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L1CAM signaling through planar cell polarity drives SOX2 expression and lung adenocarcinoma metastasis
Frontline CLL: lessons from the final analysis of CLL13-GAIA
Catechin–Folate nano-niosomes from Osbeckia parvifolia Arn. induce apoptotic cell death in Ovarian cancer
Nuclear-fusion firm says plant will deliver electricity to grid — but big questions remain
The alx gene family confers segmental identity to frontonasal cranial neural crest cells
Multinucleated plasma cells and IgG λ myeloma in a patient with TEMPI syndrome and renal cell carcinoma
Lithological identification for mixed carbonate and clay sediments employing principal component analysis of geophysical logging
Structural dissection of the catalytic domain of the serine threonine kinase StkP of Streptococcus pneumoniae
Abstract Serine/threonine kinases of the Hanks family are key regulators of bacterial physiology. Among them, membrane-associated PASTA-Hanks kinases govern bacterial cytokinesis and morphogenesis, yet their activation mechanism remains unclear. Here, we report crystal structures of the catalytic domain of the PASTA-Hanks kinase StkP of the human pathogen Streptococcus pneumoniae , carrying phosphoablative or phosphomimetic mutations in its activation loop. These structures demonstrate that phosphorylation of two threonine residues modulates the activation loop’s organization and dynamics and reveal an alternative mode of dimerization of the catalytic domain. Analytical ultracentrifugation, SAXS and cell imaging allow to propose a model postulating that the local concentration of StkP at the division septum promotes an inactive dimeric state in which the activation loop hampers substrate binding. The reorganization into active dimers would activate StkP and allow endogenous substrate phosphorylation. This work thus provides a mechanistic framework of the regulation of PASTA Hanks kinase for the regulation of bacterial cell division.
The prevalence and clinical significance of clonal monocytosis
Abstract The terms clonal monocytosis of undetermined significance (CMUS) and clonal cytopenia and monocytosis of undetermined significance (CCMUS) were introduced by the International Consensus Classification of Myeloid Neoplasms to describe cases of clonal hematopoiesis (CH) and concurrent monocytosis that did not meet the diagnostic criteria of chronic myelomonocytic leukemia. To date, their practical relevance as clinicopathological entities at a population level has not been assessed. Here, we assess the prevalence, significance, and natural history of CMUS and CCMUS among 431 531 UK Biobank participants through analysis of clinical, genomic, and health outcome data. We find that CMUS with an absolute monocytosis and CCMUS are high-risk entities strongly associated with incident myeloid neoplasia (MN), cardiovascular disease, and renal disease. Noting the overall higher monocyte counts in men and the low rate of progression of DNMT3A-CMUS, we reveal that amending the definition of CMUS/CCMUS to incorporate sex-specific monocyte thresholds and the exclusion of isolated DNMT3A mutations from the definition significantly strengthens the association with incident MN. Finally, given their association with poor outcomes, we develop MoSAIC, a machine-learning classifier, to infer the presence of SRSF2 mutations (associated with high MN risk) among individuals with monocytosis, based on complete blood count indices alone. We corroborate our findings in an independent cohort of 625 328 Danish primary care patients. Our findings underscore the clinical relevance of CMUS and CCMUS as distinct high-risk states within the spectrum of CH and establish an evidence base to refine their diagnostic definition.
Bandgap engineering and high-throughput defect dynamics in two-terminal CsGeI3-Si monolithic tandem solar cells
Abstract Simulation-driven investigations are presented on highly efficient monolithic tandem solar cells with climate-efficient nano-scaled perovskite and crystalline silicon for green energy generation. Tandem solar cells comprise a lead-free CsGeI 3 perovskite top cell and a silicon bottom sub-cell. A Cu 2 O hole transport material layer and a ZnO electron transport material layer was used. Optimizations were performed by varying doping, defect concentration, thickness, and band gap to obtain valuable insights into material properties. These perovskite-silicon tandem solar cells, with a wide band gap and optimized parameters, yielded power conversion efficiencies above the Shockley-Queisser limit for single-junction cells. The structure of perovskite-silicon tandem solar cells is Glass/FTO/ZnO/CsGeI 3 /Cu 2 O/RL/Si(p + )/Si(p)/Si(n)/Au. After optimization, the results show a power conversion efficiency of 37.23%, a J sc of 23.95 mA/cm 2 , a Voc of 1.895 V, and an FF of 82%. This research shows that through this hybrid perovskite-silicon technology, one is assured of increased energy output while decreasing carbon footprints and increasing renewable energy use.
