Prognostic significance of CRLF2 in patients with acute lymphoblastic leukemia: a meta-analysis and systematic review.

The association between cytokine receptor-like factor 2 (CRLF2) and clinical outcomes in acute lymphoblastic leukemia (ALL) has been a topic of ongoing debate, with divergent findings. This article intended to investigate the influence of CRLF2 alterations on ALL prognosis. Following the PRISMA 2020 guidelines, this meta-analysis was conducted. Hazard ratio (HR) values and confidence intervals (CIs) were the primary statistical measures used. Data heterogeneity was judged using the chi-square test and I2 statistic. Publication bias was appraised with funnel plots, Begg's test, and Egger's test. 16 studies with 6771 patients were finally screened out. CRLF2 over-expression (CRLF2 OE) was associated with poorer event-free survival (EFS) (HR = 1.70, 95% CI = 1.18-2.44, P = 0.004) and relapse-free survival (RFS) (HR = 1.70, 95% CI = 1.28-2.24, P = 0.000) in pediatric ALL. Patients with CRLF2-deregulation (CRLF2-d), also known as CRLF2 rearrangement, exhibited shorter overall survival (OS) (HR = 2.22, 95% CI = 1.49-3.32, P = 0.000), EFS (HR = 1.93, 95% CI = 1.43-2.60, P = 0.000), and RFS (HR = 2.2, 95% CI = 1.53-3.18, P = 0.000) compared to those without CRLF2-d. Subgroup analysis of multivariate HRs and corresponding CIs indicated that childhood with CRLF2 OE had a shorter RFS (HR = 1.70, 95% CI = 1.28-2.24, P = 0.006), and CRLF2-d was identified as an independent prognostic biomarker for OS (HR = 2.22, 95% CI = 1.49-3.32, P = 0.000), EFS (HR = 1.95, 95% CI = 1.44-2.64, P = 0.000), and RFS (HR = 2.2, 95% CI = 1.53-3.18, P = 0.000) in pediatric ALL patients. Both CRLF2 OE and CRLF2-d are associated with poor prognosis in ALL patients.

Analysis of Intestinal Microbiota in Schizophrenic Patients with Type 2 Diabetes Mellitus.

Objective: Our goal is to examine the correlation between gut microbiota and the cooccurrence of schizophrenia and type 2 diabetes. Methods: We conducted a study on the intestinal microbiota of 4 distinct groups: simple schizophrenia group (SC), schizophrenia with type 2 diabetes group (TS), type 2 diabetes group (T2DM), and normal population control group (HC), comprising a total of 35 subjects. Results: The bacteria phyla Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Verrucobacteria were consistently present across all 4 groups. Significantly higher intestinal microbiota richness was observed in the T2DM compared to the other group, and the intestinal microbiota richness in TS significantly lower than that of the SC. Conclusion: Our study suggests that the presence of type 2 diabetes in individuals with schizophrenia may affect the composition of their gut microbiota. We hypothesize that the concurrent existence of both diseases could potentially lead to alterations in the structure of gut microbiota, potentially influencing treatment effectiveness and outcomes.

Study on the Compressive Strength and Reaction Mechanism of Alkali-Activated Geopolymer Materials Using Coal Gangue and Ground Granulated Blast Furnace Slag.

By reutilizing industrial byproducts, inorganic cementitious alkali-activated materials (AAMs) contribute to reduced energy consumption and carbon dioxide (CO2) emissions. In this study, coal gangue (CG) blended with ground granulated blast furnace slag (GGBFS) was used to prepare AAMs. The research focused on analyzing the effects of the GGBFS content and alkali activator (i.e., Na2O mass ratio and alkali modulus [SiO2/Na2O]) on the mechanical properties and microstructures of the AAMs. Through a series of spectroscopic and microscopic tests, the results showed that the GGBFS content had a significant influence on AAM compressive strength and paste fluidity; the optimal replacement of CG by GGBFS was 40-50%, and the optimal Na2O mass ratio and alkali modulus were 7% and 1.3, respectively. AAMs with a 50% GGBFS content exhibited a compact microstructure with a 28 d compressive strength of 54.59 MPa. Increasing the Na2O mass ratio from 6% to 8% promoted the hardening process and facilitated the formation of AAM gels; however, a 9% Na2O mass ratio inhibited the condensation of SiO4 and AlO4 ions, which decreased the compressive strength. Increasing the alkali modulus facilitated geopolymerization, which increased the compressive strength. Microscopic analysis showed that pore size and volume increased due to lower Na2O concentrations or alkali modulus. The results provide an experimental and theoretical basis for the large-scale utilization of AAMs in construction.

