Investigation of high-risk antibiotic resistance bacteria and their associated antibiotic resistance genes in different agricultural soils with biogas slurry from China.

High-risk antibiotic-resistant bacteria (ARB) and their accompanying antibiotic resistance genes (ARGs) seriously threaten public health. As a crucial medium for ARB and ARGs spread, soils with biogas slurry have been widely investigated. However, few studies focused on high-risk multi-drug resistant bacteria (MDRB) and their associated ARGs. This study examined ARB distribution in different agricultural soils with biogas slurry across 12 districts in China. It identified high-risk MDRB in various soil backgrounds, elucidating their resistance and spread mechanism. The findings revealed that diverse cultured ARB were enriched in soils with biogas slurry, especially soil ciprofloxacin ARB, which were enriched (>2.5 times) in 68.4 % of sampling sites. Four high-risk MDRB isolated from Hebei, Zhejiang, Shanxi, and Gansu districts were identified as severe or opportunistic pathogens, which carried abundant mobile genetic elements (MGEs) and 14 known high risk ARGs, including aac(3)-IId, aac(6')-Ib3, aph(6)-Id, aac(6')-Ib3, aadA1, blaOXA-10, blaTEM-1B, dfrA12, dfrA14, cmlA1, sul1, floR, tet(M) and tet(L). The antibiotics accumulation, diverse ARGs and MGEs enrichment, and proliferation of pathogenic bacteria could be potential driving factors of their occurrence and spread. Therefore, the coexistence of the high-risk MDRB and ARGs combined with the associated MGEs in soils with biogas slurry should be further investigated to develop technology and policy for reducing their negative influences on the effectiveness of clinical antibiotics.

Effectiveness of low-intensity ultrasound on anaerobic bioaugmentation of phenolic wastewater: Model optimization and system stabilization.

The study optimized the parameters of low-intensity ultrasound (LIUS), including ultrasound density (0.25 W·mL-1), duration (12 min), and interval time (48 h), through a combination of uniform experiments and response surface prediction. The optimized parameters were aimed at enhancing the removal efficiency of phenolic wastewater to approximately 80%. Furthermore, they facilitate the production of hydrolytic gases in anaerobic digestion, resulting in methane accumulation of up to 237.3 mL·(g VS)-1. Following the long-term experiment, LIUS has been demonstrated to effectively enhance the enzyme activity of anaerobic organisms while also damaging the bacterial structure of microorganisms. However, microbiological analysis indicates that the ultrasound-induced screening mechanism effectively increases the relative abundance of dominant bacterial communities. This facilitated the removal of persistent phenolic contaminants and stabilized the balanced development of the overall anaerobic environment. These findings suggest that LIUS can enhance biological activity and improve the anaerobic treatment of phenolic wastewater.

Low-dose hypomethylating agents cooperate with ferroptosis inducers to enhance ferroptosis by regulating the DNA methylation-mediated MAGEA6-AMPK-SLC7A11-GPX4 signaling pathway in acute myeloid leukemia.

BACKGROUND: Ferroptosis is a new form of nonapoptotic and iron-dependent type of cell death. Glutathione peroxidase-4 (GPX4) plays an essential role in anti-ferroptosis by reducing lipid peroxidation. Although acute myeloid leukemia (AML) cells, especially relapsed and refractory (R/R)-AML, present high GPX4 levels and enzyme activities, pharmacological inhibition of GPX4 alone has limited application in AML. Thus, whether inhibition of GPX4 combined with other therapeutic reagents has effective application in AML is largely unknown. METHODS: Lipid reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) assays were used to assess ferroptosis in AML cells treated with the hypomethylating agent (HMA) decitabine (DAC), ferroptosis-inducer (FIN) RAS-selective lethal 3 (RSL3), or their combination. Combination index (CI) analysis was used to assess the synergistic activity of DAC + RSL3 against AML cells. Finally, we evaluated the synergistic activity of DAC + RSL3 in murine AML and a human R/R-AML-xenografted NSG model in vivo. RESULTS: We first assessed GPX4 expression and found that GPX4 levels were higher in AML cells, especially those with MLL rearrangements, than in NCs. Knockdown of GPX4 by shRNA and indirect inhibition of GPX4 enzyme activity by RSL3 robustly induced ferroptosis in AML cells. To reduce the dose of RSL3 and avoid side effects, low doses of DAC (0.5 µM) and RSL3 (0.05 µM) synergistically facilitate ferroptosis by inhibiting the AMP-activated protein kinase (AMPK)-SLC7A11-GPX4 axis. Knockdown of AMPK by shRNA enhanced ferroptosis, and overexpression of SLC7A11 and GPX4 rescued DAC + RSL3-induced anti-leukemogenesis. Mechanistically, DAC increased the expression of MAGEA6 by reducing MAGEA6 promoter hypermethylation. Overexpression of MAGEA6 induced the degradation of AMPK, suggesting that DAC inhibits the AMPK-SLC7A11-GPX4 axis by increasing MAGEA6 expression. In addition, DAC + RSL3 synergistically reduced leukemic burden and extended overall survival compared with either DAC or RSL3 treatment in the MLL-AF9-transformed murine model. Finally, DAC + RSL3 synergistically reduced viability in untreated and R/R-AML cells and extended overall survival in two R/R-AML-xenografted NSG mouse models. CONCLUSIONS: Our study first identify vulnerability to ferroptosis by regulating MAGEA6-AMPK-SLC7A11-GPX4 signaling pathway. Combined treatment with HMAs and FINs provides a potential therapeutic choice for AML patients, especially for R/R-AML.

