Browse Articles

Experimental and coupling analysis of municipal solid waste (MSW) shear strength under multiple influencing parameters

The production of municipal solid waste (MSW) in China is growing rapidly, and landfill is the primary treatment method. The shear strength of MSW is crucial to the stability and safety of landfills. However, there is limiting research available on how different environmental and compositional factors interactively influence MSW shear strength since some existing studies typically examine these variables in isolation. Through integrated testing and statistical modeling this looks into how environmental factors (moisture content 30–230%, organic matter content 15–75%, temperature 10–65°C and degradation time 15–190days) work together to change the shear strength of MSW. One hundred MSW samples were prepared according to field waste composition from Xi’an and were subjected to direct shear tests over a 190-day degradation period. The test results show that cohesion ( c ) decreased over time, to a minimum value of 0.17 kPa at 190 days, while angle of internal friction ( φ ) increased to 42.39° at 190 days. Both c and φ showed an initial increase followed by a decrease with temperature changes. The effect of organic matter on c decline was negligible, though φ increased during the early stage of degradation. Higher moisture content (80–130%) and organic matter (45–60%) along with temperatures between 10–35°C resulted in high φ values. High c values were achieved with 130% moisture content 15–30% organic matter and temperatures between 10 and 35 °C. Under the controlled conditions of the study the Mohr–Coulomb equation was modified to incorporate degradation effects, and multiple linear regression together with automatic linear modeling (ALM) were used to predict c and φ , yielding R 2 values of 0.622 and 0.468 respectively, demonstrating the models’ predictive accuracy. In practical engineering, the study’s outcomes will help to understand the effect of different parameters on the shear strength of MSW which can lead to achieve the landfill slope stability and the use of MSW as backfill material in building foundations under the controlled conditions of the study.

MRD is a new therapeutic target in AML

An H3K14ub-H3K9me3 feedback circuit governs heterochromatin spreading and inheritance in fission yeast

Abstract Heterochromatin is a bistable chromatin state essential for genome stability and gene regulation. Its spreading and inheritance have long been explained by a “read-write” cycle in which histone methyltransferases bind pre-existing tri-methylation of histone H3 lysine 9 (H3K9me3) and propagate this mark to neighboring nucleosomes. However, the weak affinity and limited catalytic stimulation provided by H3K9me3 alone challenge this model. The fission yeast H3K9 methyltransferase Clr4 functions within the CLRC complex, which also catalyzes histone H3 lysine 14 ubiquitination (H3K14ub). Here we show that H3K14ub and H3K9me3 form a feedback loop: H3K14ub strongly stimulates Clr4 activity on nucleosomes, while both H3K14ub and H3K9me3 stabilize CLRC binding to chromatin. Even subtle perturbations that disrupt this feedback, such as mutating one of the three H3 genes to prevent ubiquitination or methylation, or impairing Clr3-mediated H3K14 deacetylation, compromises heterochromatin spreading and inheritance. Conversely, counteracting activities, such as H3K14 acetylation by Mst2 and H3K9 demethylation by Epe1, synergistically constrains heterochromatin expansion. Thus, rather than relying solely on the weak H3K9me3 “read-write” cycle, heterochromatin is maintained through an integrated circuit of ubiquitination, deacetylation, and methylation, which governs spreading and inheritance.

Investigating the correlation between candidate teachers’ acceptance of generative artificial intelligence and artificial intelligence literacy across various disciplines