[Prognosis and immune biomarkers of multiple myeloma].

Multiple myeloma (MM) is a highly heterogeneous hematological malignancy. The complex cytogenetic changes, immune cell infiltration and genetic mutations in MM jointly promote the proliferation, survival and drug resistance of MM cells. Therefore, understanding the tumor biological characteristics of MM and exploring the prognosis and immune biomarkers of MM are crucial for improving MM patient outcomes. Immune biomarkers, such as neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), and platelet/monocyte ratio (PLR), are of great significance for risk stratification and evaluation of treatment response in MM. Currently, new prognostic biomarkers for MM are being explored to provide new insights into the diagnosis and treatment of MM.

Shifts in reproductive strategies in the evolutionary trajectory of plant lineages.

Understanding the maintenance and shift in reproductive strategies is a fundamental question in evolutionary research. Although many efforts have been made to compare different reproductive strategies, the association between reproductive strategies and lineage divergence is largely unknown. To explore the impact of different reproductive strategies on lineage divergence, we investigated the evolution of clonality in Saxifraga sect. Irregulares+Heterisia. By integrating several lines of evidence, we found that the loss of clonality in Irregulares+Heterisia was associated with a progressive increase in diversification rate and intraspecific morphological diversity but with a reduction in species distribution range. Our findings provide insights into the ecological and evolutionary effects of different reproductive strategies, suggesting the necessity of integrating clonality into ecological and evolutional research.

Combination of BCL-2 inhibitors and immunotherapy: a promising therapeutic strategy for hematological malignancies.

The rapid development of high-throughput sequencing in recent years has facilitated great progress in the molecular-targeted therapy of hematological malignancies, including leukemia, lymphoma, and multiple myeloma. BCL-2 inhibitors are among the most important molecular-targeted agents. Immunotherapy for hematologic malignancy has rapidly increased in popularity in recent years and has been proven to improve the overall survival rate. However, few clinical studies have investigated combination therapy with BCL-2 inhibitors and immunotherapies, such as immune molecule-targeted drugs or immune cell adoptive therapy. In this review, we discuss the drug discovery process, current clinical application status, and resistance and tolerance issues associated with BCL-2 inhibitors. We emphasize their important role in regulating the immune system and propose that the combination of BCL-2 inhibitors with immunotherapy may be one of the most promising treatment methods for hematologic malignancies.

DARS expression in BCR/ABL1-negative myeloproliferative neoplasms and its association with the immune microenvironment.

DARS, encoding for aspartyl-tRNA synthetase, is implicated in the pathogenesis of various cancers, including renal cell carcinoma, glioblastoma, colon cancer, and gastric cancer. Its role in BCR/ABL1-negative myeloproliferative neoplasms (MPNs), however, remains unexplored. This study aimed to elucidate the expression of DARS in patients with MPNs (PV 23, ET 19, PMF 16) through immunohistochemical analysis and to examine the profiles of circulating immune cells and cytokines using flow cytometry. Our findings indicate a significant overexpression of DARS in all MPNs subtypes at the protein level compared to controls (P < 0.05). Notably, elevated DARS expression was linked to splenomegaly in MPNs patients. The expression of DARS showed a negative correlation with CD4+ T cells (R = - 0.451, P = 0.0004) and CD4+ T/CD8+ T cell ratio (R = - 0.3758, P = 0.0040), as well as with CD68+ tumor-associated macrophages (R = 0.4037, P = 0.0017). Conversely, it was positively correlated with IL-2 (R = 0.5419, P < 0.001), IL-5 (R = 0.3161, P = 0.0166), IL-6 (R = 0.2992, P = 0.0238), and IFN-γ (R = 0.3873, P = 0.0029). These findings underscore a significant association between DARS expression in MPNs patients and specific clinical characteristics, as well as immune cell composition. Further investigation into the interplay between DARS and the immune microenvironment in MPNs could shed light on the underlying mechanisms of MPNs pathogenesis and immune dysregulation.