The novel HLA-B*40:555 allele identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*40:555 differs from HLA-B*40:01:02:01 by one nucleotide in exon 3.

m5 C regulator-mediated methylation modification patterns and tumor microenvironment infiltration characteristics in acute myeloid leukemia.

BACKGROUND: Recently, many studies have been conducted to examine immune response modification at epigenetic level, but the candidate effect of RNA 5-methylcytosine (m5 C) modification on tumor microenvironment (TME) of acute myeloid leukemia (AML) is still unknown at present. METHODS: We assessed the patterns of m5 C modification among 417 AML cases by using nine m5 C regulators. Thereafter, we associated those identified modification patterns with TME cell infiltration features. Additionally, stepwise regression and LASSO Cox regression analyses were conducted for quantifying patterns of m5 C modification among AML cases to establish the m5 C-score. Meanwhile, we validated the expression of genes in the m5C-score model by qRT-PCR. Finally, the present work analyzed the association between m5 C-score and AML clinical characteristics and prognostic outcomes. RESULTS: In total, three different patterns of m5 C modification (m5 C-clusters) were identified, and highly differentiated TME cell infiltration features were also identified. On this basis, evaluating patterns of m5 C modification in single cancer samples was important for evaluating the immune/stromal activities in TME and for predicting prognosis. In addition, the m5 C-score was established, which showed a close relation with the overall survival (OS) of test and training set samples. Moreover, multivariate Cox analysis suggested that our constructed m5 C-score served as the independent predicting factor for the prognosis of AML (hazard ratio = 1.57, 95% confidence interval = 1.38-1.79, p < 1e-5 ). CONCLUSIONS: This study shows that m5 C modification may be one of the key roles in the formation of diversity and complexity of TME. Meanwhile, assessing the patterns of m5 C modification among individual cancer samples is of great importance, which provides insights into cell infiltration features within TME, thereby helping to develop relevant immunotherapy and predict patient prognostic outcomes.

Tracing the transfer characteristics of antibiotic resistance genes from swine manure to biogas residue and then to soil.

Based on laboratory simulation experiments and metagenomic analysis, this study tracked the transmission of antibiotic resistance genes (ARGs) from swine manure (SM) to biogas residue and then to soil (biogas residue as organic fertilizer (OF) application). ARGs were abundant in SM and they were assigned to 11 categories of antibiotics. Among the 383 ARG subtypes in SM, 43 % ARG subtypes were absent after anaerobic digestion (AD), which avoided the transfer of these ARGs from SM to soil. Furthermore, 9 % of the ARG subtypes in SM were introduced into soil after amendment with OF. Moreover, 43 % of the ARG subtypes in SM were present in OF and soil, and their abundances increased slightly in the soil amended with OF. The bacterial community in the soil treated with OF was restored to its original state within 60 to 90 days, probably because the abundances of ARGs were elevated but not significantly in the soil. Network analysis identified 31 potential co-host bacteria of ARGs based on the relationships between the bacteria community members, where they mainly belonged to Firmicutes, followed by Bacteroidetes, Actinobacteria, and Proteobacteria. This study provides a basis for objectively evaluating pollution by ARGs in livestock manure for agricultural use.

