Clonal evolution from B-cell acute lymphoblastic leukemia with BCR::ABL1 multilineage involvement to acute myeloid leukemia after multiple anti-CD19 chimeric antigen receptor T-cell therapy.

Not available.

Exposure to coal dust exacerbates cognitive impairment by activating the IL6/ERK1/2/SP1 signaling pathway.

Coal dust (CD) is a common pollutant, and epidemiological surveys indicate that long-term exposure to coal dust not only leads to the occurrence of pulmonary diseases but also has certain impacts on cognitive abilities. However, there is little open-published literature on the effects and specific mechanisms of coal dust exposure on the cognition of patients with Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). An animal model has been built in this study with clinical population samples to explore the changes in neuroinflammation and cognitive abilities with coal dust exposure. In the animal model, compared to C57BL/6 mice, APP/PS1 mice exposed to coal dust exhibited more severe cognitive impairment, accompanied by significantly elevated levels of neuroinflammatory factors Apolipoprotein E4 (AOPE4) and Interleukin-6 (IL6) in the hippocampus, and more severe neuronal damage. In clinical sample sequencing, it was found that there is significant upregulation of AOPE4, neutrophils, and IL6 expression in the peripheral blood of MCI patients compared to normal individuals. Mechanistically, cell experiments revealed that IL6 could promote the phosphorylation of ERK1/2 and enhance the expression of transcription factor SP1, thereby promoting AOPE4 expression. The results of this study suggest that coal dust can promote the upregulation of IL6 and AOPE4 in patients, exacerbating cognitive impairment.

In vivo imaging reveals a synchronized correlation among neurotransmitter dynamics during propofol and sevoflurane anesthesia.

General anesthesia is widely applied in clinical practice. However, the precise mechanism of loss of consciousness induced by general anesthetics remains unknown. Here, we measured the dynamics of five neurotransmitters, including γ-aminobutyric acid, glutamate, norepinephrine, acetylcholine, and dopamine, in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter perspective. Results revealed that the concentrations of γ-aminobutyric acid, glutamate, norepinephrine, and acetylcholine increased in the cortex during propofol-induced loss of consciousness. Dopamine levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol anesthesia. Notably, the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness. Furthermore, the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic groups. These findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness.

Mechanisms of secondary biogenic coalbed methane formation in bituminous coal seams: a joint experimental and multi-omics study.

Coal seam microbes, as endogenous drivers of secondary biogenic gas production in coal seams, might be related to methane production in coal seams. In this study, we carried out anaerobic indoor culture experiments of microorganisms from three different depths of bituminous coal seams in Huainan mining area, and revealed the secondary biogas generation mechanism of bituminous coal seams by using the combined analysis of macro-genome and metabolism multi-omics. The results showed that the cumulative mass molar concentrations (Molality) of biomethane production increased with the increase of the coal seam depth in two consecutive cycles. At the genus level, there were significant differences in the bacterial and archaeal community structures corresponding to the three coal seams 1#, 6#, and 9#(p < 0.05). The volatile matter of air-dry basis (Vad) of coal was significantly correlated with differences in genus-level composition of bacteria and archaea, with correlations of R bacterial = 0.368 and R archaeal = 0.463, respectively. Functional gene analysis showed that the relative abundance of methanogenesis increased by 42% before and after anaerobic fermentation cultivation. Meanwhile, a total of 11 classes of carbon metabolism homologues closely related to methanogenesis were detected in the liquid metabolites of coal bed microbes after 60 days of incubation. Finally, the fatty acid, amino acid and carbohydrate synergistic methanogenic metabolic pathway was reconstructed based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The expression level of mcrA gene within the metabolic pathway of the 1# deep coal sample was significantly higher than that of the other two groups (p < 0.05 for significance), and the efficient expression of mcrA gene at the end of the methanogenic pathway promoted the conversion of bituminous coal organic matter to methane. Therefore, coal matrix compositions may be the key factors causing diversity in microbial community and metabolic function, which might be related to the different methane content in different coal seams.