Computing cell state discriminates the aberrant hematopoiesis and activated microenvironment in Myelodysplastic syndrome (MDS) through a single cell genomic study.

BACKGROUND: Myelodysplastic syndrome (MDS) is a complicated hematopoietic malignancy characterized by bone marrow (BM) dysplasia with symptoms like anemia, neutropenia, or thrombocytopenia. MDS exhibits considerable heterogeneity in prognosis, with approximately 30% of patients progressing to acute myeloid leukemia (AML). Single cell RNA-sequencing (scRNA-seq) is a new and powerful technique to profile disease landscapes. However, the current available scRNA-seq datasets for MDS are only focused on CD34+ hematopoietic progenitor cells. We argue that using entire BM cell for MDS studies probably will be more informative for understanding the pathophysiology of MDS. METHODS: Five MDS patients and four healthy donors were enrolled in the study. Unsorted cells from BM aspiration were collected for scRNA-seq analysis to profile overall alteration in hematopoiesis. RESULTS: Standard scRNA-seq analysis of unsorted BM cells successfully profiles deficient hematopoiesis in all five MDS patients, with three classified as high-risk and two as low-risk. While no significant increase in mutation burden was observed, high-risk MDS patients exhibited T-cell activation and abnormal myelogenesis at the stages between hematopoietic stem and progenitor cells (HSPC) and granulocyte-macrophage progenitors (GMP). Transcriptional factor analysis on the aberrant myelogenesis suggests that the epigenetic regulator chromatin structural protein-encoding gene HMGA1 is highly activated in the high-risk MDS group and moderately activated in the low-risk MDS group. Perturbation of HMGA1 by CellOracle simulated deficient hematopoiesis in mouse Lineage-negative (Lin-) BM cells. Projecting MDS and AML cells on a BM cell reference by our newly developed MarcoPolo pipeline intuitively visualizes a connection for myeloid leukemia development and abnormalities of hematopoietic hierarchy, indicating that it is technically feasible to integrate all diseased bone marrow cells on a common reference map even when the size of the cohort reaches to 1,000 patients or more. CONCLUSION: Through scRNA-seq analysis on unsorted cells from BM aspiration samples of MDS patients, this study systematically profiled the development abnormalities in hematopoiesis, heterogeneity of risk, and T-cell microenvironment at the single cell level.

Osteocyte-derived exosomes regulate the DLX2/wnt pathway to alleviate osteoarthritis by mediating cartilage repair.

BACKGROUND: Chondrocyte viability, apoptosis, and migration are closely related to cartilage injury in osteoarthritis (OA) joints. Exosomes are identified as potential therapeutic agents for OA. OBJECTIVE: This study aimed to investigate the role of exosomes derived from osteocytes in OA, particularly focusing on their effects on cartilage repair and molecular mechanisms. METHODS: An injury cell model was established by treating chondrocytes with IL-1ß. Cartilage repair was evaluated using cell counting kit-8, flow cytometry, scratch test, and Western Blot. Molecular mechanisms were analyzed using quantitative real-time PCR, bioinformatic analysis, and Western Blot. An OA mouse model was established to explore the role of exosomal DLX2 in vivo. RESULTS: Osteocyte-released exosomes promoted cell viability and migration, and inhibited apoptosis and extracellular matrix (ECM) deposition. Moreover, exosomes upregulated DLX2 expression, and knockdown of DLX2 activated the Wnt pathway. Additionally, exosomes attenuated OA in mice by transmitting DLX2. CONCLUSION: Osteocyte-derived exosomal DLX2 alleviated IL-1ß-induced cartilage repair and inactivated the Wnt pathway, thereby alleviating OA progression. The findings suggested that osteocyte-derived exosomes may hold promise as a treatment for OA.