Facilitating mitigation of agricultural non-point source pollution and improving soil nutrient conditions: The role of low temperature co-pyrolysis biochar in nitrogen and phosphorus distribution.

The current study generated co-pyrolysis biochar by pyrolyzing rice straw and pig manure at 300 °C and subsequently applying it in a field. Co-pyrolysis biochar demonstrated superior efficiency in mitigating agricultural non-point source pollution compared to biochar derived from individual sources. Furthermore, it displayed notable capabilities in retaining and releasing nutrients, resulting in increased soil levels of total nitrogen, total phosphorus, and organic matter during the maturation stage of rice. Moreover, co-pyrolysis biochar influences soil microbial communities, potentially impacting nutrient cycling. During the rice maturation stage, the soil treated with co-pyrolysis biochar exhibited significant increases in available nutrients and rice yield compared to the control (p < 0.05). These findings emphasize the potential of co-pyrolysis biochar for in-situ nutrient retention and enhanced soil nutrient utilization. To summarize, the co-pyrolysis of agricultural waste materials presents a promising approach to waste management, contributing to controlling non-point source pollution, improving soil fertility, and promoting crop production.

An oral triple pill-based cocktail effectively controls acute myeloid leukemia with high translation.

Acute myeloid leukemia (AML) is a deadly hematological malignancy characterized by oncogenic translational addiction that results in over-proliferation and apoptosis evasion of leukemia cells. Various chemo- and targeted therapies aim to reverse this hallmark, but most show only modest efficacy. Here we report a single oral pill containing a low-dose triple small molecule-based cocktail, a highly active anti-cancer therapy (HAACT) with unique mechanisms that can effectively control AML. The cocktail comprises oncogenic translation inhibitor HHT, drug efflux pump P-gpi ENC and anti-apoptotic protein Bcl-2i VEN. Mechanistically, the cocktail can potently kill both leukemia stem cells (LSC) and bulk leukemic cells via co-targeting oncogenic translation, apoptosis machinery, and drug efflux pump, resulting in deep and durable remissions of AML in diverse model systems. We also identified EphB4/Bcl-xL as the cocktail response biomarkers. Collectively, our studies provide proof that a single pill containing a triple combination cocktail might be a promising avenue for AML therapy.

Comparison of anti-thymocyte globulin-based immunosuppressive therapy and allogeneic hematopoietic stem cell transplantation in patients with transfusion-dependent non-severe aplastic anaemia: a retrospective study from a single centre.

OBJECTIVES: The selection and timing of anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST) or allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with transfusion-dependent non-severe aplastic anemia (TD-NSAA) pose significant clinical challenges. This study aims to compare the efficacy and long-term outcomes of the two treatments in TD-NSAA. METHODS: Patients who underwent ATG-based IST or allo-HSCT between July 2011 and December 2019 were reviewed. We gathered their clinical information, treatment response, survival data, and subsequently analysed the associated risk factors. RESULTS: A total of 97 TD-NSAA patients were reviewed, and 55 patients who underwent either ATG-based IST (n = 27) or allo-HSCT (n = 28) were enrolled. We observed a significant disparity in the 12-month overall response rate (ORR) (48.1% in IST vs 78.6% in HSCT, p < 0.05), but not in five-year overall survival (OS) and event-free survival (EFS). Multivariate Cox regression analysis identified the transfusion of ≥78.75 units of red blood cells (RBCs) as the sole independent risk factor for OS (HR: 17.04, p = 0.039) in the IST group. For the HSCT group, disease duration (DD) ≥20 months and transfusion of ≥78.75 units of RBCs predicted an adverse EFS. Frontline IST exhibited superior 12-month ORR (68.8% vs 18.2%, p = 0.018) and five-year EFS when compared to non-frontline. Patients with a DD ranging from 6 to 20 months displayed a better EFS (p = 0.016) in HSCT group than those in the ATG-based IST group. CONCLUSIONS: Prior treatment history, disease duration, and serum ferritin levels should be carefully weighed when making the choice between ATG-based IST and allo-HSCT for TD-NSAA.