Effects of Mechanical Properties on Gas-Water Flow Characteristics around Boreholes: Implementation of Damage-Based Coupling Models.

Neglecting the coal damage effect around a borehole could result in low accuracy of gas extraction seepage analysis. A fluid-solid coupling model incorporating coal stress and damage, gas diffusion, and seepage was established. Reliability of the proposed model was validated using field data. Variation characteristics of gas-water phase parameters in the borehole damage zone during gas drainage were analyzed. Meanwhile, effects of equivalent plastic strain, lateral pressure coefficient, internal friction angle, cohesion, Young's modulus, and Poisson's ratio on the damage state and spatiotemporal change properties of gas extraction flow were investigated. Results indicate that due to coal damage, permeability shows a three-zone distribution around the borehole, among which the fracture zone has the highest permeability, approximately 40 times of the original value. Permeability in the plastic zone decreases rapidly, while permeability is the smallest in the elastic zone. Coal permeability within the damage zone increases with continuous gas extraction. A smooth and low-value zone occurs for both fracture and matrix gas pressures. With the increase in equivalent plastic strain, the damage zone decreases, while peak permeability in the damage zone rises, and gas pressure in the smooth low-pressure zone continues to drop. The damage zone becomes smaller with an increasing lateral pressure coefficient, while those plastic and elastic zones become larger. The damage zone area corresponding to the lateral pressure coefficient of 0.89 is 82.3% smaller compared with that of 0.56. As internal friction angle and cohesion rise, the damage zone gradually decreases and shifts from a butterfly shape to elliptical shape. When Young's modulus is heterogeneously distributed, except for concentrated shear damage zones around the borehole, punctate microdamage zones are also found at positions far from the borehole. Those damage zones gradually become smaller as shape parameters of the Weibull distribution get larger. The above findings are expected to offer theoretical support and practical guidance for borehole drilling and efficient extraction of clean methane resources.

Effect of intraoperative dexmedetomidine on recovery of gastrointestinal function after caesarean section undergoing spinal and epidural anesthesia: A randomized, double blind, placebo-controlled clinical trial.

OBJECTIVE: Gastrointestinal dysfunction after cesarean section negatively affects postoperative recovery. Dexmedetomidine has been shown to improve postoperative gastrointestinal function in patients undergoing lumbar spinal fusion surgery and laparoscopic gastrectomy, but its role in cesarean section has not been fully elucidated. The study aimed to investigate the effect of dexmedetomidine on gastrointestinal function after cesarean section. STUDY DESIGN: 220 pregnant women who underwent elective cesarean section were randomized into group D and group S. Group D patients received a loading dose of 0.5 µg/kg of dexmedetomidine for 10 mins followed by a maintenance dose of 0.5 µg/kg/h intravenously immediately after the umbilical cord was cut intraoperatively, whereas the other group (group S) received an equivalent quantity of normal saline as loading and maintenance dose IV by infusion pump. The primary outcome was time to first flatus after surgery (hours). Secondary outcomes included time to first feces and first bowel sounds (hours), incidence rates of postoperative gastrointestinal complications, and the length of postoperative hospital stay (days). RESULTS: Modified intention-to-treat analysis showed that patients in Group D had a significantly shorter time to first flatus (21 [16 to 28.25] vs. 25 [18 to 32.25] h; P = 0.014), time to first feces (45.5 [35.75 to 55.25] vs. 53 [40 to 60] h; P = 0.019), and time to first bowel sounds (P = 0.010), a lower incidence of abdominal distension (21[20.6 %] vs. 36[34.3 %], P = 0.027), shorter length of postoperative hospital stay (P = 0.010) compared to patients in Group S. CONCLUSION: Intraoperative dexmedetomidine infusion reduces the time to first flatus, the incidence of abdominal distension, and shortens the length of hospital stay, promoting gastrointestinal function after cesarean section.

