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Higher magnesium depletion score increases the risk of all‑cause and cardiovascular mortality in US adults with diabetes

Background Both dietary magnesium and serum magnesium are associated with the prognosis of diabetic patients. However, the impact of the magnesium depletion score (MDS), which assesses systemic magnesium deficiency, on the prognosis of diabetic patients remains unclear. This cohort study aims to explore the potential association between the MDS and all-cause and cardiovascular mortality in diabetic patients. Methods In this study, we analyzed data from 5,219 diabetic individuals from National Health and Nutrition Examination Survey (NHANES) 2003–2018. Participant mortality information was sourced from the National Death Index records. MDS was divided into lower MDS (0–1 points), middle MDS (2 points), and higher MDS (3–5 points) groups. Weighted multivariable Cox regression was utilized to explore the potential association between MDS and mortality in diabetic patients. Stratified analyses and sensitivity analyses were employed to validate the robustness of our findings. Results Among the 5,219 participants included in this study, 1,212 experienced all-cause mortality, and 348 experienced cardiovascular mortality. Weighted multivariable Cox regression indicated that higher MDS was strongly linked to a heightened risk of mortality in all models, including the fully adjusted model (all-cause mortality: HR = 1.58, 95% CI: 1.20–2.08; cardiovascular mortality: HR = 1.92, 95% CI: 1.28–2.88). In the stratified analysis, we found that the association between MDS and all-cause mortality was stronger among individuals aged <60 years. No significant differences were found in the relationship between MDS and mortality within other subgroups. In the sensitivity analyses, our results remained robust. Conclusions An increase in MDS is significantly correlated with a higher risk of all-cause and cardiovascular mortality in diabetic patients. The risk of all-cause mortality was higher in diabetic patients aged <60. Early monitoring and management of MDS, as well as optimizing magnesium nutritional status, may benefit diabetic patients.

Increasing certainty in projected local extreme precipitation change

Motivation, barriers and preferences of lifestyle changes among older adults with frailty and mild cognitive impairments: A scoping review of qualitative analysis

Lifestyle intervention has proven effective in managing older adults’ frailty and mild cognitive impairment issues. What remains unclear is how best to encourage lifestyle changes among older adults with frailty and Mild Cognitive Impairment (MCI). We conducted searches in electronic literature searches such as PubMed, Scopus, Cochrane Reviews, ProQuest, and grey resources to find articles published in English between January 2010 and October 2023. This review focused on research using a qualitative study design. We extracted data on publication year, location, the aim of the study, study population, involved intervention, barriers, motivations, and preferences reported in the articles. Out of 5226 retrieved, 253 articles were selected after the deletion of duplicates, title, abstract screening, and. We included fourteen articles for final analysis at the end of the review process. The two main themes generated from this review are intrinsic and extrinsic factors in motivations and barriers to lifestyle changes. The most reported motivators were the perceived benefits of lifestyle intervention and self-efficacy. Among the obstacles participants face are perceived adverse effects of intervention, lack of knowledge, existing impairment (physical or mental), and social support. Lifestyle change motivations and barriers among older adults mainly were intrinsic factors such as the perceived benefit of the intervention, self-efficacy, knowledge, familial commitment, and existing impairments. There is a need to empower older adults to overcome the barriers with support from healthcare professionals, the community, and the family.

Dynamic allostery in the peptide/MHC complex enables TCR neoantigen selectivity

Abstract The inherent antigen cross-reactivity of the T cell receptor (TCR) is balanced by high specificity. Surprisingly, TCR specificity often manifests in ways not easily interpreted from static structures. Here we show that TCR discrimination between an HLA-A*03:01 (HLA-A3)-restricted public neoantigen and its wild-type (WT) counterpart emerges from distinct motions within the HLA-A3 peptide binding groove that vary with the identity of the peptide’s first primary anchor. These motions create a dynamic gate that, in the presence of the WT peptide, impedes a large conformational change required for TCR binding. The neoantigen is insusceptible to this limiting dynamic, and, with the gate open, upon TCR binding the central tryptophan can transit underneath the peptide backbone to the opposing side of the HLA-A3 peptide binding groove. Our findings thus reveal a novel mechanism driving TCR specificity for a cancer neoantigen that is rooted in the dynamic and allosteric nature of peptide/MHC-I binding grooves, with implications for resolving long-standing and often confounding questions about T cell specificity.