This study examines Generative Artificial Intelligence (GenAI) acceptance and Artificial Intelligence Literacy (AIL) levels among prospective teachers, using variables for comparative analysis and identifying influencing factors. The research uses an explanatory sequential mixed methods approach. Quantitative data were obtained from 723 prospective teachers and qualitative data from 48 prospective teachers. Data collection included an Information Form, GenAI Acceptance Scale, and AIL Scale for quantitative data, with interview forms for qualitative data. Parametric tests, independent samples t-test, ANOVA, and Pearson correlation analyzed quantitative data, while factors influencing GenAI acceptance and AIL were identified through themes using MAXQDA. Acceptance levels showed no significant differences by gender or daily internet use; however, differences emerged regarding department, grade level, AI tools used, and self-perceived proficiency. AIL showed significant differences in gender, department, grade, tool usage, and proficiency level, with higher scores among those trained in artificial intelligence. Qualitative data clarify the quantitative findings. Factors affecting GenAI acceptance include daily use, problem-solving, learning applications, mentor usage, assistance from others, proficiency, productivity, discipline-specific skills, and task efficiency. Factors influencing AIL include understanding AI importance, ethical considerations, AI support in daily life, explaining AI, understanding deep learning and machine learning relationships, big data knowledge, AI decision-making processes, knowledge of AI tools, interpretation of AI technologies, critical evaluation, data privacy importance, machine learning knowledge, and evaluation of AI applications in their discipline.

Pretransplant promise for PD-1 in Hodgkin lymphoma

TCL1A mediates DNA methylation defects in recurrent hydatidiform mole with NLRP7 pathogenic variants

Selective B-cell subset depletion underlies increased infection risk in patients with MM treated with anti-BCMA vs anti-GPRC5D bsAbs

Abstract Infections remain a challenge during treatment of patients with multiple myeloma (MM) with anti–B-cell maturation antigen (BCMA) and anti–G protein-coupled receptor class C group 5 member D (GPRC5D) bispecific antibodies (bsAbs). However, the mechanism underlying different rates and severity of infections induced by the 2 bsAbs remains poorly understood. Single-cell RNA sequencing of bone marrow (BM) aspirates of 11 patients with MM and 8 healthy donors revealed BCMA expression on mature B cells and, surprisingly, in small pre-B cells within B-cell precursors. GPRC5D expression was restricted to malignant and less to normal plasma cells (PCs). Next-generation flow cytometry immune profiling showed that anti-BCMA bsAbs severely depleted BM mature B cells, from 4.9% to 0% (P< .001), and normal PCs, from 0.17% to <0.0002% (P< .001), during treatment of 62 patients with relapsed MM. This was observed throughout therapy. Additional flow cytometry (n = 31) and single-cell RNA sequencing studies (n = 8) demonstrated that, in contrast to anti-GPRC5D, anti-BCMA bsAbs also depleted immature and small pre-B cells. The MIcγ1 mouse model was used as a negative control of BCMA expression in all stages of the B-cell lineage, confirming no depletion of any B-cell subset after anti-BCMA treatment. In conclusion, we show that although GPRC5D bsAbs selectively target PCs, anti-BCMA bsAbs target both PCs and B cells from the small pre-B stage onward. Our study provides mechanistic insight into the increased infection risk with anti-BCMA therapy and supports individualized bsAb strategies in MM. Moreover, dual targeting of B cells and PCs may have therapeutic potential in other B-cell malignancies or autoimmune diseases.

Segmented filamentous bacteria are worldwide human gut commensals

Abstract Segmented filamentous bacteria (SFB) describe morphologically similar gut commensals found in mammals, fish and birds. In mice, SFB intimately colonizes the ileal epithelium at the time of weaning and elicits a strong pleiotropic immune activation that fosters colonization resistance while augmenting disease severity in various disease models. SFB is therefore critical in both health and disease but information regarding SFB in humans remains limited. Here, we first identify and characterize a human SFB species with SFB-specific morphology, including the hook-like tip structure that mediates attachment, and unique genome features, including a starch and glycogen degradation module. This species, which we name Anisomitus miae and establish as the nomenclature type for the SFB genus, is within a SFB lineage common across Africa. We then bioinformatically identify, based on the 16S rRNA gene V3-V4 variable region sequence, four major, and two minor, human SFB lineages in forty-four countries distributed across all six inhabited continents. We provide evidence towards the co-colonization potential of the SFB lineages and their colonization dynamics, including a potent but short-lived colonization peak in children between one to five years of age. This study establishes the presence of multiple SFB species in the human population and SFB as a minor but wide-spread group of commensals in humans.