[Research Progress on Solidification and MICP Remediation of Soils in Heavy Metal Contaminated Site].

Heavy metal pollution in soils of smelting sites is an important environmental problem to be solved urgently. Solidification technology has become one of the mainstream technologies for heavy metal remediation in contaminated sites owing to its shorter remediation time, low cost, and high treatment efficiency. On the basis of summarizing the latest research progress on the remediation of heavy metal pollution in sites by solidification in the past 10 years, this study focused on the mechanisms of solidification technology and analyzed the advantages and disadvantages of different mechanisms (mechanism of inorganic materials, mechanism of organic materials, mechanism of mechanical ball milling, and mechanism of microbial-induced carbonate mineralization (MICP)) and their scope of application. Then, according to the research focus and development trend presented by CiteSpace, the application prospects and limiting factors of MICP technology for the solidification and remediation of heavy metal pollution in sites were summarized from three aspects:the application of MICP in multi-metal remediation, the application of MICP composites in contaminated sites, and the influencing factors of MICP technology application. Finally, the prospects and challenges in solidification technology were put forward in order to provide reference for the future development.

Catalytic reduction of nitrogen monoxide using iron-nickel oxygen carriers derived from electroplating sludge: Novel method for the collaborative emission decrease of polluting gases.

The valorization of electroplating sludge (ES) for high added value presents greater economic and environmental benefits than conventional treatment methods such as thermal processing, solidification, and landfill. Inspired by the mechanism of chemical looping combustion (CLC), this study developed a novel cost-effective method for denitrification by preparing FeNi-OCs from ES to achieve the synergistic reduction of CO and NO emissions. The phase structure, micromorphology, and valence state changes of the FeNi-OC catalyst during the CO-catalyzed reduction of NO and the pathway for catalytic denitrification using FeNi-OCs were analyzed. Results showed that CO could reduce FeNi-OCs to FeNi, and the reduced FeNi was subsequently oxidized back to FeNi-OCs by NO, a process analogous to CLC. During experiments, the simultaneous consumption of CO and NO gases was observed at 350 °C. This phenomenon was highly pronounced at 600 °C, where the CO and NO concentrations decreased from initial values of 8550 and 470 ppm, respectively, to 6719 and 0 ppm, respectively, with conversion rates of 21.41 % and 100 %, respectively. Hence, synergistic emission reduction was achieved. Further experiments also indicated that the addition of 1.5 % ES during iron ore sintering could substantially reduce the CO and NO concentrations in the sintering flue gas from 1268.32 and 244.81 ppm, respectively, to 974.51 and 161.11 ppm, respectively.

Experimental Study on the Effect of Gas Pressure on the Pore Structure and Dynamic Mechanical Properties of Coal.

Understanding the effect of gas pressure on coal pore structure and dynamic mechanical properties can better guide the accurate monitoring of stress and gas in gas-containing coal seams in coal mines and efficiently prevent and control coal/rock-gas composite dynamic hazards. In this study, the characterization of the pore structure of the coal body under different gas pressures and three-dimensional impact compression tests were carried out. The findings demonstrate that when the axial static load and confining pressure are fixed, the gas pressure determines the amount of gas adsorbed by the coal samples and its pore structure changes. The effect of gas pressure on the pore structure of the micropores is not obvious, but it has an obvious dilatation effect on the pore structure of the macropores. Within the range of conditions and gas pressures studied in this paper, gas-containing coals' dynamic compressive strength and failure strain decrease linearly with increasing gas pressure. The average dynamic strength deterioration rate of gas-containing coals increases linearly with an increase of gas pressure, which plays a deteriorating role in the dynamic mechanical properties of coal bodies. When the gas pressure increases from 0.7 to 2.8 MPa, the radius of the macropores inside the gas-containing coal increases 0.63 times, and the increased pores and cracks produce a stress concentration effect around the pores and cracks and the shorter time required for instability damage of the coal samples to occur when subjected to dynamic loading. The research results improve the basic theory of gas-containing coal dynamics and provide a theoretical basis for the mine coal/rock-gas composite dynamics disaster.