PPh3-Promoted Direct Deoxygenation of Epoxides to Alkenes.

Deoxygenation of epoxides into alkenes is one of the most important strategies in organic synthesis, biomass conversions, and medicinal chemistry. Although metal-catalyzed direct deoxygenation provides one of the most commonly encountered protocols for the conversion of epoxides to alkenes, the requirement of expensive catalysts and extra reductants has largely limited their universal applicability. Herein, we report an efficient PPh3-promoted metal-free strategy for deoxygenation of epoxides to generate alkene derivatives. The success of deoxyalkenylation of epoxides bearing a wide range of functional groups to give terminal, 1,1-disubstituted, and 1,2-disubstituted alkenes manifests the powerfulness and versatility of this strategy. Moreover, gram-scale synthesis with excellent yield and modification of biologically active molecules exemplifies its generality and practicability.

[The clinical treatment of laryngotracheal rupture injury].

Objective:To investigate the therapeutic effect of laryngotracheal rupture injury and management of related complications. Methods:A retrospective analysis was conducted on 10 patients with laryngotracheal rupture injury caused by trauma, admitted between October 2014 and October 2022. Results:Anti-shock treatment, local debridement, tracheal-cricoid cartilage or tracheal-tracheal anastomosis, laryngeal cartilage reduction and fixation, local transposition flaps repair and phase-Ⅱ airway reconstruction were performed respectively on 10 patients. Nine patients underwent operations of tracheal-cricoid cartilage or tracheal-tracheal anastomosis, with five of these were performed by cartilage broken reduction and fixation, placed with intraluminal stents of iodoform gauze fingerstalls for （8.2±1.6） days. Tracheal reconstruction surgery was performed on 2 cases during phase-Ⅱ and both were placed with T-shaped silicone tube to support for 3 months. Two cases required tracheoesophageal fistula surgical repair, and vocal cord suturing was conducted for three vocal fold injuries. Anti-shock treatment was given to one emergency case and closed thoracic drainage treatment was given to another one. We removed the tracheal cannula from 10 patients after surgery and one case was diagnosed with Ⅰ-level swallowing function of sub-water test. All cases recovered to take food per-orally. Conclusion:Maintenance of circulation and respiration functions is the major target during early treatment of laryngotracheal rupture. It should strive to complete the reconstruction of airway structure on phase-Ⅰ, among which end-to-end anastomosis to reconstruct airway and broken laryngeal cartilage reduction and fixation are the vital methods for airway structure reconstruction to achieve good results. It is suggested that the reconstruction of trachea and esophagus structures should be performed simultaneously to patients with tracheoesophageal fistula.

A method for predicting methane production from anaerobic digestion of kitchen waste under small sample conditions.

Anaerobic digestion (AD) has the great potential to treat organic waste and achieve remarkable results effectively. However, it is very tough to establish an accurate mechanistic model for this process. Data-driven modeling technology has opened a new door to solving this problem. While when the sample set is small, traditional data-driven modeling methods are often powerless. In this paper, an effective method is proposed for data-driven high-precision modeling in small sample scenarios. A time series generative adversarial network (TimeGAN) is first utilized to augment the original high-quality small-sample data collected during the AD methane production. A novel hybrid kernel extreme learning machine (HKELM) is then designed to form a better structure of the data-driven model, whose regularization coefficient C0 is optimized by the sparrow search algorithm (SSA). Finally, this semi-finished model (SSA-HKELM) is trained by the augmented data to form the final mathematical model (TimeGAN-SSA-HKELM) for the AD methane generation process. Comparative experiments of the methane daily production prediction error have verified the effectiveness of the method, which can be extended to other similar small sample data-driven modeling scenarios.

High-risk ARGs (HRA) Chip: A high-throughput qPCR-based array for assessment of high-risk ARGs from the environment.