A high-valence bismuth(V) nanoplatform triggers cancer cell death and anti-tumor immune responses with exogenous excitation-free endogenous H2O2- and O2-independent ROS generation

Fast 3D printing of fine, continuous, and soft fibers via embedded solvent exchange

Centromere positioning orchestrates telomere bouquet formation and the initiation of meiotic differentiation

Positively charged specificity site in cyclin B1 is essential for mitotic fidelity

Abstract Phosphorylation of substrates by cyclin-dependent kinases (CDKs) is the driving force of cell cycle progression. Several CDK-activating cyclins are involved, yet how they contribute to substrate specificity is still poorly understood. Here, we discover that a positively charged pocket in cyclin B1, which is exclusively conserved within B-type cyclins and binds phosphorylated serine- or threonine-residues, is essential for correct execution of mitosis. HeLa cells expressing pocket mutant cyclin B1 are strongly delayed in anaphase onset due to multiple defects in mitotic spindle function and timely activation of the E3 ligase APC/C. Pocket integrity is essential for APC/C phosphorylation particularly at non-consensus CDK1 sites and full in vitro ubiquitylation activity. Our results support a model in which cyclin B1’s pocket facilitates sequential substrate phosphorylations involving initial priming events that assist subsequent pocket-dependent phosphorylations even at non-consensus CDK1 motifs.

A dendritic hexamer acceptor enables 19.4% efficiency with exceptional stability in organic solar cells

Abstract To achieve the commercialization of organic solar cells (OSCs), it is crucial not only to enhance power conversion efficiency (PCE) but also to improve device stability through rational molecular design. Recently emerging giant molecular acceptor (GMA) materials offer various advantages, such as precise chemical structure, high molecular weight (beneficial to film stability under several external stress), and impressive device efficiency, making them a promising candidate. Here, we report a dendritic hexamer acceptor developed through a branch-connecting strategy, which overcomes the molecular weight bottleneck of GMAs and achieves a high production yield over 58%. The dendritic acceptor Six-IC exhibits modulated crystallinity and miscibility with the donor, thus better morphology performance compared to its monomer, DTC8. Its charge transport ability is further enhanced by additional channels between the armed units. Consequently, the binary OSCs based on D18:Six-IC achieves a cutting-edge efficiency of 19.4% for high-molecular weight acceptor based systems, as well as decent device stability and film ductility. This work reports high-performance OSCs based on dendritic molecule acceptor with a molecular weight exceeding 10000 g/mol and shares the understanding for designing comprehensively high-performing acceptor materials.

A data-consistent model of the last glaciation in the Alps achieved with physics-driven AI

Abstract 25 thousand years ago, the European Alps were covered by the kilometre-thick Alpine Ice Field. Numerical modelling of this glaciation has been challenged by model-data disagreements, including overestimations of ice thickness. We tackle this issue by applying the Instructed Glacier Model, a three-dimensional model enhanced with physics-informed machine learning. This approach allows us to produce 100 Alps-wide and 17 thousand-year-long simulations at 300 m resolution. Previously unfeasible due to computational costs, our experiment both increases model-data agreement in ice extent and reduces the offset in ice thickness by between 200% and 450% relative to previous studies. Our results have implications for better estimating former ice velocities, ice temperature, basal conditions, erosion processes, and paleoclimate in the Alps. This study demonstrates that physics-informed machine learning can help overcome the bottleneck of high-resolution glacier modelling and better test parameterisations, both of which are required to accurately describe complex topographies and ice dynamics.

Fluorescein-based SynNotch adaptors for regulating gene expression responses to diverse extracellular and matrix-based cues

Camel milk is a neglected source of brucellosis among rural Arab communities

Abstract The World Health Organization describes brucellosis as one of the world’s leading zoonotic diseases, with the Middle East a global hotspot. Brucella melitensis is endemic among livestock populations in the region, with zoonotic transmission occurring via consumption of raw milk, amongst other routes. Control is largely via vaccination of small ruminant and cattle populations. Due to sociocultural and religious influences camel milk (camelus dromedarius) is widely consumed raw, while milk from other livestock species is largely boiled. To investigate the potential public health impact of Brucella in camels we conduct a cross-sectional study in southern Jordan including 227 herds and 202 livestock-owning households. Here we show daily consumption of raw camel milk is associated with Brucella seropositive status among the study population, ORadj 2.19 (95%CI 1.23–3.94) on multivariable analysis, highlighting the need for socioculturally appropriate control measures; targeted interventions among the camel reservoir being crucial for effective control.