Investigations of the prognostic value of RUNX1 mutation in acute myeloid leukemia patients: Data from a real-world study.

RUNX1 is one of the recurrent mutated genes in newly diagnosed acute myeloid leukemia (AML). Although historically recognized as a provisional distinct entity, the AML subtype with RUNX1 mutations (AML-RUNX1mut) was eliminated from the 2022 WHO classification system. To gain more insight into the characteristics of AML-RUNX1mut, we retrospectively analyzed 1065 newly diagnosed adult AML patients from the First Affiliated Hospital of Soochow University between January 2017 and December 2021. RUNX1 mutations were identified in 112 patients (10.5%). The presence of RUNX1 mutation (RUNX1mut) conferred a lower composite complete remission (CRc) rate (40.2% vs. 58.4%, P＜0.001), but no significant difference was observed in the 5-year overall survival (OS) rate (50.2% vs. 53.9%; HR=1.293; P=0.115) and event-free survival (EFS) rate (51.5% vs. 49.4%; HR=1.487, P=0.089), even within the same risk stratification. Multivariate analysis showed that RUNX1mut was not an independent prognostic factor for OS (HR=1.352, P=0.068) or EFS (HR=1.129, P=0.513). When patients were stratified according to induction regimen, RUNX1mut was an unfavorable factor for CRc both on univariate and multivariate analysis in patients receiving conventional chemotherapy, and higher risk stratification predicted worse OS. In those who received venetoclax plus hypomethylating agents, RUNX1mut was not predictive of CRc and comparable OS and EFS were seen between intermediate-risk and adverse-risk groups. The results of this study revealed that the impact of RUNX1mut is limited. Its prognostic value depended more on treatment and co-occurrent abnormalities. VEN-HMA may abrogate the prognostic impact of RUNX1, which merits a larger prospective cohort to illustrate.

Insight into the relationship between metabolic enzymes and oxadiazon degradation in Oryza sativa for reducing environmental risks.

Oxadiazon (ODZ) is extensively utilized in agricultural fields for weed control owing to its strong effectiveness. However, excessive loading of ODZ in water bodies and agricultural soils can lead to various environmental concerns. Therefore, it is crucial to understand the ODZ metabolic process and associated mechanisms in crops to assess the likelihood of ODZ contamination in the environment. This study aimed to assess the effects of ODZ on the growth and toxicological responses of rice (Oryza sativa). The growth of rice tissues was notably compromised with the increase in ODZ concentrations. RNA sequencing in combination with liquid chromatography-quadrupole-time-of-flight-high-resolution mass spectrometry/mass spectrometry (LC-Q-TOF-HRMS/MS) analysis allowed for the identification of numerous transcriptional components associated with ODZ metabolism. Four libraries comprising rice roots and shoots exposed to ODZ were RNA-sequenced in triplicate. The application of environmentally realistic ODZ concentrations upregulated the expression of 844 genes in shoots and 1476 genes in roots. Gene enrichment analysis revealed the presence of multiple enzymes involved in ODZ metabolism and detoxification. These enzymes play a critical role in mitigating environmental stress and facilitating xenobiotic metabolism. Notably, among differentially expressed genes, several key enzymes were identified, including cytochrome P450s, protein kinases, aminotransferases, and ATP-binding cassette transporters involved in the metabolic process. Using LC-Q-TOF-HRMS/MS, 3 metabolites and 13 conjugates were identified in multiple metabolic pathways involving oxidation, hydrolysis, glycosylation, acetylation, and methylation. This study successfully established a potential link between the specific metabolic products of ODZ and increased activities of their corresponding enzymes. Moreover, this study considerably elucidates the detailed pathways and mechanisms involved in ODZ metabolism. The study findings provide valuable insights into the development of genotypes for reducing ODZ residues in paddy fields and minimizing their accumulation in rice crops.