The global surge in antibiotic resistance genes (ARGs) presents a serious public health challenge. While methods like metagenomic analysis and qPCR arrays have been instrumental in investigating ARG distributions and dynamics, the vast diversity of ARGs often complicates effective monitoring and risk assessment. Here, we developed a High-Risk ARGs (HRA) chip based on high-capacity quantitative PCR array targeting previously identified high-risk ARGs. These ARGs are known to be prevalent in human-related environments, exhibit gene mobility, and are present in ESKAPE pathogens. The HRA chip include 101 primer sets and the 16S rRNA gene as a reference. These primer sets consist of 34 obtained from previous studies, and 67 newly designed primer sets which were validated in silico and experimentally. Absolute quantification of targeted ARGs is accomplished by generating standard curves for all ARGs with serially ten-fold diluted mixed plasmids containing targeted ARG sequences. The amplification efficiencies of all ARGs exceed 99% via plasmid template dilution tests, suggesting high reliability in quantification. The performance of HRA chip is further evaluated by practical applications in environmental samples from wastewater treatment plants (WWTPs) and soils with various land use types and fertilization regimes. The results indicate the dynamics of high-risk ARGs during wastewater treatment process, and reveal the profiles of soil high-risk ARGs which is distinct from those derived via metagenomic approaches. These findings highlight the potentials of HRA Chip in the evaluation of anthropogenic impacts on the environmental resistome with a more focused spectrum of high-risk ARGs. Overall, the HRA Chip emerges as a powerful and efficient high-throughput tool for rapid detection and quantification of high-risk ARGs, facilitating comprehensive profiling of high-risk resistomes in environmental samples which is essential for human health risk assessment of ARGs.

Role of TSP-1 and its receptor ITGB3 in the renal tubulointerstitial injury of focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS), a common cause of primary glomerulonephritis, has a poor prognosis and is pathologically featured by tubulointerstitial injury. Thrombospondin-1 (TSP-1) is an extracellular matrix protein that acts in combination with different receptors in the kidney. Here, we analyzed the tubular expression of TSP-1 and its receptor integrin ß3 (ITGB3) in FSGS. Previously the renal interstitial chip analysis of FSGS patients with tubular interstitial injury showed that the expression of TSP-1 and ITGB3 were upregulated. We found that the expression of TSP-1 and ITGB3 increased in the tubular cells of FSGS patients. The plasma level of TSP-1 increased and was correlated to the degree of tubulointerstitial lesions in FSGS patients. TSP-1/ITGB3 signaling induced renal tubular injury in HK-2 cells exposure to bovine serum albumin and the adriamycin (ADR)-induced nephropathy model. THBS1 KO ameliorated tubular injury and renal fibrosis in ADR-treated mice. THBS1 knockdown decreased the expression of KIM-1 and caspase 3 in the HK-2 cells treated with bovine serum albumin, while THBS1 overexpression could induce tubular injury. In vivo, we identified cyclo-RGDfK as an agent to block the binding of TSP-1 to ITGB3. Cyclo-RGDfK treatment could alleviate ADR-induced renal tubular injury and interstitial fibrosis in mice. Moreover, TSP-1 and ITGB3 were colocalized in tubular cells of FSGS patients and ADR-treated mice. Taken together, our data showed that TSP-1/ITGB3 signaling contributed to the development of renal tubulointerstitial injury in FSGS, potentially identifying a new therapeutic target for FSGS.

Analyzing Differences in Hematological and Immunological Characteristics Related to Common Gene Mutations in Myelodysplastic Syndromes.