The selection and timing of anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST) or allogeneic hematopoietic stem cell transplantation (allo-HSCT) present notable clinical challenges for individuals with transfusion-dependent non-severe aplastic anaemia (TD-NSAA).In terms of treatment outcomes, allo-HSCT exhibited a higher 12-month overall response rate (ORR) in comparison to ATG-based IST among TD-NSAA patients. Nevertheless, comparable rates of 5-year overall survival (OS) and event-free survival (EFS) were observed between the two therapeutic approaches.Several factors warrant consideration when deliberating between ATG-based IST and allo-HSCT for TD-NSAA. These factors include the patient's prior treatment history, disease duration, number of packed red cell transfusions received, and serum ferritin levels.

In-situ retention of nitrogen, phosphorus in agricultural drainage and soil nutrients by biochar at different temperatures and the effects on soil microbial response.

This study conducted a two-year experiment to investigate the impacts of biochar with various temperatures (350 °C, 500 °C, and 650 °C), on the reduction of pollutants in agricultural runoff and the enhancement of soil fertility. The results showed that the biochar significantly reduced the concentrations of total nitrogen and total phosphorus in farmland runoff. Moreover, higher-temperature biochar demonstrated greater efficacy in decreasing pollutants in farmland drainage. Treatment with RB650 resulted in a reduction of the total nitrogen and total phosphorus output load by 29.31-30.67 % and 21.92-25.21 %, respectively, compared to RB350. Furthermore, biochar exhibited substantial enhancements in soil fertility. This was supported by heightened soil organic matter content, increased availability of nutrients, and a noteworthy (P < 0.05) upsurge in pH, organic matter, total nitrogen, and total phosphorus content observed in the second year following the application of biochar. Biochar has the potential to enhance soil enzyme activity and affect microbial community composition, thereby facilitating nutrient cycling. The findings illustrated the regenerative and recyclable characteristics of biochar's adsorption activity throughout crop growth. This process enables sustained improvement in soil nutrient retention capacity and fertility. Thus, it emphasizes the potential of biochar as an in-situ model for nutrient retention and recycling, offering an effective approach to mitigate agricultural non-point source (NPS) pollution and enhance soil fertility.

High-throughput profiling the effects of zinc on antibiotic resistance genes in the anaerobic digestion of swine manure.

The problem of antibiotic resistance genes (ARGs) caused by heavy metals has attracted extensive attention of human beings. Zn, a widely used feed additive, has a very high residue in swine manure, but the distribution characteristics of ARGs imposed by Zn in anaerobic digestion (AD) products are not clear. In this study, the behaviour of mobile genetic elements (MGEs), bacterial community, and their association with ARGs were determined in the presence of 125 and 1250 mg L-1 Zn in AD system of swine manure. Zn-treated enriched the abundance of ARGs, and produced some new genotypes that were not detected in CK treatment. In addition, low concentration of Zn significantly increased the relative abundance of ARGs, as compared to higher Zn and CK group. Correspondingly, the abundances of most top30 genus were highest in ZnL (125 mg L-1 Zn), followed by CK and ZnH (1250 mg L-1 Zn). Notably, network analysis showed that the relationship between ARGs and MGEs is closer than that ARGs and bacteria, suggesting that ARGs increased in Zn-treated, especially low level Zn, may be due to the amplification transfer of ARGs among varied microorganisms by horizontal transfer with MGEs. Therefore, strengthen the management of in livestock manure is crucial to control the spread of ARGs in organic fertilizers.

Modified biochar prepared from Retinervus luffae fructus for dyes adsorption and aerobic sludge granulation.

Retinervus luffae fructus biochar (RLFB) and ZnCl2 pretreated Retinervus luffae fructus biochar (ZRLFB) were prepared by pyrolysis. The as-prepared biochar was investigated for its applicability as a dye adsorber using sunset yellow (SY) and basic red 46 (BR46) dyes. Additionally, ZRLFB was used for the experimental cultivation of granular sludge. The results indicated that the adsorption effect of ZRLFB on the two dyes was higher than RLFB. The adsorption of RLFB to SY was related to the Langmuir and Freundlich models, whereas the adsorption of RLFB-BR46, ZRLFB-SY, and ZRLFB-BR46 was more in line with the Langmuir model. The adsorption process of dyes on two kinds of biochars can be described using pseudo-second-order mechanisms. The maximum adsorption capacity obtained was 1.9586 (RLFB-SY), 6.1286 (RLFB-BR46), 49.2611 (ZRLFB-SY), and 181.4882 mg g-1 (RLFB-BR46). The result of the SBR operation showed that ZRLFB can potentially be applied as the core of aerobic granular sludge.