Improved Formation of Biomethane by Enriched Microorganisms from Different Rank Coal Seams.

The influence of enrichment of culturable microorganisms in in situ coal seams on biomethane production potential of other coal seams has been rarely studied. In this study, we enriched culturable microorganisms from three in situ coal seams with three coal ranks and conducted indoor anaerobic biomethane production experiments. Microbial community composition, gene functions, and metabolites in different culture units by 16S rRNA high-throughput sequencing combined with liquid chromatography-mass spectrometry-time-of-flight (LC-MS-TOF). The results showed that biomethane production in the bituminous coal group (BC)cc resulted in the highest methane yield of 243.3 µmol/g, which was 12.3 times higher than that in the control group (CK). Meanwhile, Methanosarcina was the dominant archaeal genus in the three experimental groups (37.42 ± 11.16-52.62 ± 2.10%), while its share in the CK was only 2.91 ± 0.48%. Based on the functional annotation, the relative abundance of functional genes in the three experimental groups was mainly related to the metabolism of nitrogen-containing heterocyclic compounds such as purines and pyrimidines. Metabolite analysis showed that enriched microorganisms promoted the degradation of a total of 778 organic substances in bituminous coal, including 55 significantly different metabolites (e.g., purines and pyrimidines). Based on genomic and metabolomic analyses, this paper reconstructed the heterocyclic compounds degradation coupled methane metabolism pathway and thereby preliminarily elucidated that enriched culturable bacteria from different coal-rank seams could promote the degradation of bituminous coal and intensify biogenic methane yields.

Clinical application of a connection device consisting of a bag valve mask and nebulizer in first aid: Two case reports.

In clinical practice, several emergencies may threaten the life of patients, and these emergencies can be unpredictable and challenging. During the coronavirus disease 2019 pandemic, in January 2023, a patient developed respiratory distress caused by coronavirus, but was unable to access respiratory support due to shortages of medical resources, intensive care unit beds and ventilators. The medical staff quickly created a portable high-flow atomized oxygen therapy apparatus consisting of a simple breathing bag connected to a nebulizer to provide breathing support. In addition, the Ambulatory Surgery Center, The First Affiliated Hospital of Anhui Medical University (Hefei, China) witnessed a case of severe laryngeal spasm after tracheal extubation during the recovery period from general anesthesia. Due to the lack of an anesthesia machine nebulizer, the aforementioned device was used to provide oxygen under pressure and initiate treatment to quickly relieve the symptoms of laryngeal obstruction. The present case report describes how the medical staff quickly applied emergency airway management skills and knowledge to create a portable high-flow atomized oxygen therapy apparatus in a resource-poor setting to save the lives of two patients.

Intraoperative electroencephalogram features related to frailty in older patients: an exploratory prospective observational study.

Frailty is an independent risk factor for the increased incidence of postoperative delirium (POD). To date, the effect of frailty on intraoperative electroencephalogram (EEG) changes remains unexplored. The present study, an exploratory analysis of a prospective cohort study, aimed to investigate the differences in EEG characteristics between frail and robust patients. This prospective observational study was conducted between December 2020 and November 2021. The preoperative frailty status was assessed using the FRAIL scale. The patients' baseline (before anesthesia) and intraoperative EEG data were collected using a brain function monitor. Finally, 20 robust and 26 frail older patients scheduled for elective spinal surgery or transurethral prostatectomy under propofol-based general anesthesia were included in the final analysis. Baseline and intraoperative EEG spectrogram and power spectra were compared between the frail and robust groups. No differences were observed in baseline EEG between the frail and robust groups. When the intraoperative EEG spectral parameters were compared, the alpha peak frequency (10.56 ± 0.49 vs. 10.14 ± 0.36 Hz, P = 0.002) and alpha peak, delta, theta, alpha, and beta powers were lower in the frail group. After adjusting for age, Charlson Comorbidity Index (CCI), and mini-mental state examination (MMSE) score, the FRAIL score was still negatively associated with total, delta, theta, alpha, and beta powers. Frail patients had reduced EEG (0-30 Hz) power after the induction of propofol-based general anesthesia. After adjusting for age, CCI, and MMSE score, frail patients still showed evidence of reduced δ, θ, α, and ß power.