Azacitidine to treat measurable residual disease in patients with MDS/AML: final long-term results of the RELAZA2 trial

Abstract Measurable residual disease (MRD) can predict relapse in patients with advanced myelodysplastic neoplasms (MDS) or acute myeloid leukemia (AML). We report the long-term efficacy and safety of MRD-guided preemptive azacitidine treatment to prevent relapse in the phase 2 Relapse Prevention With Azacitidine (RELAZA2) trial. Patients with MDS or AML after either intensive chemotherapy only or consecutive allogeneic stem cell transplantation were prospectively screened for imminent relapse by molecular MRD assessment. Patients who became MRD positive (MRDpos) during screening received azacitidine for up to 2 years to prevent relapse. The primary end point was the proportion of patients alive and relapse-free 6 months after azacitidine start. Of 357 patients screened, 119 (33.3%) became MRDpos, of whom 95 (79.8%) were eligible for azacitidine treatment. The primary end point was met; 60 (63%) patients were relapse free (95% confidence interval, 54-71; P< .0001) 6 months after azacitidine initiation with no new safety signals. Of 60 patients achieving MRD response during the first 6 cycles of azacitidine, 31 (52%) maintained response without hematological relapse for ≥2 years after azacitidine initiation. The median treatment-free duration after azacitidine discontinuation was 20.8 months; the longest ongoing response was 104 months. After a median follow-up of 6.6 years, 15 initial responders (25%) remained alive and in remission. Among screened patients who remained continuously MRD negative, 60-month overall survival and relapse-free survival were 88% and 79%, respectively. Patients with continuously negative MRD display a very favorable prognosis. Most patients with MRD positivity can be effectively treated with azacitidine with potential long-term remission even after termination of azacitidine. This trial was registered at www.clinicaltrials.gov as #NCT01462578.

TCF21 promotes epithelial-to-mesenchymal transition and cytoskeleton reorganization in uterine development and endometriosis

IFN-γ increases δ-globin gene expression through activation of the JAK/STAT pathway in erythroid cells

Abstract Sickle cell disease (SCD) and β-thalassemia, caused by mutations or deletions in the β-globin gene, are among the most prevalent genetic disorders worldwide, significantly affecting global health and mortality. Recently, reactivation of δ-globin gene expression has been proposed as a potential therapeutic strategy for these conditions. In this study, we found that interferon gamma (IFN-γ) and IFN-β significantly enhance δ-globin expression and activate the JAK/STAT signaling pathway in erythroid cells, with IFN-γ exerting a stronger effect than IFN-β. In erythroid cells derived from CD34+ progenitors, IFN-γ not only increased δ-globin expression but also promoted differentiation, as confirmed by quantitative polymerase chain reaction, western blotting, high-performance liquid chromatography, and flow cytometry. Inhibition of the JAK/STAT pathway, either through a JAK1/2 inhibitor (AZD1840 or ruxolitinib) or via small interfering RNAs targeting JAK1, JAK2, STAT1, or STAT3, significantly decreased both basal and IFN-γ–induced δ-globin expression in HBD-HiBiT knockin HUDEP2 cells. Mutation or removal of the putative IRF-1/STAT2 binding site (˗265 to ˗242) and the adjacent STAT binding site (˗243 to ˗231) in the δ-globin promoter impaired IFN-γ–induced δ-promoter activity. Chromatin immunoprecipitation assays confirmed enhanced binding of interferon regulatory factor 1 (IRF-1) and STAT1 upon IFN-γ treatment. Our elucidation of the mechanism by which a specific molecule induces δ-globin expression suggests that IFN-γ may hold therapeutic potential for patients with SCD, and that screening for compounds that can induce δ-globin could offer a novel pharmaceutical strategy for treating β-hemoglobinopathies.