Whole-exome sequencing identifies FANC heterozygous germline mutation as an adverse factor for immunosuppressive therapy in Chinese aplastic anemia patients aged 40 or younger: a single-center retrospective study.

Acquired aplastic anemia (AA) is a bone marrow failure disorder characterized by pancytopenia, and immunosuppressive therapy (IST) is the optional first-line management. Several studies identified the influencing factors on IST response; however, there are still a considerable number of patients suffering from poor prognoses. In this study, we enrolled 61 AA patients aged ≤ 40 years old, and whole-exome sequencing (WES) found unexpected high FANC heterozygous germline mutations (28/61, 45.9%). Patients with FANC mutations have a significantly lower absolute reticulocyte count and CD34+ % in the bone marrow and also lower 3-, 6-, and 9-month IST response than that without mutation, which were 0% vs. 25% (P = 0.017), 26.3% vs. 42.1% (P = 0.495), and 29.4% vs. 72.2% (P = 0.011), especially in anti-thymocyte globulin combined with the cyclosporin A (ATG + CsA) group, which were 0% vs.33.4% (P = 0.143), 25% vs.83.3% (P = 0.103), and 25% vs. 100% (P = 0.003), respectively. The event-free survival in the FANCwt group was also better than that in the FANCmut group (P = 0.016) and also showed in patients who received ATG + CsA treatment (P = 0.045). In addition, all the adverse effects of FANC germline mutation were not significant in stem cell-transplanted group. Our result indicated that the WES-based detection of FANC heterozygous germline mutations may have a great meaning in predicting IST response of acquired AA. This study was registered at chictr.org.cn (# ChiCTR2100054992).

Circular RNA PVT1 Regulates Cell Proliferation, Migration, and Apoptosis by Stabilizing c-Myc and Downstream Target CXCR4 Expression in Acute Myeloid Leukemia

Objective: This study aimed to investigate the role and mechanism of circular RNA PVT1 (circPVT1) in patients with acute myeloid leukemia (AML). Materials and Methods: The expression of circPVT1 in 23 patients with de novo AML (not acute promyelocytic leukemia, not APL) and cell lines were detected by RT-qPCR. Loss of function assays were carried out to explore the influence of silenced circPVT1 on the proliferation, migration, and apoptosis in the THP-1 cell line. CCK-8 assays, trans-well assays, and annexin V/PI staining assays were performed to assess proliferation, migration, and apoptosis, respectively. Results: CircPVT1 was highly expressed in AML patients and myeloid cell lines compared to healthy controls. Higher expression of circPVT1 was related to shorter overall survival (OS) and relapse-free survival (RFS) in AML patients. Cell viability and migration were inhibited and apoptosis was increased when circPVT1 was knocked down in THP-1 cells. Knockdown of circPVT1 resulted in marked suppression of c-Myc protein with no significant change in mRNA levels. We also found that circPVT1 knockdown markedly increased the phosphorylation of c-Myc Thr-58, which was responsible for c-Myc degradation. Silencing of c-Myc caused a significant decrease in CXCR4 mRNA and protein expression, whereas the overexpression of c-Myc caused the opposite result, suggesting that CXCR4 is a target molecule of c-Myc. Finally, we found that overexpression of c-Myc could partially reverse circPVT1 knockdown-induced anti-tumor effects on THP-1 cells in vitro. Conclusion: Our findings showed that circPVT1 was highly expressed in AML patients and was related to shorter OS and RFS. CircPVT1 may exert an oncogenic effect in THP-1 cells by stabilizing c-Myc protein expression and downstream target CXCR4 expression. These data indicate that circPVT1 may be a promising therapeutic target for AML.

Effect of graphene and graphene oxide on antibiotic resistance genes during copper-contained swine manure anaerobic digestion.