Rational design, synthesis and binding mechanisms of novel benzyl geranate derivatives as potential eco-friendly aphid repellents.

BACKGROUND: The push-pull strategy is considered as a promising eco-friendly method for pest management. Plant volatile organic compounds (PVOCs) act as semiochemicals constitute the key factor in implementing this strategy. Benzyl alcohol and geraniol, as functional PVOCs, were reported to regulate insect behavior, showing the potential application in pest control. Using geraniol as lead, a geraniol derivative 5i with fine repellent activity was discovered in our previous work. In order to explore novel, eco-friendly aphid control agents, a series of benzyl geranate derivatives was designed and synthesized using 5i as the lead and benzyl alcohol as the active fragment. RESULTS: Benzyl alcohol was firstly evaluated to have repellent activity to Acyrthosiphon pisum. Based on this repellent fragment, a series of novel benzyl geranate derivatives was rationally designed and synthesized using a scaffold-hopping strategy. Among them, compound T9, with a binding affinity (Kd = 0.43 µm) and a substantial repellency of 64.7% against A. pisum, is the most promising compound. Molecule docking showed that hydrophobic and hydrogen-bonding interactions substantially influenced the binding affinity of compounds with ApisOBP9. Additionally, T9 exhibited low-toxicity to honeybees and ladybugs. CONCLUSION: Using a simple scaffold-hopping strategy combined with active fragment benzyl alcohol, a new derivative T9, with high aphid-repellency and low-toxicity to nontarget organisms, can be considered as a novel potential eco-friendly aphid control agent for sustainable agriculture. © 2023 Society of Chemical Industry.

Uptake, translocation, accumulation, and metabolism of fluroxypyr-meptyl and oxidative stress induction in rice seedling.

Fluroxypyr-meptyl (FLUME) is heterocyclic herbicide with internal absorption and transmission characteristics. Owing to its low cost and rapid efficacy, it has been widely used to control broad-leaved weeds in wheat, corn, and rice fields. However, the uptake, translocation, accumulation, and metabolism of FLUME in rice seedlings and the extent of oxidative stress induced by it remain largely unknown, which consequently restricts the comprehensive risk assessment of FLUME residues in the environment during rice production. Hence, we systematically investigated the growth and physiological responses of rice to FLUME and analyzed its uptake, translocation, accumulation, and metabolism in rice seedlings. The results indicated that under 0-0.12 mg/L FLUME treatment, only a small proportion of FLUME was translocated upward and accumulated in rice shoots following absorption via roots, with all the translocation factor values being < 1. Moreover, the distribution and enrichment ability of FLUME in rice seedlings were greater in roots than in shoots. Furthermore, we revealed that FLUME accumulation in rice seedlings evidently inhibited their growth and activated the defense system against oxidative stress, with an increase in the activity of antioxidant and detoxifying enzymes. In addition, multiple metabolic reactions of FLUME were observed in rice seedlings, including dehalogenation, hydroxylation, glycosylation, acetylation, and malonylation. Our study provides systematic insights into the uptake, translocation, accumulation, and metabolism of FLUME in rice seedlings as well as the oxidative stress induced by FLUME accumulation, which can help improve FLUME applications and environmental risk assessments in crops.

Preemptive inotuzumab ozogamicin eradicated measurable residual disease in Ph-negative acute lymphoblastic leukemia relapsed post CD19 CART therapy.

There are no reports of application of inotuzumab ozogamicin (InO) for the treatment of MRD in r/r B-ALL. We firstly report the efficacy of InO for a patient experienced morphological relapse after HSCT and molecular relapse after CART therapy.