Effect of stepwise nutritional intervention based on GLIM standard on children with leukemia undergoing transplantation: a retrospective study

The eco-evolutionary assembly of complex communities with multiple interaction types

Abstract Identifying the mechanisms that generate structure in complex ecological communities is fundamental for understanding their assembly. Yet a comprehensive picture of how ecology and evolution combine to generate these patterns remains limited. We use an eco-evolutionary model of community assembly that incorporates interaction-driven population dynamics and evolutionary processes, including speciation and inheritance of interactions, to unveil the mechanisms generating and maintaining biodiversity in complex species interaction networks. Importantly, our model unpicks the effects of selection of interaction types from those of inheritance by comparing evolutionary assembly with invasion-based assembly under different combinations of interaction types. We find that a cost-benefit balance in accumulating interactions separates communities into two distinct types. Weakly beneficial interactions produce sparse, competition-dominated networks, whereas strongly beneficial interactions generate highly mutualistic, more connected communities. Mutualism, driven by both selection and inheritance, facilitates the emergence of large communities with increased complexity. Comparing model results with empirical patterns from microbial communities, we identify potential drivers of ecosystem assembly and characteristic interaction structures. Our results provide a classification system of complex ecosystems based on their composition of ecological interactions, thus generating testable hypotheses on the conditions under which different community types (mutualistic vs. competitive) might emerge.

From Equity to Efficiency — Navigating Changes to the AHEAD Model

Mechanical degradation induced by the alkaline water effects of weakly cemented fine-grained sandstone

Tailoring the glassy phase in polymer semiconductors tunes their optical properties

Shunting for Idiopathic Normal-Pressure Hydrocephalus

Do pastoral and agro-pastoral perceptions align with observed climate extremes? Evidence from the Koh-e-Suleiman Range, Pakistan

Abstract This study examined the relationship between climate perceptions and observed trends among pastoralist and agro-pastoralist communities in the Koh-e-Suleiman Range, Pakistan. Household perception data were collected from 198 respondents and analyzed alongside climatic records across two time scales (1980–2022; 2013–2022). Data from the Pakistan Meteorological Department were used to compute 29 extreme climate indices, and trends were assessed using the Mann–Kendall and Sen’s slope tests. Perceptions of seven climate variables were compared with observed trends through accuracy tests, bias classification, regression, and machine-learning models. Perceptions aligned closely with observed trends for floods, rain intensity, temperature, and warm spells ( $$\ge$$ 80% accuracy), and moderately for cold spells (71.7%) and rainfall (60.6%). Perceptions of drought spells were predominantly inaccurate, with 75.3% of respondents overestimating their occurrence. Regression analyses identified education, age, and livestock ownership as associated with perception accuracy. Classification and Regression Tree (CART) machine learning analysis, in contrast, revealed non-linear effects: income, age, and livestock herd size shaped drought spell perception, while livestock numbers and age influenced rainfall perception. These findings highlight the value of integrating observed climate extremes with local perceptions to better understand perception observation alignment and inform context- sensitive climate risk communication in data-scarce pastoral regions.

Post-catalysis structures of mitochondrial complex I with ubiquinol-10 bound in the active site

Abstract Respiratory complex I is a multi-subunit energy-transducing membrane enzyme essential for mitochondrial and cellular energy metabolism. It couples NADH oxidation and ubiquinone-10 (Q 10 ) reduction to the concomitant pumping of four protons to generate the proton-motive force that powers oxidative phosphorylation. Despite recent advances in structural knowledge of complex I, many mechanistic aspects including the reactive binding poses of Q 10 , how Q 10 reduction initiates the proton transfer cascade, and how protons move through the membrane domain, remain unclear. Here, we use electron cryomicroscopy to determine structures of mammalian complex I, reconstituted into phospholipid nanodiscs containing exogenous Q 10 and reduced by NADH, to global resolutions of 2.0 to 2.6 Å. Two conformations of a reduced Q 10 H 2 molecule are observed, fully inserted into the Q-binding channel in the turnover-relevant closed state. By comparing the quinone species bound in oxidised and reduced complex I structures, paired with molecular dynamics simulations to investigate the charge states of key surrounding residues, we propose a series of substrate binding poses that Q 10 transits through for reduction. Our highly hydrated structures exhibit near-continuous proton-transfer connections along the length of the membrane domain, enabling comparisons between them to assist in identifying the proton-transfer control points that are essential to catalysis.

Strategies to Reinvigorate the Bedside Clinical Encounter