, 0.22 [95% CI, 0.08-0.64]; P = .005; allo-SCT: HR, 0.25 [95% CI, 0.11-0.59]; P = .001) vs chemotherapy. In addition, auto-SCT showed better GRFS than allo-SCT (HR, 0.45 [95% CI, 0.21-0.98]; P = .04) in this group. Among participants with MRD after 1 or 2 courses of chemotherapy but no MRD after 3 courses, allo-SCT had superior cumulative incidence of relapse (HR, 0.10 [95% CI, 0.06-0.94]; P = .04) and leukemia-free survival (HR, 0.18 [95% CI, 0.05-0.68]; P = .01) compared with chemotherapy, but no advantageous cumulative incidence of relapse (HR, 0.15 [95% CI, 0.02-1.42]; P = .10) and leukemia-free survival (HR, 0.23 [95% CI, 0.05-1.08]; P = .06) compared with auto-SCT. Among participants with MRD after 3 courses of chemotherapy, allo-SCT had superior cumulative incidences of relapse, leukemia-free survival, and overall survival compared with chemotherapy (relapse: HR, 0.16 [95% CI, 0.08-0.33]; P < .001; leukemia-free survival: HR, 0.19 [95% CI, 0.10-0.35]; P < .001; overall survival: HR, 0.29 [95% CI, 0.15-0.55]; P < .001) and auto-SCT (relapse: HR, 0.25 [95% CI, 0.12-0.53]; P < .001; leukemia-free survival: HR, 0.35 [95% CI, 0.18-0.73]; P = .004; overall survival: HR, 0.54 [95% CI, 0.26-0.94]; P = .04). Among participants with recurrent MRD, allo-SCT was also associated with advantageous cumulative incidence of relapse, leukemia-free survival, and overall survival compared with chemotherapy (relapse: HR, 0.12 [95% CI, 0.04-0.33]; P < .001; leukemia-free survival: HR, 0.24 [95% CI, 0.10-0.56]; P = .001; overall survival: HR, 0.31 [95% CI, 0.13-0.75]; P = .01) and auto-SCT (relapse: HR, 0.28 [95% CI, 0.09-0.81]; P = .02; leukemia-free survival: HR, 0.30 [95% CI, 0.12-0.76]; P = .01; overall survival: HR, 0.26 [95% CI, 0.10-0.70]; P = .007). Conclusions and Relevance: This study suggests that clinical decisions based on dynamic MRD might be associated with improved therapy stratification and optimized PRT for patients with IR-AML. Prospective multicenter trials are needed to further validate these findings.