BACKGROUND: Genetic mutations play a crucial role in the development and progression of myelodysplastic syndromes (MDS), impacting the immune microenvironment and influencing the choice of treatment regimen, as well as the efficacy and prognosis of patients. The objective of this study was to examine variations in hematological and immunological characteristics associated with common gene mutations in MDS patients and establish a foundation for the precise treatment of MDS. METHODS: The hematological, immunological, and other clinical features of 71 recently diagnosed MDS patients from January 1, 2019, to July 31, 2023, were retrospectively analyzed. These patients were categorized based on their gene mutations, and the variances in hematological and immunological characteristics among distinct groups were compared. RESULTS: Hematological variances were observed among different gene mutation groups. Specifically, platelet counts in the splicing factor 3B subunit 1 (SF3B1) mutation group were notably higher compared to the wild-type group (p = 0.009). Conversely, in the additional sex combs like 1 (ASXL1) mutation groups, monocyte ratios were significantly elevated in comparison to the wild-type group (p = 0.046), and in the ten-eleven translocation 2 (TET2) mutation group, lymphocyte ratios were significantly lower (p = 0.022). Additionally, the leukocyte (p = 0.005), neutrophil ratio (p = 0.002), and lymphocyte ratio (p = 0.001) were significantly higher in the Runt-related transcription factor 1 (RUNX1) mutation group. Regarding immunological distinctions, the Natural Killer (NK) cell ratio demonstrated a significant increase in the SF3B1 mutation group (p = 0.005). Moreover, the TET2 mutation group exhibited a significantly higher Interleukin-8 (IL-8) level (p = 0.017). In contrast, the U2 small nuclear RNA auxiliary factor 1 (U2AF1) group displayed significantly lower levels of IL-1ß (p = 0.033), IL-10 (p = 0.033), and Tumour Necrosis Factor-α (TNF-α) (p = 0.009). CONCLUSION: Distinct variations exist in the immune microenvironment of MDS associated with different genetic mutations. Further studies are imperative to delve into the underlying mechanisms that drive these differences.

Identification of Yellow Advanced Glycation End Products in Human Skin.

Skin yellowness is a hallmark of dull or unhealthy skin, particularly among Asians. Previous research has indicated a link between skin glycation and skin yellowness. However, the specific glycated chemicals contributing to yellowish skin appearance have not been identified yet. Using HPLC-PDA-HRMS coupled with native and artificially glycated human epidermal explant skin, we identified intensely yellow colored glycated chromophores "(1R, 8aR) and (1S, 8aR)-4-(2-furyl)-7-[(2-furyl)-methylidene]-2-hydroxy-2H,7H,8AH-pyrano-[2,3-B]-pyran-3-one" (abbreviated as AGEY) from human skin samples for the first time. The abundance of AGEY was strongly correlated with skin yellowness in the multiple skin explant tissues. We further confirmed the presence of AGEY in cultured human keratinocytes and 3D reconstructed human epidermal (RHE) models. Additionally, we demonstrated that a combination of four cosmetic compounds with anti-glycation properties can inhibit the formation of AGEY and reduce yellowness in the RHE models. In conclusion, we have identified specific advanced glycation end products with an intense yellow color, namely AGEY, in human skin tissues for the first time. The series of study results highlighted the significant contribution of AGEY to the yellow appearance of the skin. Furthermore, we have identified a potential cosmetic solution to mitigate AGEY formation, leading to a reduction in yellowness in the in vitro RHE models.

Targeting TNF-α: The therapeutic potential of certolizumab pegol in the early period of cerebral ischemia reperfusion injury in mice.

The neuroinflammatory response triggered by cerebral ischemia-reperfusion injury (CIRI) is characterized by the upsurge of pro-inflammatory cytokines, including TNF-α, IL-1ß, and IL-6, which promote leukocyte infiltration and subsequent accumulation in the ischemic zone. This accumulation further intensifies inflammation and aggravates ischemic damage. Certolizumab pegol (CZP), a monoclonal antibody targeting TNF-α, is widely used in treating various inflammatory diseases. This study explored the therapeutic potential of CZP in a mouse model of CIRI, induced by middle cerebral artery occlusion (MCAO), focusing on its influence on the microglial inflammatory response. In vitro analyses revealed that CZP markedly inhibits TNF-α-stimulated inflammation in primary microglia with an EC50 of 1.743 ng/mL. In vivo, MCAO mice treated with CZP (10 µg/mouse, i.p.) for 3 days showed reduced infarct volume, partially improved neurological function, and diminished blood-brain barrierdisruption. Additionally, CZP treatment curtailed microglial activation and the release of pro-inflammatory mediators in the early stages of stroke. It also favorably modulated microglial M1/M2 polarization, rebalanced Th17/Treg cells dynamics, and inhibited Caspase-8-mediated GSDMD cleavage, preventing microglial pyroptosis. Collectively, this study described that the treatment with CZP reversed damaging process caused by CIRI, offering a promising therapeutic strategy for the treatment of ischemic stroke.