Hydration control in molecular salts through counterion selection
Abstract Predicting when and why molecular salts form hydrates has remained a significant problem in solid-state chemistry, despite its impact on the stability and performance of industrially relevant materials. Here, we identify counterion charge localization as a key determinant of hydrate formation in molecular salts, providing a framework for predicting and controlling solid-state hydration. By analyzing over 31,000 crystal structures and performing electron density calculations, we show that delocalized counterion charge suppresses hydrate formation, while localized charge promotes it. This principle makes hydration propensity a more tuneable property (from ~80% to <10%) through considered counterion selection. Guided by these insights and the Δp K a rule, we experimentally demonstrate rational control of hydration in salts of 4-aminoacetanilide. Our results establish a direct link between molecular electrostatics and crystallization outcomes, affording predictive design of molecular salts with tailored hydration behavior.
The RELEVANCE of long-term follow-up in follicular lymphoma
Physics-informed learning–based fault-tolerant control for robust wireless power transfer in electric vehicles
Enantioselective construction of polychiral helical compounds via dynamic kinetic resolution
Lenalidomide plus rituximab for previously untreated advanced follicular lymphoma: the 10-year RELEVANCE trial analysis
Abstract In the multinational, phase 3 RELEVANCE trial, 1030 patients with previously untreated follicular lymphoma were randomized to receive rituximab + lenalidomide (R2; n = 513) or rituximab-based immunochemotherapy (R-Chemo; n = 517). In the final analysis, at 120 months of follow-up, median progression-free survival (PFS) was comparable between the treatment groups: 110.6 months with R2 vs 102.8 months with R-Chemo, according to the independent review committee assessment. The 10-year PFS rates were 46.4% for R2 and 46.6% for R-chemo. Median overall survival (OS) and time-to-next lymphoma treatment (TTNLT) were not reached in either arm; 10-year OS rates were 82.4% for R2 and 81.1% for R-chemo, and 10-year TTNLT rates were 62.2% for R2 and 66.3% for R-chemo. Overall, patients with progression of disease within 24 months (POD24) had a poorer prognosis than those without POD24 (hazard ratio, 6.215; P&lt; .0001); however, no difference was observed between the study groups. The incidence of second primary malignancies (SPMs) was 2.11 cases per 100 patient-years (95% confidence interval, 1.80-2.46). Only 9 transformations occurred after 24 months (3 with R2 vs 6 with R-chemo). In each study group, 87 patients died, mainly because of lymphoma progression and SPMs. This long-term follow-up of RELEVANCE confirmed that R2 provides a chemotherapy-free alternative to immunochemotherapy in this patient population. This trial was registered at www.clinicaltrials.gov as NCT01476787 and NCT01650701 and at EudraCT as 2011-002792-42.
Au complexes with 5-S-alkylated-2-amino-1,3,4-thiadiazoles: from Au(III)-based ionic liquids to rare dinuclear Au(II) coordination compounds
Abstract The reaction of 5-amino-1,3,4-thiadiazole-2-thiols, S-modified with highly flexible trimethylsilylpropyl (H₂L 1 ) and n -hexyl (H₂L 2 ) groups, with HAuCl₄ afforded ionic salts of the type (H 3 L n ) (+) [AuCl 4 ] (-) (n = 1, 2). The structures of the resulting complexes were elucidated by single-crystal X-ray crystallography (SC-XRD) and/or spectroscopic analyses, whose results support their ionic nature. Based on their appearance and DSC data, (H 3 L 1 )[AuCl 4 ] melts at 55 °C, whereas (H 3 L 2 )[AuCl 4 ] is liquid at room temperature. The electroactive behavior of both cations and anions in such environments, as demonstrated by cyclic voltammetry for (H 3 L 2 )[AuCl 4 ], reflects their mobility and ability to participate in redox processes and is typical of ionic liquid electrolytes. Thus, these compounds show ionic liquid behavior at low temperatures. In the presence of water, rare dinuclear Au(II) complexes, [(HL n ) 2 Au 2 Cl 2 ], are formed, with a relatively short Au···Au distance, as demonstrated by crystallographic and additional analyses.
Multi-hazard exposure and vulnerability drive rising agricultural risk in global breadbasket regions
Abstract Climate extremes increasingly threaten global food production, yet global multi-hazard agricultural risk assessments that jointly consider multiple hazards, crop exposure and socioeconomic vulnerability are still missing. This gap limits our ability to identify where climate shocks to croplands are most likely to translate into high agricultural risk. Here we present a global agricultural risk assessment that quantifies the exposure of croplands and ten major crop groups to heatwaves, droughts, floods and compound hot–dry events, and combines this with a vulnerability index constructed from socio-economic and institutional indicators using latent factor modelling. Using ensembles of climate and hydrological models under multiple future scenarios, we show widespread increases in multi-hazard exposure, with the strongest intensification across South Asia, Sub-Saharan Africa and major U.S. and European breadbaskets. A significant relationship between vulnerability and cropland exposure emerges in future scenarios but is absent historically, indicating a growing role for vulnerability in shaping future agricultural risk. These results demonstrate that reliably identifying future agricultural risk hotspots requires jointly accounting for multi-hazard exposure and socioeconomic vulnerability, so that adaptation efforts can be targeted to regions where intensifying extremes coincide with high vulnerability.