Copper is an important selectors for antibiotic resistance genes (ARGs) transfer because of metal-antibiotic cross-resistance and/or coresistance. Due to carbon-based materials' good adsorption capacity for heavy metals, graphene and graphene oxide have great potential to reduce ARGs abundance in the environment with copper pollution. To figure out the mechanics, this study investigated the effects of graphene and graphene oxide on the succession of ARGs, mobile genetic elements (MGEs), heavy metal resistance genes (HMRGs), and bacterial communities during copper-contained swine manure anaerobic digestion. Results showed that graphene and graphene oxide could reduce ARGs abundance in varying degrees with the anaerobic reactors that contained a higher concentration of copper. Nevertheless, graphene decreased the abundance of ARGs more effectively than graphene oxide. Phylum-level bacteria such as Firmicutes, Bacteroidetes, Spirochaetes, and Verrucomicrobiaat were significantly positively correlated with most ARGs. Network and redundancy analyses demonstrated that alterations in the bacterial community are one of the main factors leading to the changes in ARGs. Firmicutes, Bacteroidetes, and Spirochaetes were enriched lower in graphene reactor than graphene oxide in anaerobic digestion products, which may be the main reason that graphene is superior to graphene oxide in reduced ARGs abundance. Additionally, ARGs were close to HMRGs than MGEs in the treatments with graphene, the opposite in graphene oxide reactors. Therefore, we speculate that the reduction of HMRGs in graphene may contribute to the result that graphene is superior to graphene oxide in reduced ARGs abundance in anaerobic digestion.

Measurement and summary of photoionization data for biomass-derived compounds.

RATIONALE: Biomass is a potential feedstock for making liquid fuels and valuable chemicals. Quantitative analysis of biomass conversion in real time by photoionization mass spectrometry (PIMS) is an important way to understand the reaction process. However, the lack of photoionization data for biomass-derived compounds limits the research using PIMS. METHODS: Measurements of photoionization data were performed with synchrotron vacuum ultraviolet PIMS. Toluene and methanol were used as calibrated references and solvents in this experiment since their photoionization cross-sections (PICS) are well documented in the literature. RESULTS: The ionization energies (IEs) of 23 biomass-derived compounds were measured. Among them, the PICSs of 14 compounds were calibrated and presented. Besides, the IEs of 95 other biomass-derived compounds and their typical fragment ions were also summarized. CONCLUSIONS: A photoionization database related to IEs and PICSs of biomass-derived compounds (m/z < 200) is established. PICSs of most biomass-derived compounds have low values at the most frequently used photoionization energy of 10.5 eV. Lignin-derived compounds have lower IEs than carbohydrate-derived compounds.

Acute myeloid leukemia with myelodysplasia-related changes and blasts of the mixed T/myeloid phenotype: a case report.

A rare but clinically important diagnostic dilemma arises when cases meet the criteria for both acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) and mixed phenotype acute leukemia, especially those that evolve from myelodysplastic syndrome. We describe a 56-year-old male patient who presented with cytopenias and was initially diagnosed with myelodysplastic syndrome with single lineage dysplasia. Nearly 1 year later, this patient progressed to acute leukemia, and his blast cells simultaneously expressed T-lymphoid and myeloid antigens. Cytogenetic analysis showed a 20q deletion, and next-generation sequencing showed mutations of ASXL1, NRAS, PHF6, RUNX1, TP53, and PIGA. He was diagnosed with AML-MRC with blasts of the mixed T/myeloid phenotype according to the latest World Health Organization guidelines. In accordance with the treatment principles of AML-MRC, we chose an AML-like regimen for four cycles, but the patient did not achieve remission. Finally, we adhered to the treatment principles of mixed phenotype acute leukemia, and he achieved remission after a course of ALL-like regimen chemotherapy.

Combination of Haploidentical Hematopoietic Stem Cell Transplantation with Umbilical Cord-Derived Mesenchymal Stem Cells in Patients with Severe Aplastic Anemia: A Retrospective Controlled Study