Lycorine attenuated proliferation and induced apoptosis on imatinib-resistant K562 cell by inhibiting autophagy.

BACKGROUND: Tyrosine kinase inhibitor (TKI) resistance is a significant factor exacerbating the burden on chronic myeloid leukemia (CML) patients and impacting clinical efficacy. The main goal is to offer new insights into overcoming drug resistance in treating CML. METHODS: Imatinib (IM) resistant K562/IM cells were generated using gradient induction. Responses to IM, lycorine, and autophagy modulators were assessed using CCK-8. Protein expression of Beclin-1, Atg5, LC3, Caspase-3, P62, Bax, Bcl-2, and P-gp was detected using Western blot. Lycorine-induced apoptosis and cell cycle changes were evaluated through flow cytometry, while autophagy alterations were detected using monodansylcadaverine (MDC) staining. In the K562/IM mice model, non-obese diabetic severe combined immunodeficent (NOD-SCID) mice were subcutaneously inoculated with K562/IM cells. After 17 days of lycorine injection, assessments included tumor size, hematoxylin-eosin (HE) staining, and Ki67 expression. RESULTS: After 72 h of IM treatment, K562/IM cells showed a 55.86-fold increase in drug resistance compared to K562 cells. Lycorine treatment for 24 h inhibited cell proliferation and induced G0/G1 phase cell cycle arrest and apoptosis in both K562 and K562/IM cells. MDC staining indicated reduced autophagy in K562/IM cells, mitigated by lycorine. In vivo experiments demonstrated reduced tumor size and Ki67 proliferation index in the lycorine treatment group (K562+L, K562/IM+L) compared to the control group, particularly in the drug-resistant group. However, no significant change in Ki67 was observed in the K562 group after lycorine treatment. CONCLUSION: In summary, K562/IM cells displayed heightened autophagy levels compared to K562 cells. Lycorine effectively impeded the proliferation of K562/IM cells through diverse mechanisms, including reduced autophagy, enhanced apoptosis, and induced cell cycle arrest.

Effects of photochemical aging on the molecular composition of organic aerosols derived from agricultural biomass burning in whole combustion process.

Biomass burning organic aerosols (BBOA) are key components of atmospheric particulate matter, yet the effects of aging process on their chemical composition and related properties remain poorly understood. In this study, fresh smoke emissions from the combustion of three types of agricultural biomass residues (rice, maize, and wheat straws) were photochemically aged in an oxidation flow reactor. The changes in BBOA composition were characterized by offline analysis using ultrahigh performance liquid chromatography coupled with Orbitrap mass spectrometry. The BBOA molecular composition varied dramatically with biomass type and aging process. Fresh and aged BBOA were predominated by CHO and nitrogen-containing CHON, CHN, and CHONS species, while with very few CHOS and other non­oxygen species. The signal peak area variations revealed that individual molecular species underwent dynamic changes, with 77-81 % of fresh species decreased or even disappeared and 33-46 % of aged species being newly formed. A notable increase was observed in the number and peak area of CxHyO≥6 compounds in aged BBOA, suggesting that photochemical process served as an important source of highly oxygenated species. Heterocyclic CxHyN2 compounds mostly dominated in fresh CHN species, whereas CxHyN1 were more abundant in aged ones. Fragmentation and homologs oxidation by addition of oxygen-containing functional groups were important pathways for the BBOA aging. The changes in BBOA composition with aging would have large impacts on particle optical properties and toxicity. This study highlights the significance of photochemical aging process in altering chemical composition and related properties of BBOA.