Non-linear enhancement of ultrafast X-ray diffraction through transient resonances

Abstract Diffraction-before-destruction imaging with ultrashort X-ray pulses can visualize non-equilibrium processes, such as chemical reactions, with sub-femtosecond precision in the native environment. Here, a nanospecimen diffracts a single X-ray flash before it disintegrates. The sample structure can be reconstructed from the coherent diffraction image (CDI). State-of-the-art X-ray snapshots lack high spatial resolution because of weak diffraction signal. Bleaching effects from photo-ionization significantly restrain image brightness scaling. We find that non-linear transient ion resonances can overcome this barrier if X-ray laser pulses are shorter than in most experiments. We compared snapshots from individual  ≈ 100 nm Xe nanoparticles as a function of pulse duration and incoming X-ray fluence. Our experimental results and Monte Carlo simulations suggest that transient resonances can increase ionic scattering cross sections significantly beyond literature values. This provides a novel avenue towards substantial improvement of the spatial resolution in CDI in combination with sub-femtosecond temporal precision at the nanoscale.

Spatiotemporal transcriptome and metabolome landscapes of cotton fiber during initiation and early development

Super elastic and negative triboelectric polymer matrix for high performance mechanoluminescent platforms

Sun-simulated-driven production of high-purity methanol from carbon dioxide

Reconstructing skeletal homeostasis through allogeneic hematopoietic stem cell transplantation in myelofibrosis

Abstract Myeloproliferative neoplasm-associated myelofibrosis is a clonal stem cell process characterized by pronounced bone marrow fibrosis associated with extramedullary hematopoiesis and splenomegaly. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only curative treatment leading to bone marrow fibrosis regression. Here we provide an in-depth skeletal characterization of myelofibrosis patients before and after allo-HSCT utilizing clinical high-resolution imaging, laboratory analyses, and bone biopsy studies. Despite unimpaired bone microarchitecture at peripheral skeletal sites, we observe a marked increase in bone mineral density at the lumbar spine and proximal femur, which is histologically related to severe bone marrow fibrosis and osteosclerosis, fully normalizing after allo-HSCT. Importantly, the regression of fibrosis is accompanied by vanishing osteosclerosis along with restored osteoclastic resorption activity and whole-body calcium homeostasis. Together, our results provide evidence for an extensive reconstruction of skeletal homeostasis by allo-HSCT in MF, leading to rapid resolution of osteosclerosis.

‘Publish or perish’ culture blamed for reproducibility crisis

Paralysed man flies virtual drone using brain implant

Nomogram models for predicting outcomes in thyroid cancer patients with distant metastasis receiving 131iodine therapy

Abstract This study aimed to establish and validate prognostic nomogram models for patients who underwent 131I therapy for thyroid cancer with distant metastases. The cohort was divided into training (70%) and validation (30%) sets for nomogram development. Univariate and multivariate Cox regression analyses were used to identify independent predictors for overall survival (OS) and progression-free survival (PFS). Nomograms were developed based on these predictors, and Kaplan-Meier curves were constructed for validation. Among 451 patients who were screened, 412 met the inclusion criteria and were followed-up for a median duration of 65.2 months. The training and validation sets included 288 and 124 patients, respectively. Pathological type, first 131I administrated activity, and lesion 131I uptake in lesions were independent predictors for PFS. For OS, predictors included gender, age, metastasis site, first 131I administrated activity, 131I uptake, pulmonary lesion size, and stimulated thyroglobulin levels. These predictors were used to construct nomograms for predicting PFS and OS. Low-risk patients had significantly longer PFS and OS compared to high-risk patients, with 10-year PFS rates of 81.1% vs. 51.9% and 10-year OS rates of 86.2% vs. 37.4%. These may aid individualized prognostic assessment and clinical decision-making, especially in determining the prescribed activity for the first 131I treatment.