Objective: We retrospectively compared the outcomes of patients with severe aplastic anemia (SAA) who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT) combined or not combined with umbilical cord-derived mesenchymal stem cells (UC-MSCs). Materials and Methods: A total of 101 patients with SAA were enrolled in this study and treated with haplo-HSCT plus UC-MSC infusion (MSC group, n=47) or haplo-HSCT alone (non-MSC group, n=54). Results: The median time to neutrophil engraftment in the MSC and non-MSC group was 11 (range: 8-19) and 12 (range: 8-23) days, respectively (p=0.049), with a respective cumulative incidence (CI) of 97.82% and 97.96% (p=0.101). Compared to the non-MSC group, the MSC group had a lower CI of chronic graft-versus-host disease (GVHD) (8.60±0.25% vs. 24.57±0.48%, p=0.048), but similar rates of grades II-IV acute GVHD (23.40±0.39% vs. 24.49±0.39%, p=0.849), grades III-IV acute GVHD (8.51±0.17% vs. 10.20±0.19%, p=0.765), and moderate-severe chronic GVHD (2.38±0.06% vs. 7.45±0.18%, p=0.352) were observed. The estimated 5-year overall survival (OS) rates were 78.3±6.1% and 70.1±6.3% (p=0.292) while the estimated 5-year GVHD-free, failure-free survival (GFFS) rates were 76.6±6.2% and 56.7±6.9% (p=0.045) in the MSC and non-MSC groups, respectively. Conclusion: In multivariate analysis, graft failure was the only adverse predictor for OS. Meanwhile, graft failure, grades III-IV acute GVHD, and moderate-severe chronic GVHD could predict worse GFFS. Our results indicated that haplo-HSCT combined with UC-MSCs infusion was an effective and safe option for SAA patients.

A Selective Small-Molecule c-Myc Degrader Potently Regresses Lethal c-Myc Overexpressing Tumors.

MYC oncogene is involved in the majority of human cancers and is often associated with poor outcomes, rendering it an extraordinarily desirable target, but therapeutic targeting of c-Myc protein has been a challenge for >30 years. Here, WBC100, a novel oral active molecule glue that selectively degrades c-Myc protein over other proteins and potently kills c-Myc overexpressing cancer cells is reported. WBC100 targets the nuclear localization signal 1 (NLS1)-Basic-nuclear localization signal 2 (NLS2) region of c-Myc and induces c-Myc protein degradation through ubiquitin E3 ligase CHIP mediated 26S proteasome pathway, leading to apoptosis of cancer cells. In vivo, WBC100 potently regresses multiple lethal c-Myc overexpressing tumors such as acute myeloid leukemia, pancreatic, and gastric cancers with good tolerability in multiple xenograft mouse models. Identification of the NLS1-Basic-NLS2 region as a druggable pocket for targeting the "undruggable" c-Myc protein and that single-agent WBC100 potently regresses c-Myc overexpressing tumors through selective c-Myc proteolysis opens new perspectives for pharmacologically intervening c-Myc in human cancers.

Biochars derived from bamboo and rice straw for sorption of basic red dyes.

The primary purpose of this study is to eliminate Basic Red 46 dye from aqueous solutions utilizing batch experiments by adsorption on biochars prepared from bamboo and rice straw biomass. Biochars prepared from bamboo (B), and rice straw (R) was pyrolyzed at 500°C (B500 and R500). Scanning Electron Microscopy (SEM), Fourier Transform Infrared (FTIR) Spectroscopy, X-ray Diffraction (XRD), and surface area and porosity analyzers were used to characterize the B500 and R500 samples. The characterization results indicated that the biochars possessed an amorphous porous structure with many functional groups consisting primarily of silicates. The adsorption rate of BR46 was evaluated using two kinetic models (pseudo-first-order and pseudo-second-order), and the results indicated that the pseudo-second-order model fitted to the experimental data well (R2>0.99). Nearly 24 h was sufficient to achieve equilibrium with the dye adsorption for the two biochars. R500 had a greater adsorption efficiency than B500. As pH levels increased, the dye's adsorption capability increased as well. The Langmuir and Freundlich isotherm models were used to investigate the equilibrium behavior of BR46 adsorption, and the equilibrium data fitted well with the Langmuir model (R2>0.99) compared to the Freundlich model (R2>0.89). The maximum adsorption capacities of BR46 are 9.06 mg/g for B500 and 22.12 mg/g for R500, respectively. Additionally, adsorption capacity increased as temperature increased, indicating that adsorption is favored at higher temperatures. The electrostatic interaction is shown to be the dominant mechanism of BR46 adsorption, and BR46 acts as an electron-acceptor, contributing to n-π EDA (Electron Donor-Acceptor) interaction. Thermodynamic parameters for the dye-adsorbent system revealed that the adsorption process is spontaneous and feasible. The values of the adsorption coefficient (Kd) were on the order of 102-103. Kd of R500 was greater than that of B500, indicating that R500 had a greater adsorption capacity. The results showed that R500 could be used as a low-cost alternative adsorbent for removing BR46 from effluents.